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FLASH GENE
Symbol HNF4A contributors: mct/npt/pgu - updated : 28-02-2019
HGNC name hepatocyte nuclear factor 4, alpha
HGNC id 5024
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
  • HES6 subsequently represses HNF4A (HNF-4A)-activated PPARG gene expression by direct inhibition of HNF4A transcriptional activity
  • 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
  • HNF4A contributes to the transcriptional regulation of SLC2A9
  • Hippo signaling may affect hepatocyte differentiation by influencing HNF4A and FOXA2 interactions with temporal enhancers
  • HNF4A is a regulatory factor that bound endogenous CLDN7 promoter in differentiating intestinal epithelial cell (IEC) and stimulated CLDN7 promoter activity
  • HNF4A is a major transcriptional regulator of SLC22A9
  • HNF4A is a vital transcription factor in the SHBG synthesis process
    • 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)
    constitutional germinal mutation     loss of function
    dominant inactivating mutations in children with transient, diazoxide-responsive hyperinsulinism (HI) without clear history of perinatal stress
    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