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

Gene ID: 3172, updated on 9-Jun-2018
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; 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; FRTS4; 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]
Expression
Biased expression in duodenum (RPKM 37.7), colon (RPKM 32.8) and 7 other tissues See more
Orthologs
See HNF4A in Genome Data Viewer
Location:
20q13.12
Exon count:
13
Annotation release Status Assembly Chr Location
109 current GRCh38.p12 (GCF_000001405.38) 20 NC_000020.11 (44355801..44432845)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 20 NC_000020.10 (42984441..43061485)

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

  • 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 Jun 15 11:32:44 2016

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

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
Discovery and refinement of loci associated with lipid levels.
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
Genome-wide trans-ancestry meta-analysis provides insight into the genetic architecture of type 2 diabetes susceptibility.
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
  • AMP-activated Protein Kinase (AMPK) Signaling, organism-specific biosystem (from WikiPathways)
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  • Developmental Biology, organism-specific biosystem (from REACTOME)
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    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...
  • Generic Transcription Pathway, organism-specific biosystem (from REACTOME)
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  • HIF-1-alpha transcription factor network, organism-specific biosystem (from Pathway Interaction Database)
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    HIF-1-alpha transcription factor network
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  • Maturity onset diabetes of the young, organism-specific biosystem (from KEGG)
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  • 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...
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  • 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...
  • Regulation of nuclear SMAD2/3 signaling, organism-specific biosystem (from Pathway Interaction Database)
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Products Interactant Other Gene Complex Source Pubs Description

Markers

Homology

Clone Names

  • FLJ39654

Gene Ontology Provided by GOA

Function Evidence Code Pubs
DNA binding IDA
Inferred from Direct Assay
more info
PubMed 
DNA-binding transcription factor activity IDA
Inferred from Direct Assay
more info
PubMed 
RNA polymerase II activating transcription factor binding ISS
Inferred from Sequence or Structural Similarity
more info
 
RNA polymerase II proximal promoter sequence-specific DNA binding IEA
Inferred from Electronic Annotation
more info
 
RNA polymerase II transcription factor activity, sequence-specific DNA binding ISA
Inferred from Sequence Alignment
more info
 
RNA polymerase II transcription factor activity, sequence-specific DNA binding ISM
Inferred from Sequence Model
more info
PubMed 
RNA polymerase II transcription factor activity, sequence-specific DNA binding NAS
Non-traceable Author Statement
more info
PubMed 
fatty acid binding IDA
Inferred from Direct Assay
more info
PubMed 
nuclear receptor activity IEA
Inferred from Electronic Annotation
more info
 
protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
protein homodimerization activity IDA
Inferred from Direct Assay
more info
PubMed 
signaling receptor binding IDA
Inferred from Direct Assay
more info
PubMed 
steroid hormone receptor activity IEA
Inferred from Electronic Annotation
more info
 
transcription factor activity, RNA polymerase II distal enhancer sequence-specific binding IEA
Inferred from Electronic Annotation
more info
 
transcription regulatory region DNA binding IDA
Inferred from Direct Assay
more info
PubMed 
transcriptional activator activity, RNA polymerase II proximal promoter sequence-specific DNA binding ISS
Inferred from Sequence or Structural Similarity
more info
 
zinc ion binding IEA
Inferred from Electronic Annotation
more info
 
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 
cholesterol homeostasis ISS
Inferred from Sequence or Structural Similarity
more info
 
glucose homeostasis ISS
Inferred from Sequence or Structural Similarity
more info
 
intracellular receptor signaling pathway IEA
Inferred from Electronic Annotation
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 transcription by RNA polymerase II IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of transcription by RNA polymerase II 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 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 by RNA polymerase II IDA
Inferred from Direct Assay
more info
PubMed 
regulation of transcription by RNA polymerase II 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
 
steroid hormone mediated signaling pathway 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 IDA
Inferred from Direct Assay
more info
 
nucleoplasm TAS
Traceable Author Statement
more info
 
nucleus IDA
Inferred from Direct Assay
more info
PubMed 
Preferred Names
hepatocyte nuclear factor 4-alpha
Names
HNF4alpha10/11/12
TCF-14
hepatic nuclear factor 4 alpha
nuclear receptor subfamily 2 group A member 1
transcription factor 14
transcription factor HNF-4

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 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, AW134564, BP274413, HQ692869
    Consensus CDS
    CCDS13330.1
    UniProtKB/Swiss-Prot
    P41235
    UniProtKB/TrEMBL
    F1D8T1
    Related
    ENSP00000312987.3, OTTHUMP00000031060, ENST00000316099.8, OTTHUMT00000079363
    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_001030003.2NP_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)
    AL132772, AW134564, AY680696
    Consensus CDS
    CCDS46604.1
    UniProtKB/Swiss-Prot
    P41235
    Related
    ENSP00000396216.1, OTTHUMP00000274119, ENST00000457232.5, OTTHUMT00000472004
    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_001030004.2NP_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)
    AL132772, AY680698
    Consensus CDS
    CCDS68131.1
    UniProtKB/Swiss-Prot
    P41235
    Related
    ENSP00000476609.1, OTTHUMP00000274118, ENST00000609795.5, OTTHUMT00000472003
    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_001258355.1NP_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_001287182.1NP_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)
    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_001287183.1NP_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)
    AL132772, AW134564, AY680697, FJ608822
    Consensus CDS
    CCDS74728.1
    UniProtKB/Swiss-Prot
    P41235
    UniProtKB/TrEMBL
    A0A087WXV4, B9VVT8
    Related
    ENSP00000481331.1, ENST00000619550.4
    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_001287184.1NP_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)
    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_175914.4NP_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)
    AL132772, AW134564, AY680697
    Consensus CDS
    CCDS42876.1
    UniProtKB/Swiss-Prot
    P41235
    UniProtKB/TrEMBL
    F1D8T0
    Related
    ENSP00000315180.4, OTTHUMP00000031059, ENST00000316673.8, OTTHUMT00000079362
    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_178849.2NP_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, OTTHUMP00000274121, ENST00000415691.2, OTTHUMT00000472006
    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_178850.2NP_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, OTTHUMP00000031062, ENST00000443598.6, OTTHUMT00000079365
    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 Annotation Release 109 details...Open this link in a new tab

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

Reference GRCh38.p12 Primary Assembly

Genomic

  1. NC_000020.11 Reference GRCh38.p12 Primary Assembly

    Range
    44355801..44432845
    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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