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FLASH GENE
Symbol HNF4A contributors: mct/npt/pgu - updated : 28-02-2015
HGNC name hepatocyte nuclear factor 4, alpha
HGNC id 5024
Corresponding disease
MODY1 maturity onset diabetes of the young, type 1
Location 20q13.12      Physical location : 42.984.440 - 43.060.029
Synonym name
  • hepatic nuclear factor 4 alpha
  • transcription factor-14
  • nuclear receptor subfamily 2 group A member 1
  • Synonym symbol(s) HNF4, NR2A21, TCF14, HNF4a7, HNF4a8, HNF4a9, FLJ39654, HNF4alpha10/11/12, NR2A1
    DNA
    TYPE functioning gene
    STRUCTURE 30.11 kb     10 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter
    Binding site   enhancer
    MAPPING cloned   linked N status confirmed
    Map cen - D20S101 - SRC - PLCG1 - HNF4A - D20S17 - D20S75 - D20S109 - qter
    Physical map
    L3MBTL 20q13.12 l(3)mbt-like (Drosophila) SGK2 20q13.2 serum/glucocorticoid regulated kinase 2 C20orf9 20q12-q13.1 chromosome 20 open reading frame 9 RPL27AP 20q13.11 ribosomal protein L27a pseudogene MYBL2 20q13.1 v-myb myeloblastosis viral oncogene homolog (avian)-like 2 C20orf65 20q13.11 chromosome 20 open reading frame 65 C20orf100 20q13.11 chromosome 20 open reading frame 100 JPH2 20q12-q13.1 junctophilin 2 C20orf111 20q13.11 chromosome 20 open reading frame 111 GDAP1L1 20q12 ganglioside-induced differentiation-associated protein 1-like 1 C20orf142 20q13.12 chromosome 20 open reading frame 142 R3HDML 20 R3H domain (binds single-stranded nucleic acids) containing-like FLJ39654 20q13.12 hypothetical protein FLJ39654 LOC149704 20q13.12 hypothetical LOC149704 HNF4A 20q12-q13.1 hepatocyte nuclear factor 4, alpha RPL37AP1 20q12 ribosomal protein L37a pseudogene 1 C20orf121 20q13.11 chromosome 20 open reading frame 121 TDE1 20q13.1-q13.3 tumor differentially expressed 1 PKIG 20q13.2-q13.13 protein kinase (cAMP-dependent, catalytic) inhibitor gamma ADA 20q12 adenosine deaminase MGC5566 20q13.12 hypothetical protein MGC5566 WISP2 20q12-q13.1 WNT1 inducible signaling pathway protein 2 KCNK15 20q12-q13 potassium channel, subfamily K, member 15 RIMS4 20 regulating synaptic membrane exocytosis 4 LOC391252 20 similar to piggyBac transposable element derived 4 YWHAB 20q13.1 tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, beta polypeptide LOC200226 20q13.12 similar to Polyadenylate-binding protein 2 (Poly(A)-binding protein 2) (PABP 2) TOMM34 20q12-q13.11 translocase of outer mitochondrial membrane 34 STK4 20q11.2-q13.2 serine/threonine kinase 4 KCNS1 20q12 potassium voltage-gated channel, delayed-rectifier, subfamily S, member 1 WFDC5 20q13.11 WAP four-disulfide core domain 5 WFDC12 20q12-q13.1 WAP four-disulfide core domain 12 PI3 20q12-q13 protease inhibitor 3, skin-derived (SKALP) SEMG1 20q13.1 semenogelin I SEMG2 20q13.1 semenogelin II LOC149709 20q13.12 similar to RIKEN cDNA 1700049M11 SLPI 20q12-q13.2 secretory leukocyte protease inhibitor (antileukoproteinase)
    RNA
    TRANSCRIPTS type messenger
    text with the alternatively spliced isoforms HNF4A, HNF4A2, HNF4A4
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    10 - 3209 - 464 - 1998 9852068
    10 - 3239 - 474 - 1998 9852068
    8 - 1600 - 417 - 1998 9852068
    10 - 1369 - 452 - 1998 9852068
    10 - 1339 - 442 - 1998 9852068
    8 - 1192 - 395 - 1998 9852068
    EXPRESSION
    Type restricted
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveintestinelarge intestinecolon moderately Homo sapiens
     intestinesmall intestineduodenum highly Homo sapiens
     liver   moderately Homo sapiens
    Endocrinepancreas   moderately Homo sapiens
    respiratorylungbronchi   
    Urinarykidney   moderately Homo sapiens
     kidneytubuleconvoluted tubuleproximal tubule  Homo sapiens
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Epithelialsecretoryglandularendocrine  Homo sapiens
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Digestiveepithelial cell Homo sapiens
    Endocrineislet cell (alpha,beta...) Homo sapiens
    Urinaryepithelial cell Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • N terminal transactivation domain
  • a DNA binding protein
  • a potential ligand binding and dimerization domain
  • a second transactivation domain
  • mono polymer homomer , dimer
    HOMOLOGY
    Homologene
    FAMILY
  • nuclear hormone receptor family
  • NR2 subfamily
  • CATEGORY transcription factor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm
    intracellular,nucleus,nucleoplasm
    intracellular,nucleus,chromatin/chromosome
    basic FUNCTION
  • transcription factor 4, controlling the development of hepatic epithelium and liver morphogenesis
  • sex hormones-binding globulin
  • plays an essential role in the development and function of vertebrate organs, including hepatocytes and pancreatic beta-cells by regulating expression of multiple genes involved in organ development, nutrient transport, and diverse metabolic pathways
  • having a function in the regulation of intestinal vitamin A absorption and metabolism
  • modulates Wnt/beta-catenin signaling and controls intestinal epithelium homeostasis, cell function, and cell architecture
  • fundamental role of dynamic regulatory interactions between HNF4A, HES6, PPARA, and PPARG in the coordinated expression of genes involved in fatty acid transport and metabolism
  • plays a central role in the transdifferentiation process of hematopoietic cells into hepatocytes
  • might be important for intestinal glycolipid metabolism
  • may play a key role in intestinal lipid metabolism as well as intestinal anti-oxidative and anti-inflammatory defense mechanisms
  • hepatic HNF4a is essential for controlling the basal expression of numerous genes involved in lipid metabolism and is indispensable for maintaining normal lipid homeostasis
  • controls the expression of many critical metabolic pathways, and the Mediator complex occupies a central role in recruiting RNA polymerase II (Pol II) to these gene promoters
  • acting not only as a global player in many cellular processes, but also as one of the components of inflammatory response in the liver
  • both HNF4A activator and repressor functions are necessary for the identity of hepatocytes
  • essential for specification of hepatic progenitor cells by establishing the expression of the network of transcription factors that controls the onset of hepatocyte cell fat
  • HNF4A is likely involved in maintenance of the ER
  • CELLULAR PROCESS nucleotide, transcription, regulation
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism carbohydrate
    signaling
    a component
    INTERACTION
    DNA binding
    RNA
    small molecule
    protein
  • interacting with HNF1A for regulation of gene activity and chromatin structure of serpin cluster (PI)
  • interacting with CYP8B1 for its transcription and its repression by bile acids
  • interaction with RBP2 (regulates RBP2)
  • interacts with other hepatocyte nuclear factors in regulating transthyretin gene expression
  • interacting with MED25 (MED25, an associated member of the Mediator complex, is required for the association of HNF4A with Mediator, its several cofactors, and RNA Pol II)
  • HNF4A, in cooperation with its target HNF1A, directly inhibits transcription of the EMT (epithelial-to-mesenchymal transition) master regulatory genes SNAI1, SNAI2, and HMGA2 and of several mesenchymal markers
  • ANKS4B is a target of HNF4A in pancreatic beta-cells
  • HNF4A regulates liver type fatty acid binding protein (FABP1) gene expression
  • NR3C1-induced expression of HNF4A may likely contribute to indirect SLC22A1 gene up-regulation by dexamethasone in primary human hepatocytes, but not in hepatocyte-derived tumor cell lines
  • Hippo signaling may affect hepatocyte differentiation by influencing HNF4A and FOXA2 interactions with temporal enhancers
  • cell & other
    REGULATION
    activated by GATA6 for establishment of the endodermally derived bronchial epithelium
    inhibited by the activation of the ERK1/2 cascade
    Other coexpressed with TCF1
    multiple post-translational modifications were identified in HNF4A and unexpected role of an HNF4A acetylation could be uncovered
    ASSOCIATED DISORDERS
    corresponding disease(s) MODY1
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional germinal mutation      
    in diazoxide responsive congenital hyperinsulinism (CHI)
    Susceptibility to type 2 diabetes mellitus
    Variant & Polymorphism SNP
  • associated with the risk of type 2 diabetes mellitus
  • late-onset diabetes mutation, -192C>G, impair the function of the HNF4A P2
  • Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    digestiveliver 
    may serve as novel targets for the treatment of liver fibrosis
    ANIMAL & CELL MODELS
    in the intestines of adult mice, loss of Hnf-4alpha led to an increased proliferation in crypts and to an increased expression of several genes controlled by the Wnt/beta-catenin system