NDUFAF5

Chr 20AR

NADH:ubiquinone oxidoreductase complex assembly factor 5

Also known as: C20orf7, MC1DN16, bA526K24.2, dJ842G6.1

NCBI Gene: 79133 ENSG00000101247 UniProt: Q5TEU4 OMIM: 612360

The protein is required for assembly of mitochondrial respiratory chain complex I, which catalyzes electron transfer from NADH to ubiquinone. Mutations cause mitochondrial complex I deficiency, nuclear type 16, inherited in an autosomal recessive pattern. The pathogenic mechanism involves impaired complex I assembly leading to deficient mitochondrial respiratory chain function.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

The NADH-ubiquinone oxidoreductase complex (complex I) of the mitochondrial respiratory chain catalyzes the transfer of electrons from NADH to ubiquinone, and consists of at least 43 subunits. The complex is located in the inner mitochondrial membrane. This gene encodes a mitochondrial protein that is associated with the matrix face of the mitochondrial inner membrane and is required for complex I assembly. A mutation in this gene results in mitochondrial complex I deficiency. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2009]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Mitochondrial complex I deficiency, nuclear type 16MIM #618238

Clinical highlights

Gene–disease validity (ClinGen)

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.20

LOEUF

—

Mechanism

📖

GeneReview available — NDUFAF5

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.20LOEUF

pLI 0.000

Z-score 0.85

OE 0.80 (0.55–1.20)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.15Z-score

OE missense 0.97 (0.86–1.09)

187 obs / 192.9 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.80 (0.55–1.20)

0≤0.351.4

Missense OE?0.97 (0.86–1.09)

0≤0.61.4

Synonymous OE?1.06

0≤1.21.6

LoF obs/exp: 17 / 21.2Missense obs/exp: 187 / 192.9Syn Z: -0.41

Background carrier burden — how many people carry a rare variant somewhere in NDUFAF5?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 120

463 rare PASS variants

Rare truncating (LoF)

1 in 1,000

86 rare PASS variants

Rare synonymous (reference)

1 in 170

162 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for NDUFAF5. 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 160	1 in 1,000
South Asian	~43k	1 in 130	1 in 470
Remaining (unassigned)	~30k	1 in 95	1 in 1,600
European (Finnish)	~27k	1 in 590	1 in 3,300
Admixed American	~22k	1 in 280	1 in 700
African / African American	~21k	1 in 98	1 in 2,500
East Asian	~20k	1 in 89	≈ 1 in 5,000
Ashkenazi Jewish	~13k	1 in 320	1 in 1,500
Middle Eastern	~2,884	1 in 120	≈ 1 in 1,400

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): 7 of 11 coding exons well covered in gnomAD exomes; exons 3, 6, 8, 10 marginal. Genomes: all 11.? see exons ↓