SchizGenes

SCHIZOPHRENIA GENES KEGG POLYGENIC PATHWAYs traced out by these genes
and Diverse Kegg pathway analysis of GWAS and other networks
Schizophrenia: A pathogenetic autoimmune disease caused by viruses and pathogens and dependent on genes.J.Pathogens in press
PolygenicBlog on the relationships between genes and risk factors

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As of 12/02/2011 all genes have been moved to the risk factor page where genes and environmental factors are shown together.

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Genes associated with schizophrenia are grouped into families relating to their general overall function. The tables link to ENTREZ, OMIM and citations for each gene. Protein/protein interactions are generally culled from information available from the ENTREZ gene hyperlink unless otherwise referenced. (See below for chromosomal region linkage/gene association concordance).BIOCAR7TA pathway links are provided for some genes (see Terms and conditions) and Disclaimer . GeneCards links are with the kind permission of GeneCards.org: ENVIRONMENTAL RISK FACTORS ARE INCLUDED HERE

Genes2cognition proteomics: Enhanced Links to genes are provided by

A large number of the protein products of these genes (DLG2, DPYSL2, GRM3, GRM5, GRIN1, GRIN2A, GRIN2B, GRIN2D, GSK3B, HOMER1,HOMER2, LGI1, MOG, NOS1, NDUFV2, PLA2, PLP1, SLC1A2, STX1A, SYNGR1, YWHAH ) are components of the NMDA receptor complex G2C.These and others (CALR, FYN, GABBR1, GAD1, GNAS, GRIA1, GRIA4, GRM3, GRM7, KIF2, NRXN1, NUMBl, PICK1, PDE4B, PIP5K2A, S100B, SLC25A1, SOD2, MAP6, SYN2, SYN3, XRCC1) are components of the postsynaptic density G2C. ADRA1A, ARCVF, APC, DISC1 , DRPLA, NCAM1, NPTN, PAWR, PAX6, RGS4, ZDHHC8, GRIK3, GRIK4 can also be related to elements of the postsynaptic density or the control of NMDA receptor function (see below). About 25% of the genes so far associated with schizophrenia can be related to this complex.

Genes involved in both Bipolar disorder and schizophrenia

PI3K/AKT signalling, growth factors and related ANK3, AKT1, BDNF, BMP6, CABIN1, EGFR, FYN, GSK3B, IMPA2, NRG1, PIK3C3, PIK4CA, PIP5K2A, PDLIM5, RGS4, TCF4, WDFY2

Adhesion/ Junctions CNTNAP2, JAM3, NCAM1, NRXN1

NMDA and glutamate-related CIT, DAO, DAOA, DTNBP1, GRIA1, GRID1, GRIN1, GRIN2A, GRIN2B, GRIK4, GRM3, GRM4, GRM7, NOS1, NOSIAP, SNAP25, SYN3, SYNJ1

Dopaminergic/Serotonergic COMT, DRD2, DRD3, HTR2A, HTR5A, HTR6, SLC6A3, SLC6A4,SLC18A1, SLC18A2, MAOA, TDO2, TH

GABA GABRA1, GABRB2, GAD1

Circadian CLOCK, NPAS2, NR1D1, TIMELESS, PER3

Cytokines CSF2RB, IL1B, IL1RN, IL6, IL10, TNFA

Oxidative and other stress ND4, NDUFV2, MTHFR, MTHFD, MTR, NOS3

Endoplasmic reticulum stress XBP1

Miscellaneous ACE, ABCB1, ABCA13, AGT, APOE, BRD1, C10orf120, CACNA1C, CDKN2A, CHRNA7, DISC1, DPYSL2, FABP7, FBXO38. GLT8D1, GNL3, GPR50, GPR78, hCAP-D3, INTS6, ITIH3, MC5R, MCHR1, MCHR2, MLC1, MMP9, MRCL3, MRLC2, NALCN , NEK4, NPAS3, PB1, PDE4B,PFN4, PPARD, PPP3CC, PSKH1, RELN, S100B, SEMG2, SLIT3, SP4, SST, SYNGR1, TAAR6, TMEM108, TP53I3, TSNAX, TSPAN8, TUBA8, YWHAH, ZNF804A

Entrez Gene Links	General Function and protein/protein interactions	Positive association evidence
Genes controlling glutamate receptor agonist availability
DAO D-amino acid oxidase OMIM GeneCards	Metabolises the NMDA receptor glycine site agonist D-serine (Chumakov et al., 2002)	Associated in Chinese, French, German Israeli and Scottish case studies(Chumakov et al., 2002)(Korostishevsky et al., 2004;Liu et al., 2004;Ma et al., 2006;Schumacher et al., 2004)
DAOA D-amino acid oxidase activator OMIM GeneCards	Activates DAO (Chumakov et al., 2002)	Associated in American, Chinese, French, German and Israeli case studies (Addington et al., 2004;Chumakov et al., 2002;Korostishevsky et al., 2004;Schumacher et al., 2004;Wang et al., 2004). .
SRR Serine racemase GeneCards	Converts L-serine to D-Serine: Binds to PICK1 (Fujii et al., 2005 )	Association reported in a Japanese study Morita et al, 2006
CBS cystathionine-beta-synthase	converts homocysteine to cystathionine	Russian study Golimbet at al, 2009
KMO kynurenine 3-monooxygenase (kynurenine 3-hydroxylase)	Tryptophan metabolism: related to hynurenate and quinolinate: NMDA antagonists and agonists respectively	Japanese study Aoyama et al, 2006
MTR 5-methyltetrahydrofolate-homocysteine methyltransferase OMIM GeneCards	5-methyltetrahydrofolate + L-homocysteine = tetrahydrofolate + L-methionine	Association reported in a Polish case study Kempisty et al, 2007
MTHFD1 methylenetetrahydrofolate dehydrogenase (NADP+ dependent) 1, methenyltetrahydrofolate cyclohydrolase, formyltetrahydrofolate synthetase OMIM GeneCards	Multifunctional folate metabolism enzyme	Association reported in a Polish case study Kempisty et al, 2007
MTHFR Methylenetetrahydrofolate reductase OMIM 607093 GeneCards	Controls homocysteine metabolism: Homocysteine stimulates the NMDA receptor via an action at the glutamate binding site but inhibits NMDA effects via an antagonist effect at the glycine binding site (Lipton et al., 1997).	Significant association reported in a meta-analysis of 10 case studies (Muntjewerff et al., 2005). Homocysteine and NMDA
NAALAD2 N-acetylated alpha-linked acidic dipeptidase 2 GeneCards	Hydrolyses N-acetylaspartylglutamate (NAAG) to glutamate and N-acetyl aspartate. NAAG is both a metabotropic receptor agonist (GRM3) and an NMDA receptor partial agonist (Coyle, 1997)	Situated at the chromosome 11 breakpoint of the chromosome1/11 translocation reported to associate with schizophrenia (Semple et al., 2001) N-acetylaspartate schizophrenia
SLC15A1 solute carrier family 15 (oligopeptide transporter), member 1 (PEPT1) GeneCards	Dipeptide transporter whose substrates include NAAG, the NAALAD2 substrate (Sala-Rabanal et al, 2006)	Association reported in Askenazi Jewish families (Fallin et al., 2005)
PRODH Proline dehydrogenase OMIM 606810 GeneCards	Proline can be a precursor for glutamate via PRODH (Thompson et al., 1985).	Association reported in American Chinese and French family studies (Li et al., 2004a;Liu et al., 2002a),(Jacquet et al., 2002).
SLC1A2 solute carrier family 1 (glial high affinity glutamate transporter), member 2 OMIM 600300 GeneCards	Glutamate and cysteine transporter Expression in astrocytes positively modulated by GRM3 and negatively modulated by GRM5 Aronica et al, 2003. Expression increased by BDNF (Rodriguez-kern et al, 2003) and by AKT1 in astrocytes (Li et al,2006)	Association reported in a Japanese case study (Deng et al., 2004b).
SLC1A4 solute carrier family 1 (glutamate/neutral amino acid transporter), member 4	Glutamate transporter	Japanese study Deng et al, 2008
SLC1A6 solute carrier family 1 (high affinity aspartate/glutamate transporter), member 6	Glutamate transporter	Japanese study Deng et al, 2007
SLC6A5 solute carrier family 6 (neurotransmitter transporter, glycine), member 5	Transports the NMDA receptor co-agonist glycine	Japanese study Deng et al, 2008
SLC17A7 solute carrier family 17 (sodium-dependent inorganic phosphate cotransporter), member 7 (VGLUT1)	Glutamate transporter	Taiwanese study of rare variants Shen et al, 2009
SLC17A6 solute carrier family 17 (sodium-dependent inorganic phosphate cotransporter), member 6 VGLUT2		Taiwan study Shen et al, 2010
Table 2: Genes controlling glutamate packaging and release and presynaptic function
NOSIAP (CAPON) (also postsynaptic) OMIM 605551 GeneCards	Binds to NOS1 and synapsins (SYN1, SYN2, SYN3)	Linked in American family and associated in Columbian and Chinese case studies (Brzustowicz et al., 2004;Miranda et al., 2005;Zheng et al., 2005)
CPLX2 Complexin II OMIM 605033 GeneCards	Syntaxin binding protein involved in synaptic vesicle exocytosis	Association reported in a Korean case study (Lee et al., 2005).
DTNBP1 Dysbindin OMIM 607145 GeneCards	Positively regulates glutamate release and upregulates the expression of presynaptic proteins SYN1, SNAP25 (Numakawa et al., 2004). Also part of the biogenesis of organelles complex involved in endosome to lysosome transport. Dysbindin or MUTED knockdown blocks D2 dopamine receptor (DRD2) internalisation, increasing cell surface expression Iizuka et al, 2007	Association reported in multiple case and family studies (Straub et al., 2002;Tang et al., 2003b;van den Oord et al., 2003;Van Den et al., 2003;Williams et al., 2004a).
CMYA5 cardiomyopathy associated 5	Binds to dysbindin	GWAS 2010
BLOC1S3 biogenesis of lysosome-related organelles complex-1, subunit 3 GeneCards	Components of this complex are involved in the biogenesis of organelles including melanosomes and platelet-dense granules. Includes DTNB1 and MUTED inter alia See HERMANSKY-PUDLAK SYNDROME	Irish studyMorris et al, 2007
MUTED Muted GeneCards	see above. Dysbindin or MUTED knockdown blocks D2 dopamine receptor (DRD2) internalisation, increasing cell surface expression Iizuka et al, 2007	Irish studyMorris et al, 2007
ENTH Epsin 4 OMIM 607262 GeneCards	Transport of synaptic vesicles (Pimm et al., 2005)	Associated with schizophrenia in a British study (Pimm et al., 2005) and in a chinese family study (Tang et al 2006)
SHANK3 SH3 and multiple ankyrin repeat domains 3	Postsynaptic density protein Binds to SPTAN1 (DISC1 partner) and PAX6	Mutations observed in two families Gauthier et al, 2010
SNAP25 synaptosomal-associated protein, 25kDa	Synaptic vesicle and transmitter release	Irish study Fanous et al, 2010
SNAP29 OMIM 604202 GeneCards	Syntaxin binding protein involved in glutamate release; Binds to STX1A	Association reported in an American case study (Saito et al., 2001)
SYN2 Synapsin II OMIM 600755 GeneCards	Associated with synaptic vesicles and glutamate release. Binds to CAPON and SYN3 .Expression regulated by DRD1 and DRD2 receptors (Chong et al, 2006)	Association in Chinese and Korean case studies (Chen et al., 2004a;Lee et al., 2005) and in a family based chinese study {8923}
SYN3 Synapsin III OMIM 602705 GeneCards	Associated with synaptic vesicles and glutamate release. Binds to CAPON and SYN2	Association reported in American case studies(Lachman et al., 2005;Porton et al., 2004)
SYT11 Synaptotagmin XI GeneCards	Family of memrane trafficking proteins involved in transmitter release	Association reported in a Japanese study Inoue at al, 2007
STX1A Syntaxin 1a OMIM 186590 GeneCards	Function in vesicle fusion and transmitter release Binds to complexins, SLC6A3, SLC6A4, SLC6A5 and SNAP29	Association reported in a Canadian case study (Wong et al., 2004).
SYNGR1 Synaptogyrin 1 OMIM 603925 GeneCards	Associated with presynaptic vesicles.	Nonsense mutation in an Indian family (Verma et al., 2004). Association also revealed in non-familial cases (Verma et al., 2005a)
GABBR1 GABA-B receptor 1 OMIM 603540 GeneCards	Agonists inhibit glutamate release.Binds to ATF4 and ATF5 White at al, 2000(as does DISC1). Also associates with YWHAH (Couve at al, 2001)	Weakly associated with schizophrenia in Japanese family and European case studies (Imai et al., 2002) (Zai et al., 2005).
GABRG2 gamma-aminobutyric acid (GABA) A receptor, gamma 2		Canadian study Zai et al, 2009
GRM3 Metabotropic glutamate receptor mgluR3 OMIM 601115 GeneCards	Binds to PICK1 . Agonists inhibit glutamate release.	Association reported in Japanese and Chinese case studies (Fujii et al., 2003) (Chen et al., 2005) and in a family based American study (Egan et al., 2004)
GRM4 Metabotropic glutamate receptor mgluR4 OMIM 604100 GeneCards	Agonists inhibit glutamate release	Association reported in Ashenazi Jewish families (Fallin et al., 2005)
GRM7 glutamate receptor, metabotropic 7 GeneCards	Binds to PICK1 and TUBA8	Association reported in a Japanese study Ohtsuki et al, 2008
GRM8 Metabotropic glutamate receptor mgluR8 OMIM 601116 GeneCards	Agonists inhibit glutamate release	Associated with schizophrenia in a Japanese case study (Takaki et al., 2004)
APBA2 amyloid beta (A4) precursor protein-binding, family A, member 2 (X11-like) GeneCards	Binds to NRXN1 ( see Entrez gene)	Duplication observed in a UK study Kirov et al, 2007
NRXN1 Neurexin 1 GeneCards	regulates synapse formation Chubykin et al, 2005 Binds to APBA2 (see Entrez gene)	Deletion disrupting NRXN1 observed in a UK study Kirov et al, 2007
Other genes whose products affect glutamate release or uptake	BDNF enhances depolarization-evoked glutamate release in cortical neurones (Balkowiec and Katz, 2002). Nicotinic CHRNA7 agonists stimulate glutamate release in the hippocampus and frontal cortex (Liu et al., 2003b;Marchi et al., 2002).CNR1 agonists inhibit glutamate release in a number of brain regions (Wang, 2003) (Gerdeman and Lovinger, 2001). GRM3, GRM4 and GRM8 receptor activation inhibits glutamate release (DD and Marek, 2002;Guo and Ikeda, 2005). HTR2A agonists stimulate frontal cortical glutamate release (Aghajanian and Marek, 1999), HTR6 receptor antagonism selectively increases glutamate release in the frontal cortex and hippocampus (Dawson et al., 2001). DRD2 receptor activation inhibits striatal and accumbens glutamate release (Bamford et al, 2004, Kalivas and Duffy, 1997)) HTR7 stimulation inhibits glutamate release in the dorsal raphe (Harsing, Jr. et al., 2004). IL1B and TNFA inhibit glutamate uptake into astrocytes and this effect is blocked by NO synthase inhibitors and mimicked by NO donors (Hu et al., 2000;Ye and Sontheimer, 1996). S100B stimulates glutamate uptake into astrocytes (Tramontina et al, 2006). NPY inhibits hippocampal glutamate release and blocks LTP(Whittaker et al., 1999).
Genes coding for glutamate receptors and scaffold proteins, and related.
CIT Citron kinase	Binds to DISC1, GRIN1, GRIN2D	USA study Nicodemus et al, 2010
GRIA1 AMPA receptor subunit OMIM 138248 GeneCards	AMPA receptor Binds to PICK1,GRIA4, HOMER1	Association reported in an Italian case study Magri et al, 2006
GRIA3 glutamate receptor, ionotrophic, AMPA 3 GeneCards	AMPA receptor	Association restricted to females in an italian case study Magri et al, 2008
GRIA4 (AMPA receptor subunit ) OMIM 138246 GeneCards	AMPA receptor: Binds to PICK1 (Xia et al., 1999) and GRIA1	Association demonstrated in a Japanese case study(Makino et al., 2003).
GRIK2 glutamate receptor, ionotropic, kainate 2	Kainate receptor subunit	French study Bah et al, 2004
GRIK3 Kainate receptor OMIM 138243 GeneCards	Kainate receptor subunit	Association reported in an Italian case study (Begni et al., 2002).
GRIK4 Kainate receptor OMIM 600282 GeneCards	Kainate receptor subunit	Association with bipolar disorder and schizophrenia reported in a Scottish case study (Pickard et al., 2006)
GRID1 glutamate receptor, ionotropic, delta 1 GeneCards		Association reported in Askenazi Jewish families (Fallin et al., 2005)
GOPC golgi-associated PDZ and coiled-coil motif containing	Binds to GRID1 and GRID2	GWAS Moskvina et al, 2009
GRIN1 (NMDA receptor subunit NR1) OMIM 138249 GeneCards	Binds to GRIN2A, GRIN2B, DLG2	Association reported in American, Chinese and Italian case studies (Begni et al., 2003;Martucci et al., 2003;Qin et al., 2005; Zhao et al, 2006).
GRIN2A NMDA receptor subunit NR2A OMIM 138253 GeneCards	Binds to GRIN1, DLG2	Association reported in two Japanese case studies (Itokawa et al., 2003b;Iwayama-Shigeno et al., 2005)
GRIN2B NMDA receptor subunit NR2B OMIM 138252 GeneCards	Binds to GRIN1, DLG2	Association reported in Japanese Chinese and Italian case studies. (Di Maria et al., 2004;Miyatake et al., 2002;Ohtsuki et al., 2001))
GRIN2D NMDA receptor subunit NR2D OMIM 602717 GeneCards	Binds to GRIN1	Association reported in a Japanese case study (Makino et al., 2005)
GRM5 Metabotropic glutamate receptor mgluR5 OMIM 604102 GeneCards	GRM5 receptor activation potentiates both AMPA and NMDA receptor mediated responses (Ugolini et al., 1999) (Awad et al., 2000;Doherty et al., 2000) Interacts with RGS4 Schwenst and McGinty, 2007	Association in a British case study (Devon et al., 2001). Located at the Chromosome 11 breakpoint associated with schizophrenia (Semple et al., 2001) .
APC adenomatous polyposis coli (colorectal tumor suppressor) OMIM 175100 GeneCards	Binds to PSD-95 and GRIN2B and is a component of the NMDA receptor PSD-95 complex (Yanai et al, 2000)	Association in a Chinese family study(Cui et al, 2005)
ARVCF armadillo repeat gene deleted in velocardiofacial syndrome OMIM 602269 GeneCards	ARVCF binds to the PDZ domain of erbin (ERBB2IP) (Laura et al., 2002) a protein concentrated in postsynaptic membranes which binds to PSD-95 and to the NRG1 receptor ERBB2 (Huang et al., 2001)	Possible association in a Chinese family study (Xie et al., 2005).
ATXN1 (SCA1): ataxin 1) OMIM 601556 GeneCards	Metabotropic mGluR1 (GRM1), NMDA-like (GRID1/GRID2) and AMPA receptor GRIA2/3 trafficking is altered in mutant ATXN1 transgenic mice (Skinner et al., 2001). Possible role in ubiquitin-proteasome and chaperone system Davidson et al, 2000	CAG repeats in this gene have been reported to associate with schizophrenia in American case (Joo et al., 1999)or family (Pujana et al., 1997)studies (Pujana et al., 1997).Association also reported in Ashkenazi Jewish families (Fallin et al., 2005)
DLG1 discs, large homolog 1	Related to GRIN2A, GRIN2B, GRIA1, GRIK2	Japanes study Sato et al, 2008
DLG2 Chapsyn-110 OMIM 603583 GeneCards	Postsynaptic scaffold protein; Binds to GRIN1, GRIN2A, GRIN2B, NOS1 and NRG1 receptor ERBB4	DLG2 polymorphisms have not been reported in schizophrenia. However, PSZA11q14 is located in the first intron of and is antisense to DLG2 and has been suggested as a candidate gene for schizophrenia (Polesskaya et al., 2003).
DRPLA dentatorubral-pallidoluysian atrophy or atrophin-1 OMIM 607462 GeneCards	Interacts with an insulin receptor tyrosine kinase substrate BAIAP2 (Okamura-Oho et al., 1999) which is localised in postsynaptic densities and binds to PSD-95 and DLG2 (Choi et al., 2005).	Possible association of a CAG repeat in one family study(Morris-Rosendahl et al., 1997).
EFNB2 Ephrin B2		Chinese study Zhang et al, 2010
HOMER1 OMIM 604798 GeneCards	Controls the localisation and clustering of Group 1 metabotropic glutamate receptors, GRM1 and GRM5 (Ango et al., 2000;Tadokoro et al., 1999). NMDA and GRM5 receptors are linked via HOMER and Shank (Tu et al., 1999). Gene ID 9456	Borderline association in a British case study (Norton et al., 2003).
HOMER2 Homer hololog 2	Regulates GRM1 GRIA1 and GRIK1	Irish study Gilks et al, 2010
LGI1 leucine-rich, glioma inactivated 1 OMIM 604619 GeneCards	Binds to ADAM22 and potentiates AMPA responses in the hippocampus (Fukata et al, 2006	Association reported in an Askenazi case-parent trio study(Fallin et al., 2005)
NPTN neuroplastin GeneCards	Inhibits hippocampal LTP by reducing the surface expression of AMPA receptors (Empson et al, 2006)	Saito et al, 2006
PICK1 protein kinase C alpha binding protein OMIM 605926 GeneCards	Controls AMPA receptor clustering (Hanley and Henley, 2005) and binds to a number of AMPA receptor subunits including GRIA1 and GRIA4 (Xia et al., 1999).Also binds to the metabotropic receptor GRM3 (Hirbec et al., 2002) , the dopamine transporter SLC6A3 (Torres et al., 2001), NRG1 receptor ERBB2 (Jaulin-Bastard et al., 2001) and to serine racemase (SRR) an enzyme responsible for the synthesis of the NMDA co-agonist D-Serine (Fujii et al., 2005). Gene ID 2893	Association reported in Taiwanese and Japanese case studies (Fujii et al., 2005;Hong et al., 2004b).
RGS4 regulator of G-protein signalling 4 OMIM 602516 GeneCards	Binds to NRG1 receptor ERBB3 (se Gene data). nhibits signaling via GRM1 and GRM5 (Saugstad et al, 1998) Transcription regulated by PHOX2B. Grillet et al, 2003	Suggested as a susceptibility gene in Indian family, Irish case, Israeli family, and Welsh case studies (Chowdari et al., 2002;Fallin et al., 2005;Morris et al., 2004;Williams et al., 2004b)
ZDHHC8 zinc finger, DHHC domain containing 8 OMIM 608784 GeneCards	Localised to vesicle-like clusters along dendritic shafts occasionally colocalising with PSD-95 and the NMDA receptor subunit GRIN2B (Mukai et al., 2004). Gene ID 29801	Associated in American and Chinese case studies (Chen et al., 2004c;Mukai et al., 2004).
NPAS3 neuronal PAS domain protein 3 OMIM 609430 GeneCards	Altered PSD-95 expression and impaired glutamatergic signalling are observed in NPAS3 knockout mice (Brunskill et al., 2005).	Situated in the breakpoint of a t(9;14)(q34;q13) translocation in a mother and daughter affected by schizophrenia (Kamnasaran et al., 2003).
PPP1R1B protein phosphatase 1, regulatory (inhibitor) subunit 1B (dopamine and cAMP regulated phosphoprotein, DARPP-32) GeneCards	Dopamine D1 receptor simulation increases phosphorlation: Dephosphorylated by AMPA and NMDA receptor activation Nishi et al, 2002	Association observed in an american family-based study.Meyer-Lindenberg et al, 2007
Genes whose products affect NMDA receptor activation or elements of the postsynaptic scaffold Protein products associated with the postsynaptic density (Genes to Cognition)	AKT1 is activated by NMDA receptor stimulation and phosphorylates NMDA receptors, potentiating their effects (Sanchez-Perez et al, 2006) . BDNF potentiates NMDA receptor mediated responses via a specific action at GRIN2B) (Levine and Kolb, 2000). In the cortex, BDNF stimulates the expression of AMPA receptors and maintains their elevated activity (Balkowiec and Katz, 2002;Nagano et al., 2003). BDNF increases the expression of a number of PDZ domain proteins, including DLG1, GRIP1 and PICK1 in cortical culture (Jourdi et al., 2003). DISC1 binds to elements of the postsynaptic glutamate receptor scaffold (AKAP9, ACTN2, GRIPAP1, HAPIP, SPTAN1) (Millar et al., 2003). GRM5 receptor activation potentiates both AMPA and NMDA receptor mediated responses (Ugolini et al., 1999) (Awad et al., 2000). NRG1 inhibits NMDA receptor mediated responses in the prefrontal cortex and increases the internalisation of the NR1 subunit (GRIN1) of the NMDA receptor (Gu et al., 2005). PAX6 binds to elements of the postsnaptic scaffold (Cooper and Hanson, 2005) Dopamine can both potentiate and inhibit NMDA responses in the frontal cortex. The stimulatory effects are mediated by DRD1/DRD5 receptor activation (Wirkner et al., 2004) via a direct coupling of DRD1 to GRIN1 and GRIN2A (Lee et al., 2002). DRD2 and DRD4 agonists repress NMDA responses in the hippocampus via transactivation of the platelet derived growth factor receptor PDGFRA (Kotecha et al., 2002) (Ferguson, 2003) and DRD4 agonists inhibit NMDA effects in prefrontal cortex (Wang et al., 2003). EGF enhances NMDA receptor mediated responses in the hippocampus (Abe and Saito, 1992) and facilitates hippocampal LTP (Abe et al., 1991;Ishiyama et al., 1991). IL1B inhibits NMDA receptor mediated synaptic responses in the rat dentate gyrus (Coogan and O'Connor, 1997).
Table 4: Genes coding for downstream signalling effectors and related
HMBS Hydroxymethylbilane synthase (Invoved in heme synthesis) OMIM 609806 GeneCards	NOS1 (Boehning and Snyder, 2003) and PTGS2 (Percival et al., 1994) are heme dependent enzymes. HMBS is part of the heme synthesis pathway.	Association reported in an American case study (Sanders et al., 1993)
NOS1Nitric oxide synthase OMIM 163731 GeneCards BIOCARTA	Stimulated by NMDA receptor activation via PSD95 (DLG4 Gene ID 1742) which associates with NMDA and NRG1 receptors ERBB2 and ERBB4: Binds to DLG2 and CAPON:	Association described in Japanese and German case studies and in Askenazi Jewish families (Shinkai et al., 2002) (Fallin et al., 2005) (Reif et al., 2006). GWAS Moskvina et al, 2009
PLA2G4Aphospholipase A2, group IVA (Cytosolic, calcium-dependent) OMIM 600522 GeneCards	Cytosolic Phospholipase A2 activity is stimulated by the free radical derivative of nitric oxide and superoxide, peroxynitrite (Guidarelli et al., 2000;Tommasini et al., 2002) and by NMDA receptor activation in the striatum (L'hirondel et al., 1999).	Associated in American case and family, British family and Chinese family studies(Hudson et al., 1996;Tao et al., 2005b;Wei and Hemmings, 2004a;Yu et al., 2005) .
PLA2G4B OMIM 606088 GeneCards		Associated in a Chinese family (Tao et al., 2005a)
PLA2G4C OMIM 603602 GeneCards		Associated in a Chinese family study (Tao et al., 2005a)
PLA2G6 phospholipase A2, group VI (cytosolic, calcium-independent)		Brazilian study Junquiera et al, 2004
PPP3CC Calcineurin A gamma OMIM 114107 GeneCards	NMDA receptor activation stimulates NOS1 activity via calcineurin dephosphorylation of the enzyme.	Association in an American family study (Gerber et al., 2003)
PTGS2 Cyclooxygenase-2 OMIM 600262 GeneCards	Activity and expression are increased by NMDA receptor activation (Adams et al., 1996) (Pepicelli et al., 2002) Binds to TP53	Associated with schizophrenia in a British family study (Wei and Hemmings, 2004a)
SOD2 OMIM 147460 GeneCards	SOD2 activity is inhibited by NMDA receptor activation via nitration releasing superoxide into the extracellular space (Muscoli et al., 2004). Binds to TP53 (Zhao et al, 2005)	Association reported in a Turkish case study (Akyol et al., 2005).
Genes involved in neuritogenesis and plasticity
ALK (anaplastic lymphoma kinase) pleiotrophin receptor OMIM 105590 GeneCards	Promotes neurite outgrowth (Motegi et al, 2004).	Association in a Japanese case study Kunugi et al, 2006
CHN2 Chimerin (chimaerin) 2 OMIM 602857 GeneCards	CHN2 is induced by BDNF and its overexpression in cerebellar neurones prevents the inhibitory effects of myelin-associated glycoprotein (MAG) on neurite extension (Mizuno et al., 2004).	Associated with schizophrenia inmale Japanese cases (Hashimoto et al., 2005).
DPYSL2 dihydropyrimidinase-like 2 OMIM 602463 GeneCards	A member of the collapsin response mediator protein family involved in neuronal development and axon guidance (Charrier et al., 2003;Quach et al., 2004a). NMDA receptor activation results in increased calpain cleavage of DPYSL2 and the resulting product reduces the surface expression of the NMDA receptor subunit GRIN2B (Bretin et al, 2006) Binds to DISC1 (Camargo et al, 2006)	Polymorphisms in DPYSL2 have been suggested to reduce susceptibility to schizophrenia in a Japanese case study(Nakata et al., 2003). Also associated with schizophrenia in an Askenazi Jewish family study (Fallin et al., 2005) and in Caucasian and African Americans (Case study) (Hong et al., 2005)
DISC1 Disrupted in schizophrenia 1 OMIM 605210 GeneCards	Involved in neurite outgrowth and cortical development. Binds to other SZ gene products CIT, FEZ1, PCNT, PDE4B, MLC1,MYT1L, NDEL , NDE1 TRAF3IP1 and to a number of proteins associated with the glutamatergic receptor scaffold (ACTN2 ,AKAP9 , SPTAN1) as well as to DPYSL2 Camargo et al, 2006 Also binds to ATF4 and ATF5 transcription factors. (Millar et al., 2003) as does GABBR1. ATF4 binds to PTGS2 promoter (Schroer et al, 2002) ATF4 binds to nrf1 and nrf2 (NFE2L1 and NFE2L2 ) . NFE2L2 controls the transcription of genes related to glutathione/ quinone oxidative stress including GCLM, GSTM1 (Chanas et al, 2002) and NQO2 (Wang and Jaiswal, 2006) . NFE2L2 controls the expression of BDNF, CHGB, GABBR1, GSTM1, SYN2 in neurones (Lee et al, 2003) and of GSTM1 and PTGS2 in astrocytes (Lee et al, 2003). NFE2L1 controls the expression of TNF Novotny et al, 1998 and also regulates glutathione function Mhyrstad et al, 2001. The actions of NFE2L2 are inhibited by TP53 Faraonio et al,2006	DISC1 and DISC2, a non-coding sequence antisense to DISC1 are within a chromosomal translocation associated with schizophrenia and psychosis in a Scottish family (Millar et al., 2000). Subsequent American, Finnish and Scottish case studies have confirmed an association of DISC1 with schizophrenia (Blackwood and Muir, 2004;Callicott et al., 2005;Cannon et al., 2005;Hennah et al., 2003;Hodgkinson et al., 2004;Millar et al., 2001;Sachs et al., 2005;Zhang et al., 2006). MAJOR HUB GENE
FEZ1 OMIM 604825 GeneCards	Binds to DISC1: Role in neurite development and axonal outgrowth: Binds to BRD1 (Assmann et al, 2006)	Association in a Japanese case study (Yamada et al., 2004b)
KIF2A kinesin heavy chain member 2A OMIM 602951 GeneCards	Involved in BDNF-mediated neurite extension (Pfenninger et al, 2003)	Association reported in a chinese family study (Li et al, 2006)
NDE1 LIS1-interacting protein NUDE1GeneCards	Binds to DISC1	Female-specific association in Finnish familiesHennah et al, 2006
NDEL1 nudE nuclear distribution gene E homolog (A. nidulans)-like 1 GeneCards	Thiol-activated peptidase (EOPA).Role in microtubule organisation and cell migration. Binds to DISC1	DISC1-dependent association in an American study Burdick et al, 2008
NTNG1 Netrin G1 OMIM 608818 GeneCards	Promotes neurite extension in thalamic and cortical neurones (Nakashiba et al., 2002)	Associated with schizophrenia in case and family based Japanese studies (Aoki-Suzuki et al., 2005;Fukasawa et al., 2004)
NTNG2 Netrin G2 GeneCards	Promotes neurite extension in thalamic and cortical neurones (Nakashiba et al., 2002)	Associated with schizophrenia in a Japanese family study (Aoki-Suzuki et al., 2005)
PLXNA2 Plexin A2 OMIM 601054 GeneCards	Semaphorin receptor involved in axon guidance	Associated with schizophrenia in an american case study (Mah et al., 2006)
PNOC Prepronociceptin GeneCards	Precursor for nocipeptin/orphanin. Induced by BDNF in thehippocampus and plays a role in neurite outgrowth Ring et al, 2006	Association reported in an Askenazi case-parent trio study Fallin et al., 2005)
RTN4 reticulon 4 (NOGO) 604475 GeneCards	Potent neurite outgrowth inhibitor acting via RTN4R	A CAA insertion observed in schizophrenia is in the 3' untranslated region of the gene (Novak et al., 2002). Also associated with schizophrenia in females but not males in a Singaporean case study (Tan et al., 2005). .
RTN4R Reticulon 4 receptor OMIM 605566 GeneCards	RTN4 receptor that also binds to MAG.	Mutations in the RTN4R receptor were found in 3/120 schizophrenic patients and in 0/300 normal subjects. Two of the schizophrenic patients with a missense mutation were resistant to neuroleptic treatment (Sinibaldi et al., 2004).
Other genes controlling neurite/ dendrite morphology	APOE (Qiu et al., 2004), BDNF (Alonso et al., 2004),CHL1 (Demyanenko et al., 2004), CHN2 (Mizuno et al., 2004),CNR1 (Zhou and Song, 2001), DISC1 (Miyoshi et al., 2003), DPYSL2 (Quach et al., 2004b), EGF (Mark et al., 1995), FEZ1 (Miyoshi et al., 2003), HOMER (Sala et al., 2001),IL1B (Gilmore et al., 2004),IL2 (Jiang and Lu, 1998), LTP and NMDA receptor activation (GRIN1, GRIN2A, GRIN2B, GRIN2D)(Collin et al., 1997) , MAG (Domeniconi et al., 2002), NPAS3 (Pieper et al., 2005), NRG1 (Gerecke et al., 2004), NTF3 (Baker et al., 1998), RTN4 and RTN4R, TNFA (Gilmore et al., 2004)
Table 6: Growth factors, tyrosine kinase receptors, phoshoinositide kinase/AKT signaling
AKT1 v-akt murine thymoma viral oncogene homolog 1OMIM 164730 BIOCARTA GeneCards	Growth factor signalling. The AKT1 pathway is also activated by NMDA receptor stimulation and AKT1 phosphorylates NMDA receptors , potentiating their effects (Sanchez-Perez et al., 2006).	Reported as a schizophrenia susceptibility gene in American and Japanese case and Australian family studies (Emamian et al., 2004) (Ikeda et al., 2004;Schwab et al., 2005).
GSK3B glycogen synthase kinase 3 beta GeneCards	Serine threonine kinase involved in multiple signaling networks	Association in a Brazilian Case control study Souza et al, 2008
BDNF brain derived neurotrophic factor OMIM 113505 GeneCards	BDNF release is stimulated by NMDA receptor activation in the hippocampus (Jiang et al., 2005).BDNF enhances depolarization-evoked glutamate release in cortical neurones (Balkowiec and Katz, 2002).BDNF potentiates NMDA receptor mediated responses via a specific action at GRIN2B) (Levine and Kolb, 2000). In the cortex, BDNF stimulates the expression of AMPA receptors and maintains their elevated activity (Balkowiec and Katz, 2002;Nagano et al., 2003). BDNF increases the expression of a number of PDZ domain proteins, including DLG1, GRIP1 and PICK1 in cortical culture (Jourdi et al., 2003). Enhances phosphorylation of GRIN1 (Suen et al, 1997) GRIN2B (Lin et al, 1998) and GRIA1 (Wu et al, 2004). BDNF increases SLC1A2 expression in astrocytes (Rodriguez-kern et al, 2003) Involved in oligodendrocyte differentiation	Reported association in American case and family, French, Hungarian and Scottish case and Spanish family studies .(Fanous et al., 2004b;Krebs et al., 2000a;Krebs et al., 2000b;Muglia et al., 2003;Neves-Pereira et al., 2005;Rosa et al., 2006;Szekeres et al., 2003)
BMP6 bone morphogenetic protein 6		Taiwan study Lin et al, 2009
CNTF ciliary neurotrophic factor OMIM 118945 GeneCards	Growth factor: Potent survival factor for neurones astrocytes and oligodendrocytes; Promotes neurite extension. OLIG2 nuclear export in astrocytes is induced by CNTF via phosphorylation of OLIG2 by AKT1 (Setoguchi and Kondo 2004) Binds to APOE	Null mutation (Lin and Tsai, 2004;Thome et al., 1996)
DDR1 discoidin domain receptor family, member 1 GeneCards	Tyrosine kinase expressed in oligodendrocytes and activated by collagens Franco-Pons et al, 2006	Association reported in a Spanish case study Roig et al, 2007
DGKI diacylglycerol kinase, iota	Final step of PI3 kinase pathway: Phosphotylates diacylglycerol to phosphatidic acid	GWAS Moskvina et al, 2009
EFNB2 Ephrin B2	Tyrosine kinase	Association in a Chinese study Zhang et al, 2010
EGF Epidermal growth factor OMIM 131530 GeneCards	NRG1 inhibits EGF binding to either EGFR or the Neuregulin receptor ERBB2. Increases expression of SLC1A2 in astrocytes (Zelenaia et al, 2000) Involved in oligodendrocyte differentiation	Associated in a Finnish case study (Anttila et al., 2004). In one case study the association was conditional on a concurrent TNFA polymorphism (Kampman et al., 2005) In another case study association was only reported in men (Hanninen et al., 2005a) .
EGFR EGF receptor GeneCards	EGF/ NRG1, ERBB2, ERBB3 interact	Benzel et al, 2007
EGR2 early growth response 2 (Krox-20 homolog, Drosophila) GeneCards	Important role in peripheral myelination: Upregulated by NMDA receptor activation during hippocampal long-term potentiation Inokuchi et al, 1996	Yamada et al, 2007
EGR3 early growth response 3 GeneCards	Synthesis indiced by BDNF in hippocampus Roberts et al, 2006 by NMDA receptor activation Yamagata et al, 1994 and by NRG1 in muscle Jacobson et al, 2004	Yamada et al, 2007
EGR4 early growth response 4 GeneCards		Yamada et al, 2007
FGF1 fibroblast growth factor 1 (acidic) GeneCards	Plays a role in oligodendrocyte myelination (inter alia) Harari et al, 1997	Weak association in a Dutch case-control studyJungerius et al, 2007
FGF14 Fibroblast growth factor 14		Jungerius eyt al, 2007
FGF18 Fibroblast growth factor 18	Binds to FGFR1, 2, 3 and 4	Jungerius eyt al, 2007
FGFR1 fibroblast growth factor receptor 1 (fms-related tyrosine kinase 2, Pfeiffer syndrome) GeneCards	FGF1 and FGF2 receptor	Weak association in a Dutch case-control studyJungerius et al, 2007
FYN FYN oncogene related to SRC, FGR, YES GeneCards	Associated with BDNF receptor signalling (NTRK2) Iwasaki et al, 1998. Associates with GRIN2A and GRIN2B Takagi et al, 1999 BDNF enhances NMDA currents via FYN Xu et al, 2006. Involved in NCAM1 signalling Beggs et al, 1997	Rybakowski et al, 2007
GDNF Glial derived neurotrophic factor GeneCards	Ligand for GFRA1 and 2	Association reported in an Italian study Michelato et al, 2004
GFRA1 GDNF family receptor alpha 1GeneCards	GDNF and neurturin receptor. Possible involvement in oligodendrocyte development (Strelau and Unsicker 1999). Expression regulated by TNF in glial cells (Remy et al, 2003). Involved in the development and migration of cortical GABA neurones (Pozas and Ibanez,2005)	Association reported in an Ashkenazi Jewish case-parent trio study (Fallin et al., 2005).
GFRA2 GDNF family receptor alpha 2	GDNF and neurturin receptor	Canadian study Souza et al, 2010
GFRA3 GDNF family receptor alpha 3	Artemin receptor	Canadian study Souza et al, 2010
IGF2 insulin-like growth factor 2 (somatomedin A)		Croatian study Pal et al, 2009
LIF leukemia inhibitory factor (cholinergic differentiation factor)		Japanese study Okahisa et al, 2010
METmet proto-oncogene (hepatocyte growth factor receptor)		USA study Burdick et al, 2010
NEUROG1 Neurogenin 1		US study Fanous et al, 2007
NRG1 Neuregulin 1 OMIM 142445 GeneCards	Glial growth factor: NRG1 inhibits NMDA receptor mediated responses in the prefrontal cortex and increases the internalisation of GRIN1 (Gu et al., 2005). NRG1 receptor ERBB2, binds to the AMPA receptor clustering protein PICK1 (Jaulin-Bastard et al., 2001). A cleaved intracellular domain of NRG1 translocates to the nucleus binds to the PSD-95 (DLG4) promoter (Bao et al, 2004)	Association reported in Chinese, Icelandic, Portugese, Scottish and Welsh populations (Li et al., 2004b;Norton et al., 2005;Petryshen et al., 2005;Stefansson et al., 2002;Stefansson et al., 2003;Tang et al., 2003a;Williams et al., 2003b;Yang et al., 2003b).(Case and family studies).
NRG2 Neuregulin 2 GeneCards	Binds to ERBB3 and ERBB4	Benzel et al, 2007
NRG3 Neuregulin 3 GeneCards	Oligodendrocyte growth factor (Carteron et al, 2006): Binds to ERBB4	Association reported in an Ashkenazi Jewish case-parent trio study (Fallin et al., 2005).
ERBB2 v-erb-b2 erythroblastic leukemia viral oncogene homolog 2, neuro/glioblastoma derived oncogene homolog GeneCards	Heterodimerises with EGFR or ERBB3	Benzel et al, 2007
ERBB3 v-erb-b2 erythroblastic leukemia viral oncogene homolog 3	Neuregulin receptor interacting with EGFR and ERBB2	Chinese study Li et al, 2009
ERBB4 Neuregulin receptor OMIM 600543 GeneCards	Binds to NRG1 , DLG2 and PSD-95 (DLG4) . NRG1 induces the expression of NOS1 in cerebellar granule cells via ERBB4 (Krainock and Murphy, 2001b). A cleaved intracellular domain of ERBB4 phosphorylates the p53 activator MDM2 and increases TP53 levels in peripheral cells (Arasada and Carpenter 2005)	Interaction between NRG1 and ERBB4 in a UK casestudy (Norton et al., 2005). Association also reported in an Israeli case study(Silberberg et al., 2006).
IMPA2 inositol(myo)-1(or 4)-monophosphatase 2 OMIM 605922 GeneCards	PI signalling and inositol phosphate metabolism	IMPA2 associates with schizophrenia in a Japanese case study (Yoshikawa et al., 2001).
JARID2 jumonji, AT rich interactive domain 2 OMIM GeneCards	Negative regulation of cell growth Toyoda et al, 2000	Pedrosa et al,2006
NRN1 Neuritin 1		Australian study Chandler et al, 2010
NTF3 neurotrophin 3 OMIM 162660 GeneCards	Neurotrophin; Ligand for NTRK3: Promotes oligodendrocyte survival	NTF3 polymorphisms associating with schizophrenia have been reported in Japanese case studies (Hattori and Nanko, 1995;Nanko et al., 1994) and in male schizophrenics in England (case study) (Dawson et al., 1995). A metaanalysis combining case results from Caucasian patients with a Swedish study provided support for an association between NTF3 and schizophrenia (Jonsson et al., 1997).
NTRK3 neurotrophic tyrosine kinase, receptor, type 3	Receptor for NTF3	GWAS European ancestry Shi et al, 2009
PDGFRB platelet-derived growth factor receptor, beta polypeptide GeneCards	Binds to EGFR and FYN	Association in a Korean study Kim et al, 2008
PIK3C2G phosphoinositide-3-kinase, class 2, gamma polypeptide GeneCards	PI3 kinase: Not fully characterised	Weak association in a Dutch case-control studyJungerius et al, 2007
PIK3C3 phosphoinositide-3-kinase, class 3 OMIM 602609 GeneCards	Converts Phosphatidylinositol to Phosphatidylinositol 3 phosphate (Volinia et al. 1995) Involved in EGF receptor endocytosis (Zheleznova et al, 2003)	A promoter variant of PIK3C3 is associated with bipolar disorder and schizophrenia in case studies(Stopkova et al., 2004). Also associated in a family based chinese study (Duan et al 2005)
PI4KA phosphatidylinositol 4-kinase, catalytic, alpha GeneCards	Catalyzes the first step in the biosynthesis of phosphatidylinositol 4,5-bisphosphate	Association in a Dutch case-control studyJungerius et al, 2007
PIK42B phosphatidylinositol 4-kinase type 2 beta		Scottish study Houlihan et al, 2009
PI4KA phosphatidylinositol 4-kinase, catalytic, alpha (PIK4CA)	Synthesis of phosphatidylinositol 4,5-bisphosphate	Dutch study Jungerius et al, 2007
PIP4K2A phosphatidylinositol-5-phosphate 4-kinase, type II, alpha		Irish study Thistleton et al, 2010
PIP5K2A phosphatidylinositol-4-phosphate 5-kinase, type II, alpha OMIM 603140 GeneCards	Metabolises Phosphatidylinositol 3 phosphate to phosphatidylinositol 3,4-biphosphate and phosphatidylinositol 3,4,5-triphosphate (Zhang et al. 1997). Also metabolises phosphatidylinositol-4-phosphate, and phosphatidylinositol-5-phosphate (Rameh et al. 1997) (products of phosphatidylinositol 4- and 5-kinases to phosphatidylinositol-4,5-bisphosphate (Loijens et al. 1996) and is thus capable of generating multiple second messengers.Phosphatidylinositol 3,4,5-triphosphate inhibits the GTPase activating effects of RGS4 Ishii et al,2002	Associated with both bipolar disorder and schizophrenia in case studies (Stopkova et al., 2003).
PLCB1 phospholipase C, beta 1 (phosphoinositide-specific)	catalyzes the formation of inositol 1,4,5-trisphosphate and diacylglycerol from phosphatidylinositol 4,5-bisphosphate	GWAS Moskvina et al, 2009
PTPRZ1 protein tyrosine phosphatase, receptor-type, Z polypeptide 1 OMIM GeneCards	Involved in NRG1/ERBB4 signaling Buxbaum et al, 2007 Activates ALK Perez-Pinera et al, 2007 and FYN Pariser et al, 2005 LTP enhanced in knockout miceNiisato et al, 2005	UK case studyBuxbaum et al, 2007
SEMA3D Semaphorin 3D		Japanese study Fuji et al, 2010
SPRY4 sprouty homolog 4 GeneCards	Negative regulator of FGF signaling and of the MAPK pathway	Association in UK trios Zaharieva et al, 2008
WDFY2 WD repeat and FYVE domain containing 2	Binds to AKT1	GWAS Moskvina et al, 2009
Oligodendrocyte related genes
ARHGEF10 Rho guanine nucleotide exchange factor (GEF) 10 GeneCards	Role in myelination of peripheral nerves	Weak association in a Dutch case-control studyJungerius et al, 2007
CNP 2',3'-cyclic nucleotide 3' phosphodiesterase OMIM 123830 GeneCards	Almost exclusively localised in myelin containing cells	Described as a susceptibility gene in a UK case study (Peirce et al., 2006)
GNPAT glyceronephosphate O-acyltransferase OMIM 602744 GeneCards	Involved in the synthesis of plasmalogens which are important constrituents of myelin. Abnormal myelinisation is observed in GNPAT deficiency (Szrriha et al, 1997)	Polymorphism reported in Taiwan (Lin et al, 2006)
MAG myelin-associated glycoprotein OMIM 159460 GeneCards	Mediates myelin-neuron cell-cell interactions; Inhibits neurite extension via RTN4R Splicing controlled by QK1. Coimmunoprecipitates with MBP and PLP1.Also binds to FYN and PLCG1 Jaramillo et al, 1994 Arvanitis et al, 2002	Polymorphism associated with schizophrenia in a chinese family study (Wan et al., 2005)
MOG myelin oligodendrocyte glycoprotein OMIM 159465 GeneCards	May be involved in completion and maintenance of the myelin sheath and in cell-cell communication. Recognised by HLA-DRB1.	Associated with schizophrenia in a Chinese family study (Liu et al., 2005b).
CSPG5 Neuroglycan C	Midkine receptor: Promotes oligodedrocyte growth Ishihara_tanaka et al, 2006	Chinese study So et al, 2010
MYT1L myelin transcription factor 1-like	Binds to DISC1	Copy number variation Vrijenhioek et al, 2008
NOTCH4 Notch homolog 4 OMIM 164951 GeneCards	NOTCH signalling in general plays an important role in oligodendrocyte development (Park and Appel, 2003;Popko, 2003) but the role of NOTCH4 has not been specifically examined.Ckeaved by PSEN2	Association reported in African American case and family, Indian family and Chinese mixed pedigree studies (Luo et al., 2004;Prasad et al., 2004;Skol et al., 2003;Wang et al., 2005). Japanese and Chinese studies suggest association only in subsets of early onset patients and/or with negative symptoms (Takahashi et al., 2003) and in a GWAS study Stefanssonnet al, 2009.
OLIG2 oligodendrocyte lineage transcription factor 2 OMIM 606386 GeneCards	Key transcription factor in oligodendrocyte development (Ligon et al, 2006). Inhibits astrocyte differentiation and reactive astrocytosis (Cassiani-Ingoni et a, 2006). Transport from nucleus to cytoplasm may be needed in relation to inhibitory effects on astrocyte differentiation.This export is induced by CNTF via phosphorylation of OLIG2 by AKT1 (Setoguchi and Kondo 2004). See also PAX6 and PHOX2B interactions with OLIG2 in development	Association reported in a UK case study Georgieva et al, 2006
PAX6paired box gene 6 (aniridia, keratitis) OMIM 607108 GeneCards	Regulates oligodendrocyte development and NRG1 expression (Assimacopoulos et al., 2003;Sun et al., 1998). Binds to HOMER3 ( a partner of GRM5), DYNLL1 (a NOS1 inhibitor) and TRIM11 (Cooper and Hanson 2005) and SHANK3	Promoter polymorphism associates with schizophrenia in a German case study (Stober et al., 1999).
PLP1 OMIM 300401 GeneCards	Proteolipid protein with role in myelinisation. Coimmunoprecipitates with MAG and MBP. Arvanitis et al, 2002	Weak association in males in a family-based chinese study (Qin et al., 2005c)
PSAP Prosaposin GeneCards	Myelinotrophic factor	Weak association in a Dutch case-control studyJungerius et al, 2007
SOX10 SRY (sex determining region Y)-box 10 OMIM GeneCards	Transcription factor with a key role in oligodendrocyte development. Targets include CNTF Ito et al, 2006, ERBB3 Britsch et al, 2001, MBP Wei et al, 2004 TYR Murisier et al, 2007. Regulated by QK1 Aberg et al, 2006	Associated in a Japanese study Maeno et al, 2007
TF Transferrin GeneCards	Iron transport: Important role in oligodendrocyte function Connor and Menzies, 1996	Association in the Chinese Han population Qu et al, 2007
QK1 Quaking OMIM 609590 GeneCards	Required for oligodendrocyte differentiation and myelinisation in mice. Controls the messenger RNA translation or splicing of both myelin basic protein and MAG (Ryder and Williamson, 2004;Wu et al., 2002) Regulates PLP1, MAG, MBP, TF, SOX10, and CDKN1BAberg et al, 2006. Binds to PTPB2 Lim et al, 2006	Associated with schizophrenia in Swedish family-based study (Aberg et al., 2005)
Genes whose products kill oligodendrocytes	AMPA (Yoshioka et al., 1995), kainate (Sanchez-Gomez and Matute, 1999) and NMDA (Salter and Fern, 2005) receptor activation (cf GRIA4, GRIK3. GRIN1, 2A,2B,2D), dopamine (Khorchid et al., 2002), IL1B (Takahashi et al., 2003a) , LTA)(Plo et al., 1999), Lysophosphatidylcholine (Fressinaud and Vallat, 1994) a product of PLA2G4, Nitric oxide (Rosenberg et al., 1999) or peroxynitrite (Mitrovic et al., 1996;Scott et al., 2003) products of NOS1, TGF beta (Schuster et al., 2002;Schuster et al., 2003), which signals via PCQAP (Kato et al., 2002) TNFA (D'Souza et al., 1996), TP53 (Eizenberg et al., 1995).
Genes whose products protect oligodendrocytes or are involved in their development	CNR1 agonists (Molina-Holgado et al., 2002), CNTF DRD2 and DRD3 receptor activation (Rosin et al., 2005).GRM5 receptor agonists (Deng et al., 2004a). Inhibition of the PI3 kinase cell survival pathway produces apoptosis in oligodendrocytes (Vemuri and McMorris, 1996) (cf AKT1 , PIK3C3, PIP5K2A). BDNF, (Du et al., 2003), NOTCH signalling (Park and Appel, 2003) (cf NOTCH4 ), NTF3 (Barres et al., 1994;Heinrich et al., 1999;Kumar et al., 1998), NRG1 (Calaora et al., 2001;Fernandez et al., 2000;Flores et al., 2000), PAX6 (Sun et al., 1998), IL2 (Jiang and Lu, 1998), IL10 (Molina-Holgado et al., 2001) S100B (Deloulme et al., 2004). Glutathione (cf SLC1A2, GSTM1) protects against diverse toxic insults(Liu et al., 2002b) (Khorchid et al., 2002;Lee et al., 2004) (Richter-Landsberg and Vollgraf, 1998). Nitric oxide (NOS1) protects oligodendrocytes in conditions of thiol depletion (Rosenberg et al., 1999).
Dopaminergic system genes
ALDH3B1 Aldehyde dehydrogenase 3 family, member B1 OMIM 600466 GeneCards	Multiple substrates include catecholamine metabolites.	Association in Chinese case studies (Sun et al., 2005b;Xu et al., 2004):
COMT Catechol-O-methyltransferase OMIM 116790 GeneCards	Methylates catecholamines and catecholamine derived quinones (Zhu, 2004). COMT activation also increases the synthesis and release of homocysteine from astrocytes (Huang et al, 2005) (related to S-adenosylmethionine metabolism)	A meta-analysis of case and family based data suggested a stronger effect in patients of European ancestry (Glatt et al., 2003a). See (Munafo et al., 2005) for conflicting conclusion.
CHGA Chromogranin A GeneCards	Role in tranmitter/hormone secretion in neural and endocrine cells	Association in a Japanese case-control Takahashi et al, 2006
CHGB Chromogranin B OMIM 118920 GeneCards	Plays a role in dopamine storage.	Suggested as a susceptibility gene in Japanese and Chinese case studies (Kitao et al., 2000) (Zhang et al., 2002)
DBH Dopamine beta hydroxylase	Cinverts dopamine to noradrenaline	Croatian study Pal et al, 2009
SLC6A3 DAT1 dopamine transporter OMIM 126455 GeneCards	Binds to PICK1 and STX1A	Reported association in American case and family and Chinese case studies (Blum et al., 1997;Fanous et al., 2004a;Zhang et al., 2003)
DRD2 Dopamine receptor OMIM 126450 IUPHAR GeneCards	Target of most neuroleptics: Dysbindin or MUTED knockdown blocks D2 dopamine receptor (DRD2) internalisation, increasing cell surface expression Iizuka et al, 2007. Agonists attenuate oligodendrocyte damage induced by glutamate or oxidative stress Roisin et al, 2005	Significant association in a meta-analysis of 24 case studies (Glatt et al., 2003b)
DRD3 Dopamine receptor OMIM 126451 IUPHAR GeneCards	Agonists attenuate oligodendrocyte damage induced by glutamate or oxidative stress Roisin et al, 2005	Significant association reported in a meta-analysis of over 30 case studies (Williams et al., 1998)
DRD4 Dopamine receptor OMIM 126452 IUPHAR GeneCards		No overall association in a meta-analysis of 19 worldwide independent samples but significant association reported in Caucasian subjects especialy in family studies (Lung et al., 2002;Williams et al., 1998)
DRD5 Dopamine receptor OMIM 126453 IUPHAR GeneCards		Association in two British case studies (Williams et al., 1997) (Muir et al., 2001)
KCNN3 small conductance calcium-activated potassium channel, (Alias KCa2.3, SK3, SKCA3, hSK3) OMIM 602983 GeneCards	Controls the firing rate of dopaminergic neurones in the substantia nigra (Wolfart et al., 2001)	Associated with schizophrenia in Israeli ,Indian, Serbian and Taiwanese case studies (Dror et al., 1999;Ivkovic et al., 2006;Ritsner et al., 2002;Saleem et al., 2000;Tsai et al., 1999a)
MAOA Monoamine oxidase A OMIM 309850 GeneCards	Oxidises monoamines, generating hydrogen peroxide RCH2NH2 + H2O + O2 = RCHO + NH3 + H2O2	Association reported in British and Swedish case studies (Jonsson et al., 2003;Wei and Hemmings, 1999).
MAOB monoamine oxidase B		Spanish study Carrera et al, 2008
RNLS FAD-dependent amine oxidase (c10orf59)MAOC	Metabolises catecholamines Luft, 2005	GWAS African American Shi et al, 2009
NCKAP5 NCK-associated protein 5	Partner binds to dopamine receptors	GWAS Wang et al, 2010
PAHPhenylalanine hydroxylase OMIM 261600 GeneCards	L-phenylalanine + tetrahydrobiopterin + O2 = L-tyrosine + 4a-hydroxytetrahydrobiopterin	Weak association reported in an American sib-pair study (Wilcox et al., 2002).
SLC18A1 solute carrier family 18 (vesicular monoamine), member 1 GeneCards	Dopamine, noradrenaline and serotonin vesicular uptake	Association reported in a Japanese study Richards et al, 2006
SLC18A2 solute carrier family 18 (vesicular monoamine), member 2 GeneCards		Association reported in a spanish studyGutierrez et al, 2007
TH Tyrosine hydroxylase OMIM 191290 GeneCards	L-tyrosine + tetrahydrobiopterin + O2 = L-DOPA + 4a-hydroxytetrahydrobiopterin	Association reported in French, Japanese , Korean and Welsh case studies (Kurumaji et al., 2001;Meloni et al., 1995;Pae et al., 2003b;Thibaut et al., 1997;Wei et al., 1995)
CCKAR cholecystokinin A receptor OMIM 118444 GeneCards	Regulates dopamine release	Association reported in Japanese and Spanish case studies and weak (Tachikawa et al., 2000;Wang et al., 2002;Zhang et al., 2000) association reported in an America case study (Sanjuan et al., 2004)
Glutathione, quinone and oxidative stress related genes For an interesting history on quinones and schizophrenia see Smythies 1997 .
GCLC glutamate-cysteine ligase, catalytic subunit GeneCards	First rate limiting enzyme of glutathione synthesis. Expression controlled by NFE2L2, binding partner of ATF4 (see DISC1, GABBR1): Glutathione depletion impairs synaptic plasticity (LTP) and reduces NMDA receptor-mediated effects Steullet et al, 2006	Association reported in a Swiss study Gysin et al, 2007
GCLM glutamate-cysteine ligase, modifier subunit OMIM 600176 GeneCards	First rate limiting enzyme of glutathione synthesis. Expression controlled by NFE2L2, binding partner of ATF4 (see DISC1, GABBR1)	Association reported in two case and one family study Tosic et al, 2006
GSS Glutathione synthase	ATP-dependent conversion of gamma-L-glutamyl-L-cysteine to glutathione	Swiss Study Tosic et al, 2006
GSTM1 Glutathione transferase M1 OMIM 138350 GeneCards	Cyclised quinones formed from dopamine or other catecholamines are conjugated by glutathione, a reaction catalysed principally by the mu class of glutathione transferases (Baez et al., 1997) including GSTM1. Expression controlled by NFE2L2, binding partner of ATF4 (see DISC1, GABBR1)	A GSTM1 deletion has been associated with schizophrenia in Japanese and Korean case studies (Harada et al., 2001;Pae et al., 2004).
GSTT1 glutathione S-transferase theta 1 GeneCards		Saadat et al, 2007
HP Haptoglobin OMIM GeneCards	Potent antioxidant: Binds to hemoglobin preventing induction of oxidative stress.	Association reported in a Chinese study Wan et al, 2007
MDR1/ABCB1 P-glycoprotein 1 OMIM GeneCards	Involved in NO-related glutathione efflux Watts et al, 2006	Association reported in a female Croatian case-study Bozina et al, 2006 GWAS Moskvina et al, 2009
ME2 malic enzyme 2, NAD(+)-dependent, mitochondrial GeneCards	Plays an important role in regenerating reduced glutathione Vogel et al, 1999	Lee et al, 2007 (psychosis and mania)
MSRA Methionine sulfoxide reductase GeneCards	Converts methionine sulfoxide to methionine: Possible role in repairing damage to oxidised proteins	Costa Rica Family study Walss-Bass et al, 2008
NQO2 NAD(P)H dehydrogenase, quinone 2 OMIM 160998 GeneCards	Quinone reductases play a role in eliminating dopamine-derived quinones (Graumann et al., 2002).Expression controlled by NFE2L2, binding partner of ATF4 (see DISC1, GABBR1)	A deletion in the promoter region of the NQO2 gene is associated with schizophrenia in a Japanese case study (Harada et al., 2003).
S100B Catecholase OMIM 176990 GeneCards	Converts DOPA to dopachrome, adrenaline to adrenochrome and noradrenaline to noradrenachrome (Senior et al., 2003). Role in neurite extension and astrocytosis and oligodendrocyte development (Deloulme et al., 2004) Binds to TP53	Associated with schizophrenia in a Chinese case study (Liu et al., 2005a)
SOD2 Manganese-dependent superoxide dismutase OMIM147460 GeneCards	2 superoxide + 2 H(+) <=> O₂ + H₂O₂ Binds to TP53 in mitochondria (Zhao et al, 2005)	Association reported in a Turkish case study (Akyol et al., 2005).
TYR Tyrosinase OMIM 606933 GeneCards	L-tyrosine + L-dopa + O(2) <=> L-dopa + dopaquinone + H(2)O. Expression controlled by TP53 (Khlgatian et al, 2002)	Schizophrenia has been linked to a chromosomal translocation at (1:11)(q42.1, q14.3). Genes within the chromosome 11 breakpoint include GRM5, NAALADase II and TYR (Petit et al., 1999;Semple et al., 2001).
TP53 tumor protein p53 OMIM 191170 GeneCards	Numerous binding partners including PTGS2, SOD2 and S100B. Controls TYR expression (Khlgatian et al, 2002). A cleaved intracellular domain of ERBB4 phosphorylates the p53 activator MDM2 and increases TP53 levels in peripheral cells (Arasada and Carpenter 2005) . Activated by nitric oxide (Zhou et al, 2004).The actions of NFE2L2 (see DISC1) are inhibited by TP53 Faraonio et al,2006	Associated with schizophrenia in Canadian case and family studies, Chinese and Korean case studies and portugese families (Ni et al., 2005;Park et al., 2004;Yang et al., 2004).
TP53I3 tumor protein p53 inducible protein 3	Binds to TP53:Possible quinone reductase	GWAS Moskvina et al, 2009
ND4 NADH dehydrogenase subunit 4 OMIM 516003 GeneCards	Oxidative phosphorylation Complex 1	Reported to associate with schizophrenia, particularly in males in a UK case study(Marchbanks et al., 2003).
NDUFV2 24-kDa subunit of Complex I; NADH dehydrogenase (ubiquinone) flavoprotein 2 (24kD) GeneCards	Oxidative phosphorylation Complex 1	Association reported in a Japanese study (Waskizuka et al, 2006)
UCP2 Uncoupling protein 2 OMIM 601693 GeneCards	Regulates mitochondrial glutathione levels in microglia (de Bilbao et al, 2004. Binds to YWHAZ	Assocation reported in a Japanese study (Yasuno et al, 2006)
UCP4 (SLC25A27) Uncoupling protein 4 GeneCards	Mitochondrial uncoupling reduces the generation of reactive oxygen species and increases the resistance of cells to oxidative stress (Liu et al, 2006)	Assocation reported in a Japanese study (Yasuno et al, 2006)
Other related genes: SLC1A2 mediates the glial uptake of the glutathione precursor cysteine and controls glutathione levels (Chen and Swanson, 2003). Quinones can be formed spontaneously from the oxidation of dopamine or from the enzymatic catalysis of dopamine by PTGS2 (arachidonate or H2O2 + dopamine leading to the formation of aminochrome) (Hastings, 1995). COMT methylation of catecholamines prevents quinone generation and COMT methylates dopamine-derived quinones (Zhu, 2004). AKT1, BDNF, CAPON, CCKAR, CHRNA7, CNR1, COMT, DNTBP1, GAD1, GRM3, IL10, MLC1, NOTCH4, NRG1, PRODH, RGS4, RTN4 and TNF, are subject to regulation by hypoxia (Schmidt-Kastner et al, 2006).
Serotonin related
HTR1A 5-hydroxytryptamine (serotonin) receptor 1A		US study Huang et al, 2004
HTR1B 5-hydroxytryptamine (serotonin) receptor 1B		Croatian Study Pal et al, 2009
HTR2A Serotonin receptor OMIM 182135 IUPHAR GeneCards	Binds to PSD-95 (DLG4)	Significant association in a meta-analysis of 31 case-control association studies (Abdolmaleky et al., 2004).
HTR2C 5-hydroxytryptamine (serotonin) receptor 2C		Croatian Study Pal et al, 2009
HTR4 5-hydroxytryptamine (serotonin) receptor 4		Japanese study Suzuki et al, 2003
HTR5A Serotonin receptor OMIM 601305 IUPHAR GeneCards		Association reported in Japan (case) and France (family) (Iwata et al., 2001; Dubertret et al 2004)
HTR6 Serotonin receptor OMIM 601109 IUPHAR GeneCards		Association reported in Taiwan (case study)(Tsai et al., 1999b).
HTR7 Serotonin receptor OMIM 182137 IUPHAR GeneCards		Association reported in Japan (case study)(Ikeda et al., 2005)
SLC6A4 Serotonin transporter OMIM 182138 GeneCards	Binds to STX1A	Meta-analysis of 10 separate case studies supports association.
TDO2 tryptophan 2,3-dioxygenase		US Study Miller et al, 2009
TPH1 Tryptophan hydroxylase OMIM 191060 GeneCards	Activated by YWHAH	Association reported in American, Japanese and Taiwanese case studies (Hong et al., 2001;Nolan et al., 2000;Sekizawa et al., 2004;Shinkai et al., 2000)
YWHAE tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, epsilon polypeptide [Homo sapiens]		Japanese study Ikeda et al, 2008
YWHAH tyrosine 3-monooxygenase/tryptophan 5-monooxygenase-activation protein, eta polypeptide, 14-3-3 eta. OMIM 113508 GeneCards	Family members activate TH and TPH1 (inter alia). Associates with GABBR1 (Couve at al, 2001)	Associates with schizophrenia in a family-based Canadian study (Wong et al., 2003) and with early onset schizophrenia in a Japane case study (Toyooka et al., 1999) .
GABA-A receptors and other GABAergic (see above for GABBR1)
GAD1 Glutamate decarboxylase 1 OMIM 605363 GeneCards	GABA synthesis	Associated with childhood-onset schizophrenia in an American family based study (Addington et al., 2005)
GABRA1 gamma-aminobutyric acid (GABA) A receptor, alpha 1 GeneCards	GABA-A receptors are formed from multiple permutations of diverse subunits, of which these are members Bollan et al, 2003	Petryshen et al, 2005
GABRA6 gamma-aminobutyric acid (GABA) A receptor, alpha 6 GeneCards		Petryshen et al, 2005
GABRB2 gamma-aminobutyric acid (GABA) A receptor, beta 2 GeneCards		Lo et al, 2004
GABRP gamma-aminobutyric acid (GABA) A receptor, pi GeneCards		Petryshen et al, 2005
Other Receptors, peptides, downstream signalling and neurotransmitter metabolising enzymes
ACE Angiotensin converting enzyme (synthesises angiotensin II) OMIM 106180 GeneCards	Converts angiotensin 1 to angiotensin 2	A strong interaction between a low activity COMT genotype and a high activity ACE genotype has been observed in schizophrenic patients non-responsive to neuroleptics. The risk of possessing this combination of polymorphisms is 10 times higher in the schizophrenic non-responsive group (Illi et al., 2003).
ADCYAP1 adenylate cyclase activating polypeptide 1 (pituitary)(PACAP) OMIM GeneCards	Enhances NMDA receptor function and increases BDNF expression Yaka et al, 2003 Influences oligodendrocyte proliferation Lelievre et al, 2006. Involved in DISC1 signalingHattori et al, 2007	Hashimoto et al, 2007
ADIPOR2 adiponectin receptor 2		GWAS European ancestry Shi et al, 2009
ADORA1Adenosine A1 receptor	Interacts with DRD1 and GRM1	Japanese study Gotoh et al, 2009
ADRA1A adrenergic, alpha-1A-, receptor GeneCards	Adrenoceptor: Modulates NMDA recptors via RGS4 Liu et al, 2006 Binds to Neuregulin receptor ERBB3 Thaminy et al, 2003	Association reported in a Spanish population (Clark et al,2005)
CHAT Choline acetyl transferase GeneCards	Acetlycholine synthesis	Mancama et al, 2007
CHRFAM7A CHRNA7 (cholinergic receptor, nicotinic, alpha 7, exons 5-10) and FAM7A (family with sequence similarity 7A, exons A-E) fusion		US Study Sincus et al, 2009
CHRM5 cholinergic receptor, muscarinic 5		Canadian study De Luca et al, 2004
CHRNA4 cholinergic receptor, nicotinic, alpha 4		Canadian study De Luca et al, 2006
CHRNA7 Nicotinic receptor alpha subunit OMIM 118511 GeneCards	Stimulates glutamate release	Associated with schizophrenia in American family, French case, South African family and Azorean family studies (Freedman et al., 2001;Houy et al., 2004;Leonard et al., 2002;Raux et al., 2002;Riley et al., 2000;Xu et al., 2001) .
CHRNB2 cholinergic receptor, nicotinic, beta 2 (neuronal)		Canadian study De Luca et al, 2006
CNR1 Cannabinoid receptor 1 OMIM 114610 GeneCards	Activation inhibits glutamate release (Auclair et al., 2000;Wang, 2003). CNR1 receptor stimulation promotes the survival of oligodendrocyte progenitor cells (Molina-Holgado et al., 2002).	Association reported in French and Japanese case studies (Leroy et al., 2001;Ujike et al., 2002).
GPR78 Orphan GPCR OMIM 606921 GeneCards	Orphan receptor	Suggestive association in a Scottish case study (Underwood et al,2006
GPR85 G protein-coupled receptor 85 (SREB2) GeneCards	Orphan receptor: Overexpression reduces brain weight, increases ventricular size and produces schizophrenia-like behavioural effects in mice Matsumoto et al, 2008	Association in an American family study Matsumoto et al, 2008
HRH2 H2 Histamine receptor OMIM 142703 GeneCards	Histamine receptor	Associated with schizophrenia in a British case study (Orange et al., 1996).
MCHR1 (GPR24) Melanocyte concentrating hormone receptor 1 OMIM 601751 GeneCards	Regulates mesolimbic dopamine signaling Pissios et al, 2008. GRIN1 expression reduced in knockout mice Adamantidis et al, 2005	Association reported in a Faroese/Scottish study Severinsen et al, 2006
MCHR2 melanin-concentrating hormone receptor 2		US study Miller et al, 2009
MC5R melanocortin 5 receptor		US study Miller et al, 2009
NPY Neuropeptide Y OMIM 162640 GeneCards	Inhibits glutamate release	Associated with schizophrenia in ta Japanese case study (Itokawa et al., 2003a) .
OPCML opioid binding protein/cell adhesion molecule-like		GWAS O'Donovan et al, 2008
OPRS1 opioid receptor, sigma 1 OMIM 601978 GeneCards	Regulates oligodendrocyte differentiation Hayash and Su, 2004	Association in a Japanese case study(Ishiguro et al., 1998).
OPRM1 opioid receptor, mu 1		Czech republic Sery et al, 2010
PDE4B Phosphodiesterase 4B OMIM 600127 GeneCards	Binds to DISC1 (Millar et al., 2005). Activated by NMDA receptors during hippocampal LTP (Ahmed and Frey 2003)	Disrupted by a balanced translocation in a subject diagnosed with schizophrenia and a relative with chronic psychiatric illness (Millar et al., 2005)
PDE4D phosphodiesterase 4D, cAMP-specific (phosphodiesterase E3 dunce homolog		Finnish study Tommpo et al, 2009
PDE7B phosphodiesterase 7B		Japanese and UK study Ikeda et al, 2010
PDYN Prodynorphin		Chinese study Zhang et al, 2004
RGS2 regulator of G-protein signaling 2, 24kDa GeneCards	Binds to GNAS	American study Campbell et al, 2008
RGS5 regulator of G-protein signaling 5 GeneCards		American study Campbell et al, 2008
TAAR6 Trace amine receptor 6 (ex 4) OMIM 608923 GeneCards	Orphan receptor	Association reported in an American study of european and african american pedigrees(Duan et al., 2004)
Adhesion Molecules
CDH4 Cadherin 4		International schizophrenia consortium O'Dushlaine et al, 2010
CHL1 cell adhesion molecule with homology to L1CAM (close homolog of L1) OMIM 607416 GeneCards	A soluble form of CHL1 promotes neurite extension in cerebellar granule cells (Naus et al., 2004)	Associates with schizophrenia in a Japanese case study (Sakurai et al., 2002).
L1CAM L1 cell adhesion molecule		Japanese studyKuramaji et al, 2001
CNTNAP2 contactin associated protein-like 2 GeneCards	Member of the neurexin family of adhesion molecules and receptors. Involved in the clustering of potassium channels in myelinated axons Poliak et al, 2002	Haploinsufficiency in association with epilepsy and schizophrenia in the Amish population Friedman et al, 2007
CNTN1 Contactin 1		International schizophrenia consortium O'Dushlaine et al, 2010
GLG1 golgi glycoprotein 1		International schizophrenia consortium O'Dushlaine et al, 2010
HLA-DQA2		International schizophrenia consortium O'Dushlaine et al, 2010
JAM3 junction adhesion molecule 3	GWAS Moskvina et al, 2009	GWAS Moskvina et al, 2009
NCAM1 Neural cell adhesion molecule 1 GeneCards	Promotes assembly of the PSD signaling complex Sytnyk et al, 2006. Stimulates PI3K/AKT signaling (Ditlevsen et al, 2003). TrkB phosphorylation and BDNF signaling is impaired in NCAM knockout mice Muller at al, 2000. Polysialylated-NCAM interacts with BDNF (Vutskits et al, 2001et al. 2001). Oligodendrocytes express GRIN1 and activation of NMDA receptors in these cells increases the expression of polysialylated NCAM1 that is required for oligodendrocyte migration (Wang et al, 1996).Polysialylated by ST8S1A2 Kojima et al, 1996	Sullivan et al, 2006
NRXN1 Neurexin 1		International schizophrenia consortium O'Dushlaine et al, 2010
PDCD1LG2 programmed cell death 1 ligand 2		International schizophrenia consortium O'Dushlaine et al, 2010
Tight junction
CDC42, CTNNA2, HCLS1, HRAS, PRKCH, MYH11, MYH15 and PARD3)	In progress	International schizophrenia consortium O'Dushlaine et al, 2010
Glycan structures
MAN2A1, GALNT2, GALNT13, OGT and XYLT1	In progress	International schizophrenia consortium O'Dushlaine et al, 2010
Snares STX18 and TSNARE1	""	International schizophrenia consortium O'Dushlaine et al, 2010
cell cycle MAD1L1	""	International schizophrenia consortium O'Dushlaine et al, 2010
Circadian
CLOCK circadian locomoter output cycles kaput protein; clock OMIM GeneCards	Controls the expression of ATF4 (see DISC1, GABBR1) Igarashi et al, 2007 Circadian control	Association repoted in a Japanese study Takao et al, 2007
NPAS2 neuronal PAS domain protein 2		USA study Mansour et al, 2009
PER3 period homolog 3 OMIM GeneCards	Circadian control	Association reported in an American study Mansour et al, 2006
TIMELESS OMIM GeneCards	Circadian control	Association reported in an American study Mansour et al, 2006
Glycolysis and Krebs Cycle
ENO2 Enolase 2 (gamma neuronal) GeneCards	2-phospho-D-glycerate = phosphoenolpyruvate + H2O	Association reported in a Scandinavian study Olsen et al, 2008
FBP1 fructose-1,6-bisphosphatase 1 GeneCards	D-fructose 1,6-bisphosphate + H2O = D-fructose 6-phosphate + phosphate	Association reported in a Scandinavian study Olsen et al, 2008
PCK1 phosphoenolpyruvate carboxykinase 1 (soluble) GeneCards	GTP + oxaloacetate = GDP + phosphoenolpyruvate + CO2	Association reported in a Scandinavian study Olsen et al, 2008
Cytokines and immune-related
BTN2A2 butyrophilin, subfamily 2, member A2		GWAS Shi et al, 2009
BTN3A1 butyrophilin, subfamily 3, member A1		GWAS Shi et al, 2009
BTN3A2 butyrophilin, subfamily 3, member A2		GWAS Shi et al, 2009
C3 complement component 3		Spanish study: Fannanas et al, 1992
C4A complement component 4A (Rodgers blood group)		UK study Rudduck et al, 1985
C4B complement component 4B (Chido blood group)		UK study Rudduck et al, 1985
CFB complement factor B		Spanish study: Fannanas et al, 1992
CCR5 chemokine (C-C motif) receptor 5 GeneCards	MCP-2, Mip1-alpha and Mip1-beta chemokine receptor expressed on T-cells and macrophages	32bp deletion associated with late-onset schizophrenia in a Danish study Rasmussen et al, 2006
CD4 CD4 molecule		Belgian study Zamani et al,1994
CLU Clusterin		Chinese study Zhou at al, 2010
CSF2RA colony stimulating factor 2 receptor, alpha, low-affinity (granulocyte-macrophage) OMIM GeneCards	receptor for colony stimulating factor 2, a cytokine which controls the production, differentiation, and function of granulocytes and macrophages.	Lencz et al, 2007
CSF2RB colony stimulating factor 2 receptor, beta, low-affinity (granulocyte-macrophage) GeneCards	Common beta receptor subunit for IL3, IL5 and GM-CSF signaling	Chen et al, 2007
CTLA4 cytotoxic T-lymphocyte-associated protein 4 OMIM 123890 GeneCards	Member of the immunoglobulin superfamily which transmits an inhibitory signal to T cells	Association with schizophrenia has been reported in a Korean case study (Jun et al., 2002a).
CHI3L1 chitinase 3-like 1 (cartilage glycoprotein-39) Alias: GP39, HC-gp39, HCGP-3P, YKL40, YYL-40 GeneCards	Inhbits effects of TNF and IL1B in peripheral cells Ling and Recklies,2004. Signals via AKT1 Recklies et al,2002	Zhao et al, 2007
EBF3 Early B-cell factor 3		GWAS O'Donovan et al, 2008
IFNG Interferon gamma		Associated in males but not females in a polish study Paul-Samojedny et al, 2010
IL1A Interleukin 1 alpha		Chinese study Chowdari et al, 2006
IGH@ immunoglobulin heavy locus	Immunoglobulins recognize foreign antigens and initiate immune responses	Italian study Frezza et al, 2009
IL1B Interleukin 1B OMIM 147720 GeneCards	Cytokine inducing PTGS2 in the CNS. Toxic effects on oligodendrocytes	Associated with schizophrenia in Italian, German and Finnish case studies (Katila et al., 1999;Meisenzahl et al., 2001;Zanardini et al., 2003)
IL1RN Interleukin 1 receptor antagonist OMIM 147679 GeneCards	Inhibits activity of IL1B	A polymorphism in IL1RA has been reported to exert a protective effect in an Italian case study (Zanardini et al., 2003). Polymorphisms associated with schizophrenia have also been reported in spanish and korean case studies (Kim et al., 2004;Papiol et al., 2005)
IL2: Interleukin 2 OMIM 147680 GeneCards	Cytokine; Stimulates oligodendrocyte proliferation and maturation (Jiang and Lu 1998)	Association reported in a German case study (Schwarz et al., 2005)
IL3 interleukin 3 (colony-stimulating factor, multiple) OMIM GeneCards	Cytokine ligand for IL3RA	Chen et al, 2007
IL3RA interleukin 3 receptor, alpha (low affinity) OMIM GeneCards	IL3 specific component of a heteromeric receptor unit, that includes CSF2RB	Lencz et al, 2007 Association in a chinese studySun et al, 2008
IL4: Interleukin 4 OMIM 147780 GeneCards	Cytokine: protects oligodendrocytes ()	Association reported in a German case study (Schwarz et al., 2005)
IL6R Interleukin 6 receptor		Chinese study Sun et al, 2008
IL9 Interleukin 9		US study Chen et al, 2008
IL12B interleukin 12B (natural killer cell stimulatory factor 2, cytotoxic lymphocyte maturation factor 2, p40) GeneCards	Cytokineimportant for sustaining a sufficient number of memory/effector Th1 cells to mediate long-term protection to an intracellular pathogen.	Associated with schizophreniai in an American case-control study Shirts et al, 2008
IL18 interleukin 18 (interferon-gamma-inducing factor) GeneCards	Proinflammatory cytokine inducing interferon-gamma production in T-cells, Binds to IL18 R1 and IL18RAP	Associated with schizophrenia and cytomegalovirus seropositivity in an American case-control study Shirts et al, 2008
IL18R1 interleukin 18 receptor 1 GeneCards	Il18 cytokine recptor: expression induced by IL12	Associated with schizophrenia and with cytomegalovirus seropositivity in an American case-control study Shirts et al, 2008
IL18RAP interleukin 18 receptor accessory protein GeneCards	Potentiates the IL18 binding activity of IL18R1 (IL1RRP), a ligand binding subunit of the IL18 receptor	Associated with schizophrenia and HSV-1 and cytomegalovirus seropositivity in an American case-control study Shirts et al, 2008
LTA Lymphotoxin alpha OMIM 153440 GeneCards	Cytokine: Toxic effects on oligodendrocytes	Associates with schizophrenia in a Korean case study (Jun et al., 2003).
IL10 Interleukin-10 OMIM 124092 BIOCARTA GeneCards	Anti-inflammatory Cytokine: Protective effects on oligodendrocytes Generally represses effects of TNF and IL1B	Promoter polymorphisms have been associated with schizophrenia in Italy (case) and China (case and family) (Chiavetto et al., 2002) (He et al., 2006;Jun et al., 2002b;Yu et al., 2004).
IL10RA Interleukin 10 receptor GeneCards	IL10 receptor signalling via AKT pathway	Association reported in an Austrian case study Schosser et al, 2006
TNFA: Tumor necrosis factor alpha OMIM 191160 GeneCards	Proinflammatory cytokine: Expression controlled by NFE2L1 in mice (Prieschl et al, 1998 (see DISC1). Toxic effects on oligodendrocytes ()	Association reported in Chinese case, male Finnish case, German family, Italian case and Singaporean case studies (Boin et al., 2001b;Boin et al., 2001a;Hanninen et al., 2005b;Schwab et al., 2003;Tan et al., 2003;Zhang et al., 2005)
TNFR2 = TNFRSF1B	TNF receptor	Thabet et al, 2010
TRAF3IP1 TNF receptor-associated factor 3 interacting protein 1	Binds to DISC1	Finnish study (stage 1)Tomppo et al, 2009
HLA-A (HLA-A10) major histocompatibility complex, class I, A GeneCards	Immune system	In association with chlamydophila infection Fellerhoff et al, 2007
HLA-B major histocompatibility complex, class I, B GeneCards	Immune system	HLA-B maternal-fetal genotype-matching effect on schizophrenia demonstrated for female offspring : related to birth complications rather than schizophrenia (see environmental risk factors) Palmer et al, 2006
HLA-DRB1 DRB1*04 major histocompatibility complex, class II, DR beta 1 OMIM 142857	HLA-DRB1 recognises peptides generated from myelin oligodendrocyte glycoprotein (MOG) (Weissert et al., 2002). It also recognises peptides derived from the influenza virus (Hennecke and Wiley, 2002;Wedderburn et al., 1995) , from the spirochete Borrelia burgdorferi (Steere et al., 2003;Willett et al., 2004) which causes Lyme disease carried by Ixodes ticks and from peptides derived from the Rubella virus (Neepom et al, 1997)	The frequency of this allele is positively associated with rheumatoid arthritis (Reveille, 1998)and reduced in schizophrenic patients and their healthy mothers (Wright et al., 1996). The incidences of schizophrenia and rheumatoid arthritis are inversely correlated (Eaton et al., 1992;Gorwood et al., 2004;Vinogradov et al., 1991). Association also reported in chinese family (Yu et al,2003 and 2 Japanese case studies (Sasaki et al,1999; Arinami et al, 1998 and in Kuwaiti arabs (case study) Heider et al,2000
HLADQA1 major histocompatibility complex, class II, DQ alpha 1		GWAS Shi et al, 2009
MICB MHC class I polypeptide-related sequence B OMIM GeneCards	ligand for the NKG2D type II receptor of natural killer cells.	Associated with Herpes virus seropositivity and schizophrenia Shirts et al, 2007
PRSS16 protease, serine, 16 (thymus)	Thought to play a role in the alternative antigen presenting pathway used by cortical thymic epithelial cells during the positive selection of T cells.	GWAS Shi et al, 2009
TGIF1 TGFB-induced factor homeobox 1 GeneCards	Transcriptional repressor of SMAD signaling (part of the TGF beta pathway) and of retinoic acid receptor(RXRalpha) signaling (See Zaharieva et al, 2008 for potential association with SMAD5 or TGFB1.	Association reporterd in an American study Chavarria-Siles et al, 2007
Protein sorting and ER stress
CALR Calreticulin	Calcium storage protein in the endoplasmic reticulum	Point mutation obsreved in a single schizophrenia patient (1/100) and not in 280 controls Aghajani et al, 2006
HSPA1B HSP70-2 GeneCards	Heat shock protein (molecular chaperones that assist other proteins in their folding, transport and assembly into complexes)	Association suggested in a Korean study Pae et al, 2005
HSPA1L heat shock 70kDa protein 1-like GeneCards	see above	Association in a Korean case-control study Kim et al, 2008
XBP1 X-box binding protein 1. OMIM 194355 GeneCards	Endoplasmic reticulum stress	Associated with schizophrenia in Chinese and Japanese case studies (Chen et al., 2004c;Kakiuchi et al., 2004)
WNT Signalling
DAAM1 dishevelled associated activator of morphogenesis 1		UK study Proitsi et al, 2008
DAAM2 dishevelled associated activator of morphogenesis 2		UK study Proitsi et al, 2008
DKK4 dickkopf homolog 4 GeneCards	Role in Wnt signaling	Association in chinese trios and a Hong Kong case study Proitsi et al, 2008
FZD3 Frizzled 3 OMIM 606143 GeneCards	Receptor for wingless	Associated with schizophrenia in Japanese case and Chinese case and family studies (Katsu et al., 2003;Yang et al., 2003a;Zhang et al., 2004) .
KREMEN1 kringle containing transmembrane protein 1	Binds to DKK1	Association in a Japanese study Aleksic et al, 2010
SFRP1 secreted frizzled-related protein 1		UK study Proitsi et al, 2008
Extracellular matrix proteins, structural , intracellular transport and related
CAPZA2 capping protein (actin filament) muscle Z-line, alpha 2		US study Burdick et al, 2010
FLNB Filamin B	Binds to actin cytoskeleton	UK study Proitsi et al, 2008
ITGA3 integrin, alpha 3 (antigen CD49C, alpha 3 subunit of VLA-3 receptor) GeneCards	Component of an integrin receptor interacting with several extracellular matrix proteins. Binds to CALR	Scandinavian case-control Kahler et al, 2008
KIF2A kinesin heavy chain member 2A	Microtubule-associated motor protein	Chinese study Li et al, 2006
MAP4 microtubule-associated protein 4		Chinese study So et al, 2009
MAP6 Microtubule-associated protein 6 OMIM 601783 GeneCards	Calmodulin-binding and calmodulin-regulated protein involved in microtubule stabilization.	Associated in a Japanese case study Shimizu et al, 2006
MYH9 myosin, heavy chain 9, non-muscle		Association in a Chinese study Liu et al, 2008
MYO9B Myosin IXb GeneCards	Myosin motor	Association reported in a Dutch study Jungerius et al, 2007
MYO18B Myosin XVIII b		US study Purcell et al, 2009
MXRA5 matrix-remodelling associated 5		GWAS European ancestry Shi et al, 2009
RELN Reelin GeneCards	Secreted extracellular matrix protein thought to control cell-cell interactions critical for cell positioning and neuronal migration during brain development. Signals via PI3K AKT1 pathway, inter alia Jossin and Goffinet, 2007 Controls the surface expression of NMDA receptors (GRIN1, GRIN2B) Groc et al, 2007 and AMPA receptors Qiu and Weeber, 2007	Associated with working memory in Finnish schizophrenia families Wedenoja et al, 2007 and in GWAS in women Shifman et al, 2008
SPARCL1 SPARC-like 1 (mast9, hevin) GeneCards	Extracellular matrix protein localised in postsynaptic terminals and enveloping glia Liveley et al, 2007
TNXB: tenascin XB OMIM 600985 GeneCards	Exracellular matrix protein	SNP's within the TNXB locus associate with schizophrenia in a UK family based study (Wei and Hemmings, 2004c)
Retinol Metabolism
ADH1B alcohol dehydrogenase IB (class I), beta polypeptide OMIM 103720 GeneCards	Multiple substrates include catecholamine metabolites.	Association in a Chinese case study (Xu et al., 2004) and an American family study (Vawter et al, 2006)
ALDH1A2 aldehyde dehydrogenase 1 family, member A2	Catalyzes the synthesis of retinoic acid (RA) from retinaldehyde.	Chinese study Wan et al, 2010
CYP1A2 cytochrome P450, family 1, subfamily A, polypeptide 2		Turkish study Boke et al, 2007
CYP3A4 cytochrome P450, family 3, subfamily A, polypeptide 4		Chinese study Du et al, 2009
CYP3A5 cytochrome P450, family 3, subfamily A, polypeptide 5		Chinese study Du et al, 2009
RBP1 Retinol binding protein 1, cellular GeneCards	Retinol (Vitamin A alcohol) transport	Genome-wide UK associationstudy using pooled samples Kirov et al, 2008
Ion Channels
CACNA1C calcium channel, voltage-dependent, L type, alpha 1C subunit		UK Study Green et al 2009
CACNA1F calcium channel, voltage-dependent, L type, alpha 1F subunit		UK study Wei et al, 2006
CACNG2 calcium channel, voltage-dependent, gamma subunit 2 [	Related to DLG4, GRIA1, GRIA4 and GRIN1	Association in a Chinese study Liu et al, 2008
KCNH2potassium voltage-gated channel, subfamily H (eag-related), member 2		US study Hiffaker et al, 2009
NALCN sodium leak channel, non-selective		GWAS Wang et al, 2010
TRPA1 transient receptor potential cation channel, subfamily A, member 1	Cannabinoid receptor-operated channel Jordt et al, 2004	GWAS African American Shi et al, 2009
Mitochondrial Genes
ATP6 mitochondrially encoded ATP synthase 6		Japanese study Ueno et al, 2009
CYTB mitochondrially encoded cytochrome b	Oxidative phosphorylation	Swedish study Lindholm et al, 1997
MT-haplo
ND2 mitochondrially encoded NADH dehydrogenase 2	Oxidative phosphorylation	US study Rollins et al, 2009
ND4 mitochondrially encoded NADH dehydrogenase 4	Oxidative phosphorylation	UK study Marchbanks et al, 2003
RNR1 mitochondrially encoded 12S RNA		US study Rollins et al, 2009
Transporters
ABCA13 ATP-binding cassette, sub-family A (ABC1), member 13		UK study Knight et al, 2009
SLCO6A1 solute carrier organic anion transporter family, member 6A1		GWAS Stefansson et al, 2009
SLC12A2 solute carrier family 12 (sodium/potassium/chloride transporters), member 2		GWAS USA Potkin et al, 2009
SLC17A1 solute carrier family 17 (sodium phosphate), member 1		GWAS Shi et al, 2009
SLC17A3 solute carrier family 17 (sodium phosphate), member 3		GWAS Shi et al, 2009
Nuclear import export
IPO5 Importin 5		Chinese study Wang et al, 2010
KPNA3 karyopherin alpha 3 (importin alpha 4) OMIM 601892 GeneCards	Nuclear transport: Involved in the nuclear import of Influenza viral nucleoprotein Melen et al, 2003	Associated in a British family study (Wei and Hemmings, 2005b)
KPNB3 (RANBP5) GeneCards OMIM 602008	Nuclear transport : Important role in the nuclear import of Influenza viral RNA polymerase Deng et al, 2006	Associated in a British family study (Wei and Hemmings, 2004c)
RANBP1 RAN binding protein 1	Ran involved in nucleocytoplasmic transport Yudin et al, 2009	USA study Liu et al, 2002
MicroRNA
MIR-30E microRNA		Xu et al, 2010
MIR-198 MicroRNA (Link is to Sanger Mirbase)		Hansen et al, 2007 (PLOS)
MIR-206 MicroRNA (Link is to Sanger Mirbase)		Hansen et al, 2007 (PLOS)
Miscellaneous
ACSL6 acyl-CoA synthetase long-chain family member 6		US study Chen et al, 2006
ACSM1 acyl-CoA synthetase medium-chain family member 1 (same as BUCS1)	Butanoate metabolism Kegg	GWAS Sullivan et al, 2008
ADAM12 ADAM metallopeptidase domain 12		GWAS O'Donovan et al, 2009
ADSS adenylosuccinate synthase	Converts IMP to AMP	Zhang et al, 2008
AGA aspartylglucosaminidase GeneCards	N-glycan degradation : Impaired myelinisation in AGA knockout mice . (Tenhunen et al, 1998)	Linkage in an American family study related to expression change (Vawter et al, 2006)
AGBL1 ATP/GTP binding protein-like 1 [		GWAS Sullivan et al, 2008
AHI1 Abelson helper integration site 1GeneCards	Required for cerebellar and cortical development	Association reported in an Arab-Israeli family (Amman-Zankelstein et al, 2006
AMACR alpha-methylacyl-CoA racemase		Bespalova et al,2010
ANK3 Ankyrin 3	Binds to L1CAM Hortsch et al, 2009	Althanasiu et al, 2010
ANKK1 ankyrin repeat and kinase domain containing 1		French study Dubertret et al, 2010
APOE Apolipoprotein E OMIM 107741 GeneCards	Lipoprotein involved in cholesterol transport. Binds to and potentiates actions of CNTF. Involved in the cerebral uptake of Herpes simplex virus Burgos et al, 2006	Increased frequency of the APOE4 allele reported in a British study (Harrington et al., 1995a) and associated with earlier age of onset an American studies (Arnold et al., 1997;Martorell et al., 2001). A decreased frequency of the APOE2 allele has been associated with early onset schizophrenia in Japan (Kimura et al., 1997) and an increased frequency of APOE3 has been reported in China (Chen et al., 1999). A Chinese study has also shown that increased frequency of the APOE4 allele and decreased frequency of APOE3 are associated with schizophrenia. This association is modified by date of birth and restricted to individuals born during times of famine (Liu et al., 2003a).
APOL2 Apolipoprotein L,2		Japanese study: Takahishi et al, 2008
AR Androgen receptor		UK study Crow et al, 1993
ARHGAP18 Rho GTPase activating protein 18		US study Potkin et al, 2009
ARHGEF10 Rho guanine nucleotide exchange factor (GEF) 10		Dutch study: Jungerius et al, 2008
ARRB1 arrestin, beta 1		GWAS Moskvina et al, 2009
ASTN1 Asrotactin 1 GeneCards	Role in neuronal migration Adams et al, 2002	Scandinavian case-control Kahler et al, 2008
ASTN2 Astrotactin 2		Copy number variation Vrijenhioek et al, 2008
ATE1 arginyltransferase 1	Involved in ubiquitination	GWAS O'Donovan et al, 2009
ATF4 activating transcription factor 4 (tax-responsive enhancer element B67) (CREB2)	Binds to DISC1 and GABBR1 . Key transcription factor activated by stress-provoked eif2alpha phosphorylation (see EIS2S1) Rutkowski and Kaufman, 2003 and eif2b page	Associated with male patients in a Chinese case control study Qu et al, 2008
ATG9B ATG9 autophagy related 9 homolog B		US study Huffaker et al, 2009
ATM ataxia telangiectasia mutated		Chinese polulation Zhang et al, 2008
ATN1 Atrophin1		German study Morris-Rosendahl et al, 1997
ATXN3 Ataxin 3	Binds to PICK1	Yugoslavian study Culjkovic et al, 2000
B3GAT1 beta-1,3-glucuronyltransferase 1 (Synthesises HNK-1) OMIM 151290 GeneCards	Key enzyme in the biosynthesis of the carbohydrate epitope HNK-1 (human natural killer-1, also known as CD57 and LEU7). HNK-1 is a component of MOG. Mice deficient in HNK-1 show reduced hippocampal LTP (Mikol et al., 1990;Yamamoto et al., 2002)	Located at a chromosomal breakpoint whose translocation (t(6;11)(q14.2;q25) ) segregates with a schizophrenia-like psychosis (Jeffries et al., 2003).
BAK1 BCL2-antagonist/killer 1		UK study Proitsi et al, 2008
BRD1 Bromodomain containing 1 GeneCards	Binds to FEZ1 (Assmann et al, 2006)	Association reported in a Danish case control study Severinsen et al, 2006)
BZRP TSPO translocator protein (18kDa) aka peripheral benzodiazepine receptor GeneCards	Important role in controlling cholesterol import into mitochondria and steroid biosynthesis.	Fallin et al., 2005
C6orf85=SLC22A23solute carrier family 22, member 23 [		GWAS Moskvina et al, 2009
C10orf120		GWAS O'Donovan et al, 2009
C18orf1		Iceland study Ingason et al, 2007
CBX2 chromobox homolog 2 (Pc class homolog, Drosophila)		GWAS African American Shi et al, 2009
CCDC60 coiled-coil domain containing 60 GeneCards	Unknown function	Genome-wide UK associationstudy using pooled samples Kirov et al, 2008
CCDC102B coiled-coil domain containing 102B		GWAS Moskvina et al, 2009
CDC42SE2 CDC42 small effector 2		US study Chen et al, 2006
CDKN2A cyclin-dependent kinase inhibitor 2A (melanoma, p16, inhibits CDK4)		GWAS Moskvina et al, 2009
CENTG2= AGAP1 ArfGAP with GTPase domain, ankyrin repeat and PH domain 1		GWAS European ancestry Shi et al, 2009
CLDN5 Claudin 5 OMIM 602101 GeneCards	Tight junction protein involved in blood-brain barrier regulation	Associated in Chinese and British family studies (Sun et al., 2004;Wei and Hemmings, 2005)
CLINT1clathrin interactor 1	Intracellular traffic	UK study Pimm et al, 2005
CPXM2 carboxypeptidase X (M14 family), member 2		UK GWAS O'Donovan et al, 2009
CTNND2 catenin (cadherin-associated protein), delta 2 (neural plakophilin-related arm-repeat protein)		Copy number variation Vrijenhioek et al, 2008
CREB3L1 cAMP responsive element binding protein 3-like 1		GWAS Moskvina et al, 2009
CTXN3 Cortexin 3 5q23.2		GWAS USA Potkin et al, 2009
CYP2D6 cytochrome P450, family 2, subfamily D, polypeptide 6 [		Spanish study Llerena et al, 2007
DDX31 DEAD (Asp-Glu-Ala-Asp) box polypeptide 31	RNA Helicase	GWAS African American Shi et al, 2009
DGCR2 DiGeorge syndrome critical region gene 2		UK study Shifman et al, 2006
DGCR5 DiGeorge syndrome critical region gene 5		UK study Shifman et al, 2006
DGCR6 DiGeorge syndrome critical region gene 6	Binds to GABBR1	US study Liu et al, 2006 GWAS Moskvina et al, 2009
DLX1 distal-less homeobox 1 GeneCards	Homeobox gene implcated in TGF beta signaling. Role in the migration of GABA neurones to the cortex Cobos et al, 2007. Negatively regulates OLIG2-dependent oligodendrocyte development Petryniak et al, 2007	Scandinavian case-control Kahler et al, 2008
DNMT3B DNA (cytosine-5-)-methyltransferase 3 beta		Chinese study Zhang et al, 2005
DYM Dymeclin		Japanese study Yazaki et al, 2010
ELP3 elongation protein 3 homolog (S. cerevisiae)		GWAS African American Shi et al, 2009
EML5 echinoderm microtubule associated protein like 5		GWAS European ancestry Shi et al, 2009
ENAH enabled homolog (Drosophila) GeneCards	Regulates the actin skeleton Menzies et al, 2004	Scandinavian case-control Kahler et al, 2008
ESD Esterase D		Spanish study Fananas et al, 1990
ESR1 estrogen receptor 1 GeneCards	Interacts with TP53: activated by XBP1(see gene data):Phoshorylated by EGFR activation Marquez et al, 2007	American case control Weickert et al, 2008
EVPL Envoplakin		GWAS Moskvina et al, 2009
FABP7 fatty acid binding protein 7, brain GeneCards	Fatty acid binding protein: Target of PAX6 Arai et al, 2005	Association reported in a Japanese study Watanabe et al, 2007
FBXL21 F-box and leucine-rich repeat protein 21 GeneCards	F-box proteins are subunits of the "SKP1-cullin-F-box" ubiquitin protein ligase complex. Role in phosphorylation-dependent ubiquitinati

Genes involved in both Bipolar disorder and schizophrenia
PI3K/AKT signalling, growth factors and related	ANK3, AKT1, BDNF, BMP6, CABIN1, EGFR, FYN, GSK3B, IMPA2, NRG1, PIK3C3, PIK4CA, PIP5K2A, PDLIM5, RGS4, TCF4, WDFY2
Adhesion/ Junctions	CNTNAP2, JAM3, NCAM1, NRXN1
NMDA and glutamate-related	CIT, DAO, DAOA, DTNBP1, GRIA1, GRID1, GRIN1, GRIN2A, GRIN2B, GRIK4, GRM3, GRM4, GRM7, NOS1, NOSIAP, SNAP25, SYN3, SYNJ1
Dopaminergic/Serotonergic	COMT, DRD2, DRD3, HTR2A, HTR5A, HTR6, SLC6A3, SLC6A4,SLC18A1, SLC18A2, MAOA, TDO2, TH
GABA	GABRA1, GABRB2, GAD1
Circadian	CLOCK, NPAS2, NR1D1, TIMELESS, PER3
Cytokines	CSF2RB, IL1B, IL1RN, IL6, IL10, TNFA
Oxidative and other stress	ND4, NDUFV2, MTHFR, MTHFD, MTR, NOS3
Endoplasmic reticulum stress	XBP1
Miscellaneous	ACE, ABCB1, ABCA13, AGT, APOE, BRD1, C10orf120, CACNA1C, CDKN2A, CHRNA7, DISC1, DPYSL2, FABP7, FBXO38. GLT8D1, GNL3, GPR50, GPR78, hCAP-D3, INTS6, ITIH3, MC5R, MCHR1, MCHR2, MLC1, MMP9, MRCL3, MRLC2, NALCN , NEK4, NPAS3, PB1, PDE4B,PFN4, PPARD, PPP3CC, PSKH1, RELN, S100B, SEMG2, SLIT3, SP4, SST, SYNGR1, TAAR6, TMEM108, TP53I3, TSNAX, TSPAN8, TUBA8, YWHAH, ZNF804A

Entrez Gene Links

GRIN1 (NMDA receptor subunit NR1) OMIM 138249 GeneCards

ATXN1 (SCA1): ataxin 1) OMIM 601556 GeneCards

PPP3CC Calcineurin A gamma

DPYSL2 dihydropyrimidinase-like 2 OMIM 602463 GeneCards

RTN4R Reticulon 4 receptor OMIM 605566 GeneCards

AKT1 v-akt murine thymoma viral oncogene homolog 1OMIM 164730

BDNF

CNTF ciliary neurotrophic factor OMIM 118945 GeneCards

EGF Epidermal growth factor OMIM 131530 GeneCards

CNP 2',3'-cyclic nucleotide 3' phosphodiesterase OMIM 123830 GeneCards

MAG myelin-associated glycoprotein OMIM 159460 GeneCards

MOG myelin oligodendrocyte glycoprotein OMIM 159465 GeneCards

TH Tyrosine hydroxylase OMIM 191290 GeneCards

GSTM1 Glutathione transferase M1 OMIM 138350 GeneCards

NQO2 NAD(P)H dehydrogenase, quinone 2 OMIM 160998 GeneCards

S100B Catecholase

TP53 tumor protein p53 OMIM 191170 GeneCards

HTR2A Serotonin receptor OMIM 182135 IUPHAR GeneCards

TPH1 Tryptophan hydroxylase OMIM 191060 GeneCards

TAAR6 Trace amine receptor 6 (ex 4) OMIM 608923 GeneCards

LTA Lymphotoxin alpha OMIM 153440 GeneCards

HLA-DRB1 DRB1*04