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HNF4A Gene

protein-coding   GIFtS: 70
GCID: GC20P042984

Hepatocyte Nuclear Factor 4, Alpha


(Previous symbols: TCF14, MODY, MODY1)
Microbiology & Infectious Diseases Congress
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(According to 1HGNC, 2Entrez Gene,
3UniProtKB/Swiss-Prot, 4UniProtKB/TrEMBL, 5OMIM, 6GeneLoc, 7Ensembl, 8DME, 9miRBase, 10fRNAdb, 12H-InvDB, 13NCBI, 14NONCODE, and/or 15RNAdb)
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Aliases
Hepatocyte Nuclear Factor 4, Alpha1 2     HNF4a72
TCF141 2 3 5     HNF4a82
MODY11 2 5     HNF4a92
MODY1 2     HNF4alpha2
Nuclear Receptor Subfamily 2 Group A Member 12 3     HNF4alpha10/11/122
Transcription Factor 142 3     NR2A212
Transcription Factor HNF-42 3     TCF2
HNF42 3     Hepatic Nuclear Factor 4 Alpha2
NR2A12 3     Hepatocyte Nuclear Factor 4-Alpha2
TCF-142 3     HNF-4-alpha3

External Ids:    HGNC: 50241   Entrez Gene: 31722   Ensembl: ENSG000001010767   OMIM: 6002815   UniProtKB: P412353   

Export aliases for HNF4A gene to outside databases

Previous GC identifers: GC20P042758 GC20P043668 GC20P043715 GC20P042463 GC20P039720


(According to Entrez Gene, GeneCards, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
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Entrez Gene summary for HNF4A Gene:
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)

GeneCards Summary for HNF4A Gene:
HNF4A (hepatocyte nuclear factor 4, alpha) is a protein-coding gene. Diseases associated with HNF4A include monogenic diabetes, and hnf4a-related hyperinsulinism. GO annotations related to this gene include sequence-specific DNA binding and sequence-specific DNA binding transcription factor activity. An important paralog of this gene is RXRA.

UniProtKB/Swiss-Prot: HNF4A_HUMAN, P41235
Function: Transcriptionally controlled transcription factor. Binds to DNA sites required for the transcription of
alpha 1-antitrypsin, apolipoprotein CIII, transthyretin genes and HNF1-alpha. May be essential for development of
the liver, kidney and intestine

Gene Wiki entry for HNF4A (Hepatocyte nuclear factor 4 alpha) Gene


(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 75), Regulatory elements and Epigenetics data according to QIAGEN, and/or SwitchGear Genomics)
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RefSeq DNA sequence:
NC_000020.11  NT_011362.11  NC_018931.2  
Regulatory elements:
   Regulatory transcription factor binding sites in the HNF4A gene promoter:
         Sp1   NRSF form 1   NRSF form 2   
         Other transcription factors

SwitchGear Promoter luciferase reporter plasmids (see all 2): HNF4A promoter sequence
   Search Chromatin IP Primers for HNF4A

Epigenetics:
DNA Methylation CpG Assay Predesigned for Pyrosequencing in human, mouse, rat HNF4A


Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 20q13.12   Ensembl cytogenetic band:  20q13.12   HGNC cytogenetic band: 20q13.12

HNF4A Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
HNF4A gene location

GeneLoc information about chromosome 20         GeneLoc Exon Structure

GeneLoc location for GC20P042984:  view genomic region     (about GC identifiers)

Start:
42,984,340 bp from pter      End:
43,061,485 bp from pter
Size:
77,146 bases      Orientation:
plus strand

(According to 1UniProtKB, HORDE, 2neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, and/or Cloud-Clone Corp.,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Cloud-Clone Corp., Antibodies by EMD Millipore, R&D Systems, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, LSBio, Abcam, and/or Cloud-Clone Corp.)
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UniProtKB/Swiss-Prot: HNF4A_HUMAN, P41235 (See protein sequence)
Recommended Name: Hepatocyte nuclear factor 4-alpha  
Size: 474 amino acids; 52785 Da
Subunit: Homodimerization is required for HNF4-alpha to bind to its recognition site
Miscellaneous: Binds fatty acids
Sequence caution: Sequence=CAA54248.1; Type=Erroneous initiation; Sequence=CAA61133.1; Type=Frameshift;
Positions=2, 7; Sequence=CAA61134.1; Type=Frameshift; Positions=2, 7; Sequence=CAA61135.1; Type=Frameshift;
Positions=2, 7;
5 PDB 3D structures from and Proteopedia for HNF4A:
1PZL (3D)        3CBB (3D)        3FS1 (3D)        4B7W (3D)        4IQR (3D)    
Secondary accessions: A5JW41 B2RPP8 O00659 O00723 Q14540 Q5QPB8 Q6B4V5 Q6B4V6 Q6B4V7 Q92653
Q92654 Q92655 Q99864 Q9NQH0
Alternative promoter usage, Alternative splicing: 7 isoforms:  P41235-1   P41235-2   P41235-3   P41235-4   P41235-5   P41235-6   P41235-7   (Produced by alternative splicing of isoform HNF4-Alpha-7)

Explore the universe of human proteins at neXtProt for HNF4A: NX_P41235

Explore proteomics data for HNF4A at MOPED

Post-translational modifications: 

  • Phosphorylated on tyrosine residue(s); phosphorylation is important for its DNA-binding activity. Phosphorylation
    may directly or indirectly play a regulatory role in the subnuclear distribution. Phosphorylation at Ser-313 by
    AMPK reduces the ability to form homodimers and bind DNA1
  • Acetylation at Lys-458 lowers transcriptional activation by about two-fold1
  • Ubiquitination2 at Lys234, Lys307
  • Modification sites at PhosphoSitePlus

  • See HNF4A Protein Expression from SPIRE MOPED, PaxDB, and MaxQB

    REFSEQ proteins (10 alternative transcripts): 
    NP_000448.3  NP_001025174.1  NP_001025175.1  NP_001245284.1  NP_001274111.1  NP_001274112.1  NP_001274113.1  NP_787110.2  
    NP_849180.1  NP_849181.1  

    ENSEMBL proteins: 
     ENSP00000315180   ENSP00000476609   ENSP00000396216   ENSP00000476310   ENSP00000362011  
     ENSP00000410911   ENSP00000312987   ENSP00000412111  
    Reactome Protein details: P41235

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    (According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
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    HGNC Gene Families:
    NR: Nuclear hormone receptors

    IUPHAR Guide to PHARMACOLOGY protein family classification: Hepatocyte nuclear factor-4-alpha
    2A. Hepatocyte nuclear factor-4 receptors

    Selected InterPro protein domains (see all 6):
     IPR008946 Nucl_hormone_rcpt_ligand-bd
     IPR003068 COUP_TF
     IPR001723 Str_hrmn_rcpt
     IPR013088 Znf_NHR/GATA
     IPR000536 Nucl_hrmn_rcpt_lig-bd_core

    Graphical View of Domain Structure for InterPro Entry P41235

    ProtoNet protein and cluster: P41235

    2 Blocks protein domains:
    IPB000003 Retinoic acid receptor signature
    IPB001723 Steroid hormone receptor signature


    UniProtKB/Swiss-Prot: HNF4A_HUMAN, P41235
    Similarity: Belongs to the nuclear hormone receptor family. NR2 subfamily
    Similarity: Contains 1 nuclear receptor DNA-binding domain


    HNF4A for domains           About GeneDecksing


    (According to 1UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or 2DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, inGenious Targeting Laboratory, genOway,
    transcription factor targeting from QIAGEN and/or HOMER, miRNA Gene Targets from miRTarBase, shRNA from OriGene, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, SwitchGear Genomics, Gene Editing from DNA2.0, Clones from OriGene, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, ESI BIO, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Molecular Function:

         UniProtKB/Swiss-Prot Summary: HNF4A_HUMAN, P41235
    Function: Transcriptionally controlled transcription factor. Binds to DNA sites required for the transcription of
    alpha 1-antitrypsin, apolipoprotein CIII, transthyretin genes and HNF1-alpha. May be essential for development of
    the liver, kidney and intestine

         Genatlas biochemistry entry for HNF4A:
    transcription factor 4,hepatocyte nuclear factor 4 alpha,steroid/thyroid hormone receptor superfamily,coexpressed
    with TCF1 and binding TCF1 promoter (see also RGHE),including the alternatively spliced isoforms
    HNF4A1,HNF4A2,HNF4A4,expressed in pancreatic beta cells,regulating expression of genes required for glucose
    transport and metabolism,and of sex hormones-binding globulin,interacting with TCF1 for regulation of gene
    activity and chromatin structure of serpin cluster (PI)

         Gene Ontology (GO): Selected molecular function terms (see all 14):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0001077RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription ISS--
    GO:0001102RNA polymerase II activating transcription factor binding ISS--
    GO:0003677DNA binding IDA10551874
    GO:0003700sequence-specific DNA binding transcription factor activity IDA10330009
    GO:0003705RNA polymerase II distal enhancer sequence-specific DNA binding transcription factor activity IEA--
         
    HNF4A for ontologies           About GeneDecksing


    Phenotypes:
         1 GenomeRNAi human phenotype for HNF4A:
     Increased G1 DNA content 

         8 MGI mutant phenotypes (inferred from 10 alleles(MGI details for Hnf4a):
     cellular  embryogenesis  growth/size/body  homeostasis/metabolism  liver/biliary system 
     mortality/aging  nervous system  normal 

    HNF4A for phenotypes           About GeneDecksing

    Animal Models:
         MGI mouse knock-outs for HNF4A: Hnf4atm1.2Gonz Hnf4atm1Dnl

       inGenious Targeting Laboratory: Let us create your new Knockout/Knockin mouse model for HNF4A
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       genOway customized KO model: permanent, tissue-specific or time-controlled inactivation for HNF4A
       genOway customized Knockin model: humanization, point mutation, expression monitoring, etc. for HNF4A

    Transcription Factor Targeting: 
    Targeting motifs: HOMER Transcription Factor Regulatory Elements motif viewer 
                                          Consensus sequence:  CAGAGGNCAAAGTCCA 

    miRNA
    Products:
        
    miRTarBase miRNAs that target HNF4A:
    hsa-mir-34c-5p (MIRT006263), hsa-mir-24-3p (MIRT003355), hsa-mir-765 (MIRT006266), hsa-mir-34b-5p (MIRT006265), hsa-mir-629-5p (MIRT006542), hsa-mir-197-3p (MIRT003822), hsa-mir-766-3p (MIRT006264), hsa-mir-34a-5p (MIRT003356), hsa-mir-449a (MIRT006262)

    Block miRNA regulation of human, mouse, rat HNF4A using miScript Target Protectors
    4 qRT-PCR Assays for microRNAs that regulate HNF4A:
    hsa-miR-374a* hsa-miR-185* hsa-miR-26b* hsa-miR-378*
    SwitchGear 3'UTR luciferase reporter plasmids (see all 2): HNF4A 3' UTR sequence
    Inhib. RNA
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    Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for HNF4A


    (According to UniProtKB, COMPARTMENTS Subcellular localization database, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Subcellular locations from UniProtKB/Swiss-Prot
    HNF4A_HUMAN, P41235: Nucleus
    Subcellular locations from COMPARTMENTS: 

    CompartmentConfidence
    nucleus5
    cytoskeleton2
    cytosol2
    extracellular2
    peroxisome2
    plasma membrane2
    golgi apparatus1
    mitochondrion1

    Gene Ontology (GO): 3 cellular component terms:    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005634nucleus IDA14563941
    GO:0005654nucleoplasm TAS--
    GO:0005737cytoplasm IDA14563941

    HNF4A for ontologies           About GeneDecksing


    (SuperPaths according to PathCards, Pathways according to R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Sino Biological, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to QIAGEN, and/or STRING, Interactions according to 1UniProtKB, 2MINT, 3I2D, and/or 4STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene).
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    SuperPaths for HNF4A About   (see all 22)  
    See pathways by source

    SuperPathContained pathways About
    1Regulation of beta-cell development
    Regulation of beta-cell development0.64
    Maturity onset diabetes of the young0.61
    Regulation of gene expression in beta cells0.64
    2Nuclear Receptor transcription pathway
    Nuclear Receptor transcription pathway0.67
    Nuclear Receptors0.67
    3Human Embryonic Stem Cell Pluripotency
    Factors Promoting Cardiogenesis in Vertebrates0.50
    Human Embryonic Stem Cell Pluripotency0.50
    4ERK Signaling
    MAPK Signaling0.58
    ILK Signaling0.49
    5Gene Expression
    Generic Transcription Pathway0.40
    Gene Expression0.40

    Pathways by source                                                                                                                                                                 See SuperPaths
    Show all pathways

    1 R&D Systems Pathway for HNF4A
        TGF-beta Signaling Pathways

    Selected Downloadable PowerPoint Slides of GeneGlobe Pathway Central Maps for HNF4A (see all 10)
        MAPK Signaling
    Factors Promoting Cardiogenesis in Vertebrates
    HIF1Alpha Pathway
    JNK Pathway
    Epithelial Adherens Junctions

    1 Cell Signaling Technology (CST) Pathway for HNF4A
        Glucose / Energy Metabolism

    1 GeneGo (Thomson Reuters) Pathway for HNF4A
        Dichloroethylene metabolism

    Selected BioSystems Pathways for HNF4A (see all 7)
        Nuclear Receptors
    AMPK signaling
    TGF-beta Receptor Signaling Pathway
    Integrated Pancreatic Cancer Pathway
    Regulation of nuclear SMAD2/3 signaling


    2 Reactome Pathways for HNF4A
        Regulation of gene expression in beta cells
    Nuclear Receptor transcription pathway

    1 PharmGKB Pathway for HNF4A
        Anti-diabetic Drug Potassium Channel Inhibitors Pathway, Pharmacodynamics

    1 Kegg Pathway  (Kegg details for HNF4A):
        Maturity onset diabetes of the young


    HNF4A for pathways           About GeneDecksing

        Pathway & Disease-focused RT2 Profiler PCR Arrays including HNF4A (see all 6): 
              Cell Lineage Identification in human mouse rat
              Transcription Factors in human mouse rat
              Nuclear Receptors & Coregulators in human mouse rat
              Hypoxia Signaling Pathway in human mouse rat
              Fatty Liver in human mouse rat

    Interactions:

        GeneGlobe Interaction Network for HNF4A

    STRING Interaction Network Preview (showing 5 interactants - click image to see 25)

    Selected Interacting proteins for HNF4A (P412351, 2, 3 ENSP000003129874) via UniProtKB, MINT, STRING, and/or I2D (see all 120)
    InteractantInteraction Details
    GeneCardExternal ID(s)
    FOXO6A8MYZ61, 2EBI-1049011,EBI-8531039 MINT-8430144 MINT-8429213
    CITED2Q999671, 2, 3, ENSP000003566234EBI-1049011,EBI-937732 MINT-6175330 MINT-6175313 MINT-6175350 I2D: score=1 STRING: ENSP00000356623
    SREBF2Q127722, 3, ENSP000003544764MINT-16696 MINT-16697 I2D: score=3 STRING: ENSP00000354476
    FOXO1Q127783, ENSP000003688804I2D: score=3 STRING: ENSP00000368880
    PPARGC1AQ9UBK23, ENSP000002648674I2D: score=3 STRING: ENSP00000264867
    About this table

    Gene Ontology (GO): Selected biological process terms (see all 27):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0006355regulation of transcription, DNA-templated ----
    GO:0006357regulation of transcription from RNA polymerase II promoter IMP18163890
    GO:0006367transcription initiation from RNA polymerase II promoter TAS--
    GO:0006591ornithine metabolic process IMP17827783
    GO:0006629lipid metabolic process IEA--

    HNF4A for ontologies           About GeneDecksing



    (Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience, ApexBio, HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB)
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    Browse Small Molecules at EMD Millipore
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    Browse Tocris compounds for HNF4A

    1 DrugBank Compound for HNF4A    About this table
    CompoundSynonyms CAS #TypeActionsPubMed Ids
    MYRISTIC ACID-- --target--10592235

    1 IUPHAR Ligand for HNF4A (Hepatocyte nuclear factor-4-alpha)    About this table
    LigandTypeActionAffinityPubmed IDs
    linoleic acid
    AgonistFull agonist19440305

    Selected Novoseek inferred chemical compound relationships for HNF4A gene (see all 63)    About this table
    Compound   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    hmtp 74.3 40 15547294 (2), 16226723 (2)
    androstane 73.8 20 17576804 (2), 19058292 (1), 19690166 (1), 17595319 (1) (see all 13)
    glycogen 57.6 15 11915024 (2), 12808453 (1), 16352701 (1), 7508874 (1) (see all 11)
    chenodeoxycholic acid 57.1 14 15337761 (2), 16436500 (2), 11402042 (2), 15692145 (2) (see all 5)
    gw 4064 55.7 1 15692145 (1)
    sterol 51.9 10 12957378 (1), 16368706 (1), 14685799 (1), 17403900 (1) (see all 8)
    phosphoenolpyruvate 49.9 12 19252740 (1), 7508874 (1), 15468681 (1), 16488887 (1) (see all 9)
    retinoic acid 46.7 30 10799735 (4), 8288643 (3), 9792724 (3), 9886825 (2) (see all 12)
    glucose 41.2 80 9812974 (3), 11916906 (3), 20382893 (2), 9371825 (2) (see all 47)
    cholesterol 36.4 28 18080173 (2), 14748721 (2), 11535594 (1), 15123688 (1) (see all 20)



    HNF4A for compounds           About GeneDecksing



    (Secondary structures according to fRNAdb,
    GenBank/EMBL/DDBJ Accessions according to
    Unigene (Build 236 Homo sapiens; Apr 25 2013) or GenBank,
    RefSeq according to Entrez Gene,
    DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
    Conferences by KenesGroup, exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
    siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN, SwitchGear Genomics,
    Tagged/untagged cDNA clones from OriGene, GenScript, DNA2.0, Vector BioLabs, Primers from OriGene, and/or QIAGEN )
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    REFSEQ mRNAs for HNF4A gene (10 alternative transcripts): 
    NM_000457.4  NM_001030003.2  NM_001030004.2  NM_001258355.1  NM_001287182.1  NM_001287183.1  NM_001287184.1  NM_175914.4  
    NM_178849.2  NM_178850.2  

    Unigene Cluster for HNF4A:

    Hepatocyte nuclear factor 4, alpha
    Hs.116462  [show with all ESTs]
    Unigene Representative Sequence: NM_001258355
    8 Ensembl transcripts including schematic representations, and UCSC links where relevant:
    ENST00000316673 ENST00000609795 ENST00000457232(uc010zwo.1) ENST00000609262
    ENST00000372920(uc010ggq.3) ENST00000443598(uc002xlt.3 uc002xly.3)
    ENST00000316099(uc002xlv.3 uc002xma.3) ENST00000415691(uc002xlu.3 uc002xlz.3)

    Congresses - knowledge worth sharing:
    European Congress of Clinical Microbiology and Infectious Diseases (ECCMID) 10 - 13 May 2014

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    SwitchGear 3'UTR luciferase reporter plasmids (see all 2): HNF4A 3' UTR sequence
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      QuantiTect SYBR Green Assays in human, mouse, rat HNF4A
      QuantiFast Probe-based Assays in human, mouse, rat HNF4A

    Additional mRNA sequence: 

    AB307703.1 AY680696.1 AY680697.1 AY680698.1 BC137539.1 BC137540.1 FJ608822.1 HQ692860.1 
    HQ692868.1 HQ692869.1 X76930.1 X87870.1 X87871.1 X87872.1 Z49825.1 

    12 DOTS entries:

    DT.100756991  DT.107774  DT.452485  DT.87046459  DT.120822103  DT.100756993  DT.95363008  DT.120822062 
    DT.120822074  DT.75128134  DT.435193  DT.92414368 

    Selected AceView cDNA sequences (see all 33):

    NM_178849 AI052807 AI631717 AI033279 AI301528 NM_178850 AY680696 BE221792 
    AY680698 AV658197 BF062005 CB161598 AY680697 NM_000457 BF766102 Z49825 
    AW082799 X87872 X87871 X76930 AI056785 BX112336 CB163279 AI140507 

    GeneLoc Exon Structure


    (RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, Protein expression images according to data from SPIRE 1MOPED, 2PaxDb, and 3MaxQB, plus additional links to SOURCE, and/or BioGPS, and/or UniProtKB,
    PCR Arrays from QIAGEN, Primers from OriGene, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
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    HNF4A expression in normal human tissues (normalized intensities)
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS <intensity>2/3
    CGAP TAG: --
    HNF4A Expression
    About this image


    HNF4A expression in embryonic tissues and stem cells    About this table
    Data from LifeMap, the Embryonic Development and Stem Cells Database
     selected tissues (see all 18) fully expand
     
     Liver (Hepatobiliary System)    fully expand to see all 17 entries
             Hepatic Endoderm Cells Ventral Foregut Endoderm
             Hepatic progenitor cells
     
     Pancreas (Endocrine System)    fully expand to see all 10 entries
             Endocrine Progenitor Cells Ventral Pancreatic Bud
             Pancreatic progenitor-like cells
     
     Epithelial Cells
             Hepatic Endoderm Cells Ventral Foregut Endoderm
     
     Gut Tube (Gastrointestinal Tract)    fully expand to see all 4 entries
             Hepatic Endoderm Cells Ventral Foregut Endoderm
             Midgut
             Anterior foregut progenitor cells
     
     NULL (Uncategorized)    fully expand to see all 7 entries
             Primitive gut tube-like cells
    HNF4A Protein expression data from MOPED1, PaxDb2 and MaxQB3    About this image

    HNF4A Protein Expression

    SOURCE GeneReport for Unigene cluster: Hs.116462
        Pathway & Disease-focused RT2 Profiler PCR Arrays including HNF4A (see all 6): 
              Cell Lineage Identification in human mouse rat
              Transcription Factors in human mouse rat
              Nuclear Receptors & Coregulators in human mouse rat
              Hypoxia Signaling Pathway in human mouse rat
              Fatty Liver in human mouse rat

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    (Orthologs according to 1,2HomoloGene (2older version, for species not in 1newer version), 3euGenes, 4SGD , 5MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or 6Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
    About This Section

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    This gene was present in the common ancestor of animals.

    Orthologs for HNF4A gene from Selected species (see all 16)    About this table
    Organism Taxonomic
    classification
    Gene Description Human
    Similarity
    Orthology
    Type
    Details
    mouse
    (Mus musculus)
    Mammalia Hnf4a1 , 5 hepatic nuclear factor 4, alpha1, 5 89.73(n)1
    95.78(a)1
      2 (84.32 cM)5
    153781  NM_008261.21  NP_032287.21 
     1635068085 
    chicken
    (Gallus gallus)
    Aves HNF4A1 hepatocyte nuclear factor 4, alpha 82.16(n)
    87.89(a)
      419198  NM_001030855.1  NP_001026026.1 
    lizard
    (Anolis carolinensis)
    Reptilia HNF4A6
    hepatocyte nuclear factor 4, alpha
    86(a)
    1 ↔ 1
    4(144113117-144141514)
    African clawed frog
    (Xenopus laevis)
    Amphibia hnf4-prov2 hepatic nuclear factor 4 76.87(n)    Z37526.1 
    zebrafish
    (Danio rerio)
    Actinopterygii hnf4a2 hepatocyte nuclear factor 4, alpha 75.61(n)   322358  BC056550.1 
    fruit fly
    (Drosophila melanogaster)
    Insecta Hnf46
    Hepatocyte nuclear factor 4
    35(a)
    1 → many
    2L(8687281-8709038)
    worm
    (Caenorhabditis elegans)
    Secernentea nhr-646
    nhr-696
    (see all 3)
    Protein NHR-69 (nhr-69) mRNA, complete cds
    (see all 3)
    42(a)
    38(a)
    (see all 3)
    many ↔ many
    many ↔ many
    (see all 3)
    I(3104363-3109542) WBGene00003654
    I(9879189-9881504) WBGene00003659


    ENSEMBL Gene Tree for HNF4A (if available)
    TreeFam Gene Tree for HNF4A (if available)

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
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    Paralogs for HNF4A gene
    RXRA2  RXRG2  NR2F12  NR2F22  HNF4G2  NR2C12  NR2F62  NR2E12  
    RXRB2  NR2C22  
    Selected SIMAP similar genes for HNF4A using alignment to 3 protein entries:     HNF4A_HUMAN (see all proteins) (see all similar genes):
    HNF4alpha    NR2A1    HNF4G    NR2A2    NR2A3    NR2B2
    RXRB    NR2B1    NR2B3    RXRG    RXRA    NR2F2
    NR2F1    NR2F6    ESRRG    NR3B3    NR2E1    NR2E3

    HNF4A for paralogs           About GeneDecksing



    (SNPs/Variants according to the 1NCBI SNP Database, 2Ensembl, 3PupaSUITE, 4UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD), the Human Cytochrome P450 Allele Nomenclature Database, and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers, Cancer Mutation PCR Arrays and Assays, and Copy Number PCR Arrays from QIAGEN)
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    Selected SNPs for HNF4A (see all 1899)    About this table    
    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr 20 posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    rs1378533361,2,,4
    CMaturity-onset diabetes of the young 1 (MODY1)4 pathogenic143013019(+) GGGACC/TGGATC 14 R W mis10--------
    VAR_0106014
    Maturity-onset diabetes of the young 1 (MODY1)4--see VAR_0106012 E Q mis40--------
    rs617371451,2
    C,Fnon-pathogenic143027713(+) ACCAAC/TGTCAT 10 N syn13Minor allele frequency- T:0.00NS NA EU 5919
    rs412820261,2
    C,Fprobable-non-pathogenic143005400(+) AACGCG/ACCCAA 14 /A syn12Minor allele frequency- A:0.00NA EU 5637
    rs1939224731,2
    Cprobable-non-pathogenic143013060(+) AGCCTA/GCCCTC 14 L syn10--------
    rs1133080871,2
    C,Fprobable-non-pathogenic143013072(+) ATCAAT/CGCGCT 14 /N syn12Minor allele frequency- C:0.01CSA NA 4548
    rs1500789781,2
    C,Fprobable-non-pathogenic143019051(+) CGGCAC/TTGCCC 14 H syn11Minor allele frequency- T:0.01NA 4552
    rs60315921,2
    C,F,Hprobable-non-pathogenic143019099(+) CTTGAC/TGAGCT 14 D syn1 ese37Minor allele frequency- T:0.00NS EA CSA NA 4974
    rs1815590881,2
    Cprobable-non-pathogenic143023336(+) GGGCTA/GAGCGA 14 L syn10--------
    rs1401462231,2
    Cprobable-non-pathogenic143023420(+) GACTCA/G/TCGTGG 14 S syn11NA 4512

    HapMap Linkage Disequilibrium report for HNF4A (42984340 - 43061485 bp)

    Structural Variations
         Database of Genomic Variants (DGV) 3 variations for HNF4A:    About this table    
    Variant IDTypeSubtypePubMed ID
    esv2663976CNV Deletion23128226
    esv2504273CNV Insertion19546169
    nsv819556CNV Insertion19587683

    Human Gene Mutation Database (HGMD): HNF4A
    Locus Specific Mutation Databases (LSDB): HNF4A

    Site Specific Mutation Identification with PCR Assays
    SeqTarget long-range PCR primers for resequencing HNF4A
    DNA2.0 Custom Variant and Variant Library Synthesis for HNF4A

    (in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Conferences by KenesGroup, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
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    OMIM gene information: 600281   
    OMIM disorders: 125850  125853  
    UniProtKB/Swiss-Prot: HNF4A_HUMAN, P41235
  • Maturity-onset diabetes of the young 1 (MODY1) [MIM:125850]: A form of diabetes that is characterized by
    an autosomal dominant mode of inheritance, onset in childhood or early adulthood (usually before 25 years of
    age), a primary defect in insulin secretion and frequent insulin-independence at the beginning of the disease.
    Note=The disease is caused by mutations affecting the gene represented in this entry
  • Diabetes mellitus, non-insulin-dependent (NIDDM) [MIM:125853]: A multifactorial disorder of glucose
    homeostasis caused by a lack of sensitivity to the body's own insulin. Affected individuals usually have an obese
    body habitus and manifestations of a metabolic syndrome characterized by diabetes, insulin resistance,
    hypertension and hypertriglyceridemia. The disease results in long-term complications that affect the eyes,
    kidneys, nerves, and blood vessels. Note=Disease susceptibility may be associated with variations affecting the
    gene represented in this entry

  • Selected diseases for HNF4A (see all 75):    
    About MalaCards
    monogenic diabetes    hnf4a-related hyperinsulinism    hyperinsulinism due to hnf4a deficiency    maturity-onset diabetes of the young, type 1
    maturity-onset diabetes of the young, type 3    factor vii deficiency    familial hyperinsulinism    hyperinsulinism
    strabismus    insulin resistance    hepatitis    maturity-onset diabetes of the young
    diabetes mellitus, noninsulin-dependent    hemophilia b    type 2 diabetes mellitus    hyperinsulinemic hypoglycemia
    diabetic ketoacidosis    hypoglycemia    diabetes mellitus    ureteral obstruction

    4 diseases from the University of Copenhagen DISEASES database for HNF4A:
    maturity-onset diabetes of the young     Diabetes mellitus     Colorectal cancer     Familial adenomatous polyposis

    HNF4A for disorders           About GeneDecksing

    Selected Novoseek inferred disease relationships for HNF4A gene (see all 70)    About this table

    Disease   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    niddm 79.9 191 9267996 (5), 9029679 (4), 10983627 (3), 9133559 (3) (see all 99)
    familial adenomatous polyposis 68.5 12 11774242 (1), 17005722 (1), 9065401 (1), 10987283 (1) (see all 11)
    colon cancer 54.3 17 16151476 (3), 14566053 (2), 15930030 (1), 17005722 (1) (see all 14)
    hepatoblastoma 53 4 19200579 (2), 17047077 (1), 19336534 (1)
    hyperglycemia 47.7 7 16444761 (1), 11984998 (1), 10905494 (1), 9356021 (1) (see all 6)
    colon carcinoma 46.8 5 11774242 (1), 12901858 (1), 9065401 (1), 8288643 (1) (see all 5)
    cholestasis 43.8 2 19239393 (1)
    embryonal tumor 41.2 1 11956596 (1)
    neonatal hypoglycemia 40.1 6 17407387 (2), 20164212 (1), 17891372 (1)
    diabetes mellitus 38.8 22 7951673 (2), 17563455 (2), 11590126 (1), 14654354 (1) (see all 15)

    Genetic Association Database (GAD): HNF4A
    Human Genome Epidemiology (HuGE) Navigator: HNF4A (76 documents)

    Export disorders for HNF4A gene to outside databases

    (in PubMed. Associations of this gene to articles via 1Entrez Gene, 2UniProtKB/Swiss-Prot, 3HGNC, 4GAD, 5PharmGKB, 6HMDB, 7DrugBank, 8UniProtKB/TrEMBL, 9 Novoseek, and/or 10fRNAdb)
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    PubMed articles for HNF4A gene, integrated from 10 sources (see all 937):
    (articles sorted by number of sources associating them with HNF4A)
        Utopia: connect your pdf to the dynamic
    world of online information

    1. Mutations in the hepatocyte nuclear factor-4alpha gene in maturity- onset diabetes of the young (MODY1). (PubMed id 8945471)1, 2, 4, 9 Yamagata K.... Bell G.I. (Nature 1996)
    2. Cloning and sequencing of cDNAs encoding the human hepatocyte nuclear factor 4 indicate the presence of two isoforms in human liver. (PubMed id 7926813)1, 2, 3 Chartier F.L.... Laine B. (Gene 1994)
    3. Mutations of maturity-onset diabetes of the young (MODY) genes in Thais with early-onset type 2 diabetes mellitus. (PubMed id 18811724)1, 4, 9 Plengvidhya N....Yenchitsomanus P.T. (Clin. Endocrinol. (Oxf) 2009)
    4. Molecular genetics and phenotypic characteristics of MODY caused by hepatocyte nuclear factor 4alpha mutations in a large European collection. (PubMed id 15830177)1, 4, 9 Pearson E.R....Hattersley A.T. (Diabetologia 2005)
    5. Variants in hepatocyte nuclear factor 4alpha are modestly associated with type 2 diabetes in Pima Indians. (PubMed id 16186411)1, 4, 9 Muller Y.L....Baier L.J. (Diabetes 2005)
    6. Studies of the genetic variability of the coding region of the hepatocyte nuclear factor-4alpha in Caucasians with maturity onset NIDDM. (PubMed id 9267996)1, 2, 9 Moeller A.M.... Pedersen O. (Diabetologia 1997)
    7. Diazoxide-responsive hyperinsulinemic hypoglycemia caused by HNF4A gene mutations. (PubMed id 20164212)1, 4, 9 Flanagan S.E....Ellard S. (Eur. J. Endocrinol. 2010)
    8. Genetic polymorphism of hepatocyte nuclear factor-4alpha influences human cytochrome P450 2D6 activity. (PubMed id 18666237)1, 4, 9 Lee S.S....Shin J.G. (Hepatology 2008)
    9. Genetic predictors of interindividual variability in hepatic CYP3A4 expression. (PubMed id 19934400)1, 4, 9 Lamba V....Schuetz E.G. (J. Pharmacol. Exp. Ther. 2010)
    10. PXR, CAR and HNF4alpha genotypes and their association with pharmacokinetics and pharmacodynamics of docetaxel and doxorubicin in Asian patients. (PubMed id 17876342)1, 4, 9 Hor S.Y....Tan T. (Pharmacogenomics J. 2008)

    (in PubMed, OMIM, and NCBI Bookshelf)
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     ANDOR
    Aliases
    Disorders
    Free Text  

      Query String
    PubMed
    OMIM
    NCBI Bookshelf
      (Note: In FireFox, select the above section and copy using Ctrl-C)

    (According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
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    Entrez Gene: 3172 HGNC: 5024 AceView: HNF4A Ensembl:ENSG00000101076 euGenes: HUgn3172
    ECgene: HNF4A Kegg: 3172 H-InvDB: HNF4A

    (According to HUGE)
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      --

    (According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, UniProtKB/TrEMBL, and/or others, e.g. Wikipedia and GeneReviews, via UniProtKB/Swiss-Prot)
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    NameDescription
    PharmGKB entry for HNF4A Pharmacogenomics, SNPs, Pathways
    GeneReviewshttp://www.ncbi.nlm.nih.gov/books/NBK1116/?term=HNF4A[genesymbol]
    Wikipedia http://en.wikipedia.org/wiki/Hepatocyte_nuclear_factors
    SeattleSNPshttp://pga.gs.washington.edu/data/hnf4a/

    (Patent information from GeneIP,
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    Patent Information for HNF4A gene:
    Search GeneIP for patents involving HNF4A

    GeneCards and IP:
    Japan Patent Office Licenses GeneCards     European Patent Office Licenses GeneCards     Improving the IP Search



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