According to the same study, NPAS1 and NPAS3 disruption leads to reduced expression of reelin, which is also consistently found to be reduced in the brains of human patients with schizophrenia and psychotic bipolar disorder. Among the 49 genomic regions that undergone rapid changes in humans compared with their evolutionary ancestors, NPAS3 was found to be located in the region 21.1
Disruption of NPAS3 was found in one family affected by schizophrenia3 and NPAS3 gene is thought to be associated with psychiatric illness and learning disability.45 In a genetic study of several hundred subjects conducted in 2008, interacting haplotypes at the NPAS3 locus were found to affect the risk of schizophrenia and bipolar disorder.6
In a pharmacogenetical study, polymorphisms in NPAS3 gene were highly associated with response to iloperidone, a proposed atypical antipsychotic.7
^ abPollard KS, Salama SR, Lambert N, Lambot MA, Coppens S, Pedersen JS, Katzman S, King B, Onodera C, Siepel A, Kern AD, Dehay C, Igel H, Ares M, Vanderhaeghen P, Haussler D (September 2006). "An RNA gene expressed during cortical development evolved rapidly in humans". Nature443 (7108): 167–72. doi:10.1038/nature05113. PMID16915236.
^Pickard BS, Malloy MP, Porteous DJ, Blackwood DH, Muir WJ (July 2005). "Disruption of a brain transcription factor, NPAS3, is associated with schizophrenia and learning disability". Am. J. Med. Genet. B Neuropsychiatr. Genet.136B (1): 26–32. doi:10.1002/ajmg.b.30204. PMID15924306.
^Pickard BS, Pieper AA, Porteous DJ, Blackwood DH, Muir WJ (2006). "The NPAS3 gene--emerging evidence for a role in psychiatric illness". Ann. Med.38 (6): 439–48. doi:10.1080/07853890600946500. PMID17008307.
^Pickard BS, Christoforou A, Thomson PA, Fawkes A, Evans KL, Morris SW, Porteous DJ, Blackwood DH, Muir WJ (September 2009). "Interacting haplotypes at the NPAS3 locus alter risk of schizophrenia and bipolar disorder". Mol. Psychiatry14 (9): 874–84. doi:10.1038/mp.2008.24. PMID18317462.
^Lavedan C, Volpi S, Mack K, et al. Whole-genome association study identifies polymorphisms in the NPAS3 gene associated with super-response to iloperidone treatment in patients with schizophrenia. Program and abstracts of the 57th Annual Meeting of the American Society of Human Genetics; October 23–27, 2007; San Diego, California. Abstract 1035/T
Kamnasaran D, Ajewung N, Rana M, Gould P (2010). "393 NPAS3 is a novel late-stage acting progression factor in gliomas with tumour suppressive functions". European Journal of Cancer Supplements8 (5): 100. doi:10.1016/S1359-6349(10)71194-0.
Long PM, Wesley UV, Jaworski DM, Rana M, Kiehl T-R, So K, Gould P, Ajewung N, Kamnasaran D (2010). "CB-01. Regulation of aminoacylase expression in neuroblastoma". Neuro-Oncology12 (Supplement 4): iv7–iv25. doi:10.1093/neuonc/noq116.s2.
Wong J, Duncan CE, Beveridge NJ, Webster MJ, Cairns MJ, Shannon Weickert C (January 2012). "Expression of NPAS3 in the Human Cortex and Evidence of Its Posttranscriptional Regulation by miR-17 During Development, With Implications for Schizophrenia". Schizophr Bull. doi:10.1093/schbul/sbr177. PMID22228753.
Fonseca DJ, Prada CF, Siza LM, Angel D, Gomez YM, Restrepo CM, Douben H, Rivadeneira F, de Klein A, Laissue P (March 2012). "A de novo 14q12q13.3 interstitial deletion in a patient affected by a severe neurodevelopmental disorder of unknown origin". Am. J. Med. Genet. A158A (3): 689–93. doi:10.1002/ajmg.a.35215. PMID22315208.