PABPC4

Chr 1

poly(A) binding protein cytoplasmic 4

Also known as: APP-1, APP1, PABP4, iPABP

The protein binds to the poly(A) tail of mRNA and regulates mRNA stability and metabolism, with particularly high expression in activated T cells and platelets. Mutations in PABPC4 cause autosomal dominant oculopharyngodistal myopathy, a progressive muscle disorder affecting the eyes, throat, and distal limbs. The gene is highly constrained against loss-of-function variants (pLI = 1.0, LOEUF = 0.23), indicating intolerance to protein-disrupting mutations.

ResearchSummary from RefSeq, UniProt
LOFmechanismLOEUF 0.23
Clinical SummaryPABPC4
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.
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.23LOEUF
pLI 0.999
Z-score 4.87
OE 0.09 (0.040.23)
Highly constrained

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

Missense Constraint
2.92Z-score
OE missense 0.59 (0.530.66)
233 obs / 396.7 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.09 (0.040.23)
00.351.4
Missense OE0.59 (0.530.66)
00.61.4
Synonymous OE1.18
01.21.6
LoF obs/exp: 3 / 33.4Missense obs/exp: 233 / 396.7Syn Z: -1.67
DN
0.5575th %ile
GOF
0.3292th %ile
LOF
0.67top 25%

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

LOFprediction above median · LOEUF 0.23

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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

PABPC4 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

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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