PHC3

Chr 3

polyhomeotic homolog 3

Also known as: EDR3, HPH3

NCBI Gene: 80012 ENSG00000173889 UniProt: Q8NDX5 OMIM: 620031

Predicted to enable chromatin binding activity and histone binding activity. Predicted to be involved in negative regulation of DNA-templated transcription. Located in nucleoplasm. Part of PRC1 complex. [provided by Alliance of Genome Resources, Jul 2025]

OMIM Research

OMIM ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.10

Clinical Summary— PHC3

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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.

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ClinVar Variants

119 VUS of 141 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.10LOEUF

pLI 1.000

Z-score 6.36

OE 0.02 (0.01–0.10)

Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint?

1.72Z-score

OE missense 0.79 (0.73–0.86)

425 obs / 537.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.02 (0.01–0.10)

0≤0.351.4

Missense OE?0.79 (0.73–0.86)

0≤0.61.4

Synonymous OE?1.14

0≤1.21.6

LoF obs/exp: 1 / 49.1Missense obs/exp: 425 / 537.2Syn Z: -1.55

This gene — mechanism propensity

0.2599th %ile

GOF

0.2397th %ile

LOF

0.80top 5%

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

LOFprediction above median · LOEUF 0.10

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

141 submitted variants in ClinVar

ClinVar

Classification Summary

VUS119

Likely Benign1

119

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	119	0	119
Likely Benign	0	1	1
Benign	0	0	0
Total	119	1	120

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

View in ClinVar →

22 pathogenic / likely-pathogenic (of 26) ClinVar copy-number / structural variants overlap PHC3 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →