PHC1

Chr 12AR

polyhomeotic homolog 1

Also known as: EDR1, HPH1, MCPH11, RAE28

NCBI Gene: 1911ENSG00000111752UniProt: P78364

This gene is a homolog of the Drosophila polyhomeotic gene, which is a member of the Polycomb group of genes. The gene product is a component of a multimeric protein complex that contains EDR2 and the vertebrate Polycomb protein BMH1. The gene product, the EDR2 protein, and the Drosophila polyhomeotic protein share 2 highly conserved domains, named homology domains I and II. These domains are involved in protein-protein interactions and may mediate heterodimerization of the protein encoded by this gene and the EDR2 protein. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

?Microcephaly 11, primary, autosomal recessiveMIM #615414
AR
0
Active trials
38
Pathogenic / LP
230
ClinVar variants
5
Pubs (1 yr)
1.9
Missense Z
0.24
LOEUF· LoF intolerant
Clinical Summary— PHC1
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
38 Pathogenic / Likely Pathogenic· 147 VUS of 230 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint
0.24LOEUF
pLI 0.999
Z-score 5.40
OE 0.12 (0.06–0.24)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
1.92Z-score
OE missense 0.76 (0.69–0.82)
375 obs / 495.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.12 (0.06–0.24)
0≤0.351.4
Missense OE0.76 (0.69–0.82)
0≤0.61.4
Synonymous OE1.01
0≤1.21.6
LoF obs/exp: 5 / 43.3Missense obs/exp: 375 / 495.1Syn Z: -0.12
LOF
DN
0.2897th %ile
GOF
0.2796th %ile
LOF
0.80top 5%

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

LOFprediction above median · LOEUF 0.24

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

230 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic35
Likely Pathogenic3
VUS147
Likely Benign18
Benign27
35
Pathogenic
3
Likely Pathogenic
147
VUS
18
Likely Benign
27
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
35
0
35
Likely Pathogenic
0
1
2
0
3
VUS
0
140
6
1
147
Likely Benign
0
4
3
11
18
Benign
0
3
20
4
27
Total01486616230

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

PHC1 · protein map & ClinVar variants

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

Gene2Phenotype Curations

PHC1-related primary microcephaly

limited
ARUndeterminedAltered Gene Product Structure
Dev. Disorders
G2P ↗
missense variantinframe deletioninframe insertion

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Landmark / reviewRecent case evidence
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients