ONECUT1
One Cut Homeobox 1: A key transcription factor in pancreatic and hepatic development
Gene Information Card
| Symbol | ONECUT1 |
|---|---|
| Full Name | One Cut Homeobox 1 |
| Gene Type | Protein-coding |
| Chromosomal Location | 15q21.3 |
| NCBI Gene ID | 3175 ncbi.nlm.nih.gov/gene/3175 |
| Ensembl ID | ENSG00000169856 |
| UniProt ID | Q9UBC0 |
| OMIM ID | 604164 |
| HGNC ID | 8139 |
| Aliases | HNF6, HNF-6, HNF6A |
Description
ONECUT1 (One Cut Homeobox 1), also known as HNF6, encodes a transcription factor belonging to the cut-homeodomain family. It is essential for the development and function of the pancreas, liver, and biliary tract. ONECUT1 regulates the expression of genes involved in glucose metabolism, cell differentiation, and organogenesis. Mutations in ONECUT1 are associated with maturity-onset diabetes of the young (MODY) and other pancreatic disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Maturity-Onset Diabetes of the Young (MODY) | Loss-of-function mutations impair pancreatic beta-cell development and insulin secretion, leading to early-onset diabetes. | ClinVar, OMIM |
| Pancreatic Agenesis | Homozygous or compound heterozygous mutations disrupt pancreatic development, resulting in complete or partial absence of the pancreas. | OMIM, PubMed |
| Neonatal Diabetes | Severe loss-of-function variants cause insulin-dependent diabetes in infancy due to defective beta-cell formation. | ClinVar, PubMed |
| Liver and Biliary Tract Malformations | ONECUT1 deficiency alters hepatobiliary gene expression, contributing to cholestasis and ductal plate malformations. | OMIM, PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 12.5 | High |
| Pancreas | 8.2 | Medium |
| Kidney | 3.1 | Low |
| Small Intestine | 2.8 | Low |
| Stomach | 1.5 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 15.0 | Hepatocellular carcinoma cell line |
| PANC-1 | 9.5 | Pancreatic ductal adenocarcinoma cell line |
| MIA PaCa-2 | 7.8 | Pancreatic carcinoma cell line |
| HEK 293 | 0.5 | Low expression in embryonic kidney cells |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.826C>T (p.Arg276*) | Nonsense | Rare | Premature stop codon; loss of DNA-binding domain; loss of function |
| c.109G>A (p.Gly37Arg) | Missense | Rare | Impaired transactivation activity; associated with MODY |
| c.1A>G (p.Met1?) | Start loss | Very rare | No protein production; complete loss of function |
| c.1174C>T (p.Arg392Trp) | Missense | Rare | Reduced nuclear localization and transcriptional activity |
Mutation functional classification
Loss of Function (LOF)
Most ONECUT1 mutations are loss-of-function, leading to haploinsufficiency or complete absence of functional protein, impairing pancreatic and hepatic development.
Gain of Function (GOF)
No gain-of-function mutations have been reported for ONECUT1.
Dominant Negative (DN)
Some missense mutations may exert dominant-negative effects by interfering with wild-type protein function, though evidence is limited.
View complete mutation data：
Gene Ontology (GO)
| • DNA-binding transcription factor activity | • RNA polymerase II cis-regulatory region sequence-specific DNA binding |
| • chromatin binding | • positive regulation of transcription by RNA polymerase II |
| • liver development | • pancreas development |
| • cell differentiation | • glucose homeostasis |
Pathways
• Hepatocyte differentiation
• Pancreatic beta-cell development
• Insulin secretion regulation
• Bile acid metabolism
Protein Summary
ONECUT1 is a 465-amino acid transcription factor containing a single cut domain and a homeodomain. It binds to DNA sequences with a consensus ATCAAT motif and regulates target genes such as HNF1B, HNF4A, and FOXA2. The protein is predominantly nuclear and plays a critical role in endodermal organogenesis.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ONECUT1 Knockout HEK293 Cell Line | EDJ-KQ4890 | Human | 3175 | Details Get a Quote |
| ONECUT1 Knockout HeLa Cell Line | EDJ-KQ53540 | Human | 3175 | Details Get a Quote |
| ONECUT1 Knockout A-549 Cell Line | EDJ-KQ62011 | Human | 3175 | Details Get a Quote |
| ONECUT1 Knockout HCT 116 Cell Line | EDJ-KQ70488 | Human | 3175 | Details Get a Quote |
