EZHIP (EZH Inhibitory Protein)
A chromatin regulator involved in posterior fossa ependymoma and neurodevelopment
Gene Information Card
| Symbol | EZHIP |
|---|---|
| Full Name | EZH inhibitory protein |
| Gene Type | Protein coding |
| Chromosomal Location | Xp11.22 |
| NCBI Gene ID | 79969 ncbi.nlm.nih.gov/gene/79969 |
| Ensembl ID | ENSG00000101981 |
| UniProt ID | Q5T7P8 |
| OMIM ID | 300990 |
| HGNC ID | 26099 |
| Aliases | CXorf67, MGC27016 |
Description
EZHIP (EZH inhibitory protein) encodes a nuclear protein that directly binds to and inhibits the methyltransferase activity of EZH2, a core component of the Polycomb repressive complex 2 (PRC2). By reducing H3K27me3 levels, EZHIP acts as a chromatin regulator. Overexpression or gain-of-function mutations in EZHIP are recurrently found in posterior fossa type A (PFA) ependymomas, where they drive a PRC2-inactive state and promote tumorigenesis. The gene is located on chromosome X and is predominantly expressed in the brain and testis.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Posterior fossa ependymoma type A (PFA) | Overexpression or gain-of-function mutations in EZHIP inhibit PRC2 activity, reducing H3K27me3 and altering gene expression programs that drive tumor formation. | PMID: 29657128, PMID: 30361399 |
| Neurodevelopmental disorders | Rare loss-of-function variants in EZHIP have been associated with intellectual disability and developmental delay, likely due to dysregulated PRC2 activity during neurodevelopment. | ClinVar: VCV000599695 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Testis | 8.3 | Medium |
| Heart | 2.1 | Low |
| Liver | 0.5 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 15.2 | High expression |
| SH-SY5Y | 9.8 | Medium expression |
| U87MG | 6.4 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G (p.Met1?) | Start loss | Rare | Loss of function |
| c.302C>T (p.Pro101Leu) | Missense | Unknown | Gain of function (in PFA ependymoma) |
| c.487G>A (p.Glu163Lys) | Missense | Unknown | Gain of function (in PFA ependymoma) |
Mutation functional classification
Loss of Function (LOF)
Rare start-loss or nonsense variants that reduce EZHIP protein levels, leading to increased PRC2 activity and H3K27me3; associated with neurodevelopmental phenotypes.
Gain of Function (GOF)
Missense mutations (e.g., p.Pro101Leu, p.Glu163Lys) that enhance EZHIP's inhibition of EZH2, decreasing H3K27me3; recurrent in PFA ependymoma.
Dominant Negative (DN)
Not described for EZHIP.
View complete mutation data：
Gene Ontology (GO)
| • protein binding (GO:0005515) | • nucleus (GO:0005634) |
| • histone methyltransferase inhibitor activity (GO:0035098) | • negative regulation of transcription, DNA-templated (GO:0045892) |
Pathways
• PRC2-mediated H3K27me3 regulation
• Polycomb repressive complex 2 (PRC2) signaling
Protein Summary
EZHIP is a 405-amino-acid nuclear protein that contains a conserved EZH-binding domain. It directly interacts with the catalytic SET domain of EZH2, blocking its methyltransferase activity and reducing global H3K27me3 levels. The protein is highly expressed in the brain and testis, and its dysregulation is implicated in posterior fossa ependymoma and neurodevelopmental disorders.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| EZHIP Knockout HEK293 Cell Line | EDJ-KQ13347 | Human | 340602 | Details Get a Quote |
| EZHIP Knockout HeLa Cell Line | EDJ-KQ59691 | Human | 340602 | Details Get a Quote |
| EZHIP Knockout A-549 Cell Line | EDJ-KQ68162 | Human | 340602 | Details Get a Quote |
| EZHIP Knockout HCT 116 Cell Line | EDJ-KQ76538 | Human | 340602 | Details Get a Quote |
