PDX1
Pancreatic and Duodenal Homeobox 1: A Master Regulator of Pancreatic Development and Beta-Cell Function
Gene Information Card
| Symbol | PDX1 |
|---|---|
| Full Name | Pancreatic and duodenal homeobox 1 |
| Gene Type | protein-coding |
| Chromosomal Location | 13q12.2 |
| NCBI Gene ID | 3651 ncbi.nlm.nih.gov/gene/3651 |
| Ensembl ID | ENSG00000139515 |
| UniProt ID | P52945 |
| OMIM ID | 600733 |
| HGNC ID | 6107 |
| Aliases | IPF1, MODY4, IUF1, GSF, IDX-1, STF-1 |
Description
PDX1 (pancreatic and duodenal homeobox 1) encodes a homeodomain transcription factor essential for pancreatic development, beta-cell differentiation, and maintenance of glucose homeostasis. It regulates insulin, somatostatin, glucokinase, and other genes critical for beta-cell function. Loss-of-function mutations cause pancreatic agenesis and maturity-onset diabetes of the young type 4 (MODY4). PDX1 is also implicated in pancreatic ductal adenocarcinoma, where its expression is frequently lost or reduced.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Maturity-onset diabetes of the young type 4 (MODY4) | Heterozygous loss-of-function mutations in PDX1 impair beta-cell function and insulin secretion, leading to early-onset diabetes. | OMIM #600733; ClinVar |
| Pancreatic agenesis | Homozygous or compound heterozygous loss-of-function mutations in PDX1 result in complete absence of the pancreas at birth. | OMIM #260370; NCBI Gene |
| Pancreatic ductal adenocarcinoma | Reduced or absent PDX1 expression in pancreatic cancer cells correlates with dedifferentiation and poor prognosis; epigenetic silencing and loss of heterozygosity are observed. | COSMIC; PMID: 19029981 |
| Type 2 diabetes | Common variants near PDX1 (e.g., rs11605924) are associated with reduced insulin secretion and increased risk of type 2 diabetes. | ClinVar; GWAS catalog |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Pancreas | 149.2 | High |
| Duodenum | 12.3 | Low |
| Stomach | 5.1 | Low |
| Liver | 0.2 | Not detected |
| Skeletal muscle | 0.1 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| INS-1 (rat beta-cell line) | High | Model for beta-cell function studies |
| MIN6 (mouse beta-cell line) | High | Model for insulin secretion |
| PANC-1 (human pancreatic cancer) | Low | Reduced expression in dedifferentiated cancer cells |
| HeLa | Not detected | Negative control |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.188C>T (p.Pro63Leu) | Missense | Rare | Loss of DNA-binding activity; associated with MODY4 |
| c.184C>T (p.Arg62Trp) | Missense | Rare | Impaired transactivation; associated with pancreatic agenesis |
| c.1A>G (p.Met1?) | Start loss | Rare | Complete loss of protein; homozygous causes pancreatic agenesis |
| c.731G>A (p.Arg244His) | Missense | Rare | Reduced nuclear localization; MODY4 |
Mutation functional classification
Loss of Function (LOF)
Most PDX1 mutations (e.g., p.Pro63Leu, p.Arg62Trp, start loss) reduce or abolish DNA binding and transcriptional activation, leading to impaired beta-cell development and function.
Gain of Function (GOF)
No well-characterized gain-of-function mutations reported in PDX1.
Dominant Negative (DN)
Heterozygous missense mutations (e.g., p.Pro63Leu) can exert dominant-negative effects by interfering with wild-type PDX1 activity, contributing to MODY4.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Regulation of insulin secretion (Reactome: R-HSA-422356)
• Pancreatic beta-cell development (KEGG: hsa04950)
• Type II diabetes mellitus (KEGG: hsa04930)
• Maturity onset diabetes of the young (KEGG: hsa04950)
Protein Summary
PDX1 is a 283-amino-acid homeodomain transcription factor (UniProt P52945) that binds to the insulin promoter and activates insulin gene expression. It is critical for pancreatic beta-cell identity and glucose-responsive insulin secretion. The protein contains an N-terminal transactivation domain, a homeodomain (DNA-binding), and a C-terminal domain involved in nuclear localization and interaction with cofactors. Post-translational modifications include phosphorylation and acetylation, which modulate its activity and stability.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PDX1 Knockout HEK293 Cell Line | EDJ-KQ5004 | Human | 3651 | Details Get a Quote |
| PDX1 Knockout HCT 116 Cell Line | EDJ-KQ26684 | Human | 3651 | Details Get a Quote |
| PDX1 Knockout HeLa Cell Line | EDJ-KQ27907 | Human | 3651 | Details Get a Quote |
| PDX1 Knockout A-549 Cell Line | EDJ-KQ62145 | Human | 3651 | Details Get a Quote |
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