NDUFC2

Chr 11AR

NADH:ubiquinone oxidoreductase subunit C2

Also known as: B14.5b, CI-B14.5b, HLC-1, MC1DN36, NADHDH2

NCBI Gene: 4718 ENSG00000151366 UniProt: O95298 OMIM: 603845

Predicted to enable NADH dehydrogenase (ubiquinone) activity. Involved in mitochondrial respiratory chain complex I assembly. Located in mitochondrial inner membrane. Part of respiratory chain complex I. Implicated in nuclear type mitochondrial complex I deficiency. [provided by Alliance of Genome Resources, Jul 2025]

OMIM Research

OMIM ResearchGenerating clinical summary…

DNmechanismARLOEUF 0.801 OMIM phenotype

Clinical Summary— NDUFC2

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Gene-Disease Validity (ClinGen)

Leigh syndrome · ARModerate

Moderate evidence — consider for supplementary testing

2 total gene-disease associations curated

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Population Constraint (gnomAD)

Moderately constrained gene (pLI 0.68) — some intolerance to loss-of-function variants.

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ClinVar Variants

3 unique Pathogenic / Likely Pathogenic· 2 VUS of 10 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.80LOEUF

pLI 0.681

Z-score 1.79

OE 0.00 (0.00–0.80)

Moderately constrained

Typical tolerance to LoF variation

Missense Constraint?

0.24Z-score

OE missense 0.92 (0.75–1.14)

62 obs / 67.5 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.00 (0.00–0.80)

0≤0.351.4

Missense OE?0.92 (0.75–1.14)

0≤0.61.4

Synonymous OE?0.98

0≤1.21.6

LoF obs/exp: 0 / 3.7Missense obs/exp: 62 / 67.5Syn Z: 0.06

This gene — mechanism propensity

0.6549th %ile

GOF

0.5465th %ile

LOF

0.3648th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

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

ClinVar Variant Classifications

10 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic2

Likely Pathogenic1

VUS2

Likely Benign5

Pathogenic

Likely Pathogenic

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	1	1	0	0	2
Likely Pathogenic	1	0	0	0	1
VUS	0	2	0	0	2
Likely Benign	0	0	1	4	5
Benign	0	0	0	0	0
Total	2	3	1	4	10

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

View in ClinVar →

8 pathogenic / likely-pathogenic (of 17) ClinVar copy-number / structural variants overlap NDUFC2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →