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

Gene ID: 3172, updated on 13-Apr-2014
Official Symbol
HNF4Aprovided by HGNC
Official Full Name
hepatocyte nuclear factor 4, alphaprovided by HGNC
Primary source
HGNC:5024
Locus tag
RP5-1013A22.1
See related
Ensembl:ENSG00000101076; HPRD:02612; MIM:600281; Vega:OTTHUMG00000032531
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; MODY1; NR2A1; TCF14; HNF4a7; HNF4a8; HNF4a9; NR2A21; 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]
Location :
20q13.12
Sequence :
Chromosome: 20; NC_000020.11 (44355801..44432845)
See HNF4A in Epigenomics, MapViewer

Chromosome 20 - NC_000020.11Genomic Context describing neighboring genes Neighboring gene fat storage-inducing transmembrane protein 2 Neighboring gene R3H domain containing-like Neighboring gene HNF4A antisense RNA 1 Neighboring gene microRNA 3646 Neighboring gene uncharacterized LOC101927242 Neighboring gene chromosome 20 open reading frame 62

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

Associated conditions

Description Tests
Diabetes mellitus type 2
MedGen: C0011860 OMIM: 125853 GeneReviews: Not available
Compare labs
familial hyperinsulinism
MedGen: CN043604 GeneReviews: Familial Hyperinsulinism
Compare labs
Maturity-onset diabetes of the young, type 1
MedGen: C1852093 OMIM: 125850 GeneReviews: Not available
Compare labs

NHGRI GWAS Catalog

Description
Biological, clinical and population relevance of 95 loci for blood lipids.
NHGRI GWA Catalog
Common variants at 30 loci contribute to polygenic dyslipidemia.
NHGRI GWA Catalog
Genome-wide association and population genetic analysis of C-reactive protein in African American and Hispanic American women.
NHGRI GWA Catalog
Genome-wide association study in individuals of South Asian ancestry identifies six new type 2 diabetes susceptibility loci.
NHGRI GWA Catalog
Genome-wide association study of ulcerative colitis identifies three new susceptibility loci, including the HNF4A region.
NHGRI GWA Catalog
Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease.
NHGRI GWA Catalog
Meta-analysis of genome-wide association studies identifies eight new loci for type 2 diabetes in east Asians.
NHGRI GWA Catalog
Meta-analysis of genome-wide association studies in >80 000 subjects identifies multiple loci for C-reactive protein levels.
NHGRI GWA Catalog
  • AMPK signaling, organism-specific biosystem (from WikiPathways)
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  • FOXA2 and FOXA3 transcription factor networks, organism-specific biosystem (from Pathway Interaction Database)
    FOXA2 and FOXA3 transcription factor networks, organism-specific biosystem
    FOXA2 and FOXA3 transcription factor networks
  • Gene Expression, organism-specific biosystem (from REACTOME)
    Gene Expression, organism-specific biosystemGene Expression covers the pathways by which genomic DNA is transcribed to yield RNA, the regulation of these transcription processes, and the pathways by which newly-made RNA Transcripts are process...
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    HIF-1-alpha transcription factor network, organism-specific biosystem
    HIF-1-alpha transcription factor network
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  • Maturity onset diabetes of the young, organism-specific biosystem (from KEGG)
    Maturity onset diabetes of the young, organism-specific biosystemAbout 2-5% of type II diabetic patients suffer from a monogenic disease with autosomal dominant inheritance. This monogenic form of type II diabetes is called maturity onset diabetes of the young (MO...
  • Maturity onset diabetes of the young, conserved biosystem (from KEGG)
    Maturity onset diabetes of the young, conserved biosystemAbout 2-5% of type II diabetic patients suffer from a monogenic disease with autosomal dominant inheritance. This monogenic form of type II diabetes is called maturity onset diabetes of the young (MO...
  • Nuclear Receptor transcription pathway, organism-specific biosystem (from REACTOME)
    Nuclear Receptor transcription pathway, organism-specific biosystemA classic example of bifunctional transcription factors is the family of Nuclear Receptor (NR) proteins. These are DNA-binding transcription factors that bind certain hormones, vitamins, and other s...
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    Nuclear Receptors, organism-specific biosystemNuclear receptors are a class of proteins found within the interior of cells that are responsible for sensing the presence of steroid and thyroid hormones and certain other molecules. In response, th...
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    Regulation of beta-cell development, organism-specific biosystemThe normal development of the pancreas during gestation has been intensively investigated over the past decade especially in the mouse (Servitja and Ferrer 2004; Chakrabarti and Mirmira 2003). Studie...
  • Regulation of gene expression in beta cells, organism-specific biosystem (from REACTOME)
    Regulation of gene expression in beta cells, organism-specific biosystemTwo transcription factors, PDX1 and HNF1A, play key roles in maintaining the gene expression pattern characteristic of mature beta cells in the endocrine pancreas. Targets of these regulatory molecul...
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    Regulation of nuclear SMAD2/3 signaling, organism-specific biosystem
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    TGF-beta Receptor Signaling Pathway, organism-specific biosystem"The TGF beta receptors TGFBR1 and TGFBR2 belong to a subfamily of membrane-bound serine/threonine kinases which are designated as Type I or II based on their structural and functional properties. Th...
Products Interactant Other Gene Complex Source Pubs Description

Markers

Homology

Gene Ontology Provided by GOA

Process Evidence Code Pubs
SMAD protein signal transduction IEA
Inferred from Electronic Annotation
more info
 
blood coagulation IDA
Inferred from Direct Assay
more info
PubMed 
endocrine pancreas development TAS
Traceable Author Statement
more info
 
gene expression TAS
Traceable Author Statement
more info
 
glucose homeostasis ISS
Inferred from Sequence or Structural Similarity
more info
 
lipid homeostasis IMP
Inferred from Mutant Phenotype
more info
PubMed 
lipid metabolic process IEA
Inferred from Electronic Annotation
more info
 
negative regulation of cell growth IMP
Inferred from Mutant Phenotype
more info
PubMed 
negative regulation of cell proliferation IMP
Inferred from Mutant Phenotype
more info
PubMed 
ornithine metabolic process IMP
Inferred from Mutant Phenotype
more info
PubMed 
phospholipid homeostasis ISS
Inferred from Sequence or Structural Similarity
more info
 
positive regulation of cholesterol homeostasis ISS
Inferred from Sequence or Structural Similarity
more info
 
positive regulation of transcription from RNA polymerase II promoter IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of transcription from RNA polymerase II promoter IMP
Inferred from Mutant Phenotype
more info
PubMed 
positive regulation of transcription, DNA-templated IDA
Inferred from Direct Assay
more info
PubMed 
regulation of gastrulation IEA
Inferred from Electronic Annotation
more info
 
regulation of growth hormone receptor signaling pathway NAS
Non-traceable Author Statement
more info
PubMed 
regulation of insulin secretion ISS
Inferred from Sequence or Structural Similarity
more info
 
regulation of lipid metabolic process IDA
Inferred from Direct Assay
more info
PubMed 
regulation of transcription from RNA polymerase II promoter IDA
Inferred from Direct Assay
more info
PubMed 
regulation of transcription from RNA polymerase II promoter IMP
Inferred from Mutant Phenotype
more info
PubMed 
response to glucose ISS
Inferred from Sequence or Structural Similarity
more info
 
sex differentiation IEA
Inferred from Electronic Annotation
more info
 
signal transduction involved in regulation of gene expression IEA
Inferred from Electronic Annotation
more info
 
transcription initiation from RNA polymerase II promoter TAS
Traceable Author Statement
more info
 
triglyceride homeostasis ISS
Inferred from Sequence or Structural Similarity
more info
 
xenobiotic metabolic process IMP
Inferred from Mutant Phenotype
more info
PubMed 
Component Evidence Code Pubs
cytoplasm IDA
Inferred from Direct Assay
more info
PubMed 
nucleoplasm TAS
Traceable Author Statement
more info
 
nucleus IDA
Inferred from Direct Assay
more info
PubMed 
Preferred Names
hepatocyte nuclear factor 4-alpha
Names
hepatocyte nuclear factor 4-alpha
TCF-14
HNF4alpha10/11/12
transcription factor 14
transcription factor HNF-4
hepatic nuclear factor 4 alpha
nuclear receptor subfamily 2 group A member 1

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_000457.4NP_000448.3  hepatocyte nuclear factor 4-alpha isoform HNF4alpha2

    See proteins identical to NP_000448.3

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) encodes the longest isoform (HNF4alpha2).
    Source sequence(s)
    AL132772, AW134564, BP274413, HQ692869
    Consensus CDS
    CCDS13330.1
    UniProtKB/TrEMBL
    F1D8T1
    UniProtKB/Swiss-Prot
    P41235
    Related
    ENSP00000312987, OTTHUMP00000031060, ENST00000316099, OTTHUMT00000079363
    Conserved Domains (2) summary
    cd06931
    Location:151373
    Blast Score: 1126
    NR_LBD_HNF4_like; The ligand binding domain of heptocyte nuclear factor 4, which is explosively expanded in nematodes
    cd06960
    Location:60135
    Blast Score: 428
    NR_DBD_HNF4A; DNA-binding domain of heptocyte nuclear factor 4 (HNF4) is composed of two C4-type zinc fingers
  2. NM_001030003.2NP_001025174.1  hepatocyte nuclear factor 4-alpha isoform HNF4alpha7

    See proteins identical to 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 (HNF4alpha7) has a distinct N-terminus and lacks a 10 aa protein segment in the C-terminal region compared to isoform HNF4alpha2.
    Source sequence(s)
    AL132772, AW134564, AY680696
    Consensus CDS
    CCDS46604.1
    UniProtKB/Swiss-Prot
    P41235
    Conserved Domains (2) summary
    cd06931
    Location:129351
    Blast Score: 1127
    NR_LBD_HNF4_like; The ligand binding domain of heptocyte nuclear factor 4, which is explosively expanded in nematodes
    cd06960
    Location:38113
    Blast Score: 429
    NR_DBD_HNF4A; DNA-binding domain of heptocyte nuclear factor 4 (HNF4) is composed of two C4-type zinc fingers
  3. NM_001030004.2NP_001025175.1  hepatocyte nuclear factor 4-alpha isoform HNF4alpha9

    See proteins identical to 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 (HNF4alpha9) has distinct N- and C-termini compared to isoform HNF4alpha2.
    Source sequence(s)
    AL132772, AY680698
    Consensus CDS
    CCDS68131.1
    UniProtKB/Swiss-Prot
    P41235
    Related
    ENSP00000476609, OTTHUMP00000274118, ENST00000609795, OTTHUMT00000472003
    Conserved Domains (2) summary
    cd06931
    Location:129351
    Blast Score: 1125
    NR_LBD_HNF4_like; The ligand binding domain of heptocyte nuclear factor 4, which is explosively expanded in nematodes
    cd06960
    Location:38113
    Blast Score: 407
    NR_DBD_HNF4A; DNA-binding domain of heptocyte nuclear factor 4 (HNF4) is composed of two C4-type zinc fingers
  4. NM_001258355.1NP_001245284.1  hepatocyte nuclear factor 4-alpha isoform HNF4alpha4

    See proteins identical to 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 (HNF4alpha4) has a distinct N-terminus compared to isoform HNF4alpha2.
    Source sequence(s)
    AL132772, AW134564, BP274413, HQ692869, Z49825
    UniProtKB/TrEMBL
    F1D8T1
    UniProtKB/Swiss-Prot
    P41235
    Conserved Domains (2) summary
    cd06931
    Location:144366
    Blast Score: 1130
    NR_LBD_HNF4_like; The ligand binding domain of heptocyte nuclear factor 4, which is explosively expanded in nematodes
    cd06960
    Location:53128
    Blast Score: 427
    NR_DBD_HNF4A; DNA-binding domain of heptocyte nuclear factor 4 (HNF4) is composed of two C4-type zinc fingers
  5. NM_001287182.1NP_001274111.1  hepatocyte nuclear factor 4-alpha isoform HNF4alpha10

    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 (HNF4alpha10) has a distinct N-terminus and lacks a 10 aa protein segment in the C-terminal region compared to isoform HNF4alpha2.
    Source sequence(s)
    AL132772, AW134564, AY680696, FJ608822
    UniProtKB/TrEMBL
    B9VVT8
    UniProtKB/Swiss-Prot
    P41235
    Conserved Domains (2) summary
    cd06931
    Location:126348
    Blast Score: 1127
    NR_LBD_HNF4_like; The ligand binding domain of heptocyte nuclear factor 4, which is explosively expanded in nematodes
    cd06960
    Location:35110
    Blast Score: 429
    NR_DBD_HNF4A; DNA-binding domain of heptocyte nuclear factor 4 (HNF4) is composed of two C4-type zinc fingers
  6. NM_001287183.1NP_001274112.1  hepatocyte nuclear factor 4-alpha isoform HNF4alpha11

    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 (HNF4alpha11) has a distinct N-terminus compared to isoform HNF4alpha2.
    Source sequence(s)
    AL132772, AW134564, AY680697, FJ608822
    UniProtKB/TrEMBL
    B9VVT8
    UniProtKB/Swiss-Prot
    P41235
    Conserved Domains (2) summary
    cd06931
    Location:126348
    Blast Score: 1129
    NR_LBD_HNF4_like; The ligand binding domain of heptocyte nuclear factor 4, which is explosively expanded in nematodes
    cd06960
    Location:35110
    Blast Score: 426
    NR_DBD_HNF4A; DNA-binding domain of heptocyte nuclear factor 4 (HNF4) is composed of two C4-type zinc fingers
  7. NM_001287184.1NP_001274113.1  hepatocyte nuclear factor 4-alpha isoform HNF4alpha12

    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 (HNF4alpha12) has distinct N- and C-termini compared to isoform HNF4alpha2.
    Source sequence(s)
    AL132772, AY680698, BC137539, FJ608822
    UniProtKB/TrEMBL
    B9VVT8
    UniProtKB/Swiss-Prot
    P41235
    Conserved Domains (2) summary
    cd06931
    Location:126348
    Blast Score: 1125
    NR_LBD_HNF4_like; The ligand binding domain of heptocyte nuclear factor 4, which is explosively expanded in nematodes
    cd06960
    Location:35110
    Blast Score: 407
    NR_DBD_HNF4A; DNA-binding domain of heptocyte nuclear factor 4 (HNF4) is composed of two C4-type zinc fingers
  8. NM_175914.4NP_787110.2  hepatocyte nuclear factor 4-alpha isoform HNF4alpha8

    See proteins identical to 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 (HNF4alpha8) has a distinct N-terminus compared to isoform HNF4alpha2.
    Source sequence(s)
    AL132772, AW134564, AY680697
    Consensus CDS
    CCDS42876.1
    UniProtKB/TrEMBL
    F1D8T0
    UniProtKB/Swiss-Prot
    P41235
    Conserved Domains (2) summary
    cd06931
    Location:129351
    Blast Score: 1129
    NR_LBD_HNF4_like; The ligand binding domain of heptocyte nuclear factor 4, which is explosively expanded in nematodes
    cd06960
    Location:38113
    Blast Score: 426
    NR_DBD_HNF4A; DNA-binding domain of heptocyte nuclear factor 4 (HNF4) is composed of two C4-type zinc fingers
  9. NM_178849.2NP_849180.1  hepatocyte nuclear factor 4-alpha isoform HNF4alpha1

    See proteins identical to 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 (HNF4alpha1) lacks a 10 aa protein segment compared to isoform HNF4alpha2.
    Source sequence(s)
    AL132772, AW134564, BP274413, HQ692860
    Consensus CDS
    CCDS46605.1
    UniProtKB/TrEMBL
    F1D8S2
    Conserved Domains (2) summary
    cd06931
    Location:151373
    Blast Score: 1124
    NR_LBD_HNF4_like; The ligand binding domain of heptocyte nuclear factor 4, which is explosively expanded in nematodes
    cd06960
    Location:60135
    Blast Score: 431
    NR_DBD_HNF4A; DNA-binding domain of heptocyte nuclear factor 4 (HNF4) is composed of two C4-type zinc fingers
  10. NM_178850.2NP_849181.1  hepatocyte nuclear factor 4-alpha isoform HNF4alpha3

    See proteins identical to 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 (HNF4alpha3) has a distinct C-terminus compared to isoform HNF4alpha2.
    Source sequence(s)
    AL132772, BC137539, BP274413
    Consensus CDS
    CCDS13331.1
    UniProtKB/Swiss-Prot
    P41235
    Related
    ENSP00000410911, OTTHUMP00000031062, ENST00000443598, OTTHUMT00000079365
    Conserved Domains (2) summary
    cd06931
    Location:151373
    Blast Score: 1122
    NR_LBD_HNF4_like; The ligand binding domain of heptocyte nuclear factor 4, which is explosively expanded in nematodes
    cd06960
    Location:60135
    Blast Score: 410
    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 Annotation Release 106

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

Reference GRCh38 Primary Assembly

Genomic

  1. NC_000020.11

    Range
    44355801..44432845
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_005260407.1XP_005260464.1  

    Conserved Domains (2) summary
    cd06931
    Location:190412
    Blast Score: 1133
    NR_LBD_HNF4_like; The ligand binding domain of heptocyte nuclear factor 4, which is explosively expanded in nematodes
    cd06960
    Location:99174
    Blast Score: 429
    NR_DBD_HNF4A; DNA-binding domain of heptocyte nuclear factor 4 (HNF4) is composed of two C4-type zinc fingers

Alternate HuRef

Genomic

  1. AC_000152.1 Alternate HuRef

    Range
    39720990..39802805
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate CHM1_1.1

Genomic

  1. NC_018931.2 Alternate CHM1_1.1

    Range
    42886684..42964390
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

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