NDUFAF3

Chr 3AR

NADH:ubiquinone oxidoreductase complex assembly factor 3

Also known as: 2P1, C3orf60, E3-3, MC1DN18

NCBI Gene: 25915ENSG00000178057UniProt: Q9BU61OMIM: 612911

The protein encoded by this gene is a mitochondrial complex I assembly protein that interacts with complex I subunits to facilitate proper assembly of the respiratory chain complex. Mutations cause mitochondrial complex I deficiency (nuclear type 18), a fatal neonatal disorder of the oxidative phosphorylation system, inherited in an autosomal recessive pattern. The pathogenic mechanism involves disrupted assembly of complex I, leading to defective mitochondrial respiratory chain function.

OMIMResearchSummary from RefSeq, OMIM, UniProt
ARLOEUF 1.071 OMIM phenotype
Clinical Summary— NDUFAF3
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Gene-Disease Validity (ClinGen)
mitochondrial disease · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.01) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
21 unique Pathogenic / Likely Pathogenic· 69 VUS of 153 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
1.07LOEUF
pLI 0.005
Z-score 1.43
OE 0.51 (0.26–1.07)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.49Z-score
OE missense 1.14 (0.98–1.32)
120 obs / 105.7 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.51 (0.26–1.07)
0≤0.351.4
Missense OE1.14 (0.98–1.32)
0≤0.61.4
Synonymous OE1.09
0≤1.21.6
LoF obs/exp: 5 / 9.8Missense obs/exp: 120 / 105.7Syn Z: -0.47

ClinVar Variant Classifications

153 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic16
Likely Pathogenic5
VUS69
Likely Benign39
Benign2
Conflicting15
16
Pathogenic
5
Likely Pathogenic
69
VUS
39
Likely Benign
2
Benign
15
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
4
11
0
16
Likely Pathogenic
2
1
2
0
5
VUS
1
45
21
2
69
Likely Benign
0
1
22
16
39
Benign
0
0
1
1
2
Conflicting
—15
Total4515719146

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

View in ClinVar →

Protein Context — Lollipop Plot

NDUFAF3 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Comparing divergence landscapes from reduced-representation and whole genome resequencing in the yellow-rumped warbler (Setophaga coronata) species complex.
Szarmach SJ et al.·Mol Ecol
2021
Metabolic Osteoimmune Biodegradable Zn-Mn Alloys: High Strength-Ductility and In Situ Vascular-Osteogenic Coupling.
Li XM et al.·Adv Mater
2025
Identification of lactate-related subgroups and prognostic model in triple-negative breast cancer.
Huang SS et al.·J Cancer Res Clin Oncol
2023Functional
Integrative genetics and multiomics analysis reveal mechanisms and therapeutic targets in vitiligo highlighting JAK STAT pathway regulation of CTSS.
Dong ZY et al.·Sci Rep
2025Functional
Exploring the lactate-metabolism related characteristics during the development of medulloblastoma through single-cell and bulk RNA-seq.
Wang C et al.·Transl Cancer Res
2026
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Expanding the phenotypic and biochemical spectrum of NDUFAF3-related mitochondrial disease.
van der Ven AT et al.·Mol Genet Metab
2023Case report
Immunomodulatory Mechanisms of Rehmanniae Radix Praeparata-Achyranthes Root-Chinese Angelica Root Combination in Nontraumatic Osteonecrosis of the Femoral Head: A Comprehensive Network Pharmacology and Molecular Docking Study Focusing on Immunological Pathways.
Li X et al.·Mediators Inflamm
2025Functional
Mutations in mitochondrial complex I assembly factor NDUFAF3 cause Leigh syndrome.
Baertling F et al.·Mol Genet Metab
2017Case report
NDUFAF3 variants that disrupt mitochondrial complex I assembly may associate with cavitating leukoencephalopathy.
Ishiyama A et al.·Clin Genet
2018Case report
Spectrum of Inherited Childhood-Onset Dystonia: Case Series of 19 Families With Genotype and Phenotype Characterization Highlighting the Treatable Causes.
Adarsha N et al.·Clin Genet
2025Cohort
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients