HNF1A Gene: Hepatocyte Nuclear Factor 1 Homeobox A
A master regulator of pancreatic beta-cell function and monogenic diabetes
Gene Information Card
| Symbol | HNF1A |
|---|---|
| Full Name | HNF1 homeobox A |
| Gene Type | protein-coding |
| Chromosomal Location | 12q24.31 |
| NCBI Gene ID | 6927 ncbi.nlm.nih.gov/gene/6927 |
| Ensembl ID | ENSG00000135100 |
| UniProt ID | P20823 |
| OMIM ID | 142410 |
| HGNC ID | 11630 |
| Aliases | HNF1, MODY3, TCF1, LFB1 |
Description
The HNF1A gene encodes hepatocyte nuclear factor 1 homeobox A, a transcription factor that regulates the expression of genes involved in glucose metabolism, lipid metabolism, and pancreatic beta-cell differentiation. It is critical for normal insulin secretion and glucose homeostasis. Mutations in HNF1A cause maturity-onset diabetes of the young type 3 (MODY3), a monogenic form of diabetes characterized by early-onset, non-insulin-dependent diabetes. HNF1A also plays roles in liver and kidney function.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Maturity-Onset Diabetes of the Young Type 3 (MODY3) | Heterozygous loss-of-function mutations in HNF1A impair beta-cell function, leading to progressive insulin secretory defect. | ClinVar, OMIM |
| Hepatocellular Carcinoma | Somatic mutations or altered expression of HNF1A may contribute to liver tumorigenesis, though evidence is limited. | COSMIC, literature |
| Renal Cysts and Diabetes Syndrome (RCAD) | HNF1A mutations can cause renal cysts and diabetes, often overlapping with MODY3 phenotype. | OMIM, ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Pancreas | 12.3 | High |
| Liver | 8.7 | Medium |
| Kidney | 5.2 | Medium |
| Small Intestine | 4.1 | Low |
| Stomach | 2.3 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| INS-1 (rat insulinoma) | 25.4 | Beta-cell model, high expression |
| HepG2 (human hepatoma) | 15.2 | Liver-derived, high expression |
| Caco-2 (human colorectal) | 6.8 | Intestinal, moderate expression |
| HEK293 (human embryonic kidney) | 1.2 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| p.Arg263Cys | Missense | Rare (found in MODY3 families) | Loss of DNA-binding activity, reduced transactivation |
| p.Arg159Trp | Missense | Rare | Impaired dimerization and DNA binding |
| c.872dupG | Frameshift | Rare | Premature truncation, loss of function |
| p.Gly292Ser | Missense | Rare | Reduced transcriptional activity |
Mutation functional classification
Loss of Function (LOF)
Most HNF1A mutations are loss-of-function, leading to haploinsufficiency or dominant-negative effects, impairing beta-cell function.
Gain of Function (GOF)
No clear gain-of-function mutations reported; HNF1A acts as a tumor suppressor in some contexts.
Dominant Negative (DN)
Some missense mutations in the dimerization or DNA-binding domains exert dominant-negative effects by interfering with the wild-type allele.
View complete mutation data：
Gene Ontology (GO)
| • DNA-binding transcription factor activity | • RNA polymerase II cis-regulatory region sequence-specific DNA binding |
| • protein dimerization activity | • regulation of transcription by RNA polymerase II |
| • glucose homeostasis | • pancreas development |
Pathways
• Maturity onset diabetes of the young
• Type II diabetes mellitus
• Transcriptional regulation by HNF1A
• Insulin secretion
Protein Summary
HNF1A is a 631-amino acid transcription factor containing an N-terminal dimerization domain, a DNA-binding domain with POU-like and homeodomain regions, and a C-terminal transactivation domain. It binds to inverted palindromic DNA sequences as a homodimer or heterodimer with HNF1B. It regulates genes involved in glucose transport (e.g., SLC2A2), insulin secretion (e.g., KCNJ11), and lipid metabolism (e.g., APOA2). Post-translational modifications include phosphorylation and acetylation, which modulate its activity.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| HNF1A Knockout HEK293 Cell Line | EDJ-KQ5894 | Human | 6927 | Details Get a Quote |
| HNF1A Knockout A-549 Cell Line | EDJ-KQ29397 | Human | 6927 | Details Get a Quote |
| HNF1A Knockout HeLa Cell Line | EDJ-KQ54624 | Human | 6927 | Details Get a Quote |
| HNF1A Knockout HCT 116 Cell Line | EDJ-KQ71579 | Human | 6927 | Details Get a Quote |
| HNF1A (p.L17=) Point Mutation in HAP1 Cell Line | EDC03328 | Human | 6927 | Details Get a Quote |
| HNF1A (p.I27L) Point Mutation in HAP1 Cell Line | EDC03329 | Human | 6927 | Details Get a Quote |
| HNF1A (p.T515=) Point Mutation in HAP1 Cell Line | EDC03333 | Human | 6927 | Details Get a Quote |
| HNF1A (c.326+91A>G )Point Mutation in HAP1 Cell Line | EDC03330 | Human | 6927 | Details Get a Quote |
| HNF1A (c.526+66G>C )Point Mutation in HAP1 Cell Line | EDC03331 | Human | 6927 | Details Get a Quote |
| HNF1A (c.1309+86TCAT[6] )Point Mutation in HAP1 Cell Line | EDC03332 | Human | 6927 | Details Get a Quote |
| HNF1A (c.1623+29T>C )Point Mutation in HAP1 Cell Line | EDC03334 | Human | 6927 | Details Get a Quote |
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