PAPOLB

Chr 7

poly(A) polymerase beta

Also known as: PAPT, TPAP

NCBI Gene: 56903 ENSG00000218823 UniProt: Q9NRJ5 OMIM: 607436

The protein is predicted to function as a poly(A) RNA polymerase involved in RNA 3'-end processing and mRNA processing in the nucleus. Mutations in this gene cause neurodevelopmental disorder with impaired intellectual development and progressive microcephaly, which follows an autosomal recessive inheritance pattern. This gene is not highly constrained against loss-of-function variants.

OMIM ResearchSummary from RefSeq

Predicted to enable poly(A) RNA polymerase activity. Predicted to be involved in RNA 3'-end processing and mRNA processing. Predicted to be located in endoplasmic reticulum. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 0.81

Clinical Summary— PAPOLB

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

97 VUS of 103 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.81LOEUF

pLI 0.002

Z-score 2.12

OE 0.43 (0.24–0.81)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

-0.15Z-score

OE missense 1.02 (0.94–1.12)

344 obs / 336.3 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.43 (0.24–0.81)

0≤0.351.4

Missense OE?1.02 (0.94–1.12)

0≤0.61.4

Synonymous OE?1.35

0≤1.21.6

LoF obs/exp: 7 / 16.2Missense obs/exp: 344 / 336.3Syn Z: -3.13

This gene — mechanism propensity

0.6452th %ile

GOF

0.6931th %ile

LOF

0.3065th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

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

ClinVar Variant Classifications

103 submitted variants in ClinVar

ClinVar

Classification Summary

VUS97

Likely Benign6

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	97	0	97
Likely Benign	5	1	6
Benign	0	0	0
Total	102	1	103

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

View in ClinVar →

38 pathogenic / likely-pathogenic (of 50) ClinVar copy-number / structural variants overlap PAPOLB — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →