PNPT1

Chr 2ARAD

polyribonucleotide nucleotidyltransferase 1

Also known as: COXPD13, DFNB70, OLD35, PNPASE, SCA25, old-35

The encoded protein is a 3'-to-5' exoribonuclease that localizes to the mitochondrial intermembrane space and facilitates RNA import into mitochondria. Mutations cause autosomal recessive combined oxidative phosphorylation deficiency-13, autosomal recessive nonsyndromic deafness (DFNB70) with or without adult-onset neurodegeneration, and autosomal dominant spinocerebellar ataxia 25. The pathogenic mechanism involves disrupted mitochondrial RNA processing and degradation leading to impaired oxidative phosphorylation.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismAR/ADLOEUF 0.473 OMIM phenotypes
Clinical SummaryPNPT1
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Gene-Disease Validity (ClinGen)
Leigh syndrome · ARModerate

Moderate evidence — consider for supplementary testing

Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.31) despite low pLI — interpret in context.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.47LOEUF
pLI 0.000
Z-score 4.56
OE 0.31 (0.210.47)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
0.42Z-score
OE missense 0.94 (0.861.02)
385 obs / 409.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.31 (0.210.47)
00.351.4
Missense OE0.94 (0.861.02)
00.61.4
Synonymous OE1.12
01.21.6
LoF obs/exp: 16 / 51.2Missense obs/exp: 385 / 409.1Syn Z: -1.18

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

PNPT1 · 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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Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗