HNF4A
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1PZL, 3CBB, 3FS1, 4B7W, 4IQR
Identifiers
Aliases	HNF4A, HNF4, HNF4a7, HNF4a8, HNF4a9, HNF4alpha, MODY, MODY1, NR2A1, NR2A21, TCF, TCF14, FRTS4, Hepatocyte nuclear factor 4 alpha, TCF-14
External IDs	OMIM: 600281 MGI: 109128 HomoloGene: 395 GeneCards: HNF4A
Gene location (Human) Chr. Chromosome 20 (human)[1] Band 20q13.12 Start 44,355,700 bp[1] End 44,432,845 bp[1]
Gene location (Mouse) Chr. Chromosome 2 (mouse)[2] Band 2 H3|2 84.32 cM Start 163,348,728 bp[2] End 163,414,830 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in right lobe of liver duodenum rectum jejunal mucosa kidney islet of Langerhans body of pancreas pancreatic epithelial cell retinal pigment epithelium gallbladder Top expressed in Paneth cell left colon jejunum crypt of lieberkuhn of small intestine left lobe of liver kidney duodenum yolk sac pyloric antrum ileum More reference expression data BioGPS More reference expression data
Gene ontology Molecular function DNA binding sequence-specific DNA binding DNA-binding transcription factor activity DNA-binding transcription activator activity, RNA polymerase II-specific zinc ion binding metal ion binding steroid hormone receptor activity nuclear receptor activity protein binding transcription factor activity, RNA polymerase II distal enhancer sequence-specific binding signaling receptor binding fatty acid binding protein homodimerization activity RNA polymerase II cis-regulatory region sequence-specific DNA binding DNA-binding transcription factor activity, RNA polymerase II-specific Cellular component nucleus cytoplasm nucleoplasm Biological process triglyceride homeostasis ornithine metabolic process phospholipid homeostasis regulation of transcription, DNA-templated SMAD protein signal transduction glucose homeostasis regulation of insulin secretion lipid metabolism regulation of transcription by RNA polymerase II signal transduction involved in regulation of gene expression sex differentiation blood coagulation response to glucose transcription, DNA-templated positive regulation of transcription, DNA-templated regulation of lipid metabolic process intracellular receptor signaling pathway regulation of growth hormone receptor signaling pathway negative regulation of cell growth lipid homeostasis xenobiotic metabolic process transcription initiation from RNA polymerase II promoter regulation of gastrulation steroid hormone mediated signaling pathway positive regulation of transcription by RNA polymerase II negative regulation of cell population proliferation cholesterol homeostasis type B pancreatic cell development hepatocyte differentiation regulation of circadian rhythm negative regulation of transcription, DNA-templated rhythmic process Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 3172 15378 Ensembl ENSG00000101076 ENSMUSG00000017950 UniProt P41235 P49698 RefSeq (mRNA) NM_000457 NM_001030003 NM_001030004 NM_001258355 NM_001287182 NM_001287183 NM_001287184 NM_175914 NM_178849 NM_178850 NM_008261 NM_001312906 NM_001312907 RefSeq (protein) NP_000448 NP_001025174 NP_001025175 NP_001245284 NP_001274111 NP_001274112 NP_001274113 NP_787110 NP_849180 NP_849181 NP_001299835 NP_001299836 NP_032287 Location (UCSC) Chr 20: 44.36 – 44.43 Mb Chr 2: 163.35 – 163.41 Mb PubMed search [3] [4]
Wikidata
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Hepatocyte nuclear factor 4 alpha (HNF4A) also known as NR2A1 (nuclear receptor subfamily 2, group A, member 1) is a nuclear receptor that in humans is encoded by the HNF4A gene.^[5][6]

Function

HNF-4α is a nuclear transcription factor that 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 plays a role in development of the liver, kidney, and intestines. Alternative splicing of this gene results in multiple transcript variants.^[7]

HNF4A is required for the PXR and CAR-mediated transcriptional activation of CYP3A4.^[8] Genetic mutations in the HNF4A gene can influence the activity of HNF4α's downstream proteins such as CYP2D6, in vitro and in vivo.^[9][10]

The alkaloid berberine upregulates the expression of HNF4A.^[11]

This gene also plays a pivotal role in the expression and synthesis of SHBG, an important glycoprotein made primarily in the liver,^[12] which in addition to lowering insulin-resistance also serves in reducing levels of free Estrogen as-well as prolonging the half-life of Testosterone.^{[citation needed]}

Function of HNF4A gene can be effectively examined by siRNA knockdown based on an independent validation.^[13]

Clinical significance

Mutations in the HNF4A gene are associated with a form of diabetes called maturity onset diabetes of the young (MODY),^[14] specifically MODY 1. At least 56 disease-causing mutations in this gene have been discovered.^[15]

Increased amplification of hepatocyte nuclear factor 4 alpha has been observed in colorectal cancer.^[16]

It has also associations with the appearance of Fanconi syndrome phenotypes which occurs due to a missense mutation of the gene.^[17]

Interactions

Hepatocyte nuclear factor 4 alpha has been shown to interact with:

• Beta-catenin,^[18]
• CREB binding protein,^[19][20]
• MED1,^[21][22]
• MED14,^[21][22]
• Small heterodimer partner^[23]
• Testicular receptor 4,^[24]