NDUFAF6

Chr 8AR

NADH:ubiquinone oxidoreductase complex assembly factor 6

Also known as: C8orf38, FRTS5, MC1DN17, lncREST

NCBI Gene: 137682ENSG00000156170UniProt: Q330K2

This gene encodes a protein that localizes to mitochondria and contains a predicted phytoene synthase domain. The encoded protein plays an important role in the assembly of complex I (NADH-ubiquinone oxidoreductase) of the mitochondrial respiratory chain through regulation of subunit ND1 biogenesis. Mutations in this gene are associated with complex I enzymatic deficiency. [provided by RefSeq, Nov 2011]

Primary Disease Associations & Inheritance

Fanconi renotubular syndrome 5MIM #618913
AR
Mitochondrial complex I deficiency, nuclear type 17MIM #618239
AR
373
ClinVar variants
73
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— NDUFAF6
🧬
Gene-Disease Validity (ClinGen)
Leigh syndrome · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

2 total gene-disease associations curated

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
73 Pathogenic / Likely Pathogenic· 154 VUS of 373 total submissions
Some data sources returned errors (1)

pubmed: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esummary.fcgi

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.20LOEUF
pLI 0.000
Z-score 0.95
OE 0.75 (0.49–1.20)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.57Z-score
OE missense 0.87 (0.76–1.00)
142 obs / 162.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.75 (0.49–1.20)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.87 (0.76–1.00)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.82
0≤1.21.6
LoF obs/exp: 13 / 17.3Missense obs/exp: 142 / 162.5Syn Z: 1.09

ClinVar Variant Classifications

373 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic52
Likely Pathogenic21
VUS154
Likely Benign90
Benign41
Conflicting15
52
Pathogenic
21
Likely Pathogenic
154
VUS
90
Likely Benign
41
Benign
15
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
7
5
40
0
52
Likely Pathogenic
7
4
10
0
21
VUS
1
141
12
0
154
Likely Benign
0
9
44
37
90
Benign
0
0
37
4
41
Conflicting
—15
Total1515914341373

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

View in ClinVar →

Protein Context — Lollipop Plot

NDUFAF6 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Fanconi renotubular syndrome 5

MIM #618913

Molecular basis of disorder known

Autosomal recessive

Mitochondrial complex I deficiency, nuclear type 17

MIM #618239

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — NDUFAF6
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools