NPAS3

NPAS3 or Neuronal PAS domain protein 3 is a brain-enriched is_associated_with::transcription factor belonging to the bHLH-PAS superfamily of transcription factors, the members of which carry out diverse functions, including is_associated_with::circadian oscillations, is_associated_with::neurogenesis, is_associated_with::toxin is_associated_with::metabolism, hypoxia, and tracheal development. NPAS3 contains is_associated_with::basic helix-loop-helix structural motif and is_associated_with::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.

is_associated_with::NPAS1 and NPAS3-deficient mice display behavioral abnormalities typical to the animal models of is_associated_with::schizophrenia.

According to the same study, is_associated_with::NPAS1 and NPAS3 disruption leads to reduced expression of is_associated_with::reelin, which is also consistently found to be reduced in the brains of human patients with is_associated_with::schizophrenia and psychotic is_associated_with::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.

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 is_associated_with::haplotypes at the NPAS3 locus were found to affect the risk of schizophrenia and is_associated_with::bipolar disorder.

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