PCGF3

Chr 4

polycomb group ring finger 3

Also known as: DONG1, RNF3, RNF3A

NCBI Gene: 10336 ENSG00000185619 UniProt: Q3KNV8 OMIM: 617543

PCGF3 encodes a component of Polycomb repressive complex 1 (PRC1) that maintains transcriptional silencing of developmental genes through chromatin remodeling and histone H2A monoubiquitination, including regulation of Hox genes and X-chromosome inactivation. The gene is highly constrained against loss-of-function variants, but specific disease associations and inheritance patterns have not been established. Mutations in related Polycomb genes typically cause developmental disorders affecting multiple organ systems.

OMIM ResearchSummary from RefSeq, UniProt

The protein encoded by this gene contains a C3HC4 type RING finger, which is a motif known to be involved in protein-protein interactions. The specific function of this protein has not yet been determined. [provided by RefSeq, Jul 2008]

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

0.34

LOEUF· LoF intol.

LOF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.34LOEUF

pLI 0.953

Z-score 3.22

OE 0.07 (0.02–0.34)

Highly constrained

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

Missense Constraint?

2.10Z-score

OE missense 0.52 (0.43–0.63)

78 obs / 150.6 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.07 (0.02–0.34)

0≤0.351.4

Missense OE?0.52 (0.43–0.63)

0≤0.61.4

Synonymous OE?1.26

0≤1.21.6

LoF obs/exp: 1 / 14.0Missense obs/exp: 78 / 150.6Syn Z: -1.61

Background carrier burden — how many people carry a rare variant somewhere in PCGF3?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 59

534 rare PASS variants

Rare truncating (LoF)

1 in 450

64 rare PASS variants

Rare synonymous (reference)

1 in 99

243 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for PCGF3. 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 95	1 in 950
South Asian	~43k	1 in 76	1 in 400
Remaining (unassigned)	~30k	1 in 53	1 in 510
European (Finnish)	~27k	1 in 220	1 in 1,200
Admixed American	~22k	1 in 50	1 in 260
African / African American	~21k	1 in 65	1 in 240
East Asian	~20k	1 in 78	1 in 230
Ashkenazi Jewish	~13k	1 in 320	1 in 1,200
Middle Eastern	~2,884	1 in 150	≈ 1 in 2,900

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): 6 of 8 coding exons well covered in gnomAD exomes; exons 6, 7 marginal. Genomes: all 8.? see exons ↓