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…

ARLOEUF 1.201 OMIM phenotype

Clinical Summary— NDUFAF5

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Gene-Disease Validity (ClinGen)

Leigh syndrome · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

2 total gene-disease associations curated

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

126 unique Pathogenic / Likely Pathogenic· 123 VUS of 600 total submissions

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GeneReview available — NDUFAF5

Authoritative clinical overview · Recommended first read

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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

ClinVar Variant Classifications

600 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic35

Likely Pathogenic91

VUS123

Likely Benign292

Benign31

Conflicting22

Pathogenic

Likely Pathogenic

123

VUS

292

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	22	7	6	0	35
Likely Pathogenic	72	16	3	0	91
VUS	2	107	11	3	123
Likely Benign	1	12	132	147	292
Benign	0	0	28	3	31
Conflicting	—				22
Total	97	142	180	153	594

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

View in ClinVar →

20 pathogenic / likely-pathogenic (of 33) ClinVar copy-number / structural variants overlap NDUFAF5 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →