PABPC4

Chr 1

poly(A) binding protein cytoplasmic 4

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

NCBI Gene: 8761 ENSG00000090621 UniProt: Q13310

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

Poly(A)-binding proteins (PABPs) bind to the poly(A) tail present at the 3-prime ends of most eukaryotic mRNAs. PABPC4 or IPABP (inducible PABP) was isolated as an activation-induced T-cell mRNA encoding a protein. Activation of T cells increased PABPC4 mRNA levels in T cells approximately 5-fold. PABPC4 contains 4 RNA-binding domains and proline-rich C terminus. PABPC4 is localized primarily to the cytoplasm. It is suggested that PABPC4 might be necessary for regulation of stability of labile mRNA species in activated T cells. PABPC4 was also identified as an antigen, APP1 (activated-platelet protein-1), expressed on thrombin-activated rabbit platelets. PABPC4 may also be involved in the regulation of protein translation in platelets and megakaryocytes or may participate in the binding or stabilization of polyadenylates in platelet dense granules. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. This protein has also been found to interact with coronavirus nucleocapsid proteins and is thought to inhibit coronavirus replication. [provided by RefSeq, Nov 2021]

ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.23

Clinical Summary— PABPC4

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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

33 VUS of 61 total submissions

Explore recent and relevant literature in Research Assistant →

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.23LOEUF

pLI 0.999

Z-score 4.87

OE 0.09 (0.04–0.23)

Highly constrained

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

Missense Constraint?

2.92Z-score

OE missense 0.59 (0.53–0.66)

233 obs / 396.7 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.09 (0.04–0.23)

0≤0.351.4

Missense OE?0.59 (0.53–0.66)

0≤0.61.4

Synonymous OE?1.18

0≤1.21.6

LoF obs/exp: 3 / 33.4Missense obs/exp: 233 / 396.7Syn Z: -1.67

This gene — mechanism propensity

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

61 submitted variants in ClinVar

ClinVar

Classification Summary

VUS33

Likely Benign2

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	0	33	33
Likely Benign	1	1	2
Benign	0	0	0
Total	1	34	35

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

View in ClinVar →

8 pathogenic / likely-pathogenic (of 14) ClinVar copy-number / structural variants overlap PABPC4 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →