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Disease ID:839
Associated with:7 targets
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:  5,8-9
References:  7,13-15
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:  2,10
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:  1,6
regulator of G-protein signaling 4
References:  3-4,11-12


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, Jones G, Sanders RD, Jones LA, McCarthy G, Jones S, Bassett A, Cardno AG, Owen MJ, O'Donovan MC. (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. (1992) Association between schizophrenia and homozygosity at the dopamine D3 receptor gene. J Med Genet, 29: 858-860. [PMID:1362221]

6. 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]

7. 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]

8. 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: 558-562. [PMID:8825896]

9. 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: 21-26. [PMID:7909989]

10. 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]

11. 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]

12. 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]

13. 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]

14. 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]

15. 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]