PHC1
Chr 12ARpolyhomeotic homolog 1
Also known as: EDR1, HPH1, MCPH11, RAE28
The protein is a component of the Polycomb repressive complex that regulates gene expression through chromatin modification and contains conserved domains that mediate protein-protein interactions with other Polycomb group proteins. Loss-of-function mutations cause primary microcephaly 11, an autosomal recessive disorder characterized by reduced brain size. The high pLI score indicates this gene is highly intolerant to loss-of-function variants, consistent with haploinsufficiency being pathogenic.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly LoF-intolerant (top ~10% of genes)
Mild missense constraint
Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.
The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.
ClinVar Variant Classifications
241 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 1 | 0 | 34 | 0 | 35 |
Likely Pathogenic | 0 | 1 | 2 | 0 | 3 |
VUS | 0 | 141 | 6 | 1 | 148 |
Likely Benign | 1 | 4 | 2 | 11 | 18 |
Benign | 0 | 4 | 19 | 4 | 27 |
| Total | 2 | 150 | 63 | 16 | 231 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
PHC1 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools