PCGF2

Chr 17AD

polycomb group ring finger 2

Also known as: MEL-18, RNF110, TPFS, ZNF144

NCBI Gene: 7703ENSG00000277258UniProt: P35227

The protein encoded by this gene contains a RING finger motif and is similar to the polycomb group (PcG) gene products. PcG gene products form complexes via protein-protein interaction and maintain the transcription repression of genes involved in embryogenesis, cell cycles, and tumorigenesis. This protein was shown to act as a negative regulator of transcription and has tumor suppressor activity. The expression of this gene was detected in various tumor cells, but is limited in neural organs in normal tissues. Knockout studies in mice suggested that this protein may negatively regulate the expression of different cytokines, chemokines, and chemokine receptors, and thus plays an important role in lymphocyte differentiation and migration, as well as in immune responses. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

Turnpenny-Fry syndromeMIM #618371
AD
341
ClinVar variants
10
Pathogenic / LP
0.86
pLI score
0
Active trials
Clinical Summary— PCGF2
⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.86) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
10 Pathogenic / Likely Pathogenic· 140 VUS of 341 total submissions
Some data sources returned errors (1)

clinvar: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.41LOEUF
pLI 0.864
Z-score 3.15
OE 0.13 (0.05–0.41)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.95Z-score
OE missense 0.81 (0.72–0.93)
169 obs / 207.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.13 (0.05–0.41)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.81 (0.72–0.93)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.05
0≤1.21.6
LoF obs/exp: 2 / 15.3Missense obs/exp: 169 / 207.6Syn Z: -0.35

ClinVar Variant Classifications

341 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic7
Likely Pathogenic3
VUS140
Likely Benign133
Benign25
Conflicting15
7
Pathogenic
3
Likely Pathogenic
140
VUS
133
Likely Benign
25
Benign
15
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
7
0
7
Likely Pathogenic
0
3
0
0
3
VUS
11
116
12
1
140
Likely Benign
0
16
49
68
133
Benign
0
8
11
6
25
Conflicting
—15
Total111437975323

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

View in ClinVar →

Protein Context — Lollipop Plot

PCGF2 · protein map & ClinVar variants

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

Gene2Phenotype Curations

PCGF2-related craniofacial neurological cardiovascular and skeletal features (Turnpenny-Fry syndrome)

strong
ADGain Of FunctionAltered Gene Product Structure
Dev. DisordersSkin
G2P ↗
missense variant

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Turnpenny-Fry syndrome

MIM #618371

Molecular basis of disorder known

Autosomal dominant
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools