NPAS3 or Neuronal PAS domain protein 3 is a brain-enriched

transcription factor In molecular biology, a transcription factor (TF) (or sequence-specific DNA-binding factor) is a protein that controls the rate of transcription (genetics), transcription of genetics, genetic information from DNA to messenger RNA, by binding t ...

belonging to the bHLH-PAS superfamily of transcription factors, the members of which carry out diverse functions, including circadian oscillations,

neurogenesis Neurogenesis is the process by which nervous system cells, the neurons, are produced by neural stem cells (NSCs). This occurs in all species of animals except the porifera (sponges) and placozoans. Types of NSCs include neuroepithelial cells ( ...

toxin A toxin is a naturally occurring poison produced by metabolic activities of living cells or organisms. They occur especially as proteins, often conjugated. The term was first used by organic chemist Ludwig Brieger (1849–1919), derived ...

metabolism Metabolism (, from ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run cellular processes; the co ...

, hypoxia, and

trachea The trachea (: tracheae or tracheas), also known as the windpipe, is a cartilaginous tube that connects the larynx to the bronchi of the lungs, allowing the passage of air, and so is present in almost all animals' lungs. The trachea extends from ...

l development. NPAS3 contains

basic helix-loop-helix Basic or BASIC may refer to: Science and technology * BASIC, a computer programming language * Basic (chemistry), having the properties of a base * Basic access authentication, in HTTP Entertainment * ''Basic'' (film), a 2003 film * Basic, one ...

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. NPAS1 and NPAS3-deficient mice display behavioral abnormalities typical to the

animal models A model organism is a non-human species that is extensively studied to understand particular biological phenomena, with the expectation that discoveries made in the model organism will provide insight into the workings of other organisms. Mod ...

schizophrenia Schizophrenia () is a mental disorder characterized variously by hallucinations (typically, Auditory hallucination#Schizophrenia, hearing voices), delusions, thought disorder, disorganized thinking and behavior, and Reduced affect display, f ...

. According to the same study, NPAS1 and NPAS3 disruption leads to reduced expression of

reelin Reelin, encoded by the ''RELN'' gene, is a large secreted extracellular matrix glycoprotein that helps regulate processes of neuronal migration and positioning in the developing brain by controlling cell–cell interactions. Besides this importa ...

, which is also consistently found to be reduced in the brains of human patients with

and psychotic

bipolar disorder Bipolar disorder (BD), previously known as manic depression, is a mental disorder characterized by periods of Depression (mood), depression and periods of abnormally elevated Mood (psychology), mood that each last from days to weeks, and in ...

. 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.

Clinical significance

Disruption of NPAS3 was found in one family affected by schizophrenia and NPAS3 gene is thought to be associated with psychiatric illness and learning disability. In a genetic study of several hundred subjects conducted in 2008, interacting

haplotype A haplotype (haploid genotype) is a group of alleles in an organism that are inherited together from a single parent. Many organisms contain genetic material (DNA) which is inherited from two parents. Normally these organisms have their DNA orga ...

s at the NPAS3 locus were found to affect the risk of schizophrenia and

. In a pharmacogenetical study, polymorphisms in NPAS3 gene were highly associated with response to iloperidone, a proposed atypical antipsychotic.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

Function

Clinical significance

References

Further reading