NDUFS8

NADH:ubiquinone oxidoreductase core subunit S8, the group of NADH:ubiquinone oxidoreductase core subunits|MicroRNA protein coding host genes

Basic information

Region (hg38): 11:68030616-68036644

Links

ENSG00000110717 ∙ NCBI:4728 ∙ OMIM:602141 ∙ HGNC:7715 ∙ Uniprot:O00217 ∙ 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 1 deficiency, nuclear type 2 (Strong), mode of inheritance: AR
• mitochondrial complex I deficiency (Supportive), mode of inheritance: AR
• Leigh syndrome with leukodystrophy (Supportive), 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 2; 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	9837812; 11743516; 15159508
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 NDUFS8 gene.

• not provided (86 variants)
• Leigh syndrome (28 variants)
• Mitochondrial complex I deficiency, nuclear type 1 (22 variants)
• Mitochondrial complex 1 deficiency, nuclear type 2 (16 variants)
• not specified (12 variants)
• Inborn genetic diseases (8 variants)
• Mitochondrial complex I deficiency (3 variants)
• Osteopetrosis (2 variants)
• See cases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NDUFS8 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			1	16		17
missense	1	5	37			43
nonsense			1			1
start loss		1				1
frameshift			1			1
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region			4	1		5
non coding		1	3	17	8	29
Total	1	7	43	33	8

Highest pathogenic variant AF is 0.0000197

Variants in NDUFS8

This is a list of pathogenic ClinVar variants found in the NDUFS8 region.

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

Position	Type	Phenotype	Significance	ClinVar
11-68030636-G-A		Leigh syndrome • Mitochondrial complex I deficiency	Uncertain significance (Jun 14, 2016)
11-68030658-C-T		Leigh syndrome • Mitochondrial complex I deficiency	Uncertain significance (Jun 14, 2016)
11-68030689-A-C		not specified • Mitochondrial complex I deficiency, nuclear type 1 • Leigh syndrome	Benign/Likely benign (Apr 13, 2018)
11-68030717-AGCG-A		not specified	Likely benign (Jan 05, 2018)
11-68030771-G-C			Likely benign (Jan 13, 2021)
11-68032013-G-C			Benign (Jul 09, 2018)
11-68032117-C-T			Likely benign (Jun 26, 2018)
11-68032152-A-G			Uncertain significance (Mar 01, 2023)
11-68032155-C-T		Leigh syndrome • Mitochondrial complex I deficiency, nuclear type 1 • Inborn genetic diseases • Mitochondrial complex 1 deficiency, nuclear type 2 • NDUFS8-related disorder	Conflicting classifications of pathogenicity (Jan 22, 2024)
11-68032156-G-A		Mitochondrial complex I deficiency, nuclear type 1 • Leigh syndrome	Uncertain significance (Jan 12, 2018)
11-68032156-G-T		Inborn genetic diseases	Uncertain significance (Nov 27, 2023)
11-68032169-G-A			Likely benign (Jun 19, 2022)
11-68032170-C-A		Mitochondrial complex I deficiency, nuclear type 1 • Leigh syndrome	Conflicting classifications of pathogenicity (Nov 27, 2023)
11-68032183-G-A		Inborn genetic diseases	Uncertain significance (Feb 24, 2022)
11-68032204-G-A			Uncertain significance (Jan 27, 2022)
11-68032204-G-T		Leigh syndrome	Uncertain significance (Aug 21, 2022)
11-68032264-C-G		Mitochondrial complex 1 deficiency, nuclear type 2	Benign (Sep 05, 2021)
11-68032269-C-T			Benign (Jan 22, 2024)
11-68032276-C-G			Likely benign (Dec 31, 2019)
11-68032291-C-T		Mitochondrial complex I deficiency • Leigh syndrome	Uncertain significance (Nov 06, 2023)
11-68032305-C-T			Likely benign (Nov 17, 2023)
11-68032311-C-T			Likely benign (Jan 22, 2024)
11-68032312-A-G			Uncertain significance (Oct 28, 2021)
11-68032459-T-C			Benign (Jun 23, 2018)
11-68032639-C-T			Likely benign (Jul 15, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
NDUFS8	protein_coding	protein_coding	ENST00000313468	6	6028

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.166	0.821	125722	0	8	125730	0.0000318

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.744	119	144	0.826	0.0000107	1345
Missense in Polyphen		45	62.831	0.7162		569
Synonymous	-0.591	64	58.3	1.10	0.00000428	415
Loss of Function	2.15	3	10.5	0.286	5.38e-7	117

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000620	0.0000615
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000355	0.0000352
Middle Eastern	0.00	0.00
South Asian	0.0000980	0.0000980
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 (By similarity). May donate electrons to ubiquinone. {ECO:0000250}.
• 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:9837812}. 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);Parkinson,s disease - Homo sapiens (human);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)

Recessive Scores

• pRec: 0.256

Intolerance Scores

• loftool: 0.194
• rvis_EVS: -0.21
• rvis_percentile_EVS: 38.58

Haploinsufficiency Scores

• pHI: 0.173
• hipred: N
• hipred_score: 0.217
• ghis: 0.598

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.801

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Ndufs8

Gene ontology

• Biological process: mitochondrial electron transport, NADH to ubiquinone;response to oxidative stress;aerobic respiration;mitochondrial respiratory chain complex I assembly
• Cellular component: mitochondrion;mitochondrial respiratory chain complex I;mitochondrial matrix
• Molecular function: NADH dehydrogenase activity;NADH dehydrogenase (ubiquinone) activity;metal ion binding;4 iron, 4 sulfur cluster binding