PABPC1

Chr 8

poly(A) binding protein cytoplasmic 1

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

NCBI Gene: 26986 ENSG00000070756 UniProt: P11940 OMIM: 604679

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.

OMIM ResearchSummary from RefSeq, UniProt

This gene encodes a poly(A) binding protein. The protein shuttles between the nucleus and cytoplasm and binds to the 3' poly(A) tail of eukaryotic messenger RNAs via RNA-recognition motifs. The binding of this protein to poly(A) promotes ribosome recruitment and translation initiation; it is also required for poly(A) shortening which is the first step in mRNA decay. The gene is part of a small gene family including three protein-coding genes and several pseudogenes.[provided by RefSeq, Aug 2010]

OMIM ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.27

Clinical Summary— PABPC1

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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.

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ClinVar Variants

2 unique Pathogenic / Likely Pathogenic· 23 VUS of 104 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Dual constrained — LoF & missense intolerant

LoF Constraint?

0.27LOEUF

pLI 0.996

Z-score 4.76

OE 0.12 (0.06–0.27)

Highly constrained

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

Missense Constraint?

4.49Z-score

OE missense 0.34 (0.30–0.40)

127 obs / 369.9 exp

Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?

LoF OE?0.12 (0.06–0.27)

0≤0.351.4

Missense OE?0.34 (0.30–0.40)

0≤0.61.4

Synonymous OE?1.03

0≤1.21.6

LoF obs/exp: 4 / 33.9Missense obs/exp: 127 / 369.9Syn Z: -0.28

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

limitedPABPC1-related developmental delayOTHERAD

This gene — mechanism propensity

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

104 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic1

Likely Pathogenic1

VUS23

Likely Benign9

Benign3

Pathogenic

Likely Pathogenic

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	1	0	0	1
Likely Pathogenic	0	1	0	0	1
VUS	1	22	0	0	23
Likely Benign	2	2	1	4	9
Benign	0	0	2	1	3
Total	3	26	3	5	37

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

View in ClinVar →

37 pathogenic / likely-pathogenic (of 42) ClinVar copy-number / structural variants overlap PABPC1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →