NDUFA6

Chr 22AR

NADH:ubiquinone oxidoreductase subunit A6

Also known as: B14, CI-B14, LYRM6, MC1DN33, NADHB14

NCBI Gene: 4700ENSG00000184983UniProt: P56556OMIM: 602138

The protein is an accessory subunit of mitochondrial Complex I (NADH dehydrogenase) that is required for proper enzyme assembly and functions in electron transfer from NADH to the respiratory chain. Mutations cause mitochondrial complex I deficiency, nuclear type 33, which follows autosomal recessive inheritance. The gene shows low constraint to loss-of-function variation (pLI 0.0001, LOEUF 1.714), suggesting haploinsufficiency is not the primary disease mechanism.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 1.711 OMIM phenotype
Clinical Summary— NDUFA6
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Gene-Disease Validity (ClinGen)
mitochondrial disease · ARModerate

Moderate evidence — consider for supplementary testing

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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ClinVar Variants
32 unique Pathogenic / Likely Pathogenic· 47 VUS of 122 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
1.71LOEUF
pLI 0.000
Z-score 0.17
OE 0.93 (0.50–1.71)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.80Z-score
OE missense 1.24 (1.06–1.45)
111 obs / 89.7 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.93 (0.50–1.71)
0≤0.351.4
Missense OE1.24 (1.06–1.45)
0≤0.61.4
Synonymous OE1.60
0≤1.21.6
LoF obs/exp: 6 / 6.5Missense obs/exp: 111 / 89.7Syn Z: -2.70
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongNDUFA6-related early onset isolated mitochondrial complex I deficiencyLOFAR

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

DN
0.7327th %ile
GOF
0.6540th %ile
LOF
0.3454th %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

122 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic30
Likely Pathogenic2
VUS47
Likely Benign27
Benign4
Conflicting3
30
Pathogenic
2
Likely Pathogenic
47
VUS
27
Likely Benign
4
Benign
3
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
3
1
26
0
30
Likely Pathogenic
1
0
1
0
2
VUS
3
31
13
0
47
Likely Benign
0
2
12
13
27
Benign
0
1
3
0
4
Conflicting
—3
Total7355513113

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

View in ClinVar →

Protein Context — Lollipop Plot

NDUFA6 · 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

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Ndufa6 regulates adipogenic differentiation via Scd1.
Zhang J et al.·Adipocyte
2021Open Access
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients