NPAS2 neuronal PAS domain protein 2 [Homo sapiens (human)] - Gene

Summary

Official Symbol: NPAS2provided by HGNC
Official Full Name: neuronal PAS domain protein 2provided by HGNC
Primary source: HGNC:HGNC:7895
See related: Ensembl:ENSG00000170485 MIM:603347; Vega:OTTHUMG00000130675
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: MOP4; PASD4; bHLHe9
Summary: The protein encoded by this gene is a member of the basic helix-loop-helix (bHLH)-PAS family of transcription factors. A similar mouse protein may play a regulatory role in the acquisition of specific types of memory. It also may function as a part of a molecular clock operative in the mammalian forebrain. [provided by RefSeq, Jul 2008]
Expression: Ubiquitous expression in esophagus (RPKM 4.7), urinary bladder (RPKM 4.5) and 22 other tissues See more
Orthologs: mouse all

Genomic context

Location:: 2q11.2

Exon count:: 25

Annotation release	Status	Assembly	Chr	Location
109	current	GRCh38.p12 (GCF_000001405.38)	2	NC_000002.12 (100820151..100996829)
105	previous assembly	GRCh37.p13 (GCF_000001405.25)	2	NC_000002.11 (101436613..101613289)

Chromosome 2 - NC_000002.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Jun 15 11:32:44 2016

Bibliography

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GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

NPAS2 hypomethylation occurs at the early stage of PD and is a moderate biomarker for distinguishing PD patients from healthy subjects.
Title: Pyrosequencing analysis of methylation levels of clock genes in leukocytes from Parkinson's disease patients.
NPAS2 has a critical role in HCC cell survival and tumor growth, which is mainly mediated by transcriptional upregulation of CDC25A.
Title: NPAS2 promotes cell survival of hepatocellular carcinoma by transactivating CDC25A.
Aggregate genetic variation in circadian rhythm and melatonin pathways were significantly associated with the risk of prostate cancer in data combining GAME-ON and PLCO, after Bonferroni correction (ppathway < 0.00625). The two most significant genes were NPAS2 (pgene = 0.0062) and AANAT (pgene = 0.00078); the latter being significant after Bonferroni correction.
Title: Inherited variation in circadian rhythm genes and risks of prostate cancer and three other cancer sites in combined cancer consortia.
Significantly, this study is the first to show that a variant copy number GGC repeat sequence in the NPAS2 clock gene associates with melanoma risk and which may be useful in the assessment of melanoma predisposition.
Title: A polymorphic GGC repeat in the NPAS2 gene and its association with melanoma.
CLOCK, ARNTL, and NPAS2 gene polymorphisms may have a role in seasonal variations in mood and behavior
Title: Association of CLOCK, ARNTL, and NPAS2 gene polymorphisms and seasonal variations in mood and behavior.
Genetic variations in NPAS2 might be a biomarker for a seasonal pattern in bipolar disorders.
Title: Genetic association study of circadian genes with seasonal pattern in bipolar disorders.
With whole-exome sequencing a novel mutation in NPAS2 was identified in a Turkish family with nonobstructive azoospermia.
Title: Whole-exome sequencing identifies novel homozygous mutation in NPAS2 in family with nonobstructive azoospermia.
NPAS2 rs2305160 polymorphism does not appear to have any association with risk of chronic lymphocytic leukemia in our Pakistani population.
Title: Lack of association of the NPAS2 gene Ala394Thr polymorphism (rs2305160:G>A) with risk of chronic lymphocytic leukemia.
distributions of allelic, genotypic, and haplotypic variants of NPAS2 (rs2305160 and rs6725296) were not significantly different between schizophrenic patients with and without RLS
Title: Association between restless legs syndrome and CLOCK and NPAS2 gene polymorphisms in schizophrenia.
Two single nucleotide polymorphisms in RORA were associated with breast cancer in the whole sample and among postmenopausal women, and we also reported an association with CLOCK, RORA, and NPAS2 in the analyses at the gene level
Title: Breast cancer risk, nightwork, and circadian clock gene polymorphisms.

Submit: New GeneRIF Correction See all GeneRIFs (31)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

NHGRI GWAS Catalog

Description
Common genetic variants associated with cognitive performance identified using the proxy-phenotype method. NHGRI GWA Catalog NHGRI GWA CatalogPubMed
Genome-wide study links MTMR7 gene to variant Creutzfeldt-Jakob risk. NHGRI GWA Catalog NHGRI GWA CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Pathways from BioSystems

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BMAL1:CLOCK,NPAS2 activates circadian gene expression, organism-specific biosystem (from REACTOME)
BMAL1:CLOCK,NPAS2 activates circadian gene expression, organism-specific biosystemAs inferred from mouse, BMAL1:CLOCK (ARNTL:CLOCK) and BMAL1:NPAS2 (ARNTL:NPAS2) heterodimers bind to sequence elements (E boxes) in the promoters of target genes and enhance transcription (Gekakis et...
Circadian Clock, organism-specific biosystem (from REACTOME)
Circadian Clock, organism-specific biosystemAt the center of the mammalian circadian clock is a negative transcription/translation-based feedback loop: The BMAL1:CLOCK/NPAS2 (ARNTL:CLOCK/NPAS2) heterodimer transactivates CRY and PER genes by b...
Circadian rhythm, organism-specific biosystem (from KEGG)
Circadian rhythm, organism-specific biosystemCircadian rhythm is an internal biological clock, which enables to sustain an approximately 24-hour rhythm in the absence of environmental cues. In mammals, the circadian clock mechanism consists of ...
Circadian rhythm, conserved biosystem (from KEGG)
Circadian rhythm, conserved biosystemCircadian rhythm is an internal biological clock, which enables to sustain an approximately 24-hour rhythm in the absence of environmental cues. In mammals, the circadian clock mechanism consists of ...
Circadian rhythm pathway, organism-specific biosystem (from Pathway Interaction Database)
Circadian rhythm pathway, organism-specific biosystem
Circadian rhythm pathway
Circadian rythm related genes, organism-specific biosystem (from WikiPathways)
Circadian rythm related genes, organism-specific biosystemThis is currently not a pathway but a list of circadian rhythm related genes and proteins. The source for this information is the gene ontology. The genes and proteins were filtered for "circadian rh...
Fatty acid, triacylglycerol, and ketone body metabolism, organism-specific biosystem (from REACTOME)
Fatty acid, triacylglycerol, and ketone body metabolism, organism-specific biosystemThe reactions involved in the metabolism of fatty acids and of the triacylglycerols and ketone bodies derived from them form a closely interrelated, coordinately regulated module that plays a central...
Metabolism, organism-specific biosystem (from REACTOME)
Metabolism, organism-specific biosystemMetabolic processes in human cells generate energy through the oxidation of molecules consumed in the diet and mediate the synthesis of diverse essential molecules not taken in the diet as well as th...
Metabolism of lipids and lipoproteins, organism-specific biosystem (from REACTOME)
Metabolism of lipids and lipoproteins, organism-specific biosystemLipids are hydrophobic but otherwise chemically diverse molecules that play a wide variety of roles in human biology. They include ketone bodies, fatty acids, triacylglycerols, phospholipids and sphi...
PPARA activates gene expression, organism-specific biosystem (from REACTOME)
PPARA activates gene expression, organism-specific biosystemThe set of genes regulated by PPAR-alpha is not fully known in humans, however many examples have been found in mice. Genes directly activated by PPAR-alpha contain peroxisome proliferator receptor e...
RORA activates gene expression, organism-specific biosystem (from REACTOME)
RORA activates gene expression, organism-specific biosystemAs inferred from mouse, RORA binds ROR elements (ROREs) in DNA and recruits the coactivators PPARGC1A (PGC-1alpha) and p300 (EP300, a histone acetylase) to activate transcription.
Regulation of lipid metabolism by Peroxisome proliferator-activated receptor alpha (PPARalpha), organism-specific biosystem (from REACTOME)
Regulation of lipid metabolism by Peroxisome proliferator-activated receptor alpha (PPARalpha), organism-specific biosystemPeroxisome proliferator-activated receptor alpha (PPAR-alpha) is the major regulator of fatty acid oxidation in the liver. PPARalpha is also the target of fibrate drugs used to treat abnormal plasma ...

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH79879 (e-PCR)
- UniSTS:85760

SHGC-33168 (e-PCR)
- UniSTS:6424

D10S275 (e-PCR)
- UniSTS:147992

SHGC-85091 (e-PCR)
- UniSTS:103471

D8S2279 (e-PCR)
- UniSTS:473907

WI-17613 (e-PCR)
- UniSTS:32310

SHGC-78601 (e-PCR)
- UniSTS:101706

SHGC-34190 (e-PCR)
- UniSTS:5223

RH71260 (e-PCR)
- UniSTS:42346

SHGC-58283 (e-PCR)
- UniSTS:34702

RH17865 (e-PCR)
- UniSTS:68248

RH16198 (e-PCR)
- UniSTS:71326

PMC19579P4 (e-PCR)
- UniSTS:271786

RH77872 (e-PCR)
- UniSTS:69042

RH45156 (e-PCR)
- UniSTS:29379

SHGC-36364 (e-PCR)
- UniSTS:20938

SHGC-132981 (e-PCR)
- UniSTS:170963

SGC34754 (e-PCR)
- UniSTS:5596

Homology

Homologs of the NPAS2 gene: The NPAS2 gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, chicken, and frog.
Orthologs from Annotation Pipeline: 189 organisms have orthologs with human gene NPAS2
The Hierarchical Catalog of Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
DNA binding	IDA Inferred from Direct Assay more info	PubMed
DNA binding	IPI Inferred from Physical Interaction more info	PubMed
DNA-binding transcription factor activity	TAS Traceable Author Statement more info	PubMed
DNA-binding transcription factor activity, RNA polymerase II-specific	ISA Inferred from Sequence Alignment more info
DNA-binding transcription factor activity, RNA polymerase II-specific	ISM Inferred from Sequence Model more info	PubMed
DNA-binding transcription factor activity, RNA polymerase II-specific	NAS Non-traceable Author Statement more info	PubMed
Hsp90 protein binding	IDA Inferred from Direct Assay more info	PubMed
RNA polymerase II distal enhancer sequence-specific DNA binding	ISS Inferred from Sequence or Structural Similarity more info
metal ion binding	IEA Inferred from Electronic Annotation more info
protein binding	IPI Inferred from Physical Interaction more info	PubMed
protein dimerization activity	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
cellular response to DNA damage stimulus	IEA Inferred from Electronic Annotation more info
central nervous system development	TAS Traceable Author Statement more info	PubMed
circadian regulation of gene expression	ISS Inferred from Sequence or Structural Similarity more info
circadian rhythm	TAS Traceable Author Statement more info
negative regulation of cell death	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of DNA repair	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of transcription by RNA polymerase II	IGI Inferred from Genetic Interaction more info	PubMed
positive regulation of transcription, DNA-templated	IDA Inferred from Direct Assay more info	PubMed
positive regulation of transcription, DNA-templated	IMP Inferred from Mutant Phenotype more info	PubMed
regulation of lipid metabolic process	TAS Traceable Author Statement more info
regulation of response to DNA damage stimulus	IMP Inferred from Mutant Phenotype more info	PubMed
response to redox state	IDA Inferred from Direct Assay more info	PubMed

Component	Evidence Code	Pubs
cytosol	IDA Inferred from Direct Assay more info
cytosol	TAS Traceable Author Statement more info
nucleoplasm	IDA Inferred from Direct Assay more info
nucleoplasm	TAS Traceable Author Statement more info
nucleus	IDA Inferred from Direct Assay more info	PubMed
transcription factor complex	IPI Inferred from Physical Interaction more info	PubMed

General protein information

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Preferred Names: neuronal PAS domain-containing protein 2

Names: PAS domain-containing protein 4; basic-helix-loop-helix-PAS protein MOP4; class E basic helix-loop-helix protein 9; member of PAS protein 4; member of PAS superfamily 4; neuronal PAS2

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_023259.1 RefSeqGene

Range

5001..181675

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_002518.3 → NP_002509.2 neuronal PAS domain-containing protein 2

See identical proteins and their annotated locations for NP_002509.2

Status: REVIEWED

Source sequence(s)

AK095806, AK128586, BC072383, BM724652, U77970

Consensus CDS

CCDS2048.1

UniProtKB/Swiss-Prot

Q99743

UniProtKB/TrEMBL

A2I2P5

Related

ENSP00000338283.5, OTTHUMP00000161260, ENST00000335681.9, OTTHUMT00000253168

Conserved Domains (5) summary

smart00091
Location:84 → 149

PAS; PAS domain

cd00083
Location:7 → 61

HLH; Helix-loop-helix domain, found in specific DNA- binding proteins that act as transcription factors; 60-100 amino acids long. A DNA-binding basic region is followed by two alpha-helices separated by a variable loop region; HLH forms homo- and heterodimers, ...

cd00130
Location:250 → 350

PAS; PAS domain; PAS motifs appear in archaea, eubacteria and eukarya. Probably the most surprising identification of a PAS domain was that in EAG-like K+-channels. PAS domains have been found to bind ligands, and to act as sensors for light and oxygen in ...

pfam13426
Location:94 → 195

PAS_9; PAS domain

pfam14598
Location:249 → 352

PAS_11; PAS domain

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 109 details...

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p12 Primary Assembly

Genomic

NC_000002.12 Reference GRCh38.p12 Primary Assembly

Range

100820151..100996829

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_011511242.2 → XP_011509544.1 neuronal PAS domain-containing protein 2 isoform X5

Conserved Domains (3) summary

cd00083
Location:7 → 61

HLH; Helix-loop-helix domain, found in specific DNA- binding proteins that act as transcription factors; 60-100 amino acids long. A DNA-binding basic region is followed by two alpha-helices separated by a variable loop region; HLH forms homo- and heterodimers, ...

cd00130
Location:220 → 320

PAS; PAS domain; PAS motifs appear in archaea, eubacteria and eukarya. Probably the most surprising identification of a PAS domain was that in EAG-like K+-channels. PAS domains have been found to bind ligands, and to act as sensors for light and oxygen in ...

pfam14598
Location:219 → 322

PAS_11; PAS domain
XM_005263953.2 → XP_005264010.1 neuronal PAS domain-containing protein 2 isoform X1

Conserved Domains (5) summary

smart00091
Location:149 → 214

PAS; PAS domain

cd00083
Location:72 → 126

HLH; Helix-loop-helix domain, found in specific DNA- binding proteins that act as transcription factors; 60-100 amino acids long. A DNA-binding basic region is followed by two alpha-helices separated by a variable loop region; HLH forms homo- and heterodimers, ...

cd00130
Location:315 → 415

PAS; PAS domain; PAS motifs appear in archaea, eubacteria and eukarya. Probably the most surprising identification of a PAS domain was that in EAG-like K+-channels. PAS domains have been found to bind ligands, and to act as sensors for light and oxygen in ...

pfam13426
Location:159 → 260

PAS_9; PAS domain

pfam14598
Location:314 → 417

PAS_11; PAS domain
XM_017004214.1 → XP_016859703.1 neuronal PAS domain-containing protein 2 isoform X2
XM_005263960.2 → XP_005264017.1 neuronal PAS domain-containing protein 2 isoform X7

Conserved Domains (3) summary

cd00083
Location:72 → 126

HLH; Helix-loop-helix domain, found in specific DNA- binding proteins that act as transcription factors; 60-100 amino acids long. A DNA-binding basic region is followed by two alpha-helices separated by a variable loop region; HLH forms homo- and heterodimers, ...

cd00130
Location:158 → 312

PAS; PAS domain; PAS motifs appear in archaea, eubacteria and eukarya. Probably the most surprising identification of a PAS domain was that in EAG-like K+-channels. PAS domains have been found to bind ligands, and to act as sensors for light and oxygen in ...

pfam13426
Location:159 → 260

PAS_9; PAS domain
XM_005263959.2 → XP_005264016.1 neuronal PAS domain-containing protein 2 isoform X4

Conserved Domains (6) summary

smart00091
Location:149 → 214

PAS; PAS domain

cd00083
Location:72 → 126

HLH; Helix-loop-helix domain, found in specific DNA- binding proteins that act as transcription factors; 60-100 amino acids long. A DNA-binding basic region is followed by two alpha-helices separated by a variable loop region; HLH forms homo- and heterodimers, ...

cd00130
Location:315 → 415

PAS; PAS domain; PAS motifs appear in archaea, eubacteria and eukarya. Probably the most surprising identification of a PAS domain was that in EAG-like K+-channels. PAS domains have been found to bind ligands, and to act as sensors for light and oxygen in ...

pfam06752
Location:590 → 719

E_Pc_C; Enhancer of Polycomb C-terminus

pfam13426
Location:159 → 260

PAS_9; PAS domain

pfam14598
Location:314 → 417

PAS_11; PAS domain
XM_017004216.1 → XP_016859705.1 neuronal PAS domain-containing protein 2 isoform X6
XM_017004217.1 → XP_016859706.1 neuronal PAS domain-containing protein 2 isoform X8
XM_017004215.1 → XP_016859704.1 neuronal PAS domain-containing protein 2 isoform X3
XM_011511243.2 → XP_011509545.1 neuronal PAS domain-containing protein 2 isoform X10

Conserved Domains (5) summary

smart00091
Location:149 → 214

PAS; PAS domain

cd00083
Location:72 → 126

HLH; Helix-loop-helix domain, found in specific DNA- binding proteins that act as transcription factors; 60-100 amino acids long. A DNA-binding basic region is followed by two alpha-helices separated by a variable loop region; HLH forms homo- and heterodimers, ...

cd00130
Location:315 → 415

PAS; PAS domain; PAS motifs appear in archaea, eubacteria and eukarya. Probably the most surprising identification of a PAS domain was that in EAG-like K+-channels. PAS domains have been found to bind ligands, and to act as sensors for light and oxygen in ...

pfam13426
Location:159 → 260

PAS_9; PAS domain

pfam14598
Location:314 → 417

PAS_11; PAS domain
XM_005263961.4 → XP_005264018.1 neuronal PAS domain-containing protein 2 isoform X9

Conserved Domains (2) summary

cd00130
Location:126 → 226

PAS; PAS domain; PAS motifs appear in archaea, eubacteria and eukarya. Probably the most surprising identification of a PAS domain was that in EAG-like K+-channels. PAS domains have been found to bind ligands, and to act as sensors for light and oxygen in ...

pfam14598
Location:125 → 228

PAS_11; PAS domain