Hepatocyte nuclear factor 4 alpha

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, which in addition to lowering insulin-resistance also serves in reducing levels of free Estrogen as-well as prolonging the half-life of Testosterone.

Function of HNF4A gene can be effectively examined by siRNA knockdown based on an independent validation.[12]

Mutations in the HNF4A gene are associated with a form of diabetes called maturity onset diabetes of the young (MODY),[13] specifically MODY 1. At least 56 disease-causing mutations in this gene have been discovered.[14]

Increased amplification of hepatocyte nuclear factor 4 alpha has been observed in colorectal cancer.[15]

It has also associations with the appearance of Fanconi syndrome phenotypes which occurs due to a missense mutation of the gene.[16]

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

• Beta-catenin,[17]
• CREB binding protein,[18][19]
• MED1,[20][21]
• MED14,[20][21]
• Small heterodimer partner[22]
• Testicular receptor 4,[23]

• Hepatocyte nuclear factor 4
• Hepatocyte nuclear factors

• FactorBook HNF4A

This article incorporates text from the United States National Library of Medicine, which is in the public domain.