PABPN1

Chr 14AD

poly(A) binding protein nuclear 1

Also known as: OPMD, PAB2, PABII, PABP-2, PABP2

The PABPN1 protein binds to poly(A) tails and is required for efficient polyadenylation of mRNA transcripts, controlling poly(A) tail length and participating in various aspects of mRNA metabolism. Mutations cause oculopharyngeal muscular dystrophy, a late-onset autosomal dominant condition primarily affecting the muscles of the eyelids and throat. This gene shows moderate constraint against loss-of-function variants (LOEUF 0.569), and the disease typically results from expansion of a GCG trinucleotide repeat in the coding region.

OMIMResearchSummary from RefSeq, OMIM, UniProt
GOFmechanismADLOEUF 0.571 OMIM phenotype
Clinical SummaryPABPN1
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.22) despite low pLI — interpret in context.
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.57LOEUF
pLI 0.392
Z-score 2.67
OE 0.22 (0.100.57)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.81Z-score
OE missense 0.59 (0.490.70)
89 obs / 151.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.22 (0.100.57)
00.351.4
Missense OE0.59 (0.490.70)
00.61.4
Synonymous OE1.31
01.21.6
LoF obs/exp: 3 / 13.6Missense obs/exp: 89 / 151.6Syn Z: -1.85
DN
0.5379th %ile
GOF
0.5170th %ile
LOF
0.57top 25%

The Badonyi & Marsh model scores loss-of-function highest, but genomic evidence most strongly supports gain-of-function as the primary mechanism.

GOF1 literature citation

Literature Evidence

GOFOPMD is generally inherited as an autosomal dominant disorder and the polyalanine expansion mutation is thought to confer a toxic gain-of-function on mutant PABPN1 which forms aggregates within skeletal myocyte nuclei.PMID:18178579

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

PABPN1 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold
Clinical Literature
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Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
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