NDUFC2

NADH:ubiquinone oxidoreductase subunit C2, the group of NADH:ubiquinone oxidoreductase supernumerary subunits

Basic information

Region (hg38): 11:78068296-78079862

Links

ENSG00000151366 ∙ NCBI:4718 ∙ OMIM:603845 ∙ HGNC:7706 ∙ Uniprot:O95298 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• mitochondrial complex 1 deficiency, nuclear type 36 (Limited), mode of inheritance: Unknown
• Leigh syndrome (Moderate), mode of inheritance: AR
• mitochondrial disease (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 36	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; Neurologic; Ophthalmologic	32969598

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the NDUFC2 gene.

• Mitochondrial complex 1 deficiency, nuclear type 36 (2 variants)
• not provided (2 variants)
• Mitochondrial disease (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NDUFC2 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						0
missense	1		1			2
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding				1		1
Total	1	0	1	1	0

Variants in NDUFC2

This is a list of pathogenic ClinVar variants found in the NDUFC2 region.

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

Position	Type	Phenotype	Significance	ClinVar
11-78069876-C-T			Likely benign (Sep 01, 2022)
11-78069900-A-G			Likely benign (Jan 01, 2024)
11-78069979-TGAAGACTTCAACGTATTGGATG-T		Mitochondrial complex 1 deficiency, nuclear type 36 • Mitochondrial disease	Pathogenic (Feb 10, 2020)
11-78073049-G-A			Uncertain significance (Jan 01, 2023)
11-78073135-T-A		Mitochondrial complex 1 deficiency, nuclear type 36 • Mitochondrial disease	Pathogenic (Feb 10, 2020)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
NDUFC2	protein_coding	protein_coding	ENST00000281031	3	11916

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.681	0.301	117701	0	2	117703	0.00000850

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.238	62	67.5	0.919	0.00000388	748
Missense in Polyphen		32	34.445	0.92901		340
Synonymous	0.0640	25	25.4	0.984	0.00000124	232
Loss of Function	1.79	0	3.73	0.00	1.54e-7	57

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.000113	0.000113
Finnish	0.00	0.00
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.000113	0.000113
South Asian	0.00	0.00
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}.
• 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;Neutrophil degranulation;Respiratory electron transport;The citric acid (TCA) cycle and respiratory electron transport;Innate Immune System;Immune System;Metabolism;Complex I biogenesis;Respiratory electron transport, ATP synthesis by chemiosmotic coupling, and heat production by uncoupling proteins. (Consensus)

Recessive Scores

• pRec: 0.0703

Intolerance Scores

• loftool: 0.493
• rvis_EVS: 0.13
• rvis_percentile_EVS: 62.74

Haploinsufficiency Scores

• pHI: 0.0391
• hipred: N
• hipred_score: 0.164
• ghis: 0.395

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: H
• gene_indispensability_pred: N
• gene_indispensability_score: 0.0733

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Ndufc2

Gene ontology

• Biological process: mitochondrial electron transport, NADH to ubiquinone;mitochondrial respiratory chain complex I assembly;neutrophil degranulation
• Cellular component: cytoplasm;mitochondrion;mitochondrial inner membrane;mitochondrial respiratory chain complex I;plasma membrane;integral component of membrane;azurophil granule membrane
• Molecular function: NADH dehydrogenase (ubiquinone) activity