PHC1: Polycomb Group Protein Involved in Transcriptional Repression and Development
Comprehensive genomic and functional analysis of PHC1, a core component of the Polycomb Repressive Complex 1 (PRC1)
Gene Information Card
| Symbol | PHC1 |
|---|---|
| Full Name | Polyhomeotic Homolog 1 |
| Gene Type | Protein-coding |
| Chromosomal Location | 12p13.31 |
| NCBI Gene ID | 1911 ncbi.nlm.nih.gov/gene/1911 |
| Ensembl ID | ENSG00000111752 |
| UniProt ID | P78364 |
| OMIM ID | 602979 |
| HGNC ID | 8910 |
| Aliases | EDR1, HPH1, RAE28, MCPH11 |
Description
PHC1 (Polyhomeotic Homolog 1) encodes a component of the Polycomb Repressive Complex 1 (PRC1), which mediates chromatin compaction and histone H2A monoubiquitination to repress gene expression. It is essential for embryonic development, stem cell maintenance, and X-chromosome inactivation. Mutations in PHC1 are associated with microcephaly and neurodevelopmental disorders, and altered expression is implicated in various cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Primary Microcephaly (MCPH11) | Loss-of-function mutations impair PRC1-mediated repression of cell cycle genes, leading to reduced neural progenitor proliferation | OMIM #615414 |
| Neurodevelopmental Disorder with Microcephaly and Seizures | Disrupted Polycomb function alters chromatin dynamics during brain development | ClinVar, PubMed |
| Breast Cancer | Overexpression of PHC1 correlates with poor prognosis; may promote proliferation via repression of tumor suppressors | COSMIC, PubMed |
| Prostate Cancer | PHC1 upregulation linked to androgen receptor signaling and disease progression | COSMIC, PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Testis | 10.2 | Medium |
| Lung | 6.8 | Low |
| Liver | 4.1 | Low |
| Heart | 3.5 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 15.3 | Embryonic kidney; high expression |
| HeLa | 11.7 | Cervical carcinoma; moderate expression |
| MCF7 | 9.4 | Breast cancer; moderate expression |
| HepG2 | 5.2 | Hepatocellular carcinoma; low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.166C>T (p.Arg56*) | Nonsense | Rare | Loss of function; truncation of SAM domain |
| c.1045G>A (p.Gly349Arg) | Missense | Rare | Impaired PRC1 complex assembly |
| c.1234_1235del (p.Lys412Glufs*3) | Frameshift | Rare | Loss of function; premature termination |
| c.788A>G (p.Tyr263Cys) | Missense | Rare | Reduced protein stability |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations (e.g., p.Arg56*, p.Lys412Glufs*3) lead to truncated or absent PHC1 protein, disrupting PRC1-mediated repression and causing microcephaly.
Gain of Function (GOF)
Not well documented; overexpression in cancers may act as a dominant oncogenic mechanism.
Dominant Negative (DN)
Missense mutations (e.g., p.Gly349Arg) may interfere with wild-type PHC1 incorporation into PRC1, reducing complex activity.
View complete mutation data：
Gene Ontology (GO)
| • protein binding (GO:0005515) | • nucleus (GO:0005634) |
| • chromatin organization (GO:0006325) | • chromatin silencing (GO:0006342) |
| • PRC1 complex (GO:0035102) | • negative regulation of transcription (GO:0045892) |
| • multicellular organism development (GO:0007275) |
Pathways
• Polycomb Repressive Complex 1 (PRC1) pathway
• Chromatin modifying enzymes
• Developmental gene regulation
• Cell cycle regulation
Protein Summary
PHC1 is a 1004-amino-acid protein containing a SAM domain (sterile alpha motif) and a zinc finger domain. It localizes to the nucleus and is a core component of PRC1, where it interacts with RING1B and BMI1 to compact chromatin and monoubiquitinate histone H2A at lysine 119. PHC1 also self-associates via its SAM domain, facilitating higher-order chromatin structures. Its expression is highest in brain and testis, and it is essential for proper neurogenesis.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PHC1 Knockout HEK293 Cell Line | EDJ-KQ3750 | Human | 1911 | Details Get a Quote |
| PHC1 Knockout A-549 Cell Line | EDJ-KQ27083 | Human | 1911 | Details Get a Quote |
| PHC1 Knockout HCT 116 Cell Line | EDJ-KQ27085 | Human | 1911 | Details Get a Quote |
| PHC1 Knockout HeLa Cell Line | EDJ-KQ27086 | Human | 1911 | Details Get a Quote |
