PCGF3

Chr 4

polycomb group ring finger 3

Also known as: DONG1, RNF3, RNF3A

NCBI Gene: 10336ENSG00000185619UniProt: Q3KNV8

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.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
4
Pubs (1 yr)
143
P/LP submissions
0%
P/LP missense
0.34
LOEUF· LoF intol.
LOF
Mechanism· predicted
Clinical Summary— PCGF3
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.95). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
143 unique Pathogenic / Likely Pathogenic· 50 VUS of 209 total submissions
Explore recent and relevant literature in Research Assistant →

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 OE0.07 (0.02–0.34)
0≤0.351.4
Missense OE0.52 (0.43–0.63)
0≤0.61.4
Synonymous OE1.26
0≤1.21.6
LoF obs/exp: 1 / 14.0Missense obs/exp: 78 / 150.6Syn Z: -1.61
DN
0.4091th %ile
GOF
0.3689th %ile
LOF
0.74top 10%

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

LOFprediction above median · LOEUF 0.34

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

209 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic139
Likely Pathogenic4
VUS50
Benign2
139
Pathogenic
4
Likely Pathogenic
50
VUS
2
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
139
0
139
Likely Pathogenic
0
0
4
0
4
VUS
0
28
22
0
50
Likely Benign
0
0
0
0
0
Benign
0
0
0
2
2
Total0281652195

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

View in ClinVar →

Protein Context — Lollipop Plot

PCGF3 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 3 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Non-synonymous, synonymous, and non-coding nucleotide variants contribute to recurrently altered biological processes during retinoblastoma progression.
Stachelek K et al.·Genes Chromosomes Cancer
2023
Imputed expression of schizophrenia-associated genes and cognitive measures in patients with schizophrenia.
Fabbri C et al.·Mol Genet Genomic Med
2022Cohort
Response Predictors of S-1, Cisplatin, and Docetaxel Combination Chemotherapy for Metastatic Gastric Cancer: Microarray Analysis of Whole Human Genes.
Kitamura S et al.·Oncology
2017Clinical trial
Epigenomic and transcriptomic landscaping unraveled candidate repositioned therapeutics for non-functioning pituitary neuroendocrine tumors.
Aydin B et al.·J Endocrinol Invest
2023
[Analysis of clinical and genetic characteristics of a child with ring chromosome 4 syndrome].
Lyu Y et al.·Zhonghua Yi Xue Yi Chuan Xue Za Zhi
2020
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