NPAS3
Encyclopedia
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 trachea
l development. NPAS3 contains basic-helix-loop-helix
structural motif and PAS domain
, like the other proteins in the superfamily.
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 of schizophrenia
.
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 region
s that undergone rapid changes in humans compared with their evolutionary ancestors, NPAS3 was found to be located in the region 21.
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
s at the NPAS3 locus were found to affect the risk of schizophrenia and bipolar disorder
.
In a pharmacogenetical
study, polymorphisms in NPAS3 gene were highly associated with response to iloperidone
, a proposed atypical antipsychotic.
Transcription factor
In molecular biology and genetics, a transcription factor is a protein that binds to specific DNA sequences, thereby controlling the flow of genetic information from DNA to mRNA...
belonging to the bHLH-PAS superfamily of transcription factors
Basic-helix-loop-helix
A basic helix-loop-helix is a protein structural motif that characterizes a family of transcription factors.- Structure :The motif is characterized by two α-helices connected by a loop. In general, transcription factors including this domain are dimeric, each with one helix containing basic amino...
, the members of which carry out diverse functions, including circadian oscillations, neurogenesis
Neurogenesis
Neurogenesis is the process by which neurons are generated from neural stem and progenitor cells. Most active during pre-natal development, neurogenesis is responsible for populating the growing brain with neurons. Recently neurogenesis was shown to continue in several small parts of the brain of...
, toxin
Toxin
A toxin is a poisonous substance produced within living cells or organisms; man-made substances created by artificial processes are thus excluded...
metabolism
Metabolism
Metabolism is the set of chemical reactions that happen in the cells of living organisms to sustain life. These processes allow organisms to grow and reproduce, maintain their structures, and respond to their environments. Metabolism is usually divided into two categories...
, hypoxia
Hypoxia (medical)
Hypoxia, or hypoxiation, is a pathological condition in which the body as a whole or a region of the body is deprived of adequate oxygen supply. Variations in arterial oxygen concentrations can be part of the normal physiology, for example, during strenuous physical exercise...
, and trachea
Vertebrate trachea
In tetrapod anatomy the trachea, or windpipe, is a tube that connects the pharynx or larynx to the lungs, allowing the passage of air. It is lined with pseudostratified ciliated columnar epithelium cells with goblet cells that produce mucus...
l development. NPAS3 contains basic-helix-loop-helix
Basic-helix-loop-helix
A basic helix-loop-helix is a protein structural motif that characterizes a family of transcription factors.- Structure :The motif is characterized by two α-helices connected by a loop. In general, transcription factors including this domain are dimeric, each with one helix containing basic amino...
structural motif and PAS domain
PAS domain
The PAS domain is a protein domain contained in many signaling proteins where it functions as a signal sensor. PAS domains are found in a large number of organisms from bacteria to humans...
, like the other proteins in the superfamily.
Function
NPAS3 is also known as human accelerated regionHuman accelerated regions
Human accelerated regions , first described in August 2006, are a set of 49 segments of the human genome which are conserved throughout vertebrate evolution but are strikingly different in humans. They are named HAR1 through HAR49 according to their degree of difference between humans and chimpanzees...
21. It may, therefore, have played a key role in differentiating humans from apes.
NPAS1
NPAS1
NPAS1 is a basic-helix-loop-helix transcription factor....
and NPAS3-deficient mice display behavioral abnormalities typical to the animal models of schizophrenia
Schizophrenia
Schizophrenia is a mental disorder characterized by a disintegration of thought processes and of emotional responsiveness. It most commonly manifests itself as auditory hallucinations, paranoid or bizarre delusions, or disorganized speech and thinking, and it is accompanied by significant social...
.
According to the same study, NPAS1
NPAS1
NPAS1 is a basic-helix-loop-helix transcription factor....
and NPAS3 disruption leads to reduced expression of reelin
Reelin
Reelin is a large secreted extracellular matrix protein that helps regulate processes of neuronal migration and positioning in the developing brain by controlling cell–cell interactions. Besides this important role in early development, reelin continues to work in the adult brain. It modulates the...
, which is also consistently found to be reduced in the brains of human patients with schizophrenia
Schizophrenia
Schizophrenia is a mental disorder characterized by a disintegration of thought processes and of emotional responsiveness. It most commonly manifests itself as auditory hallucinations, paranoid or bizarre delusions, or disorganized speech and thinking, and it is accompanied by significant social...
and psychotic bipolar disorder
Bipolar disorder
Bipolar disorder or bipolar affective disorder, historically known as manic–depressive disorder, is a psychiatric diagnosis that describes a category of mood disorders defined by the presence of one or more episodes of abnormally elevated energy levels, cognition, and mood with or without one or...
. Among the 49 genomic region
Human accelerated regions
Human accelerated regions , first described in August 2006, are a set of 49 segments of the human genome which are conserved throughout vertebrate evolution but are strikingly different in humans. They are named HAR1 through HAR49 according to their degree of difference between humans and chimpanzees...
s 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 schizophreniaand 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
Haplotype
A haplotype in genetics is a combination of alleles at adjacent locations on the chromosome that are transmitted together...
s at the NPAS3 locus were found to affect the risk of schizophrenia and bipolar disorder
Bipolar disorder
Bipolar disorder or bipolar affective disorder, historically known as manic–depressive disorder, is a psychiatric diagnosis that describes a category of mood disorders defined by the presence of one or more episodes of abnormally elevated energy levels, cognition, and mood with or without one or...
.
In a pharmacogenetical
Pharmacogenetics
The terms pharmacogenomics and pharmacogenetics tend to be used interchangeably, and a precise, consensus definition of either remains elusive...
study, polymorphisms in NPAS3 gene were highly associated with response to iloperidone
Iloperidone
Iloperidone, also known as Fanapt, Fanapta, and previously known as Zomaril, is an atypical antipsychotic for the treatment of schizophrenia. It was approved by the U.S...
, a proposed atypical antipsychotic.