PITX1 Gene: Paired-Like Homeodomain Transcription Factor 1
Key regulator of hindlimb development, pituitary function, and cancer-related signaling
Gene Information Card
| Symbol | PITX1 |
|---|---|
| Full Name | paired-like homeodomain transcription factor 1 |
| Gene Type | protein-coding |
| Chromosomal Location | 5q31.1 |
| NCBI Gene ID | 5307 ncbi.nlm.nih.gov/gene/5307 |
| Ensembl ID | ENSG00000069011 |
| UniProt ID | P78337 |
| OMIM ID | 602149 |
| HGNC ID | 9004 |
| Aliases | BFT, CCF, POTX, PTX1, HOAX1 |
Description
PITX1 encodes a member of the RIEG/PITX homeodomain family of transcription factors. It plays a critical role in embryonic development, particularly in the formation of the hindlimb, pituitary gland, and craniofacial structures. PITX1 also regulates gene expression in various adult tissues and is implicated in several cancers and developmental disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Clubfoot (Congenital Talipes Equinovarus) | Loss-of-function mutations or altered expression disrupt hindlimb development, leading to foot deformity. | ClinVar, OMIM |
| Pituitary Hormone Deficiency | PITX1 is essential for pituitary development; mutations can cause combined pituitary hormone deficiency. | OMIM, NCBI |
| Colorectal Cancer | Reduced PITX1 expression is associated with tumor progression; acts as a tumor suppressor in some contexts. | COSMIC, PubMed |
| Lung Cancer | PITX1 promoter hypermethylation leads to silencing, contributing to oncogenesis. | COSMIC, PubMed |
| Prostate Cancer | PITX1 expression is downregulated in metastatic prostate cancer, suggesting a suppressive role. | COSMIC, PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Skeletal Muscle | High | nTPM ~ 50-100 |
| Heart | Moderate | nTPM ~ 20-50 |
| Pituitary | High | nTPM ~ 100-200 |
| Lung | Low | nTPM < 10 |
| Colon | Low | nTPM < 10 |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| A549 (Lung) | Low | Reduced expression due to methylation |
| HCT116 (Colon) | Low | Tumor suppressor role |
| MCF7 (Breast) | Moderate | Expression varies |
| HEK293 (Embryonic Kidney) | High | Commonly used for overexpression studies |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.388C>T (p.Arg130Ter) | Nonsense | Rare | Loss of function; associated with clubfoot |
| c.455G>A (p.Arg152His) | Missense | Rare | Loss of DNA binding; linked to pituitary defects |
| c.112A>G (p.Thr38Ala) | Missense | Rare | Uncertain significance; possibly benign |
| Promoter hypermethylation | Epigenetic | Common in cancers | Silencing of gene expression |
Mutation functional classification
Loss of Function (LOF)
Most pathogenic mutations are loss-of-function, leading to haploinsufficiency or dominant-negative effects in limb and pituitary development.
Gain of Function (GOF)
Rare; not well-documented in literature.
Dominant Negative (DN)
Some missense mutations in the homeodomain may act as dominant-negative by interfering with wild-type protein function.
View complete mutation data：
Gene Ontology (GO)
| • DNA-binding transcription factor activity | • RNA polymerase II cis-regulatory region sequence-specific DNA binding |
| • sequence-specific double-stranded DNA binding | • transcription cis-regulatory region binding |
| • protein homodimerization activity | • nucleus |
| • regulation of transcription by RNA polymerase II | • animal organ morphogenesis |
| • cell differentiation | • embryonic skeletal system morphogenesis |
Pathways
• PITX1 in hindlimb development (Hox signaling)
• PITX1 in pituitary development (Wnt and Notch pathways)
• Tumor suppressor pathways in colorectal cancer (p53/PTEN)
• TGF-beta signaling (in cancer context)
Protein Summary
PITX1 is a 314-amino acid transcription factor with a bicoid-like homeodomain that binds to DNA and regulates target gene expression. It is critical for specifying hindlimb identity and pituitary development. In adults, it modulates gene expression in muscle and other tissues. Its dysregulation is linked to developmental disorders and cancer, where it often acts as a tumor suppressor.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PITX1 Knockout HEK293 Cell Line | EDJ-KQ4715 | Human | 5307 | Details Get a Quote |
| PITX1 Knockout A-549 Cell Line | EDJ-KQ28685 | Human | 5307 | Details Get a Quote |
| PITX1 Knockout HCT 116 Cell Line | EDJ-KQ28686 | Human | 5307 | Details Get a Quote |
| PITX1 Knockout HeLa Cell Line | EDJ-KQ28687 | Human | 5307 | Details Get a Quote |
