NDUFS3

NADH:ubiquinone oxidoreductase core subunit S3, the group of NADH:ubiquinone oxidoreductase core subunits

Basic information

Region (hg38): 11:47565336-47584562

Links

ENSG00000213619

∙ NCBI:4722 ∙ OMIM:603846 ∙ HGNC:7710 ∙ Uniprot:O75489 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

mitochondrial complex I deficiency (Supportive), mode of inheritance: AR
Leigh syndrome with leukodystrophy (Supportive), mode of inheritance: AR
mitochondrial complex I deficiency, nuclear type 8 (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 8; 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	11743516; 14729820; 22499348; 33097395
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 NDUFS3 gene.

not_provided (109 variants)
Inborn_genetic_diseases (32 variants)
Leigh_syndrome (18 variants)
Mitochondrial_complex_I_deficiency,_nuclear_type_1 (17 variants)
Mitochondrial_complex_I_deficiency,_nuclear_type_8 (15 variants)
not_specified (8 variants)
NDUFS3-related_disorder (7 variants)
Mitochondrial_complex_I_deficiency (3 variants)
Neurodevelopmental_delay (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NDUFS3 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000004551.3. 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				27 clinvar		27
missense		4 clinvar	74 clinvar	3 clinvar		81
nonsense			1 clinvar			1
start loss		2				2
frameshift	3 clinvar		3 clinvar			6
splice donor/acceptor (+/-2bp)		1 clinvar	2 clinvar			3
Total	3	7	80	30	0

Highest pathogenic variant AF is 0.0000260201

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
NDUFS3	protein_coding	protein_coding	ENST00000263774	7	19227

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000583	0.907	125699	0	49	125748	0.000195

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.0153	150	149	1.00	0.00000958	1698
Missense in Polyphen		54	59.832	0.90253		667
Synonymous	-0.767	68	60.4	1.13	0.00000345	542
Loss of Function	1.50	7	12.8	0.548	5.70e-7	154

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000264	0.000264
Ashkenazi Jewish	0.000299	0.000298
East Asian	0.000228	0.000217
Finnish	0.00	0.00
European (Non-Finnish)	0.000240	0.000237
Middle Eastern	0.000228	0.000217
South Asian	0.000134	0.000131
Other	0.000492	0.000489

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). {ECO:0000250}.;
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)

Recessive Scores

pRec: 0.367

Intolerance Scores

loftool: 0.405
rvis_EVS: -0.16
rvis_percentile_EVS: 41.64

Haploinsufficiency Scores

pHI: 0.270
hipred: N
hipred_score: 0.321
ghis: 0.584

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: S
essential_gene_gene_trap: H
gene_indispensability_pred: E
gene_indispensability_score: 0.992

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Ndufs3
Phenotype: hematopoietic system 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); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); homeostasis/metabolism phenotype; growth/size/body region phenotype;

Gene ontology

Biological process: mitochondrial electron transport, NADH to ubiquinone;substantia nigra development;negative regulation of cell growth;mitochondrial respiratory chain complex I assembly;reactive oxygen species metabolic process;negative regulation of intrinsic apoptotic signaling pathway
Cellular component: mitochondrion;mitochondrial respiratory chain complex I;mitochondrial matrix;nuclear body;mitochondrial membrane;myelin sheath
Molecular function: NADH dehydrogenase activity;protein binding;NADH dehydrogenase (ubiquinone) activity;electron transfer activity