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