NDUFS6

NADH:ubiquinone oxidoreductase subunit S6, the group of NADH:ubiquinone oxidoreductase supernumerary subunits

Basic information

Region (hg38): 5:1801407-1816048

Links

ENSG00000145494

∙ NCBI:4726 ∙ OMIM:603848 ∙ HGNC:7713 ∙ Uniprot:O75380 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

mitochondrial complex I deficiency, nuclear type (Moderate), mode of inheritance: AR
mitochondrial complex I deficiency, nuclear type 9 (Strong), mode of inheritance: AR
mitochondrial complex I deficiency (Supportive), mode of inheritance: AR
mitochondrial disease (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Mitochondrial complex I deficiency, nuclear type 9	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	11743516; 15372108; 19259137
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 NDUFS6 gene.

not_provided (173 variants)
Mitochondrial_complex_I_deficiency,_nuclear_type_9 (30 variants)
Mitochondrial_complex_I_deficiency (25 variants)
Inborn_genetic_diseases (19 variants)
Mitochondrial_complex_I_deficiency,_nuclear_type_1 (8 variants)
not_specified (5 variants)
NDUFS6-related_disorder (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NDUFS6 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000004553.6. Only rare variants are included in the table.

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.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous			3 clinvar	74 clinvar	1 clinvar	78
missense	1 clinvar	5 clinvar	43 clinvar	4 clinvar		53
nonsense	1 clinvar	3 clinvar				4
start loss			1			1
frameshift	7 clinvar	10 clinvar				17
splice donor/acceptor (+/-2bp)	1 clinvar	10 clinvar	1 clinvar			12
Total	10	28	48	78	1

Highest pathogenic variant AF is 0.000018588375

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
NDUFS6	protein_coding	protein_coding	ENST00000274137	4	15206

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0964	0.781	125733	0	15	125748	0.0000596

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.217	82	76.6	1.07	0.00000448	792
Missense in Polyphen		28	26.908	1.0406		266
Synonymous	-3.17	57	33.6	1.70	0.00000227	246
Loss of Function	1.18	2	4.78	0.419	2.01e-7	58

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000117	0.000117
Ashkenazi Jewish	0.00	0.00
East Asian	0.000114	0.000109
Finnish	0.00	0.00
European (Non-Finnish)	0.0000285	0.0000264
Middle Eastern	0.000114	0.000109
South Asian	0.000196	0.000196
Other	0.00	0.00

dbNSFP

Source: dbNSFP

Function: FUNCTION: Accessory subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I), that is believed not to be involved in 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:0000269|PubMed:27626371}.;
Disease: 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:15372108, ECO:0000269|PubMed:19259137}. 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);Metformin Pathway, Pharmacodynamic;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: 0.108

Intolerance Scores

loftool: 0.631
rvis_EVS: -0.16
rvis_percentile_EVS: 41.25

Haploinsufficiency Scores

pHI: 0.0584
hipred: N
hipred_score: 0.177
ghis: 0.573

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: E
gene_indispensability_score: 0.993

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Ndufs6
Phenotype: reproductive system 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); 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); cellular phenotype; homeostasis/metabolism phenotype; muscle phenotype; growth/size/body region phenotype;

Gene ontology

Biological process: mitochondrial electron transport, NADH to ubiquinone;fatty acid metabolic process;muscle contraction;multicellular organism aging;mitochondrial respiratory chain complex I assembly;multicellular organism growth;reproductive system development;mitochondrion morphogenesis;cardiovascular system development
Cellular component: mitochondrial inner membrane;mitochondrial respiratory chain complex I
Molecular function: NADH dehydrogenase (ubiquinone) activity;electron transfer activity