Biology:NPAS3
 Generic protein structure example |
NPAS3 or Neuronal PAS domain protein 3 is a brain-enriched transcription factor belonging to the bHLH-PAS superfamily of transcription factors, the members of which carry out diverse functions, including circadian oscillations, neurogenesis, toxin metabolism, hypoxia, and tracheal development. NPAS3 contains basic helix-loop-helix structural motif and PAS domain, like the other proteins in the superfamily.
Function
NPAS3 is also known as human accelerated region 21. It may, therefore, have played a key role in differentiating humans from apes.[1]
NPAS1 and NPAS3-deficient mice display behavioral abnormalities typical to the animal models of schizophrenia.[2]
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]
Clinical significance
Disruption of NPAS3 was found in one family affected by schizophrenia[3] and NPAS3 gene is thought to be associated with psychiatric illness and learning disability.[4][5] 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]
References
- ↑ 1.0 1.1 "An RNA gene expressed during cortical development evolved rapidly in humans". Nature 443 (7108): 167–72. Sep 2006. doi:10.1038/nature05113. PMID 16915236. Bibcode: 2006Natur.443..167P. https://dipot.ulb.ac.be/dspace/bitstream/2013/51805/3/pollard2006.pdf.
- ↑ "Behavioral and regulatory abnormalities in mice deficient in the NPAS1 and NPAS3 transcription factors". Proceedings of the National Academy of Sciences of the United States of America 101 (37): 13648–53. Sep 2004. doi:10.1073/pnas.0405310101. PMID 15347806. Bibcode: 2004PNAS..10113648E.
- ↑ "Disruption of the neuronal PAS3 gene in a family affected with schizophrenia". Journal of Medical Genetics 40 (5): 325–32. May 2003. doi:10.1136/jmg.40.5.325. PMID 12746393.
- ↑ "Disruption of a brain transcription factor, NPAS3, is associated with schizophrenia and learning disability". American Journal of Medical Genetics Part B 136B (1): 26–32. Jul 2005. doi:10.1002/ajmg.b.30204. PMID 15924306.
- ↑ "The NPAS3 gene--emerging evidence for a role in psychiatric illness". Annals of Medicine 38 (6): 439–48. 2006. doi:10.1080/07853890600946500. PMID 17008307.
- ↑ "Interacting haplotypes at the NPAS3 locus alter risk of schizophrenia and bipolar disorder". Molecular Psychiatry 14 (9): 874–84. Sep 2009. doi:10.1038/mp.2008.24. PMID 18317462.
- ↑ 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
Further reading
- "Disruption of the neuronal PAS3 gene in a family affected with schizophrenia". Journal of Medical Genetics 40 (5): 325–32. May 2003. doi:10.1136/jmg.40.5.325. PMID 12746393.
- "NPAS3 demonstrates features of a tumor suppressive role in driving the progression of Astrocytomas". The American Journal of Pathology 179 (1): 462–76. Jul 2011. doi:10.1016/j.ajpath.2011.03.044. PMID 21703424.
- "393 NPAS3 is a novel late-stage acting progression factor in gliomas with tumour suppressive functions". European Journal of Cancer Supplements 8 (5): 100. 2010. doi:10.1016/S1359-6349(10)71194-0.
- "CB-01. Regulation of aminoacylase expression in neuroblastoma". Neuro-Oncology 12 (Supplement 4): iv7–iv25. 2010. doi:10.1093/neuonc/noq116.s2.
- "Expression of NPAS3 in the human cortex and evidence of its posttranscriptional regulation by miR-17 during development, with implications for schizophrenia". Schizophrenia Bulletin 39 (2): 396–406. Mar 2013. doi:10.1093/schbul/sbr177. PMID 22228753.
- "Isolation and Characterization of Chicken NPAS3". Experimental Neurobiology 19 (2): 71–4. Sep 2010. doi:10.5607/en.2010.19.2.71. PMID 22110344.
- "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): 689–93. Mar 2012. doi:10.1002/ajmg.a.35215. PMID 22315208.
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