NDUFC2

Chr 11

NADH:ubiquinone oxidoreductase subunit C2

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

NCBI Gene: 4718 ENSG00000151366 UniProt: O95298

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 and stroke. [provided by Alliance of Genome Resources, Jun 2026]

Research

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtMitochondrial complex I deficiency, nuclear type 36

Clinical highlights

Gene–disease validity (ClinGen)

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.80

LOEUF

Mechanism· predicted

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

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

Background carrier burden — how many people carry a rare variant somewhere in NDUFC2?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 440

189 rare PASS variants

Rare truncating (LoF)

1 in 2,600

20 rare PASS variants

Rare synonymous (reference)

1 in 310

71 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for NDUFC2. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 470	1 in 2,900
South Asian	~43k	1 in 410	1 in 1,100
Remaining (unassigned)	~30k	1 in 430	1 in 4,300
European (Finnish)	~27k	1 in 2,000	≈ 1 in 13,000
Admixed American	~22k	1 in 540	1 in 520
African / African American	~21k	1 in 860	1 in 1,600
East Asian	~20k	1 in 420	1 in 1,500
Ashkenazi Jewish	~13k	1 in 360	≈ 1 in 4,300
Middle Eastern	~2,883	1 in 310	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 2 of 3 coding exons well covered in gnomAD exomes; exon 3 marginal. Genomes: all 3.? see exons ↓