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…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.10

LOEUF· LoF intol.

LOF

Mechanism· predicted

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

Background carrier burden — how many people carry a rare variant somewhere in PHC3?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 58

1,119 rare PASS variants

Rare truncating (LoF)

1 in 990

62 rare PASS variants

Rare synonymous (reference)

1 in 120

502 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for PHC3. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 91	1 in 1,000
South Asian	~43k	1 in 52	1 in 810
Remaining (unassigned)	~30k	1 in 56	1 in 1,300
European (Finnish)	~27k	1 in 120	1 in 4,300
Admixed American	~22k	1 in 65	1 in 350
African / African American	~21k	1 in 71	1 in 710
East Asian	~20k	1 in 85	1 in 960
Ashkenazi Jewish	~13k	1 in 150	1 in 720
Middle Eastern	~2,884	1 in 59	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 14 of 15 coding exons well covered in gnomAD exomes; exon 4 marginal. Genomes: all 15.? see exons ↓