HNF4A

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]

Hepatocyte Nuclear Factor 4 Alpha

Transcriptional regulator which controls the expression of hepatic genes during the transition of endodermal cells to hepatic progenitor cells, facilitating the recruitment of RNA pol II to the promoters of target genes (PubMed:30597922).

Activates the transcription of CYP2C38 (By similarity).

Represses the CLOCK-ARNTL/BMAL1 transcriptional activity and is essential for circadian rhythm maintenance and period regulation in the liver and colon cells (PubMed:30530698).

Anatomical structure development Source: GO_Central
Blood coagulation Source: BHF-UCL
Cell differentiation Source: GO_Central
Cholesterol homeostasis Source: BHF-UCL
Glucose homeostasis Source: BHF-UCL
Hepatocyte differentiation Source: InterPro
Lipid homeostasis Source: BHF-UCL
Lipid metabolic process Source: Ensembl
Negative regulation of cell growth Source: BHF-UCL
Negative regulation of cell population proliferation Source: BHF-UCL
Negative regulation of transcription, DNA-templated Source: UniProtKB
Ornithine metabolic process Source: BHF-UCL
Phospholipid homeostasis Source: BHF-UCL
Positive regulation of transcription, DNA-templated Source: BHF-UCL
Positive regulation of transcription by RNA polymerase II Source: MGI
Regulation of circadian rhythm Source: UniProtKB
Regulation of gastrulation Source: Ensembl
Regulation of growth hormone receptor signaling pathway Source: BHF-UCL
Regulation of insulin secretion Source: BHF-UCL
Regulation of lipid metabolic process Source: BHF-UCL
Regulation of transcription by RNA polymerase II Source: BHF-UCL
Response to glucose Source: BHF-UCL
Rhythmic process Source: UniProtKB-KW
Sex differentiation Source: Ensembl
Signal transduction involved in regulation of gene expression Source: Ensembl
SMAD protein signal transduction Source: Ensembl
Triglyceride homeostasis Source: BHF-UCL
Type B pancreatic cell development Source: InterPro
Xenobiotic metabolic process Source: BHF-UCL

Nucleus

Maturity-onset diabetes of the young 1 (MODY1):
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.
Diabetes mellitus, non-insulin-dependent (NIDDM):
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.
Fanconi renotubular syndrome 4 with maturity-onset diabetes of the young (FRTS4):
An autosomal dominant disease characterized by Fanconi syndrome associated with a beta cell phenotype of neonatal hyperinsulinism with macrosomia and young onset diabetes. Fanconi syndrome is a proximal tubulopathy resulting in generalized aminoaciduria, low molecular weight proteinuria, glycosuria, hyperphosphaturia and hypouricemia. Some FRTS4 patients have nephrocalcinosis, renal impairment, hypercalciuria with relative hypocalcemia, and hypermagnesemia.

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 DNA.
Acetylation at Lys-458 lowers transcriptional activation by about two-fold.