PABPC1

Chr 8

poly(A) binding protein cytoplasmic 1

Also known as: PAB1, PABP, PABP1, PABPC2, PABPL1

The poly(A) binding protein binds to the poly(A) tail of mRNAs and regulates mRNA stability, translation initiation, and mRNA decay processes. Mutations cause autosomal dominant developmental delay with variable intellectual disability, speech delays, and behavioral abnormalities including autism spectrum features. This gene is highly constrained against loss-of-function variants (pLI 0.996, LOEUF 0.27), indicating that complete loss of protein function is likely incompatible with normal development.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
62
Pubs (1 yr)
39
P/LP submissions
5%
P/LP missense
0.27
LOEUF· LoF intol.
LOF
Mechanism· predicted
Clinical SummaryPABPC1
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
39 unique Pathogenic / Likely Pathogenic· 27 VUS of 145 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Dual constrained — LoF & missense intolerant
LoF Constraint
0.27LOEUF
pLI 0.996
Z-score 4.76
OE 0.12 (0.060.27)
Highly constrained

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

Missense Constraint
4.49Z-score
OE missense 0.34 (0.300.40)
127 obs / 369.9 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios
LoF OE0.12 (0.060.27)
00.351.4
Missense OE0.34 (0.300.40)
00.61.4
Synonymous OE1.03
01.21.6
LoF obs/exp: 4 / 33.9Missense obs/exp: 127 / 369.9Syn Z: -0.28
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
limitedPABPC1-related developmental delayOTHERAD
DN
0.4586th %ile
GOF
0.2796th %ile
LOF
0.76top 10%

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

LOFprediction above median · LOEUF 0.27

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

145 submitted variants in ClinVar

Classification Summary

Pathogenic37
Likely Pathogenic2
VUS27
Likely Benign9
Benign3
37
Pathogenic
2
Likely Pathogenic
27
VUS
9
Likely Benign
3
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
1
36
0
37
Likely Pathogenic
0
1
1
0
2
VUS
1
21
5
0
27
Likely Benign
2
2
1
4
9
Benign
0
0
2
1
3
Total32545578

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

View in ClinVar →

Protein Context — Lollipop Plot

PABPC1 · 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.

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Clinical Literature
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