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    HNF4A hepatocyte nuclear factor 4 alpha [ Homo sapiens (human) ]

    Gene ID: 3172, updated on 11-Jul-2021

    Summary

    Official Symbol
    HNF4Aprovided by HGNC
    Official Full Name
    hepatocyte nuclear factor 4 alphaprovided by HGNC
    Primary source
    HGNC:HGNC:5024
    See related
    Ensembl:ENSG00000101076 MIM:600281
    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
    TCF; HNF4; MODY; FRTS4; MODY1; NR2A1; TCF14; HNF4a7; HNF4a8; HNF4a9; NR2A21; TCF-14; HNF4alpha
    Summary
    The protein encoded by this gene is a nuclear transcription factor which binds DNA as a homodimer. The encoded protein controls the expression of several genes, including hepatocyte nuclear factor 1 alpha, a transcription factor which regulates the expression of several hepatic genes. This gene may play a role in development of the liver, kidney, and intestines. Mutations in this gene have been associated with monogenic autosomal dominant non-insulin-dependent diabetes mellitus type I. Alternative splicing of this gene results in multiple transcript variants encoding several different isoforms. [provided by RefSeq, Apr 2012]
    Expression
    Biased expression in duodenum (RPKM 37.7), colon (RPKM 32.8) and 7 other tissues See more
    Orthologs
    NEW
    Try the new Gene table
    Try the new Transcript table

    Genomic context

    See HNF4A in Genome Data Viewer
    Location:
    20q13.12
    Exon count:
    13
    Annotation release Status Assembly Chr Location
    109.20210514 current GRCh38.p13 (GCF_000001405.39) 20 NC_000020.11 (44355699..44434596)
    105.20201022 previous assembly GRCh37.p13 (GCF_000001405.25) 20 NC_000020.10 (42984339..43063236)

    Chromosome 20 - NC_000020.11Genomic Context describing neighboring genes Neighboring gene fat storage inducing transmembrane protein 2 Neighboring gene uncharacterized LOC105372629 Neighboring gene R3H domain containing like Neighboring gene HNF4A antisense RNA 1 Neighboring gene microRNA 3646 Neighboring gene long intergenic non-protein coding RNA 1430 Neighboring gene long intergenic non-protein coding RNA 1620

    Genomic regions, transcripts, and products

    Expression

    • 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 Apr 4 07:08:55 2018

    Bibliography

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?

    Phenotypes

    Associated conditions

    Description Tests
    Biological, clinical and population relevance of 95 loci for blood lipids.
    GeneReviews: Not available
    Common variants at 30 loci contribute to polygenic dyslipidemia.
    GeneReviews: Not available
    Discovery and refinement of loci associated with lipid levels.
    GeneReviews: Not available
    Familial hyperinsulinism
    MedGen: C3888018 GeneReviews: Familial Hyperinsulinism
    Compare labs
    Fanconi renotubular syndrome 4 with maturity-onset diabetes of the young
    MedGen: C4014962 OMIM: 616026 GeneReviews: Not available
    Compare labs
    Genome-wide association and population genetic analysis of C-reactive protein in African American and Hispanic American women.
    GeneReviews: Not available
    Genome-wide association study in individuals of South Asian ancestry identifies six new type 2 diabetes susceptibility loci.
    GeneReviews: Not available
    Genome-wide association study of ulcerative colitis identifies three new susceptibility loci, including the HNF4A region.
    GeneReviews: Not available
    Genome-wide trans-ancestry meta-analysis provides insight into the genetic architecture of type 2 diabetes susceptibility.
    GeneReviews: Not available
    Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease.
    GeneReviews: Not available
    Maturity-onset diabetes of the young, type 1 Compare labs
    Meta-analysis of genome-wide association studies identifies eight new loci for type 2 diabetes in east Asians.
    GeneReviews: Not available
    Meta-analysis of genome-wide association studies in >80 000 subjects identifies multiple loci for C-reactive protein levels.
    GeneReviews: Not available
    Type 2 diabetes mellitus
    MedGen: C0011860 OMIM: 125853 GeneReviews: Not available
    Compare labs

    Pathways from PubChem

    Interactions

    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

    Markers

    Homology

    Clone Names

    • FLJ39654

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables DNA binding IDA
    Inferred from Direct Assay
    more info
    PubMed 
    enables DNA-binding transcription activator activity, RNA polymerase II-specific ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    enables DNA-binding transcription factor activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    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 IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    enables RNA polymerase II-specific DNA-binding transcription factor binding ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    enables chromatin binding IEA
    Inferred from Electronic Annotation
    more info
     
    enables fatty acid binding IDA
    Inferred from Direct Assay
    more info
    PubMed 
    enables nuclear receptor activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    enables protein homodimerization activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    enables sequence-specific double-stranded DNA binding IDA
    Inferred from Direct Assay
    more info
    PubMed 
    enables signaling receptor binding IDA
    Inferred from Direct Assay
    more info
    PubMed 
    enables transcription cis-regulatory region binding IDA
    Inferred from Direct Assay
    more info
    PubMed 
    enables zinc ion binding IEA
    Inferred from Electronic Annotation
    more info
     
    Process Evidence Code Pubs
    involved_in SMAD protein signal transduction IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in anatomical structure development IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    involved_in blood coagulation IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in cell differentiation IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    involved_in cholesterol homeostasis ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in glucose homeostasis ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in hepatocyte differentiation IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in intracellular receptor signaling pathway IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in lipid homeostasis IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in lipid metabolic process IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in negative regulation of cell growth IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in negative regulation of cell population proliferation IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in negative regulation of transcription, DNA-templated IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in ornithine metabolic process IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in phospholipid homeostasis ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in positive regulation of transcription by RNA polymerase II IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    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 IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in positive regulation of transcription, DNA-templated IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in regulation of circadian rhythm IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in regulation of gastrulation IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in regulation of insulin secretion ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in regulation of lipid metabolic process IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in regulation of transcription by RNA polymerase II IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    involved_in regulation of transcription by RNA polymerase II IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in regulation of transcription by RNA polymerase II IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in response to glucose ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in rhythmic process IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in sex differentiation IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in signal transduction involved in regulation of gene expression IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in triglyceride homeostasis ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in type B pancreatic cell development IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in xenobiotic metabolic process IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    Component Evidence Code Pubs
    located_in chromatin ISA
    Inferred from Sequence Alignment
    more info
     
    located_in cytoplasm IDA
    Inferred from Direct Assay
    more info
    PubMed 
    located_in nucleoplasm IDA
    Inferred from Direct Assay
    more info
     
    located_in nucleoplasm TAS
    Traceable Author Statement
    more info
     
    located_in nucleus IDA
    Inferred from Direct Assay
    more info
    PubMed 

    General protein information

    Preferred Names
    hepatocyte nuclear factor 4-alpha
    Names
    HNF4alpha10/11/12
    hepatic nuclear factor 4 alpha
    nuclear receptor subfamily 2 group A member 1
    transcription factor 14
    transcription factor HNF-4

    NCBI Reference Sequences (RefSeq)

    NEW Try the new Transcript table

    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

    1. NG_009818.1 RefSeqGene

      Range
      5001..82045
      Download
      GenBank, FASTA, Sequence Viewer (Graphics), LRG_483

    mRNA and Protein(s)

    1. NM_000457.6NP_000448.3  hepatocyte nuclear factor 4-alpha isoform 2

      See identical proteins and their annotated locations for NP_000448.3

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) encodes the longest isoform (2, also known as HNF4alpha2).
      Source sequence(s)
      AL132772
      Consensus CDS
      CCDS13330.1
      UniProtKB/Swiss-Prot
      P41235
      UniProtKB/TrEMBL
      F1D8T1
      Related
      ENSP00000312987.3, ENST00000316099.9
      Conserved Domains (2) summary
      cd06931
      Location:151373
      NR_LBD_HNF4_like; The ligand binding domain of heptocyte nuclear factor 4, which is explosively expanded in nematodes
      cd06960
      Location:60135
      NR_DBD_HNF4A; DNA-binding domain of heptocyte nuclear factor 4 (HNF4) is composed of two C4-type zinc fingers
    2. NM_001030003.3NP_001025174.1  hepatocyte nuclear factor 4-alpha isoform 4

      See identical proteins and their annotated locations for NP_001025174.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4) contains an alternate 5' terminal exon (resulting in translation initiation from an alternate upstream start codon) and uses an alternate in-frame donor splice site in the 3' coding region compared to variant 2. The resulting shorter isoform (4, also known as HNF4alpha7) has a distinct N-terminus and lacks a 10 aa protein segment in the C-terminal region compared to isoform 2.
      Source sequence(s)
      AL117382, AL132772, AW134564, AY680696
      Consensus CDS
      CCDS46604.1
      UniProtKB/Swiss-Prot
      P41235
      Related
      ENSP00000396216.1, ENST00000457232.5
      Conserved Domains (2) summary
      cd06931
      Location:129351
      NR_LBD_HNF4_like; The ligand binding domain of heptocyte nuclear factor 4, which is explosively expanded in nematodes
      cd06960
      Location:38113
      NR_DBD_HNF4A; DNA-binding domain of heptocyte nuclear factor 4 (HNF4) is composed of two C4-type zinc fingers
    3. NM_001030004.3NP_001025175.1  hepatocyte nuclear factor 4-alpha isoform 6

      See identical proteins and their annotated locations for NP_001025175.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (6) contains an alternate 5' terminal exon (resulting in translation initiation from an alternate upstream start codon) and differs at the 3' end that causes a frame-shift compared to variant 2. The resulting shorter isoform (6, also known as HNF4alpha9) has distinct N- and C-termini compared to isoform 2.
      Source sequence(s)
      AL117382, AL132772, AY680698
      Consensus CDS
      CCDS68131.1
      UniProtKB/Swiss-Prot
      P41235
      Related
      ENSP00000476609.1, ENST00000609795.5
      Conserved Domains (2) summary
      cd06931
      Location:129351
      NR_LBD_HNF4_like; The ligand binding domain of heptocyte nuclear factor 4, which is explosively expanded in nematodes
      cd06960
      Location:38113
      NR_DBD_HNF4A; DNA-binding domain of heptocyte nuclear factor 4 (HNF4) is composed of two C4-type zinc fingers
    4. NM_001258355.2NP_001245284.1  hepatocyte nuclear factor 4-alpha isoform 7

      See identical proteins and their annotated locations for NP_001245284.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (7) contains an additional coding exon in the 5' region that results in translation initiation from an alternate downstream start codon compared to variant 2. The resulting shorter isoform (7) has a distinct N-terminus compared to isoform 2.
      Source sequence(s)
      AL132772, AW134564, BP274413, HQ692869, Z49825
      UniProtKB/Swiss-Prot
      P41235
      UniProtKB/TrEMBL
      F1D8T1
      Conserved Domains (2) summary
      cd06931
      Location:144366
      NR_LBD_HNF4_like; The ligand binding domain of heptocyte nuclear factor 4, which is explosively expanded in nematodes
      cd06960
      Location:53128
      NR_DBD_HNF4A; DNA-binding domain of heptocyte nuclear factor 4 (HNF4) is composed of two C4-type zinc fingers
    5. NM_001287182.2NP_001274111.1  hepatocyte nuclear factor 4-alpha isoform 8

      Status: REVIEWED

      Description
      Transcript Variant: This variant (8) differs at the 5' end (resulting in translation initiation from an alternate upstream start codon) and uses an alternate in-frame donor splice site in the 3' coding region compared to variant 2. The resulting shorter isoform (8, also known as HNF4alpha10) has a distinct N-terminus and lacks a 10 aa protein segment in the C-terminal region compared to isoform 2.
      Source sequence(s)
      AL117382, AL132772, AW134564, AY680696, FJ608822
      UniProtKB/Swiss-Prot
      P41235
      UniProtKB/TrEMBL
      B9VVT8
      Conserved Domains (2) summary
      cd06931
      Location:126348
      NR_LBD_HNF4_like; The ligand binding domain of heptocyte nuclear factor 4, which is explosively expanded in nematodes
      cd06960
      Location:35110
      NR_DBD_HNF4A; DNA-binding domain of heptocyte nuclear factor 4 (HNF4) is composed of two C4-type zinc fingers
    6. NM_001287183.2NP_001274112.1  hepatocyte nuclear factor 4-alpha isoform 9

      Status: REVIEWED

      Description
      Transcript Variant: This variant (9) differs at the 5' end, which results in translation initiation from an alternate upstream start codon compared to variant 2. The resulting shorter isoform (9, also known as HNF4alpha11) has a distinct N-terminus compared to isoform 2.
      Source sequence(s)
      AL117382, AL132772
      Consensus CDS
      CCDS74728.1
      UniProtKB/Swiss-Prot
      P41235
      UniProtKB/TrEMBL
      A0A087WXV4, B9VVT8
      Conserved Domains (2) summary
      cd06931
      Location:126348
      NR_LBD_HNF4_like; The ligand binding domain of heptocyte nuclear factor 4, which is explosively expanded in nematodes
      cd06960
      Location:35110
      NR_DBD_HNF4A; DNA-binding domain of heptocyte nuclear factor 4 (HNF4) is composed of two C4-type zinc fingers
    7. NM_001287184.2NP_001274113.1  hepatocyte nuclear factor 4-alpha isoform 10

      Status: REVIEWED

      Description
      Transcript Variant: This variant (10) differs at the 5' end (resulting in translation initiation from an alternate upstream start codon) and at the 3' end (that causes a frame-shift) compared to variant 2. The resulting shorter isoform (10, also known as HNF4alpha12) has distinct N- and C-termini compared to isoform 2.
      Source sequence(s)
      AL117382, AL132772, AY680698, BC137539, FJ608822
      UniProtKB/Swiss-Prot
      P41235
      UniProtKB/TrEMBL
      B9VVT8
      Conserved Domains (2) summary
      cd06931
      Location:126348
      NR_LBD_HNF4_like; The ligand binding domain of heptocyte nuclear factor 4, which is explosively expanded in nematodes
      cd06960
      Location:35110
      NR_DBD_HNF4A; DNA-binding domain of heptocyte nuclear factor 4 (HNF4) is composed of two C4-type zinc fingers
    8. NM_175914.5NP_787110.2  hepatocyte nuclear factor 4-alpha isoform 5

      See identical proteins and their annotated locations for NP_787110.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (5) contains an alternate 5' terminal exon, which results in translation initiation from an alternate upstream start codon compared to variant 2. The resulting shorter isoform (5, also known as HNF4alpha8) has a distinct N-terminus compared to isoform 2.
      Source sequence(s)
      AL117382, AL132772
      Consensus CDS
      CCDS42876.1
      UniProtKB/Swiss-Prot
      P41235
      UniProtKB/TrEMBL
      F1D8T0
      Related
      ENSP00000315180.4, ENST00000316673.8
      Conserved Domains (2) summary
      cd06931
      Location:129351
      NR_LBD_HNF4_like; The ligand binding domain of heptocyte nuclear factor 4, which is explosively expanded in nematodes
      cd06960
      Location:38113
      NR_DBD_HNF4A; DNA-binding domain of heptocyte nuclear factor 4 (HNF4) is composed of two C4-type zinc fingers
    9. NM_178849.3NP_849180.1  hepatocyte nuclear factor 4-alpha isoform 1

      See identical proteins and their annotated locations for NP_849180.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) uses an alternate in-frame donor splice site in the 3' coding region compared to variant 2. The resulting shorter isoform (1, also known as HNF4alpha1) lacks a 10 aa protein segment compared to isoform 2.
      Source sequence(s)
      AL132772, AW134564, BP274413, HQ692860
      Consensus CDS
      CCDS46605.1
      UniProtKB/TrEMBL
      F1D8S2
      Related
      ENSP00000412111.1, ENST00000415691.2
      Conserved Domains (2) summary
      cd06931
      Location:151373
      NR_LBD_HNF4_like; The ligand binding domain of heptocyte nuclear factor 4, which is explosively expanded in nematodes
      cd06960
      Location:60135
      NR_DBD_HNF4A; DNA-binding domain of heptocyte nuclear factor 4 (HNF4) is composed of two C4-type zinc fingers
    10. NM_178850.3NP_849181.1  hepatocyte nuclear factor 4-alpha isoform 3

      See identical proteins and their annotated locations for NP_849181.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) has a different 3' end that causes a frame-shift compared to variant 2. The resulting shorter isoform (3, also known as HNF4alpha3) has a distinct C-terminus compared to isoform 2.
      Source sequence(s)
      AL132772, BC137539, BP274413
      Consensus CDS
      CCDS13331.1
      UniProtKB/Swiss-Prot
      P41235
      Related
      ENSP00000410911.2, ENST00000443598.6
      Conserved Domains (2) summary
      cd06931
      Location:151373
      NR_LBD_HNF4_like; The ligand binding domain of heptocyte nuclear factor 4, which is explosively expanded in nematodes
      cd06960
      Location:60135
      NR_DBD_HNF4A; DNA-binding domain of heptocyte nuclear factor 4 (HNF4) is composed of two C4-type zinc fingers

    RefSeqs of Annotated Genomes: Homo sapiens Updated Annotation Release 109.20210514

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

    Reference GRCh38.p13 Primary Assembly

    Genomic

    1. NC_000020.11 Reference GRCh38.p13 Primary Assembly

      Range
      44355699..44434596
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_005260407.4XP_005260464.1  hepatocyte nuclear factor 4-alpha isoform X1

      Conserved Domains (2) summary
      cd06931
      Location:190412
      NR_LBD_HNF4_like; The ligand binding domain of heptocyte nuclear factor 4, which is explosively expanded in nematodes
      cd06960
      Location:99174
      NR_DBD_HNF4A; DNA-binding domain of heptocyte nuclear factor 4 (HNF4) is composed of two C4-type zinc fingers
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