Hnf4a hepatic nuclear factor 4, alpha [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Hnf4aprovided by MGI
Official Full Name: hepatic nuclear factor 4, alphaprovided by MGI
Primary source: MGI:MGI:109128
See related: Ensembl:ENSMUSG00000017950 AllianceGenome:MGI:109128
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Mus musculus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
Also known as: Hnf4; HNF-4; MODY1; Nr2a1; Tcf14; TCF-14; Hnf4alpha
Summary: The protein encoded by this gene is a transcription factor involved in the development of the pancreas, liver, kidney, and intestines. The encoded protein also functions to maintain glucose homeostasis. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2015]
Expression: Biased expression in large intestine adult (RPKM 148.8), kidney adult (RPKM 141.3) and 9 other tissues See more
Orthologs: human all
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Genomic context

Location:: 2 H3; 2 84.32 cM

Exon count:: 12

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	2	NC_000068.8 (163348731..163414827)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	2	NC_000068.7 (163506811..163572907)

Chromosome 2 - NC_000068.8 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: Mouse ENCODE transcriptome data
Description: RNA profiling data sets generated by the Mouse ENCODE project.
BioProject: PRJNA66167
Publication: PMID 25409824
Analysis date: n/a

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Sustained alterations in proximal tubule gene expression in primary culture associate with HNF4A loss.
Title: Sustained alterations in proximal tubule gene expression in primary culture associate with HNF4A loss.
HNF4alpha is required for Tkfc promoter activation by ChREBP.
Title: HNF4α is required for Tkfc promoter activation by ChREBP.
Intestine-specific ablation of the Hepatocyte Nuclear Factor 4a (Hnf4a) gene in mice has minimal impact on serum lipids and ileum gene expression profile due to upregulation of its paralog Hnf4g.
Title: Intestine-specific ablation of the Hepatocyte Nuclear Factor 4a (Hnf4a) gene in mice has minimal impact on serum lipids and ileum gene expression profile due to upregulation of its paralog Hnf4g.
Dynamic RNA polymerase II occupancy drives differentiation of the intestine under the direction of HNF4.
Title: Dynamic RNA polymerase II occupancy drives differentiation of the intestine under the direction of HNF4.
Kruppel-like factor 10 protects against metabolic dysfunction-associated steatohepatitis by regulating HNF4alpha-mediated metabolic pathways.
Title: Krüppel-like factor 10 protects against metabolic dysfunction-associated steatohepatitis by regulating HNF4α-mediated metabolic pathways.
A MTA2-SATB2 chromatin complex restrains colonic plasticity toward small intestine by retaining HNF4A at colonic chromatin.
Title: A MTA2-SATB2 chromatin complex restrains colonic plasticity toward small intestine by retaining HNF4A at colonic chromatin.
TRIB3-TRIM8 complex drives NAFLD progression by regulating HNF4alpha stability.
Title: TRIB3-TRIM8 complex drives NAFLD progression by regulating HNF4α stability.
HNF4alpha ubiquitination mediated by Peli1 impairs FAO and accelerates pressure overload-induced myocardial hypertrophy.
Title: HNF4α ubiquitination mediated by Peli1 impairs FAO and accelerates pressure overload-induced myocardial hypertrophy.
HNF4alpha isoforms regulate the circadian balance between carbohydrate and lipid metabolism in the liver.
Title: HNF4α isoforms regulate the circadian balance between carbohydrate and lipid metabolism in the liver.
Protective roles of adiponectin and molecular signatures of HNF4alpha and PPARalpha as downstream targets of adiponectin in pancreatic beta cells.
Title: Protective roles of adiponectin and molecular signatures of HNF4α and PPARα as downstream targets of adiponectin in pancreatic β cells.

Submit: New GeneRIF Correction See all GeneRIFs (199)

Variation

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Alleles

Alleles of this type are documented at Mouse Genome Informatics (MGI)

Endonuclease-mediated (5) 1 citation
Targeted (16) 1 citation

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

PMC99591P1 (e-PCR)
- UniSTS:273683

AA986699 (e-PCR)
- UniSTS:160842

PMC316400P1 (e-PCR)
- UniSTS:272979

D29015 (e-PCR)
- UniSTS:159071

Hnf4a (e-PCR), detects polymorphism
- UniSTS:506981

Hnf4a (e-PCR), detects polymorphism
- UniSTS:275854

Hnf4a (e-PCR), detects polymorphism
- UniSTS:275855

Hnf4a (e-PCR), detects polymorphism
- UniSTS:275856

Hnf4a (e-PCR), detects polymorphism
- UniSTS:464792

UniSTS:465392 (e-PCR)
- UniSTS:465392

Hnf4a (e-PCR), detects polymorphism
- UniSTS:465392

D29015 (e-PCR)
- UniSTS:143356

Hnf4 (e-PCR), detects polymorphism
- UniSTS:143357

Hnf4 (e-PCR), detects polymorphism
- UniSTS:143358

Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables DNA binding	IDA Inferred from Direct Assay more info	PubMed
enables DNA binding	ISO Inferred from Sequence Orthology more info	PubMed
enables DNA-binding transcription activator activity, RNA polymerase II-specific	IDA Inferred from Direct Assay more info	PubMed
enables DNA-binding transcription activator activity, RNA polymerase II-specific	ISO Inferred from Sequence Orthology more info
enables DNA-binding transcription factor activity	IDA Inferred from Direct Assay more info	PubMed
enables DNA-binding transcription factor activity	ISO Inferred from Sequence Orthology more info	PubMed
enables DNA-binding transcription factor activity, RNA polymerase II-specific	IDA Inferred from Direct Assay more info	PubMed
enables RNA polymerase II cis-regulatory region sequence-specific DNA binding	IBA Inferred from Biological aspect of Ancestor 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-specific DNA-binding transcription factor binding	IPI Inferred from Physical Interaction more info	PubMed
enables arachidonate binding	ISO Inferred from Sequence Orthology more info
enables chromatin binding	IDA Inferred from Direct Assay more info	PubMed
enables cis-regulatory region sequence-specific DNA binding	ISO Inferred from Sequence Orthology more info
enables fatty acid binding	IEA Inferred from Electronic Annotation more info
enables fatty acid binding	ISO Inferred from Sequence Orthology more info
enables fatty-acyl-CoA binding	ISO Inferred from Sequence Orthology more info
enables long-chain fatty acyl-CoA binding	ISO Inferred from Sequence Orthology more info
enables long-chain fatty acyl-CoA hydrolase activity	ISO Inferred from Sequence Orthology more info
enables nuclear receptor activity	IBA Inferred from Biological aspect of Ancestor more info
enables nuclear receptor activity	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein domain specific binding	ISO Inferred from Sequence Orthology more info
enables protein homodimerization activity	IEA Inferred from Electronic Annotation more info
enables protein homodimerization activity	ISO Inferred from Sequence Orthology more info
enables protein-containing complex binding	ISO Inferred from Sequence Orthology more info
enables sequence-specific DNA binding	IDA Inferred from Direct Assay more info	PubMed
enables sequence-specific DNA binding	ISO Inferred from Sequence Orthology more info
enables sequence-specific double-stranded DNA binding	ISO Inferred from Sequence Orthology more info
enables signaling receptor binding	IEA Inferred from Electronic Annotation more info
enables signaling receptor binding	ISO Inferred from Sequence Orthology more info
enables stearic acid binding	ISO Inferred from Sequence Orthology more info
enables transcription cis-regulatory region binding	IDA Inferred from Direct Assay more info	PubMed
enables transcription cis-regulatory region binding	ISO Inferred from Sequence Orthology more info
enables transcription coregulator binding	ISO Inferred from Sequence Orthology more info
enables transcription corepressor binding	ISO Inferred from Sequence Orthology more info
enables zinc ion binding	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
involved_in acyl-CoA metabolic process	ISO Inferred from Sequence Orthology more info
involved_in blood coagulation	IEA Inferred from Electronic Annotation more info
involved_in blood coagulation	ISO Inferred from Sequence Orthology more info
involved_in cell differentiation	IBA Inferred from Biological aspect of Ancestor more info
involved_in cell differentiation	ISO Inferred from Sequence Orthology more info
involved_in cell-cell junction organization	ISO Inferred from Sequence Orthology more info
involved_in cholesterol homeostasis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in establishment of tissue polarity	ISO Inferred from Sequence Orthology more info
involved_in glucose homeostasis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in intracellular receptor signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in lipid homeostasis	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within lipid metabolic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of DNA-templated transcription	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of DNA-templated transcription	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of cell growth	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of cell growth	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of cell migration	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of cell population proliferation	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of cell population proliferation	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of mitotic cell cycle	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of protein import into nucleus	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of tyrosine phosphorylation of STAT protein	ISO Inferred from Sequence Orthology more info
involved_in ornithine metabolic process	ISO Inferred from Sequence Orthology more info
involved_in phospholipid homeostasis	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within positive regulation of DNA-templated transcription	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of DNA-templated transcription	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of DNA-templated transcription	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of fatty acid biosynthetic process	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of gene expression	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of gluconeogenesis	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of transcription by RNA polymerase II	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within positive regulation of transcription by RNA polymerase II	IDA Inferred from Direct Assay more info	PubMed
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	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within positive regulation of transcription by RNA polymerase II	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of transcription by RNA polymerase II	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within positive regulation of transcription by RNA polymerase II	ISO Inferred from Sequence Orthology more info	PubMed
involved_in positive regulation of transcription by RNA polymerase II	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within regulation of DNA-templated transcription	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of circadian rhythm	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of circadian rhythm	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within regulation of gastrulation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of insulin secretion	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of lipid metabolic process	IEA Inferred from Electronic Annotation more info
involved_in regulation of lipid metabolic process	ISO Inferred from Sequence Orthology more info
involved_in regulation of microvillus assembly	ISO Inferred from Sequence Orthology more info
involved_in regulation of ornithine metabolic process	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within regulation of transcription by RNA polymerase II	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within regulation of transcription by RNA polymerase II	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of transcription by RNA polymerase II	ISO Inferred from Sequence Orthology more info
involved_in response to glucose	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in response to glucose	ISO Inferred from Sequence Orthology more info
involved_in response to trichostatin A	ISO Inferred from Sequence Orthology more info
involved_in rhythmic process	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within sex differentiation	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within signal transduction involved in regulation of gene expression	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of transcription by RNA polymerase II	IDA Inferred from Direct Assay more info	PubMed
involved_in triglyceride homeostasis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in xenobiotic metabolic process	IEA Inferred from Electronic Annotation more info
involved_in xenobiotic metabolic process	ISO Inferred from Sequence Orthology more info

Component	Evidence Code	Pubs
located_in chromatin	IC Inferred by Curator more info	PubMed
located_in cytoplasm	ISO Inferred from Sequence Orthology more info
located_in cytosol	TAS Traceable Author Statement more info
located_in nucleoplasm	ISO Inferred from Sequence Orthology more info
located_in nucleoplasm	TAS Traceable Author Statement more info
located_in nucleus	IDA Inferred from Direct Assay more info	PubMed
located_in nucleus	ISO Inferred from Sequence Orthology more info	PubMed

General protein information

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Preferred Names: hepatocyte nuclear factor 4-alpha

Names: HNF4 alpha; Nuclear receptor 2A1; nuclear receptor subfamily 2 group A member 1; transcription factor 14; transcription factor HNF-4

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_001312906.1 → NP_001299835.1 hepatocyte nuclear factor 4-alpha isoform HNF4alpha11

Status: REVIEWED

Description

Transcript Variant: This variant (2) differs in the 5' UTR and coding sequence compared to variant 1. The resulting isoform (HNF4alpha11) has a shorter and distinct N-terminus compared to isoform HNF4alpha2.

Source sequence(s)

AL591488, BP765980, FJ608820

UniProtKB/TrEMBL

Z4YKX0

Conserved Domains (2) summary

cd06931
Location:126 → 348

NR_LBD_HNF4_like; The ligand binding domain of heptocyte nuclear factor 4, which is explosively expanded in nematodes

cd06960
Location:35 → 110

NR_DBD_HNF4A; DNA-binding domain of heptocyte nuclear factor 4 (HNF4) is composed of two C4-type zinc fingers
NM_001312907.1 → NP_001299836.1 hepatocyte nuclear factor 4-alpha isoform HNF4alpha10

Status: REVIEWED

Description

Transcript Variant: This variant (3) differs in the 5' UTR and coding sequence and uses an alternate in-frame splice junction in the 3' end compared to variant 1. The resulting isoform (HNF4alpha10) has a shorter and distinct N-terminus and lacks an internal segment compared to isoform HNF4alpha2.

Source sequence(s)

AL591488, BP765980, FJ608819

UniProtKB/TrEMBL

B9VVT5

Conserved Domains (2) summary

cd06931
Location:126 → 348

NR_LBD_HNF4_like; The ligand binding domain of heptocyte nuclear factor 4, which is explosively expanded in nematodes

cd06960
Location:35 → 110

NR_DBD_HNF4A; DNA-binding domain of heptocyte nuclear factor 4 (HNF4) is composed of two C4-type zinc fingers
NM_008261.3 → NP_032287.2 hepatocyte nuclear factor 4-alpha isoform HNF4alpha2

See identical proteins and their annotated locations for NP_032287.2

Status: REVIEWED

Description

Transcript Variant: This variant (1) encodes the longest isoform (HNF4alpha2).

Source sequence(s)

AK143948, AL591488, BY034048

Consensus CDS

CCDS17012.1

UniProtKB/Swiss-Prot

A2A5I5, A2ICH0, P49698, Q3UNX3, Q8CFY1

UniProtKB/TrEMBL

Z4YKX0

Related

ENSMUSP00000018094.7, ENSMUST00000018094.13

Conserved Domains (2) summary

cd06931
Location:151 → 373

NR_LBD_HNF4_like; The ligand binding domain of heptocyte nuclear factor 4, which is explosively expanded in nematodes

cd06960
Location:60 → 135

NR_DBD_HNF4A; DNA-binding domain of heptocyte nuclear factor 4 (HNF4) is composed of two C4-type zinc fingers

RefSeqs of Annotated Genomes: GCF_000001635.27-RS_2024_02

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

Reference GRCm39 C57BL/6J

Genomic

NC_000068.8 Reference GRCm39 C57BL/6J

Range

163348731..163414827

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_006498788.2 → XP_006498851.1 hepatocyte nuclear factor 4-alpha isoform X2

See identical proteins and their annotated locations for XP_006498851.1

UniProtKB/TrEMBL

Z4YKX0

Conserved Domains (2) summary

cd06931
Location:129 → 351

NR_LBD_HNF4_like; The ligand binding domain of heptocyte nuclear factor 4, which is explosively expanded in nematodes

cd06960
Location:38 → 113

NR_DBD_HNF4A; DNA-binding domain of heptocyte nuclear factor 4 (HNF4) is composed of two C4-type zinc fingers
XM_006498787.1 → XP_006498850.1 hepatocyte nuclear factor 4-alpha isoform X1

UniProtKB/TrEMBL

Z4YKX0

Conserved Domains (2) summary

cd06931
Location:151 → 373

NR_LBD_HNF4_like; The ligand binding domain of heptocyte nuclear factor 4, which is explosively expanded in nematodes

cd06960
Location:60 → 135

NR_DBD_HNF4A; DNA-binding domain of heptocyte nuclear factor 4 (HNF4) is composed of two C4-type zinc fingers