PYROXD1

Chr 12

pyridine nucleotide-disulphide oxidoreductase domain 1

Also known as: MFM8

NCBI Gene: 79912 ENSG00000121350 UniProt: Q8WU10

This protein functions as a flavoprotein that protects RTCB, the catalytic subunit of the tRNA ligase complex involved in tRNA splicing, from oxidative inactivation through direct binding and allosterically regulated release. Mutations cause early-onset myopathy with internalized nuclei and myofibrillar disorganization, with autosomal recessive inheritance. The gene is not highly constrained against loss-of-function variants.

ResearchSummary from RefSeq, UniProt

This gene encodes a nuclear-cytoplasmic pyridine nucleotide-disulphide reductase (PNDR). PNDRs are flavoproteins that catalyze the pyridine nucleotide-dependent reduction of thiol residues in other proteins. The encoded protein belongs to the class I pyridine nucleotide-disulphide oxidoreductase family but lacks the C-terminal dimerization domain found in other family members and instead has a C-terminal nitrile reductase domain. It localizes to the nucleus and to striated sarcomeric compartments. Naturally occurring mutations in this gene cause early-onset myopathy with internalized nuclei and myofibrillar disorganization. A pseudogene of this gene has been defined on chromosome 11. [provided by RefSeq, Apr 2017]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtMyopathy, myofibrillar, 8

Clinical highlights

Gene-disease validity (ClinGen)

myofibrillar myopathy 8 · ARDefinitivesufficient evidence for diagnostic panels

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.97

LOEUF

LOF

Mechanism· G2P

Some data sources returned errors (1)

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