NDUFS7

NADH:ubiquinone oxidoreductase core subunit S7, the group of NADH:ubiquinone oxidoreductase core subunits

Basic information

Region (hg38): 19:1383526-1395589

Links

ENSG00000115286 ∙ NCBI:374291 ∙ OMIM:601825 ∙ HGNC:7714 ∙ Uniprot:O75251 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• mitochondrial complex I deficiency, nuclear type 1 (Definitive), mode of inheritance: AR
• mitochondrial complex I deficiency (Supportive), mode of inheritance: AR
• Leigh syndrome with leukodystrophy (Supportive), mode of inheritance: AR
• mitochondrial complex 1 deficiency, nuclear type 3 (Strong), mode of inheritance: AR
• Leigh syndrome (Moderate), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Mitochondrial complex I deficiency, nuclear type 3; Leigh syndrome	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Biochemical; Cardiovascular; Gastrointestinal; Neurologic; Ophthalmologic	10330338; 11743516; 17275378; 17604671
Medical treatment (eg, riboflavin, ubiquinol) may be beneficial; Individuals may have cardiac involvement

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the NDUFS7 gene.

• not provided (165 variants)
• not specified (31 variants)
• Leigh syndrome (23 variants)
• Mitochondrial complex I deficiency, nuclear type 1 (18 variants)
• Mitochondrial complex 1 deficiency, nuclear type 3 (12 variants)
• Inborn genetic diseases (9 variants)
• Mitochondrial complex I deficiency (3 variants)
• Intellectual disability (1 variants)
• Deficiency of guanidinoacetate methyltransferase (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NDUFS7 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			6	35	1	42
missense		3	34	1	1	39
nonsense	1	1				2
start loss	1					1
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)		2	1			3
splice region			3	3		6
non coding		1	2	50	29	82
Total	2	7	43	86	31

Highest pathogenic variant AF is 0.00000657

Variants in NDUFS7

This is a list of pathogenic ClinVar variants found in the NDUFS7 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
19-1383551-G-C			Benign (Jun 14, 2018)
19-1383562-C-T			Likely benign (Jun 28, 2018)
19-1383644-A-G			Likely benign (Jul 07, 2018)
19-1383650-G-T			Benign (Jun 14, 2018)
19-1383919-A-C		not specified	Likely benign (Feb 26, 2018)
19-1383921-G-A		not specified	Likely benign (Mar 08, 2016)
19-1383926-G-C			Uncertain significance (Feb 23, 2022)
19-1383928-T-C			Pathogenic (Sep 30, 2013)
19-1383931-C-T		Leigh syndrome • Mitochondrial complex I deficiency, nuclear type 1 • Inborn genetic diseases	Uncertain significance (Oct 17, 2022)
19-1383932-G-A			Likely benign (Dec 21, 2023)
19-1383935-G-A			Likely benign (Dec 30, 2023)
19-1383943-G-C			Likely pathogenic (Jun 23, 2023)
19-1383948-C-T			Uncertain significance (Aug 21, 2022)
19-1383949-G-A			Likely benign (Dec 04, 2023)
19-1383954-A-G			Likely benign (May 07, 2023)
19-1383956-C-T			Likely benign (Dec 09, 2023)
19-1383957-G-A			Likely benign (Jul 22, 2023)
19-1383957-G-T			Likely benign (May 31, 2023)
19-1383958-G-A			Likely benign (Jun 11, 2023)
19-1383960-GGCGGGTGTGGGGCCGC-G			Likely benign (Jan 20, 2023)
19-1383960-G-GGCGGGTGTGGGGCCGC			Likely benign (Nov 07, 2023)
19-1384022-G-C			Likely benign (Jun 23, 2018)
19-1384247-C-T			Likely benign (Jun 14, 2018)
19-1386644-C-G		Mitochondrial complex 1 deficiency, nuclear type 3 • Leigh syndrome	Likely pathogenic (May 17, 2022)
19-1386687-G-A			Benign (Dec 01, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
NDUFS7	protein_coding	protein_coding	ENST00000233627	8	12058

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.914	0.0857	125425	0	11	125436	0.0000438

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.991	121	156	0.777	0.0000121	1358
Missense in Polyphen		40	68.929	0.58031		630
Synonymous	-1.73	80	62.6	1.28	0.00000567	423
Loss of Function	2.98	1	12.3	0.0814	6.29e-7	127

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000620	0.0000617
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000548	0.0000544
Finnish	0.0000470	0.0000462
European (Non-Finnish)	0.0000623	0.0000618
Middle Eastern	0.0000548	0.0000544
South Asian	0.0000327	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Core subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I) that is believed to belong to the minimal assembly required for catalysis. Complex I functions in the transfer of electrons from NADH to the respiratory chain. The immediate electron acceptor for the enzyme is believed to be ubiquinone. {ECO:0000305|PubMed:12611891}.
• Disease: DISEASE: Leigh syndrome (LS) [MIM:256000]: An early-onset progressive neurodegenerative disorder characterized by the presence of focal, bilateral lesions in one or more areas of the central nervous system including the brainstem, thalamus, basal ganglia, cerebellum and spinal cord. Clinical features depend on which areas of the central nervous system are involved and include subacute onset of psychomotor retardation, hypotonia, ataxia, weakness, vision loss, eye movement abnormalities, seizures, and dysphagia. {ECO:0000269|PubMed:10360771}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Mitochondrial complex I deficiency (MT-C1D) [MIM:252010]: A disorder of the mitochondrial respiratory chain that causes a wide range of clinical manifestations from lethal neonatal disease to adult-onset neurodegenerative disorders. Phenotypes include macrocephaly with progressive leukodystrophy, non-specific encephalopathy, cardiomyopathy, myopathy, liver disease, Leigh syndrome, Leber hereditary optic neuropathy, and some forms of Parkinson disease. {ECO:0000269|PubMed:10330338}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Retrograde endocannabinoid signaling - Homo sapiens (human);Non-alcoholic fatty liver disease (NAFLD) - Homo sapiens (human);Alzheimer,s disease - Homo sapiens (human);Huntington,s disease - Homo sapiens (human);Thermogenesis - Homo sapiens (human);Oxidative phosphorylation - Homo sapiens (human);Doxorubicin Pathway, Pharmacokinetics;Parkinson,s disease - Homo sapiens (human);Doxorubicin Metabolism Pathway;Electron Transport Chain;Oxidative phosphorylation;Respiratory electron transport;The citric acid (TCA) cycle and respiratory electron transport;Metabolism;Complex I biogenesis;Respiratory electron transport, ATP synthesis by chemiosmotic coupling, and heat production by uncoupling proteins. (Consensus)

Intolerance Scores

• loftool: 0.127
• rvis_EVS: -0.18
• rvis_percentile_EVS: 39.95

Haploinsufficiency Scores

• pHI: 0.0865
• hipred: Y
• hipred_score: 0.696
• ghis: 0.568

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.996

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Ndufs7
• Phenotype: cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); growth/size/body region phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); embryo phenotype

Gene ontology

• Biological process: mitochondrial electron transport, NADH to ubiquinone;aerobic respiration;electron transport coupled proton transport;mitochondrial respiratory chain complex I assembly
• Cellular component: mitochondrial respiratory chain complex I;mitochondrial matrix;neuron projection;neuronal cell body;synaptic membrane
• Molecular function: protease binding;NADH dehydrogenase activity;protein binding;NADH dehydrogenase (ubiquinone) activity;oxidoreductase activity, acting on NAD(P)H, quinone or similar compound as acceptor;metal ion binding;quinone binding;4 iron, 4 sulfur cluster binding