PITX2
Paired-like homeodomain transcription factor 2
Gene Information Card
| Symbol | PITX2 |
|---|---|
| Full Name | paired-like homeodomain transcription factor 2 |
| Gene Type | protein-coding |
| Chromosomal Location | 4q25 |
| NCBI Gene ID | 5308 ncbi.nlm.nih.gov/gene/5308 |
| Ensembl ID | ENSG00000164093 |
| UniProt ID | Q99697 |
| OMIM ID | 601542 |
| HGNC ID | 9005 |
| Aliases | ARP1, Brx1, IDG2, IGDS, IGDS2, IRID2, RIEG, RGS, RS, Rieger syndrome, PTX2, Otlx2, Solurshin |
Description
PITX2 encodes a member of the RIEG/PITX homeobox family, which is a bicoid-related homeodomain transcription factor. This protein is involved in the development of multiple organs, including the eye, heart, pituitary gland, and teeth. It plays a critical role in left-right asymmetry and is essential for the proper formation of the anterior segment of the eye. Mutations in this gene are associated with Axenfeld-Rieger syndrome, iridogoniodysgenesis, and Peters anomaly.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Axenfeld-Rieger syndrome type 1 | Loss-of-function mutations in PITX2 disrupt anterior segment development, leading to iris hypoplasia, corneal opacity, and glaucoma. | ClinVar, OMIM |
| Iridogoniodysgenesis type 2 | Heterozygous mutations impair PITX2 function, causing iris stromal hypoplasia and glaucoma. | OMIM |
| Peters anomaly | Missense mutations in PITX2 affect homeodomain DNA binding, resulting in corneal opacity and iridocorneal adhesions. | ClinVar |
| Congenital heart disease | PITX2 variants alter cardiac left-right patterning, contributing to atrial septal defects and other structural anomalies. | NCBI Gene, OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Heart | 12.3 | Medium |
| Pituitary gland | 8.7 | Medium |
| Eye (retina) | 6.5 | Low |
| Lung | 4.2 | Low |
| Skeletal muscle | 3.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| H9 (embryonic stem cells) | 15.2 | High expression in undifferentiated state |
| MCF7 (breast cancer) | 2.1 | Low expression |
| A549 (lung cancer) | 1.8 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.253C>T (p.Arg85Trp) | Missense | Rare | Disrupts homeodomain DNA binding; associated with Axenfeld-Rieger syndrome |
| c.271C>T (p.Arg91Cys) | Missense | Rare | Impairs transcriptional activity; linked to Peters anomaly |
| c.357_358delAG (p.Gly120Alafs*24) | Frameshift | Rare | Loss-of-function; causes Axenfeld-Rieger syndrome |
Mutation functional classification
Loss of Function (LOF)
Most PITX2 mutations result in haploinsufficiency or complete loss of DNA-binding and transactivation activity, leading to developmental defects.
Gain of Function (GOF)
No gain-of-function mutations have been reported for PITX2.
Dominant Negative (DN)
Some missense mutations in the homeodomain may exert dominant-negative effects by interfering with wild-type PITX2 function.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Wnt signaling pathway
• TGF-beta signaling pathway
• Left-right asymmetry signaling
Protein Summary
PITX2 is a 271-amino acid homeodomain transcription factor that binds to bicoid-like DNA sequences (TAATCC) to regulate target gene expression. It contains a conserved homeodomain (residues 68-127) and a C-terminal OAR (otp, aristaless, rax) domain. The protein is involved in cell proliferation, differentiation, and organogenesis, particularly in the eye, heart, and pituitary. Post-translational modifications include phosphorylation, which modulates its activity.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PITX2 Knockout HEK293 Cell Line | EDJ-KQ124 | Human | 5308 | Details Get a Quote |
| PITX2 Knockout A-549 Cell Line | EDJ-KQ18614 | Human | 5308 | Details Get a Quote |
| PITX2 Knockout HCT 116 Cell Line | EDJ-KQ18616 | Human | 5308 | Details Get a Quote |
| PITX2 Knockout HeLa Cell Line | EDJ-KQ18617 | Human | 5308 | Details Get a Quote |
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