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 1 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 (1 variants)
• Neurodevelopmental delay (1 variants)
• Inborn genetic diseases (1 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.

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				20		20
missense		2	63	1		66
nonsense			1			1
start loss		2				2
frameshift	3		3			6
inframe indel						0
splice donor/acceptor (+/-2bp)		1	3			4
splice region			6	2		8
non coding			3	15	4	22
Total	3	5	73	36	4

Variants in NDUFS3

This is a list of pathogenic ClinVar variants found in the NDUFS3 region.

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

Position	Type	Phenotype	Significance	ClinVar
11-47565644-G-C		not specified	Uncertain significance (Jun 22, 2023)
11-47565953-G-C		not specified	Uncertain significance (Dec 27, 2023)
11-47569721-G-A		not specified	Uncertain significance (Nov 30, 2021)
11-47569730-C-T		not specified	Uncertain significance (Jul 08, 2022)
11-47569851-G-A		not specified	Uncertain significance (May 30, 2022)
11-47571486-C-A		not specified	Uncertain significance (Feb 13, 2024)
11-47571510-G-A		not specified	Likely benign (Jan 26, 2022)
11-47571585-G-A		not specified	Uncertain significance (Oct 29, 2021)
11-47571588-C-T		not specified	Uncertain significance (Jan 09, 2024)
11-47571628-G-C			Benign (Aug 22, 2018)
11-47573018-G-A		not specified	Uncertain significance (Oct 17, 2023)
11-47573102-G-C		not specified	Uncertain significance (Aug 22, 2022)
11-47573163-C-A		not specified	Uncertain significance (Jul 27, 2021)
11-47573243-T-G		not specified	Uncertain significance (Apr 19, 2023)
11-47573329-C-A		not specified	Uncertain significance (Aug 12, 2021)
11-47573355-C-T		not specified	Uncertain significance (Apr 20, 2023)
11-47573534-C-T		not specified	Uncertain significance (May 25, 2022)
11-47573660-T-C		not specified	Uncertain significance (Dec 27, 2023)
11-47573700-C-T		not specified	Uncertain significance (Sep 20, 2023)
11-47575618-G-A		not specified	Uncertain significance (Nov 18, 2022)
11-47575636-T-C		not specified	Uncertain significance (Jul 11, 2023)
11-47575690-G-A		not specified	Uncertain significance (Apr 13, 2022)
11-47577419-A-G		not specified	Uncertain significance (May 31, 2023)
11-47577435-G-A		not specified	Uncertain significance (Apr 04, 2024)
11-47577512-T-C		not specified	Uncertain significance (May 31, 2023)

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