PNPT1

Chr 2

polyribonucleotide nucleotidyltransferase 1

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

NCBI Gene: 87178 ENSG00000138035 UniProt: Q8TCS8

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.

ResearchSummary from RefSeq, OMIM, UniProt

The protein encoded by this gene belongs to the evolutionary conserved polynucleotide phosphorylase family comprised of phosphate dependent 3'-to-5' exoribonucleases implicated in RNA processing and degradation. This enzyme is predominantly localized in the mitochondrial intermembrane space and is involved in import of RNA to mitochondria. Mutations in this gene have been associated with combined oxidative phosphorylation deficiency-13 and autosomal recessive nonsyndromic deafness-70. Related pseudogenes are found on chromosomes 3 and 7. [provided by RefSeq, Dec 2012]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtCombined oxidative phosphorylation deficiency 13

UniProtDeafness, autosomal recessive, 70, with or without adult-onset neurodegeneration

UniProtSpinocerebellar ataxia 25

Clinical highlights

Gene-disease validity (ClinGen)

Leigh syndrome · ARModerateconsider for supplementary testing

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.47

LOEUF

LOF

Mechanism· G2P

Some data sources returned errors (1)

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