NPAS4 neuronal PAS domain protein 4 [Homo sapiens (human)] - Gene

Summary

Official Symbol: NPAS4provided by HGNC
Official Full Name: neuronal PAS domain protein 4provided by HGNC
Primary source: HGNC:HGNC:18983
See related: Ensembl:ENSG00000174576 MIM:608554; AllianceGenome:HGNC:18983
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: NXF; Le-PAS; PASD10; bHLHe79
Summary: NXF is a member of the basic helix-loop-helix-PER (MIM 602260)-ARNT (MIM 126110)-SIM (see SIM2; MIM 600892) (bHLH-PAS) class of transcriptional regulators, which are involved in a wide range of physiologic and developmental events (Ooe et al., 2004 [PubMed 14701734]).[supplied by OMIM, Mar 2008]
Expression: Broad expression in brain (RPKM 1.7), endometrium (RPKM 1.7) and 14 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 11q13.2

Exon count:: 13

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	11	NC_000011.10 (66409158..66426707)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	11	NC_060935.1 (66405041..66423054)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	11	NC_000011.9 (66188475..66194178)

Chromosome 11 - NC_000011.10 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: Tissue-specific circular RNA induction during human fetal development
Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
BioProject: PRJNA270632
Publication: PMID 26076956
Analysis date: Mon Apr 2 22:54:59 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Downregulated NPAS4 in multiple brain regions is associated with major depressive disorder.
Title: Downregulated NPAS4 in multiple brain regions is associated with major depressive disorder.
Structures of NPAS4-ARNT and NPAS4-ARNT2 heterodimers reveal new dimerization modalities in the bHLH-PAS transcription factor family.
Title: Structures of NPAS4-ARNT and NPAS4-ARNT2 heterodimers reveal new dimerization modalities in the bHLH-PAS transcription factor family.
Circular RNA circ_0003420 mediates inflammation in sepsis-induced liver damage by downregulating neuronal PAS domain protein 4.
Title: Circular RNA circ_0003420 mediates inflammation in sepsis-induced liver damage by downregulating neuronal PAS domain protein 4.
Molecular characterisation of rare loss-of-function NPAS3 and NPAS4 variants identified in individuals with neurodevelopmental disorders.
Title: Molecular characterisation of rare loss-of-function NPAS3 and NPAS4 variants identified in individuals with neurodevelopmental disorders.
NPAS4 is expressed in endothelial cells, regulates VE-cadherin expression and regulates sprouting angiogenesis.
Title: The neuronal transcription factor NPAS4 is a strong inducer of sprouting angiogenesis and tip cell formation.
This review summarizes the current knowledge of the roles that Npas4 may play in neuroinflammation and ischemia. [review]
Title: The Role of the Neuroprotective Factor Npas4 in Cerebral Ischemia.
we provide the first evidence that Npas4 is expressed during embryonic development and that it may have a developmental role that is unrelated to its function in the adult brain
Title: A reduction in Npas4 expression results in delayed neural differentiation of mouse embryonic stem cells.
These results provide insight into the mechanisms of NPAS4/ARNT dimerisation and transcriptional activation.
Title: Human variants in the neuronal basic helix-loop-helix/Per-Arnt-Sim (bHLH/PAS) transcription factor complex NPAS4/ARNT2 disrupt function.
a novel NXF signaling system on neural gene promoter may be a molecular target of the adverse effects of Sim2 in the mental retardation of Down's syndrome
Title: Identification of a novel basic helix-loop-helix-PAS factor, NXF, reveals a Sim2 competitive, positive regulatory role in dendritic-cytoskeleton modulator drebrin gene expression.

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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

EBI GWAS Catalog

Description
Large-scale genome-wide association analysis of bipolar disorder identifies a new susceptibility locus near ODZ4. EBI GWAS Catalog EBI GWAS 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)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables DNA binding	IEA Inferred from Electronic Annotation more info
enables DNA-binding transcription activator activity, RNA polymerase II-specific	IDA Inferred from Direct Assay more info	PubMed
enables DNA-binding transcription factor activity, RNA polymerase II-specific	IBA Inferred from Biological aspect of Ancestor more info
enables DNA-binding transcription factor activity, RNA polymerase II-specific	IDA Inferred from Direct Assay more info	PubMed
enables DNA-binding transcription factor activity, RNA polymerase II-specific	IEA Inferred from Electronic Annotation more info
enables DNA-binding transcription factor activity, RNA polymerase II-specific	ISA Inferred from Sequence Alignment more info
enables RNA polymerase II cis-regulatory region sequence-specific DNA binding	IDA Inferred from Direct Assay more info	PubMed
enables RNA polymerase II cis-regulatory region sequence-specific DNA binding	IEA Inferred from Electronic Annotation more info
enables RNA polymerase II transcription regulatory region sequence-specific DNA binding	IBA Inferred from Biological aspect of Ancestor more info
enables RNA polymerase II transcription regulatory region sequence-specific DNA binding	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein dimerization activity	IEA Inferred from Electronic Annotation more info
enables protein heterodimerization activity	IDA Inferred from Direct Assay more info	PubMed
enables protein heterodimerization activity	IEA Inferred from Electronic Annotation more info
enables protein-containing complex binding	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
involved_in cell differentiation	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within cellular response to corticosterone stimulus	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within cellular response to stress	IEA Inferred from Electronic Annotation more info
involved_in excitatory postsynaptic potential	IEA Inferred from Electronic Annotation more info
involved_in excitatory postsynaptic potential	ISS Inferred from Sequence or Structural Similarity more info
acts_upstream_of_or_within inhibitory postsynaptic potential	IEA Inferred from Electronic Annotation more info
involved_in inhibitory postsynaptic potential	ISS Inferred from Sequence or Structural Similarity more info
involved_in inhibitory synapse assembly	IEA Inferred from Electronic Annotation more info
involved_in inhibitory synapse assembly	ISS Inferred from Sequence or Structural Similarity more info
involved_in learning	IEA Inferred from Electronic Annotation more info
involved_in learning	ISS Inferred from Sequence or Structural Similarity more info
involved_in long-term memory	IEA Inferred from Electronic Annotation more info
involved_in long-term memory	ISS Inferred from Sequence or Structural Similarity more info
involved_in nervous system development	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within positive regulation of DNA-templated transcription	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of transcription by RNA polymerase II	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within positive regulation of transcription by RNA polymerase II	IEA Inferred from Electronic Annotation more info
involved_in regulation of synaptic plasticity	IEA Inferred from Electronic Annotation more info
involved_in regulation of synaptic plasticity	ISS Inferred from Sequence or Structural Similarity more info
involved_in regulation of synaptic transmission, GABAergic	IEA Inferred from Electronic Annotation more info
involved_in regulation of synaptic transmission, GABAergic	ISS Inferred from Sequence or Structural Similarity more info
involved_in regulation of transcription by RNA polymerase II	IBA Inferred from Biological aspect of Ancestor more info
involved_in short-term memory	IEA Inferred from Electronic Annotation more info
involved_in short-term memory	ISS Inferred from Sequence or Structural Similarity more info
involved_in social behavior	IEA Inferred from Electronic Annotation more info
involved_in social behavior	ISS Inferred from Sequence or Structural Similarity more info

Component	Evidence Code	Pubs
located_in chromatin	ISA Inferred from Sequence Alignment more info
located_in cytosol	IEA Inferred from Electronic Annotation more info
located_in cytosol	TAS Traceable Author Statement more info
located_in nucleoplasm	IEA Inferred from Electronic Annotation more info
located_in nucleoplasm	TAS Traceable Author Statement more info
is_active_in nucleus	IBA Inferred from Biological aspect of Ancestor more info
located_in nucleus	IEA Inferred from Electronic Annotation more info
located_in postsynapse	IEA Inferred from Electronic Annotation more info
part_of transcription regulator complex	IBA Inferred from Biological aspect of Ancestor more info
part_of transcription regulator complex	IEA Inferred from Electronic Annotation more info

General protein information

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Preferred Names: neuronal PAS domain-containing protein 4

Names: HLH-PAS transcription factor NXF; PAS domain-containing protein 10; class E basic helix-loop-helix protein 79; neuronal PAS4

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.

mRNA and Protein(s)

NM_001318804.1 → NP_001305733.1 neuronal PAS domain-containing protein 4 isoform 2

Status: VALIDATED

Description

Transcript Variant: This variant (2) lacks an alternate coding exon compared to variant 1. The resulting isoform (2) has a shorter and distinct N-terminus compared to isoform 1.

Source sequence(s)

AK094025, AK096253, BC143630

UniProtKB/Swiss-Prot

Q8IUM7
NM_178864.4 → NP_849195.2 neuronal PAS domain-containing protein 4 isoform 1

See identical proteins and their annotated locations for NP_849195.2

Status: VALIDATED

Description

Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).

Source sequence(s)

AB049469, AK096253, AP001107

Consensus CDS

CCDS8138.1

UniProtKB/Swiss-Prot

B7ZL81, Q8IUM7, Q8N8S5, Q8N9Q9

Related

ENSP00000311196.2, ENST00000311034.7

Conserved Domains (4) summary

smart00091
Location:72 → 135

PAS; PAS domain

cd00130
Location:214 → 294

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 ...

pfam08447
Location:95 → 188

PAS_3; PAS fold

pfam14598
Location:217 → 319

PAS_11; PAS domain

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

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

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000011.10 Reference GRCh38.p14 Primary Assembly

Range

66409158..66426707

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_047426764.1 → XP_047282720.1 neuronal PAS domain-containing protein 4 isoform X1
XM_047426765.1 → XP_047282721.1 neuronal PAS domain-containing protein 4 isoform X1
XM_017017539.1 → XP_016873028.1 neuronal PAS domain-containing protein 4 isoform X3

UniProtKB/Swiss-Prot

Q8IUM7

Related

ENSP00000433135.1, ENST00000525148.1

Conserved Domains (2) summary

smart00353
Location:10 → 52

HLH; helix loop helix domain

smart00091
Location:72 → 135

PAS; PAS domain
XM_017017538.2 → XP_016873027.1 neuronal PAS domain-containing protein 4 isoform X2

Alternate T2T-CHM13v2.0

Genomic

NC_060935.1 Alternate T2T-CHM13v2.0

Range

66405041..66423054

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054368416.1 → XP_054224391.1 neuronal PAS domain-containing protein 4 isoform X1
XM_054368417.1 → XP_054224392.1 neuronal PAS domain-containing protein 4 isoform X1
XM_054368415.1 → XP_054224390.1 neuronal PAS domain-containing protein 4 isoform X1
XM_054368414.1 → XP_054224389.1 neuronal PAS domain-containing protein 4 isoform X1
XM_054368419.1 → XP_054224394.1 neuronal PAS domain-containing protein 4 isoform X4
XM_054368418.1 → XP_054224393.1 neuronal PAS domain-containing protein 4 isoform X2