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Disease ID:839
Associated with:8 targets
1 immuno-relevant target
Database Links
Disease Ontology: DOID:5419
OMIM: 181500
Orphanet: ORPHA3140


5-HT2A receptor
D3 receptor
Role:  The Ba1I restriction fragment length polymorphism (corresponding to a point mutation in the 1st exon and resulting in a serine-to-glycine substitution in the N-terminal extracellular domain of the receptor) has been associated with schizophrenia.
References:  5,10-11
References:  9,15-17
Comments:  The truncation has been found in one patient with schizophrenia. Expression of KCa2.3-1/285 causes dominant-negative suppression of KCa2.2 in Jurkat cells.
References:  2,12
Mutations:  KCa2.3 is associated with 1 mutation. Click here for details
Role:  SNPs within intron 2 of KCNH2 are associated with schizophrenia, lower intelligence quotient scores and cognitive processing speed. Additionally, postmortem examination of hippocampi from individuals with these SNPs revealed increased mRNA levels of a brain isoform of KCNH2 (KCNH2-3.1). This isoform lacks a domain that is required for slow channel deactivation and overexpression of KCNH2-3.1 in primary cortical neurons induces a high frequency, nonadapting firing pattern.
References:  1,8
regulator of G-protein signaling 4
References:  3-4,13-14
regulator of G-protein signaling 10
Comments:  Possible link to schizophrenia and depression.


No ligand related data available for Schizophrenia


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1. Apud JA, Zhang F, Decot H, Bigos KL, Weinberger DR. (2012) Genetic variation in KCNH2 associated with expression in the brain of a unique hERG isoform modulates treatment response in patients with schizophrenia. Am J Psychiatry, 169 (7): 725-34. [PMID:22706279]

2. Bowen T, Williams N, Norton N, Spurlock G, Wittekindt OH, Morris-Rosendahl DJ, Williams H, Brzustowicz L, Hoogendoorn B, Zammit S et al.. (2001) Mutation screening of the KCNN3 gene reveals a rare frameshift mutation. Mol Psychiatry, 6 (3): 259-60. [PMID:11326292]

3. Chen X, Dunham C, Kendler S, Wang X, O'Neill FA, Walsh D, Kendler KS. (2004) Regulator of G-protein signaling 4 (RGS4) gene is associated with schizophrenia in Irish high density families. Am J Med Genet B Neuropsychiatr Genet, 129B (1): 23-6. [PMID:15274033]

4. Chowdari KV, Mirnics K, Semwal P, Wood J, Lawrence E, Bhatia T, Deshpande SN, B K T, Ferrell RE, Middleton FA et al.. (2002) Association and linkage analyses of RGS4 polymorphisms in schizophrenia. Hum Mol Genet, 11 (12): 1373-80. [PMID:12023979]

5. Crocq MA, Mant R, Asherson P, Williams J, Hode Y, Mayerova A, Collier D, Lannfelt L, Sokoloff P, Schwartz JC et al.. (1992) Association between schizophrenia and homozygosity at the dopamine D3 receptor gene. J Med Genet, 29 (12): 858-60. [PMID:1362221]

6. González-Castro TB, Martínez-Magaña JJ, Tovilla-Zárate CA, Juárez-Rojop IE, Sarmiento E, Genis-Mendoza AD, Nicolini H. (2019) Gene-level genome-wide association analysis of suicide attempt, a preliminary study in a psychiatric Mexican population. Mol Genet Genomic Med, 7 (12): e983. [PMID:31578828]

7. Hishimoto A, Shirakawa O, Nishiguchi N, Aoyama S, Ono H, Hashimoto T, Maeda K. (2004) Novel missense polymorphism in the regulator of G-protein signaling 10 gene: analysis of association with schizophrenia. Psychiatry Clin Neurosci, 58 (5): 579-81. [PMID:15482592]

8. Huffaker SJ, Chen J, Nicodemus KK, Sambataro F, Yang F, Mattay V, Lipska BK, Hyde TM, Song J, Rujescu D et al.. (2009) A primate-specific, brain isoform of KCNH2 affects cortical physiology, cognition, neuronal repolarization and risk of schizophrenia. Nat Med, 15 (5): 509-18. [PMID:19412172]

9. Katsu T, Ujike H, Nakano T, Tanaka Y, Nomura A, Nakata K, Takaki M, Sakai A, Uchida N, Imamura T et al.. (2003) The human frizzled-3 (FZD3) gene on chromosome 8p21, a receptor gene for Wnt ligands, is associated with the susceptibility to schizophrenia. Neurosci Lett, 353 (1): 53-6. [PMID:14642436]

10. Kennedy JL, Billett EA, Macciardi FM, Verga M, Parsons TJ, Meltzer HY, Lieberman J, Buchanan JA. (1995) Association study of dopamine D3 receptor gene and schizophrenia. Am J Med Genet, 60 (6): 558-62. [PMID:8825896]

11. Mant R, Williams J, Asherson P, Parfitt E, McGuffin P, Owen MJ. (1994) Relationship between homozygosity at the dopamine D3 receptor gene and schizophrenia. Am J Med Genet, 54 (1): 21-6. [PMID:7909989]

12. Miller MJ, Rauer H, Tomita H, Rauer H, Gargus JJ, Gutman GA, Cahalan MD, Chandy KG. (2001) Nuclear localization and dominant-negative suppression by a mutant SKCa3 N-terminal channel fragment identified in a patient with schizophrenia. J Biol Chem, 276 (30): 27753-6. [PMID:11395478]

13. Mirnics K, Middleton FA, Stanwood GD, Lewis DA, Levitt P. (2001) Disease-specific changes in regulator of G-protein signaling 4 (RGS4) expression in schizophrenia. Mol Psychiatry, 6 (3): 293-301. [PMID:11326297]

14. Morris DW, Rodgers A, McGhee KA, Schwaiger S, Scully P, Quinn J, Meagher D, Waddington JL, Gill M, Corvin AP. (2004) Confirming RGS4 as a susceptibility gene for schizophrenia. Am J Med Genet B Neuropsychiatr Genet, 125B (1): 50-3. [PMID:14755443]

15. Wei J, Hemmings GP. (2004) Lack of a genetic association between the frizzled-3 gene and schizophrenia in a British population. Neurosci Lett, 366 (3): 336-8. [PMID:15288446]

16. Yang J, Si T, Ling Y, Ruan Y, Han Y, Wang X, Zhang H, Kong Q, Li X, Liu C et al.. (2003) Association study of the human FZD3 locus with schizophrenia. Biol Psychiatry, 54 (11): 1298-301. [PMID:14643098]

17. Zhang Y, Yu X, Yuan Y, Ling Y, Ruan Y, Si T, Lu T, Wu S, Gong X, Zhu Z et al.. (2004) Positive association of the human frizzled 3 (FZD3) gene haplotype with schizophrenia in Chinese Han population. Am J Med Genet B Neuropsychiatr Genet, 129B (1): 16-9. [PMID:15274031]