Hepatocyte Nuclear Factor 4 Alpha (HNF4a)

HNF4; HNF4a7; HNF4a8; HNF4a9; MODY; MODY1; NR2A1; NR2A21; TCF; TCF14; Nuclear Receptor Subfamily 2,Group A,Member 1; Transcription factor 14

SPN	W387
HGNC	5024
MGI	109128
PubMed	21852396
RGD	2810
UniProt	P41235
Wiki	HNF4A

Hepatocyte nuclear factor 4 alpha 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. The extinction of many hepatic functions and their reexpression are correlated with the extinction and expression of hepatocyte nuclear factor-4 (HNF4).

This gene plays 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.HNF4A is required for the PXR and CAR-mediated transcriptional activation of CYP3A4.

Reference

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Gene 173:275-280(1996) [PubMed] [Europe PMC] [Abstract]

"Human hepatocyte nuclear factor 4 isoforms are encoded by distinct and differentially expressed genes."
Mol. Cell. Biol. 16:925-931(1996) [PubMed] [Europe PMC] [Abstract]

"Mutations in the hepatocyte nuclear factor-4alpha gene in maturity-onset diabetes of the young (MODY1)."
Nature 384:458-460(1996) [PubMed] [Europe PMC] [Abstract]

"The DNA sequence and comparative analysis of human chromosome 20."
Nature 414:865-871(2001) [PubMed] [Europe PMC] [Abstract]

"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]

"Cloning and sequencing of cDNAs encoding the human hepatocyte nuclear factor 4 indicate the presence of two isoforms in human liver."
Gene 147:269-272(1994) [PubMed] [Europe PMC] [Abstract]

"Recruitment of hepatocyte nuclear factor 4 into specific intranuclear compartments depends on tyrosine phosphorylation that affects its DNA-binding and transactivation potential."
Proc. Natl. Acad. Sci. U.S.A. 92:9876-9880(1995) [PubMed] [Europe PMC] [Abstract]

"AMP-activated protein kinase regulates HNF4alpha transcriptional activity by inhibiting dimer formation and decreasing protein stability."
J. Biol. Chem. 278:27495-27501(2003) [PubMed] [Europe PMC] [Abstract]

"Multiple post-translational modifications in hepatocyte nuclear factor 4alpha."
Biochem. Biophys. Res. Commun. 410:749-753(2011) [PubMed] [Europe PMC] [Abstract]

"An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome."
J. Proteomics 96:253-262(2014) [PubMed] [Europe PMC] [Abstract]

"Structural basis for HNF-4alpha activation by ligand and coactivator binding."
J. Biol. Chem. 279:23311-23316(2004) [PubMed] [Europe PMC] [Abstract]

"Organization and partial sequence of the hepatocyte nuclear factor-4-alpha/MODY1 gene and identification of a missense mutation, R127W, in a Japanese family with MODY."
Diabetes 46:1652-1657(1997) [PubMed] [Europe PMC] [Abstract]

"A missense mutation in the hepatocyte nuclear factor 4 alpha gene in a UK pedigree with maturity-onset diabetes of the young."
Diabetologia 40:859-862(1997) [PubMed] [Europe PMC] [Abstract]

"Studies of the genetic variability of the coding region of the hepatocyte nuclear factor-4alpha in Caucasians with maturity onset NIDDM."
Diabetologia 40:980-983(1997) [PubMed] [Europe PMC] [Abstract]

"A missense mutation in hepatocyte nuclear factor-4-alpha, resulting in a reduced transactivation activity, in human late-onset non-insulin-dependent diabetes mellitus."
J. Clin. Invest. 101:521-526(1998) [PubMed] [Europe PMC] [Abstract]

"Functional characterization of the MODY1 gene mutations HNF4(R127W), HNF4(V255M), and HNF4(E276Q)."
Diabetes 48:1459-1465(1999) [PubMed] [Europe PMC] [Abstract]

"Macrosomia and hyperinsulinaemic hypoglycaemia in patients with heterozygous mutations in the HNF4A gene."
PLoS Med. 4:E118-E118(2007) [PubMed] [Europe PMC] [Abstract]

"Novel presentations of congenital hyperinsulinism due to mutations in the MODY genes: HNF1A and HNF4A."
J. Clin. Endocrinol. Metab. 97:E2026-2030(2012) [PubMed] [Europe PMC] [Abstract]

"The HNF4A R76W mutation causes atypical dominant Fanconi syndrome in addition to a beta cell phenotype."
J. Med. Genet. 51:165-169(2014) [PubMed] [Europe PMC] [Abstract]