OTX2 Gene
Orthodenticle Homeobox 2: A Key Transcription Factor in Eye, Brain, and Pituitary Development
Gene Information Card
| Symbol | OTX2 |
|---|---|
| Full Name | Orthodenticle Homeobox 2 |
| Gene Type | Protein-coding |
| Chromosomal Location | 14q22.3 |
| NCBI Gene ID | 5015 ncbi.nlm.nih.gov/gene/5015 |
| Ensembl ID | ENSG00000165588 |
| UniProt ID | P32243 |
| OMIM ID | 600037 |
| HGNC ID | 8522 |
| Aliases | MCOPS5, CPHD6, OTX2 |
Description
OTX2 encodes a homeobox-containing transcription factor essential for the development of the head, brain, eyes, and pituitary gland. It regulates gene expression during embryogenesis and is critical for the specification and maintenance of the anterior neural plate, retinal development, and pituitary organogenesis. OTX2 is also implicated in certain cancers, including retinoblastoma and medulloblastoma.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Microphthalmia, syndromic 5 (MCOPS5) | Loss-of-function mutations in OTX2 disrupt retinal and ocular development, leading to microphthalmia, anophthalmia, or coloboma. | ClinVar, OMIM |
| Combined Pituitary Hormone Deficiency 6 (CPHD6) | Heterozygous mutations impair pituitary gland development, resulting in deficiencies of growth hormone, TSH, and other pituitary hormones. | OMIM, ClinVar |
| Retinoblastoma | OTX2 overexpression or amplification promotes tumorigenesis by maintaining retinal progenitor cell identity and inhibiting differentiation. | COSMIC, NCBI |
| Medulloblastoma | OTX2 is frequently amplified in Group 3 and Group 4 medulloblastomas, driving tumor growth through sustained proliferation. | COSMIC, NCBI |
| Anophthalmia/microphthalmia (isolated) | Heterozygous loss-of-function variants cause severe eye malformations via haploinsufficiency. | ClinVar, OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain (cerebellum) | 12.5 | Medium |
| Brain (cortex) | 8.3 | Medium |
| Retina | 15.2 | High |
| Pituitary gland | 18.7 | High |
| Testis | 3.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| D283 Med (medulloblastoma) | 22.4 | High expression; OTX2 amplification common |
| Y79 (retinoblastoma) | 35.1 | Very high expression; drives proliferation |
| SH-SY5Y (neuroblastoma) | 6.8 | Moderate expression |
| HEK293 (embryonic kidney) | 1.2 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.289C>T (p.Arg97*) | Nonsense | Rare | Loss-of-function; associated with microphthalmia |
| c.404G>A (p.Arg135Gln) | Missense | Rare | Reduced DNA binding; causes pituitary hormone deficiency |
| c.1A>G (p.Met1?) | Start loss | Rare | Complete loss of protein; severe eye malformations |
| Amplification (chr14q22.3) | Copy number gain | Common in medulloblastoma | Gain-of-function; drives tumor growth |
Mutation functional classification
Loss of Function (LOF)
Heterozygous loss-of-function mutations (nonsense, frameshift, missense) cause haploinsufficiency, leading to microphthalmia, anophthalmia, coloboma, and pituitary hormone deficiencies.
Gain of Function (GOF)
Gene amplification or overexpression in medulloblastoma and retinoblastoma results in sustained proliferation and blocked differentiation, acting as an oncogenic driver.
Dominant Negative (DN)
Some missense mutations (e.g., p.Arg135Gln) produce a protein that interferes with wild-type OTX2 function, contributing to pituitary defects.
View complete mutation data：
Gene Ontology (GO)
| • DNA-binding transcription factor activity | • RNA polymerase II cis-regulatory region sequence-specific DNA binding |
| • anterior head development | • eye development |
| • pituitary gland development | • regulation of gene expression |
| • neural plate anterior/posterior pattern formation |
Pathways
• Retinal development and maintenance
• Pituitary organogenesis
• Wnt signaling pathway
• Hedgehog signaling pathway
• Cell cycle regulation in medulloblastoma
Protein Summary
OTX2 is a 297-amino acid homeodomain-containing transcription factor that binds to bicoid-like DNA sequences (TAATCC) to regulate target genes. It is highly expressed in the developing forebrain, midbrain, eye, and pituitary. The protein shuttles between nucleus and cytoplasm and interacts with co-repressors (e.g., Groucho/TLE) and co-activators. Post-translational modifications include phosphorylation and ubiquitination, which modulate its stability and activity.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| OTX2 Knockout HEK293 Cell Line | EDJ-KQ989 | Human | 5015 | Details Get a Quote |
| OTX2 Knockout HeLa Cell Line | EDJ-KQ54063 | Human | 5015 | Details Get a Quote |
| OTX2 Knockout A-549 Cell Line | EDJ-KQ62551 | Human | 5015 | Details Get a Quote |
| OTX2 Knockout HCT 116 Cell Line | EDJ-KQ71023 | Human | 5015 | Details Get a Quote |
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