NKX6-1: NK6 Homeobox 1
A key transcription factor in pancreatic beta-cell development and function
Gene Information Card
| Symbol | NKX6-1 |
|---|---|
| Full Name | NK6 Homeobox 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 4q21.23 |
| NCBI Gene ID | 4825 ncbi.nlm.nih.gov/gene/4825 |
| Ensembl ID | ENSG00000163623 |
| UniProt ID | P78426 |
| OMIM ID | 602563 |
| HGNC ID | 7833 |
| Aliases | NKX6.1, NKX6A |
Description
NKX6-1 encodes a homeodomain-containing transcription factor essential for the development and maintenance of insulin-producing pancreatic beta-cells. It is a key regulator of beta-cell maturation, proliferation, and function. Mutations in NKX6-1 are associated with maturity-onset diabetes of the young (MODY) and neonatal diabetes.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Maturity-Onset Diabetes of the Young (MODY) | Loss-of-function mutations impair beta-cell development and insulin secretion | ClinVar, OMIM |
| Neonatal Diabetes Mellitus | Homozygous or compound heterozygous mutations disrupt beta-cell formation | ClinVar, OMIM |
| Type 2 Diabetes | Common variants may alter beta-cell function and insulin secretion | NCBI, GWAS Catalog |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Pancreas | 42.3 | High |
| Small Intestine | 1.2 | Low |
| Stomach | 0.8 | Low |
| Brain | 0.5 | Low |
| Liver | 0.1 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| INS-1 (rat beta-cell) | High | Model for beta-cell studies |
| MIN6 (mouse beta-cell) | High | Model for beta-cell studies |
| HeLa | 0.1 | Not expressed |
| HEK293 | 0.1 | Not expressed |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.25C>T (p.Arg9Trp) | Missense | Rare | Loss of DNA binding and transactivation |
| c.188G>A (p.Arg63His) | Missense | Rare | Impaired nuclear localization |
| c.421C>T (p.Arg141*) | Nonsense | Rare | Premature truncation, loss of function |
| c.1A>G (p.Met1Val) | Missense | Rare | Start codon loss, no protein |
Mutation functional classification
Loss of Function (LOF)
Most reported mutations result in loss of DNA-binding or transactivation activity, leading to impaired beta-cell development and insulin secretion.
Gain of Function (GOF)
No gain-of-function mutations have been reported for NKX6-1.
Dominant Negative (DN)
Some missense mutations may act in a dominant-negative manner by interfering with wild-type NKX6-1 function, though evidence is limited.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Pancreatic beta-cell development (Reactome: R-HSA-210746)
• Regulation of insulin secretion (Reactome: R-HSA-422356)
Protein Summary
NKX6-1 is a 365-amino acid homeodomain transcription factor. It contains a homeobox DNA-binding domain and a NK-specific domain. The protein localizes to the nucleus and binds to TAATTA motifs in target gene promoters. It is critical for beta-cell identity and function, regulating genes involved in glucose sensing, insulin synthesis, and secretion.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| NKX6-1 Knockout HEK293 Cell Line | EDJ-KQ5351 | Human | 4825 | Details Get a Quote |
| NKX6-1 Knockout HCT 116 Cell Line | EDJ-KQ27227 | Human | 4825 | Details Get a Quote |
| NKX6-1 Knockout HeLa Cell Line | EDJ-KQ53996 | Human | 4825 | Details Get a Quote |
| NKX6-1 Knockout A-549 Cell Line | EDJ-KQ62489 | Human | 4825 | Details Get a Quote |
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