PCBP3

Chr 21

poly(rC) binding protein 3

Also known as: ALPHA-CP3, PCBP3-OT1, PCBP3OT

The protein encoded by this gene is a single-stranded nucleic acid binding protein that binds preferentially to cytosine-rich sequences and plays important roles in post-transcriptional RNA regulation. Mutations in PCBP3 cause autosomal recessive neurodevelopmental disorders with intellectual disability and seizures. The gene is highly constrained against loss-of-function variants, indicating that haploinsufficiency is not well-tolerated in the general population.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
4
Pubs (1 yr)
98
P/LP submissions
0%
P/LP missense
0.39
LOEUF
LOF
Mechanism· predicted
Clinical SummaryPCBP3
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.84) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
92 unique Pathogenic / Likely Pathogenic· 61 VUS of 173 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.39LOEUF
pLI 0.843
Z-score 3.75
OE 0.17 (0.080.39)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
2.02Z-score
OE missense 0.63 (0.550.72)
144 obs / 230.0 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.17 (0.080.39)
00.351.4
Missense OE0.63 (0.550.72)
00.61.4
Synonymous OE0.88
01.21.6
LoF obs/exp: 4 / 23.7Missense obs/exp: 144 / 230.0Syn Z: 0.86
DN
0.5968th %ile
GOF
0.5071th %ile
LOF
0.67top 25%

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

LOFprediction above median · LOEUF 0.39

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

173 submitted variants in ClinVar

Classification Summary

Pathogenic85
Likely Pathogenic7
VUS61
Likely Benign7
Benign4
Conflicting1
85
Pathogenic
7
Likely Pathogenic
61
VUS
7
Likely Benign
4
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
85
0
85
Likely Pathogenic
0
0
7
0
7
VUS
0
39
22
0
61
Likely Benign
0
1
4
2
7
Benign
0
0
1
3
4
Conflicting
1
Total0401195165

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

View in ClinVar →

Protein Context — Lollipop Plot

PCBP3 · 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

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Key Publications
Landmark & review papers · by relevance
PubMed
Top 2 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC