NPAS3 harbors the largest cluster ofhuman accelerated regions, suggesting it may have played a key role inhuman evolution.[6] Among this accelerated elements, HAR202 is particularly fascinating due to its differential activity between modern humans andarchaic species, even though it has only been reported in animal reporter assays.[7]
From the first set of human accelerated regions described in 2006,NPAS3locus overlaps one of the most accelerated sequences, HAR21 .[8]
NPAS1 and NPAS3-deficient mice display behavioral abnormalities typical to theanimal models ofschizophrenia.[9] Targeting the gene in astrocytes leads to autistic-like behaviours such as reduced vocalization and socialization.[10]
According to the same study,NPAS1 andNPAS3 disruption leads to reduced expression ofreelin, which is also consistently found to be reduced in the brains of human patients withschizophrenia and psychoticbipolar disorder.
Disruption of NPAS3 was found in one family affected by schizophrenia[13] and NPAS3 gene is thought to be associated with psychiatric illness and learning disability.[14][15] In a genetic study of several hundred subjects conducted in 2008, interactinghaplotypes at the NPAS3 locus were found to affect the risk of schizophrenia andbipolar disorder.[16]
In apharmacogenetical study, polymorphisms in NPAS3 gene were highly associated with response toiloperidone, a proposed atypical antipsychotic.[17]
^Stanco A, Pla R, Vogt D, Chen Y, Mandal S, Walker J, et al. (December 2014). "NPAS1 represses the generation of specific subtypes of cortical interneurons".Neuron.84 (5):940–953.doi:10.1016/j.neuron.2014.10.040.PMID25467980.
^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".American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics.136B (1):26–32.doi:10.1002/ajmg.b.30204.PMID15924306.S2CID33879828.
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 Supplements.8 (5): 100.doi:10.1016/S1359-6349(10)71194-0.
Fonseca DJ, Prada CF, Siza LM, Angel D, Gomez YM, Restrepo CM, et al. (March 2012). "A de novo 14q12q13.3 interstitial deletion in a patient affected by a severe neurodevelopmental disorder of unknown origin".American Journal of Medical Genetics. Part A.158A (3):689–693.doi:10.1002/ajmg.a.35215.PMID22315208.S2CID9506804.
