Hepatocyte nuclear factor 4 alpha

Hepatocyte nuclear factor 4 alpha (HNF4A) also known as NR2A1 (nuclear receptor subfamily 2, group A, member 1) is a is_associated_with::nuclear receptor that in humans is encoded by the HNF4A gene.

Function
HNF-4α is a nuclear is_associated_with::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 involved_in_development_of::liver, involved_in_development_of::kidney, and involved_in_development_of::intestines. Alternative splicing of this gene results in multiple transcript variants.

HNF4A is required for the PXR and CAR-mediated transcriptional activation of is_associated_with::CYP3A4.

The alkaloid is_associated_with::berberine upregulates the expression of HNF4A.

This gene also plays a pivotal role in the expression and synthesis of is_associated_with::SHBG, an important is_associated_with::glycoprotein made primarily in the is_associated_with::liver, which in addition to lowering insulin-resistance also serves in reducing levels of free is_associated_with::Oestrogen as-well as prolonging the half-life of is_associated_with::Testosterone.

Clinical significance
Mutations in this gene have been associated with monogenic autosomal dominant non-insulin-dependent is_associated_with::diabetes mellitus type I. Recently, the Clinical Proteomic Tumor Analysis Consortium identified increased amplification of Hepatocyte nuclear factor 4 alpha in colorectal cancer.

Interactions
Hepatocyte nuclear factor 4 alpha has been shown to interact with:
 * is_associated_with::Beta-catenin,
 * is_associated_with::CREB binding protein,
 * is_associated_with::MED1,
 * is_associated_with::MED14,
 * is_associated_with::Small heterodimer partner
 * is_associated_with::Testicular receptor 4,