NDUFA10

Chr 2AR

NADH:ubiquinone oxidoreductase subunit A10

Also known as: CI-42KD, CI-42k, MC1DN22

The encoded protein is a subunit of mitochondrial complex I that functions as an NADH dehydrogenase, transferring electrons from NADH to the respiratory chain in oxidative phosphorylation. Mutations cause mitochondrial complex I deficiency, nuclear type 22, which can present as Leigh syndrome, inherited in an autosomal recessive pattern. The pathogenic mechanism involves loss of function leading to impaired mitochondrial energy production.

Summary from RefSeq, OMIM, UniProt, Mechanism
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Primary Disease Associations & Inheritance

Mitochondrial complex I deficiency, nuclear type 22MIM #618243
AR
0
Active trials
9
Pubs (1 yr)
108
P/LP submissions
6%
P/LP missense
1.10
LOEUF
DN
Mechanism· predicted
Clinical SummaryNDUFA10
🧬
Gene-Disease Validity (ClinGen)
mitochondrial disease · ARModerate

Moderate evidence — consider for supplementary testing

2 total gene-disease associations curated

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
104 unique Pathogenic / Likely Pathogenic· 204 VUS of 499 total submissions
📖
GeneReview available — NDUFA10
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.10LOEUF
pLI 0.000
Z-score 1.23
OE 0.70 (0.461.10)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.36Z-score
OE missense 1.07 (0.961.21)
206 obs / 191.9 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.70 (0.461.10)
00.351.4
Missense OE1.07 (0.961.21)
00.61.4
Synonymous OE0.98
01.21.6
LoF obs/exp: 14 / 20.0Missense obs/exp: 206 / 191.9Syn Z: 0.14
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongNDUFA10-related Leigh syndromeOTHERAR

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

DN
0.7132th %ile
GOF
0.5170th %ile
LOF
0.2775th %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

499 submitted variants in ClinVar

Classification Summary

Pathogenic93
Likely Pathogenic11
VUS204
Likely Benign96
Benign57
Conflicting26
93
Pathogenic
11
Likely Pathogenic
204
VUS
96
Likely Benign
57
Benign
26
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
2
91
0
93
Likely Pathogenic
1
4
6
0
11
VUS
3
91
105
5
204
Likely Benign
0
7
62
27
96
Benign
0
1
53
3
57
Conflicting
26
Total410531735487

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

View in ClinVar →

Protein Context — Lollipop Plot

NDUFA10 · 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
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