PAX4 Gene
Paired Box 4: A Key Regulator of Pancreatic Beta Cell Development and Diabetes Susceptibility
Gene Information Card
| Symbol | PAX4 |
|---|---|
| Full Name | Paired Box 4 |
| Gene Type | Protein coding |
| Chromosomal Location | 7q32.1 |
| NCBI Gene ID | 5078 ncbi.nlm.nih.gov/gene/5078 |
| Ensembl ID | ENSG00000106331 |
| UniProt ID | O43316 |
| OMIM ID | 167413 |
| HGNC ID | 8618 |
| Aliases | KPD; MODY9; PAX-4 |
Description
PAX4 (Paired Box 4) is a transcription factor belonging to the paired box (PAX) family. It plays a critical role in the development and differentiation of pancreatic islet beta cells. PAX4 represses the expression of genes that promote alpha cell fate, thereby directing endocrine progenitor cells toward the beta cell lineage. Mutations in PAX4 are associated with maturity-onset diabetes of the young type 9 (MODY9) and increased susceptibility to type 2 diabetes (T2D). The gene is also implicated in certain cancers, including pancreatic neuroendocrine tumors.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Maturity-Onset Diabetes of the Young 9 (MODY9) | Loss-of-function mutations impair beta cell differentiation and insulin secretion, leading to early-onset diabetes. | OMIM #612225; ClinVar |
| Type 2 Diabetes (T2D) | Common variants (e.g., rs2233580, rs10229583) increase risk through reduced PAX4 transcriptional activity. | NCBI Gene; PubMed: 23567420 |
| Pancreatic Neuroendocrine Tumors | PAX4 overexpression may contribute to tumorigenesis by promoting cell proliferation and inhibiting apoptosis. | COSMIC; PubMed: 25670082 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Pancreas | 16.8 | Medium |
| Islets of Langerhans | 22.3 | Medium |
| Small Intestine | 1.2 | Low |
| Stomach | 0.8 | Low |
| Liver | 0.1 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| INS-1 (rat beta cell line) | N/A | High expression; used as model for beta cell function |
| MIN6 (mouse beta cell line) | N/A | High expression; essential for insulin production |
| PANC-1 (human pancreatic ductal carcinoma) | N/A | Low expression; not beta cell origin |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.164C>T (p.Pro55Leu) | Missense | Rare | Reduced DNA-binding and transactivation; associated with MODY9 |
| c.307G>A (p.Val103Met) | Missense | Rare | Impaired beta cell development; linked to T2D |
| c.718C>T (p.Arg240*) | Nonsense | Very rare | Premature truncation; loss of function; MODY9 |
| rs2233580 (c.124G>A, p.Gly42Ser) | Missense | Common (East Asian MAF ~0.15) | Reduced transcriptional activity; T2D risk variant |
Mutation functional classification
Loss of Function (LOF)
Most MODY9-associated mutations (e.g., p.Pro55Leu, p.Arg240*) reduce or abolish PAX4's ability to bind DNA and activate target genes, impairing beta cell differentiation.
Gain of Function (GOF)
Not well documented; some missense variants may show altered activity but no clear gain-of-function reported.
Dominant Negative (DN)
Heterozygous mutations in PAX4 can exert dominant-negative effects by interfering with wild-type PAX4 function, contributing to MODY9 pathogenesis.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Development of pancreatic beta cells (Reactome: R-HSA-210746)
• Transcriptional regulation of islet cell lineage (KEGG: hsa04950)
• Type II diabetes mellitus (KEGG: hsa04930)
Protein Summary
PAX4 is a 350-amino acid transcription factor containing a paired box DNA-binding domain and a homeodomain. It functions primarily as a transcriptional repressor, silencing genes that promote alpha cell fate (e.g., Arx) and enabling beta cell differentiation. In adult islets, PAX4 maintains beta cell identity and regulates insulin secretion. Loss-of-function mutations lead to reduced beta cell mass and early-onset diabetes. The protein is predominantly nuclear and is expressed in pancreatic islets during development and adulthood.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PAX4 Knockout HEK293 Cell Line | EDJ-KQ4634 | Human | 5078 | Details Get a Quote |
| PAX4 Knockout HeLa Cell Line | EDJ-KQ54083 | Human | 5078 | Details Get a Quote |
| PAX4 Knockout A-549 Cell Line | EDJ-KQ62571 | Human | 5078 | Details Get a Quote |
| PAX4 Knockout HCT 116 Cell Line | EDJ-KQ71041 | Human | 5078 | Details Get a Quote |
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