HNF4A
Hepatocyte Nuclear Factor 4 Alpha: A Master Regulator of Hepatic and Pancreatic Gene Expression
Gene Information Card
| Symbol | HNF4A |
|---|---|
| Full Name | Hepatocyte Nuclear Factor 4 Alpha |
| Gene Type | Protein coding |
| Chromosomal Location | 20q13.12 |
| NCBI Gene ID | 3172 ncbi.nlm.nih.gov/gene/3172 |
| Ensembl ID | ENSG00000101076 |
| UniProt ID | P41235 |
| OMIM ID | 600281 |
| HGNC ID | 5024 |
| Aliases | HNF4, HNF4alpha, MODY1, NR2A1, TCF14 |
Description
HNF4A encodes hepatocyte nuclear factor 4 alpha, a nuclear receptor transcription factor that binds DNA as a homodimer. It is essential for liver development, hepatocyte differentiation, and the regulation of genes involved in glucose, lipid, and cholesterol metabolism. HNF4A also plays a critical role in pancreatic beta-cell function and insulin secretion. Mutations in HNF4A cause maturity-onset diabetes of the young type 1 (MODY1) and are associated with other metabolic disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Maturity-Onset Diabetes of the Young Type 1 (MODY1) | Loss-of-function mutations impair HNF4A transcriptional activity, reducing insulin secretion from pancreatic beta cells. | ClinVar, OMIM |
| Familial Hyperinsulinemic Hypoglycemia | Gain-of-function mutations increase HNF4A activity, leading to excessive insulin secretion. | ClinVar, OMIM |
| Hemochromatosis Type 4 (Ferroportin Disease) | HNF4A regulates hepcidin expression; mutations disrupt iron homeostasis. | NCBI Gene, OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 68.5 | High |
| Pancreas | 32.1 | Medium |
| Kidney | 25.4 | Medium |
| Small Intestine | 20.8 | Medium |
| Colon | 15.3 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 85.2 | Hepatocellular carcinoma cell line; high expression |
| Caco-2 | 45.6 | Colorectal adenocarcinoma cell line; moderate expression |
| PANC-1 | 30.1 | Pancreatic ductal adenocarcinoma cell line; moderate expression |
| HEK293 | 5.3 | Embryonic kidney cell line; low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| p.Arg114Trp | Missense | Rare | Reduces DNA binding and transactivation; associated with MODY1 |
| p.Arg154X | Nonsense | Rare | Premature truncation; loss of function; MODY1 |
| p.Val255Met | Missense | Rare | Impaired coactivator recruitment; MODY1 |
| p.Gly115Ser | Missense | Rare | Reduced transcriptional activity; MODY1 |
Mutation functional classification
Loss of Function (LOF)
Most MODY1-associated mutations reduce or abolish HNF4A transcriptional activity, impairing beta-cell function and insulin secretion.
Gain of Function (GOF)
Rare mutations (e.g., p.Val255Met) may enhance activity, linked to hyperinsulinemic hypoglycemia.
Dominant Negative (DN)
Some missense mutations (e.g., p.Arg114Trp) act in a dominant-negative manner, interfering with wild-type HNF4A function.
View complete mutation data：
Gene Ontology (GO)
| • DNA-binding transcription factor activity | • RNA polymerase II cis-regulatory region sequence-specific DNA binding |
| • nuclear receptor activity | • ligand-activated transcription factor activity |
| • chromatin binding | • positive regulation of transcription by RNA polymerase II |
| • liver development | • glucose homeostasis |
| • insulin secretion | • lipid metabolic process |
Pathways
• Maturity onset diabetes of the young
• Transcriptional regulation of white adipocyte differentiation
• Nuclear receptors meta-pathway
• Hepatocyte nuclear factor 4 alpha signaling
Protein Summary
HNF4A is a 474-amino-acid nuclear receptor protein containing a zinc-finger DNA-binding domain and a ligand-binding domain. It forms homodimers and binds to direct repeat response elements (DR1) in target gene promoters. HNF4A regulates expression of genes involved in gluconeogenesis, lipid metabolism, and coagulation factors. Its activity is modulated by fatty acids and coactivators such as PGC-1alpha. Post-translational modifications include phosphorylation and acetylation, affecting stability and transcriptional activity.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| HNF4A Knockout HEK293 Cell Line | EDJ-KQ1865 | Human | 3172 | Details Get a Quote |
| HNF4A Knockout HCT 116 Cell Line | EDJ-KQ20432 | Human | 3172 | Details Get a Quote |
| HNF4A Knockout A-549 Cell Line | EDJ-KQ21735 | Human | 3172 | Details Get a Quote |
| HNF4A Knockout HeLa Cell Line | EDJ-KQ53538 | Human | 3172 | Details Get a Quote |
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