PYROXD1

Chr 12AR

pyridine nucleotide-disulphide oxidoreductase domain 1

Also known as: MFM8

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]

Primary Disease Associations & Inheritance

Myopathy, myofibrillar, 8MIM #617258
AR
0
Active trials
3
Pubs (1 yr)
22
P/LP submissions
0%
P/LP missense
0.97
LOEUF
LOF
Mechanism· G2P
Clinical SummaryPYROXD1
🧬
Gene-Disease Validity (ClinGen)
myofibrillar myopathy 8 · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
22 unique Pathogenic / Likely Pathogenic· 156 VUS of 300 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.97LOEUF
pLI 0.000
Z-score 1.69
OE 0.64 (0.440.97)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.10Z-score
OE missense 0.98 (0.891.09)
252 obs / 256.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.64 (0.440.97)
00.351.4
Missense OE0.98 (0.891.09)
00.61.4
Synonymous OE1.00
01.21.6
LoF obs/exp: 17 / 26.4Missense obs/exp: 252 / 256.4Syn Z: 0.03
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongPYROXD1-related early-onset myopathy with internalised nuclei and myofibrillar disorganizationLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.7034th %ile
GOF
0.6150th %ile
LOF
0.2678th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

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

ClinVar Variant Classifications

300 submitted variants in ClinVar

Classification Summary

Pathogenic15
Likely Pathogenic7
VUS156
Likely Benign101
Benign1
Conflicting2
15
Pathogenic
7
Likely Pathogenic
156
VUS
101
Likely Benign
1
Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
7
0
8
0
15
Likely Pathogenic
7
0
0
0
7
VUS
9
126
20
1
156
Likely Benign
0
5
41
55
101
Benign
0
0
1
0
1
Conflicting
2
Total231317056282

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

View in ClinVar →

Protein Context — Lollipop Plot

PYROXD1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Key Publications
Landmark & review papers · by relevance
PubMed
[PYROXD1-related myopathy].
Lornage X et al.·Med Sci (Paris)
2019Review
PYROXD1-associated myopathy.
D'Costa MS et al.·BMJ Case Rep
2024Case report
Myofibrillar myopathy in the genomic context.
Fichna JP et al.·J Appl Genet
2018Review
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC