PHC2 encodes a component of the Polycomb repressive complex 1 (PRC1) that maintains transcriptional silencing of developmental genes, including Hox genes, through chromatin remodeling and histone H2A monoubiquitination. Mutations in PHC2 cause autosomal dominant neurodevelopmental disorders with intellectual disability and developmental delay. The gene shows significant constraint against loss-of-function variants (LOEUF 0.387), indicating that such mutations are likely pathogenic.

OMIMResearchSummary from RefSeq, UniProt
LOFmechanismLOEUF 0.39
Clinical SummaryPHC2
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.55) — some intolerance to loss-of-function variants.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.39LOEUF
pLI 0.546
Z-score 4.45
OE 0.21 (0.130.39)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
2.51Z-score
OE missense 0.69 (0.640.76)
367 obs / 529.3 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.21 (0.130.39)
00.351.4
Missense OE0.69 (0.640.76)
00.61.4
Synonymous OE0.87
01.21.6
LoF obs/exp: 8 / 37.3Missense obs/exp: 367 / 529.3Syn Z: 1.48
DN
0.4289th %ile
GOF
0.3491th %ile
LOF
0.69top 10%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.39

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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

PHC2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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