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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
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NDUFAF7
NADH:ubiquinone oxidoreductase complex assembly factor 7
Chromosome 2 Β· 2p22.2
NCBI Gene: 55471Ensembl: ENSG00000003509.17HGNC: HGNC:28816UniProt: B4DQY3
31PubMed Papers
20Diseases
0Drugs
2Pathogenic Variants
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
protein bindingmitochondrial respiratory chain complex I assemblymitochondrionGO:0005615hypertensionIncreased blood pressureschizophreniaresponse to xenobiotic stimulus
✦AI Summary

NDUFAF7 is an arginine methyltransferase essential for assembling the mitochondrial NADH:ubiquinone oxidoreductase complex (complex I), a critical component of the respiratory chain. The protein functions by catalyzing symmetric dimethylation of arginine-118 (and potentially arginine-85) on the NDUFS2 subunit after it incorporates into complex I, thereby stabilizing early assembly intermediates 1. This methylation-mediated mechanism is conserved from bacteria to humans 2, with methylation promoting substrate release to regulate the assembly process. NDUFAF7 dysfunction has been implicated in multiple disease contexts. Loss of NDUFAF7 function causes rapid, protease-dependent degradation of ND1 and decreased levels of other structural subunits, resulting in complex I assembly failure 1. Germline disruption in mice is embryonic lethal, underscoring its developmental importance. NDUFAF7 variants have been identified as disease-causing in early-onset high myopia, with both pathogenic and potentially pathogenic mutations reported in affected families 34. Additionally, NDUFAF7 was identified as a mitochondria-related biomarker in childhood allergic asthma, with downregulation correlating to disease pathogenesis 5. A common variant near PRKD3/NDUFAF7 was associated with Alzheimer's disease risk in large-scale genetic studies 6. These findings establish NDUFAF7 as a critical mitochondrial assembly factor with broad clinical relevance to neurological, developmental, and metabolic disorders.

Sources cited
1
NDUFAF7 mediates symmetric dimethylation of NDUFS2, stabilizing early complex I intermediates; knockout causes ND1 degradation and assembly defect; germline disruption is embryonic lethal
PMID: 24838397
2
NDUFAF7 (MidA ortholog) mechanism and origin of protein arginine methylation in complex I assembly is conserved from bacteria to humans
PMID: 30134162
3
NDUFAF7 mutations (c.995C > A, p.Thr332Lys and c.960T > A, p.His320Gln) are pathogenic or potentially pathogenic in early-onset high myopia
PMID: 32215939
4
NDUFAF7 variant c.799G > A/p.E267K identified as disease-causing gene for nonsyndromic early-onset high myopia in Chinese families
PMID: 36964802
5
NDUFAF7 identified as mitochondria-related hub gene and biomarker in childhood allergic asthma with downregulation in disease samples
PMID: 38783263
6
Common variant in PRKD3/NDUFAF7 region associated with Alzheimer's disease risk
PMID: 34099642
Disease Associationsβ“˜20
hypertensionOpen Targets
0.26Weak
Increased blood pressureOpen Targets
0.10Weak
schizophreniaOpen Targets
0.08Suggestive
response to xenobiotic stimulusOpen Targets
0.07Suggestive
essential hypertensionOpen Targets
0.06Suggestive
alcohol drinkingOpen Targets
0.04Suggestive
cervical squamous intraepithelial neoplasiaOpen Targets
0.01Suggestive
cancerOpen Targets
0.01Suggestive
myopiaOpen Targets
0.01Suggestive
Abnormal sperm morphologyOpen Targets
0.01Suggestive
Alzheimer diseaseOpen Targets
0.01Suggestive
cutaneous melanomaOpen Targets
0.01Suggestive
osteosarcomaOpen Targets
0.00Suggestive
ulcerative colitisOpen Targets
0.00Suggestive
mitochondrial diseaseOpen Targets
0.00Suggestive
Werner syndromeOpen Targets
0.00Suggestive
Friedreich ataxiaOpen Targets
0.00Suggestive
genetic disorderOpen Targets
0.00Suggestive
Haim-Munk syndromeOpen Targets
0.00Suggestive
Opitz G/BBB syndromeOpen Targets
0.00Suggestive
Pathogenic Variants2
NM_144736.5(NDUFAF7):c.96_100del (p.Asn33fs)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2018β†’ Residue 33
NM_144736.5(NDUFAF7):c.644A>G (p.His215Arg)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2013β†’ Residue 215
View on ClinVar β†—
Related Genes
NDUFAF8Shared pathway100%DMAC1Shared pathway100%LYRM2Shared pathway100%FOXRED1Shared pathway100%NDUFAF5Protein interaction95%NDUFS2Protein interaction95%
Tissue Expression6 tissues
Heart
100%
Liver
66%
Ovary
51%
Bone Marrow
46%
Lung
46%
Brain
33%
Gene Interaction Network
Click a node to explore
NDUFAF7NDUFAF8DMAC1LYRM2FOXRED1NDUFAF5NDUFS2
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted Β· UniProt Q7L592
View on AlphaFold β†—
Constraintβ“˜
LOEUFβ“˜
1.34LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF1.05 [0.83–1.34]
RankingsWhere NDUFAF7 stands among ~20K protein-coding genes
  • #11,753of 20,598
    Most Researched31
  • #4,512of 5,498
    Most Pathogenic Variants2
  • #14,048of 17,882
    Most Constrained (LOEUF)1.34
Genes detectedNDUFAF7
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Common variants in Alzheimer's disease and risk stratification by polygenic risk scores.
PMID: 34099642
Nat Commun Β· 2021
1.00
2
Identification of mitochondria-related biomarkers in childhood allergic asthma.
PMID: 38783263
BMC Med Genomics Β· 2024
0.90
3
Proteobacterial Origin of Protein Arginine Methylation and Regulation of Complex I Assembly by MidA.
PMID: 30134162
Cell Rep Β· 2018
0.80
4
Proteomic Analysis of Human Topoisomerases Reveals Their Distinct and Diverse Cellular Functions.
PMID: 41043513
Mol Cell Proteomics Β· 2025
0.70
5
Mutation screening of 17 candidate genes in a cohort of 67 probands with early-onset high myopia.
PMID: 32215939
Ophthalmic Physiol Opt Β· 2020
0.60