Hnf4a hepatocyte nuclear factor 4, alpha [Rattus norvegicus (Norway rat)] - Gene

Summary

Official Symbol: Hnf4aprovided by RGD
Official Full Name: hepatocyte nuclear factor 4, alphaprovided by RGD
Primary source: RGD:2810
See related: Ensembl:ENSRNOG00000008895 AllianceGenome:RGD:2810
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Rattus norvegicus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Rattus
Also known as: Hnf4; Hnf4alpha
Summary: Enables several functions, including DNA-binding transcription activator activity, RNA polymerase II-specific; long-chain fatty acid binding activity; and long-chain fatty acyl-CoA binding activity. Involved in several processes, including hepatocyte differentiation; negative regulation of peptidyl-tyrosine phosphorylation; and regulation of cellular biosynthetic process. Located in cytoplasm and nucleus. Biomarker of hepatocellular carcinoma and type 2 diabetes mellitus. Human ortholog(s) of this gene implicated in Fanconi renotubular syndrome 4; familial combined hyperlipidemia; hypoglycemia; maturity-onset diabetes of the young type 1; and type 2 diabetes mellitus. Orthologous to human HNF4A (hepatocyte nuclear factor 4 alpha). [provided by Alliance of Genome Resources, Apr 2022]
Expression: Biased expression in Kidney (RPKM 1041.7) and Liver (RPKM 892.3) See more
Orthologs: human mouse all
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Genomic context

Location:: 3q42

Exon count:: 12

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCr8 (GCF_036323735.1)	3	NC_086021.1 (172606220..172667758)
RS_2023_06	previous assembly	mRatBN7.2 (GCF_015227675.2)	3	NC_051338.1 (152186787..152248320)
106	previous assembly	Rnor_6.0 (GCF_000001895.5)	3	NC_005102.4 (159902441..159965003)

Chromosome 3 - NC_086021.1 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

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Expression

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See details

Project title: A rat RNA-Seq transcriptomic BodyMap across 11 organs and 4 developmental stages
Description: 320 RNA samples isolated from 11 organs (adrenal gland, brain, heart, kidney, liver, lung, muscle, spleen, thymus, and testes or uterus) from both sexes of Fischer 344 rats across four developmental stages (2-, 6-, 21-, and 104-weeks-old)
BioProject: PRJNA238328
Publication: PMID 24510058
Analysis date: Mon Jun 6 17:44:12 2016

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Mechanism and Effect of HNF4alpha Decrease in a Rat Model of Cirrhosis and Liver Failure.
Title: Mechanism and Effect of HNF4α Decrease in a Rat Model of Cirrhosis and Liver Failure.
[Combinational Overexpression of Foxa3 and Hnf4alpha Enhance the Proliferation and Prolong the Functional Maintenance of Primary Hepatocytes].
Title: [Combinational Overexpression of Foxa3 and Hnf4α Enhance the Proliferation and Prolong the Functional Maintenance of Primary Hepatocytes].
Targeted Activation of HNF4alpha by AMPK Inhibits Apoptosis and Ameliorates Neurological Injury Caused by Cardiac Arrest in Rats.
Title: Targeted Activation of HNF4α by AMPK Inhibits Apoptosis and Ameliorates Neurological Injury Caused by Cardiac Arrest in Rats.
HNF4A Negatively Regulated Posterior Capsular Opacification via Transcriptional Inhibition of MMP2.
Title: HNF4A Negatively Regulated Posterior Capsular Opacification via Transcriptional Inhibition of MMP2.
hsa-miR-34a-5p Ameliorates Hepatic Ischemia/Reperfusion Injury Via Targeting HNF4alpha.
Title: hsa-miR-34a-5p Ameliorates Hepatic Ischemia/Reperfusion Injury Via Targeting HNF4α.
Immunohistochemical detection of hepatocyte nuclear factor-4alpha in vertebrates.
Title: Immunohistochemical detection of hepatocyte nuclear factor-4α in vertebrates.
Genetic and Epigenetic Modification of Rat Liver Progenitor Cells via HNF4alpha Transduction and 5' Azacytidine Treatment: An Integrated miRNA and mRNA Expression Profile Analysis.
Title: Genetic and Epigenetic Modification of Rat Liver Progenitor Cells via HNF4α Transduction and 5' Azacytidine Treatment: An Integrated miRNA and mRNA Expression Profile Analysis.
Maternal Malnutrition Affects Hepatic Metabolism through Decreased Hepatic Taurine Levels and Changes in HNF4A Methylation.
Title: Maternal Malnutrition Affects Hepatic Metabolism through Decreased Hepatic Taurine Levels and Changes in HNF4A Methylation.
The endoplasmic reticulum stress, confirmed at ultrastructure level, plays an important role in pathogenesis of HFD-induced hepatic steatosis. HNF4alpha downregulation as well as increased expression of hs-CRP and TNF-alpha enforce the concept of interplay between ER stress, hepatic subclinical inflammation, and disturbed gene expression regulation in the pathogenesis of HFD-induced hepatic steatosis.
Title: Molecular and ultrastructure study of endoplasmic reticulum stress in hepatic steatosis: role of hepatocyte nuclear factor 4α and inflammatory mediators.
coordinated upregulation of genes encoding CRP, interleukin-6 (IL-6), HNF1alpha, and HNF4alpha in the livers and white adipose tissue (WAT) of chronic renal failure rats, as compared to the pair-fed and control animals.
Title: Hepatocyte nuclear factors as possible C-reactive protein transcriptional inducer in the liver and white adipose tissue of rats with experimental chronic renal failure.

Submit: New GeneRIF Correction See all GeneRIFs (53)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

D3Rat244 (e-PCR), detects polymorphism
- UniSTS:227629

PMC316400P1 (e-PCR)
- UniSTS:272979

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

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

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

RH94783 (e-PCR)
- UniSTS:120030

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

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

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

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

Gene Ontology Provided by RGD

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

Process	Evidence Code	Pubs
involved_in acyl-CoA metabolic process	IDA Inferred from Direct Assay more info	PubMed
involved_in anatomical structure development	IBA Inferred from Biological aspect of Ancestor 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	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in cell-cell junction organization	IDA Inferred from Direct Assay more info	PubMed
involved_in cellular response to hypoxia	IEP Inferred from Expression Pattern more info	PubMed
involved_in cholesterol homeostasis	IEA Inferred from Electronic Annotation more info
involved_in cholesterol homeostasis	ISO Inferred from Sequence Orthology more info
involved_in establishment of tissue polarity	IDA Inferred from Direct Assay more info	PubMed
involved_in glucose homeostasis	IEA Inferred from Electronic Annotation more info
involved_in glucose homeostasis	ISO Inferred from Sequence Orthology more info
involved_in hepatocyte differentiation	IEP Inferred from Expression Pattern 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
involved_in lipid metabolic process	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within lipid metabolic process	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of DNA-templated transcription	IEA Inferred from Electronic Annotation more info
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	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of cell population proliferation	IDA Inferred from Direct Assay more info	PubMed
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	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of protein import into nucleus	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of tyrosine phosphorylation of STAT protein	IDA Inferred from Direct Assay more info	PubMed
involved_in ornithine metabolic process	IEA Inferred from Electronic Annotation more info
involved_in ornithine metabolic process	ISO Inferred from Sequence Orthology more info
involved_in phospholipid homeostasis	IEA Inferred from Electronic Annotation more info
involved_in phospholipid homeostasis	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of DNA-templated transcription	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within positive regulation of DNA-templated transcription	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of DNA-templated transcription	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of fatty acid biosynthetic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of gene expression	IGI Inferred from Genetic Interaction more info	PubMed
involved_in positive regulation of gene expression	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of gluconeogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of transcription by RNA polymerase II	IBA Inferred from Biological aspect of Ancestor more info
involved_in 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	IEA Inferred from Electronic Annotation more info
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
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	ISO Inferred from Sequence Orthology more info
involved_in regulation of circadian rhythm	IEA Inferred from Electronic Annotation more info
involved_in regulation of circadian rhythm	ISO Inferred from Sequence Orthology more info
involved_in regulation of circadian rhythm	ISS Inferred from Sequence or Structural Similarity more info
involved_in regulation of gastrulation	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within regulation of gastrulation	ISO Inferred from Sequence Orthology more info
involved_in regulation of insulin secretion	IEA Inferred from Electronic Annotation more info
involved_in regulation of insulin secretion	ISO Inferred from Sequence Orthology more info
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	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within regulation of transcription by RNA polymerase II	ISO Inferred from Sequence Orthology more info
involved_in regulation of transcription by RNA polymerase II	ISO Inferred from Sequence Orthology more info
involved_in response to cAMP	IEP Inferred from Expression Pattern more info	PubMed
involved_in response to dexamethasone	IEP Inferred from Expression Pattern more info	PubMed
involved_in response to glucose	IDA Inferred from Direct Assay more info	PubMed
involved_in response to glucose	IEA Inferred from Electronic Annotation more info
involved_in response to glucose	ISO Inferred from Sequence Orthology more info
involved_in response to lipopolysaccharide	IEP Inferred from Expression Pattern more info	PubMed
involved_in response to nutrient levels	IEP Inferred from Expression Pattern more info	PubMed
involved_in response to trichostatin A	IDA Inferred from Direct Assay more info	PubMed
involved_in response to xenobiotic stimulus	IEP Inferred from Expression Pattern more info	PubMed
involved_in rhythmic process	IEA Inferred from Electronic Annotation more info
involved_in sex differentiation	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within sex differentiation	ISO Inferred from Sequence Orthology more info
involved_in signal transduction involved in regulation of gene expression	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within signal transduction involved in regulation of gene expression	ISO Inferred from Sequence Orthology more info
involved_in steroid hormone mediated signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in transcription by RNA polymerase II	IEA Inferred from Electronic Annotation more info
acts_upstream_of transcription by RNA polymerase II	ISO Inferred from Sequence Orthology more info
involved_in triglyceride homeostasis	IEA Inferred from Electronic Annotation more info
involved_in triglyceride homeostasis	ISO Inferred from Sequence Orthology more info
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 cytoplasm	IEA Inferred from Electronic Annotation more info
located_in cytoplasm	ISO Inferred from Sequence Orthology more info
located_in nucleoplasm	IEA Inferred from Electronic Annotation more info
located_in nucleoplasm	ISO Inferred from Sequence Orthology more info
located_in nucleus	IDA Inferred from Direct Assay more info	PubMed
located_in nucleus	IEA Inferred from Electronic Annotation more info
located_in nucleus	ISO Inferred from Sequence Orthology more info

General protein information

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Preferred Names: hepatocyte nuclear factor 4-alpha

Names: HNF-4-alpha; TCF-14; alpha transcription factor 4; hepatic nuclear factor 4, alpha; 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_001270931.1 → NP_001257860.1 hepatocyte nuclear factor 4-alpha isoform 2

Status: VALIDATED

Description

Transcript Variant: This variant (2) is the longest transcript. It differs in the 5' UTR and 5' coding region, compared to variant 1. The resulting isoform (2, also known as HNF4alpha11) is shorter and has a distinct N-terminus, compared to isoform 1.

Source sequence(s)

EF193390, FJ608817, FQ095211, JAXUCZ010000003

UniProtKB/TrEMBL

A0A0G2K5P1, A6JX36

Related

ENSRNOP00000073501.1, ENSRNOT00000089893.2

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_001270933.1 → NP_001257862.1 hepatocyte nuclear factor 4-alpha isoform 3

Status: VALIDATED

Description

Transcript Variant: This variant (3) differs in the 5' UTR and has two coding region differences, compared to variant 1. The resulting isoform (3, also known as HNF4alpha10) is shorter, has a distinct N-terminus and lacks an internal segment in the C-terminal region, compared to isoform 1.

Source sequence(s)

EF193390, FJ608816, FQ095211, JAXUCZ010000003

UniProtKB/TrEMBL

A6JX36

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_022180.2 → NP_071516.2 hepatocyte nuclear factor 4-alpha isoform 1

See identical proteins and their annotated locations for NP_071516.2

Status: VALIDATED

Description

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

Source sequence(s)

CK483260, D10554, FM042560, FQ095211, JAXUCZ010000003

UniProtKB/TrEMBL

A0A0G2K0G1, A6JX36, A6JX37

Related

ENSRNOP00000071432.1, ENSRNOT00000078703.2

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_036323735.1-RS_2024_02

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

Reference GRCr8

Genomic

NC_086021.1 Reference GRCr8

Range

172606220..172667758

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_006235516.5 → XP_006235578.1 hepatocyte nuclear factor 4-alpha isoform X1

UniProtKB/TrEMBL

A6JX36

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