NDUFV2

NADH:ubiquinone oxidoreductase core subunit V2, the group of NADH:ubiquinone oxidoreductase core subunits

Basic information

Region (hg38): 18:9102630-9134345

Links

ENSG00000178127 ∙ NCBI:4729 ∙ OMIM:600532 ∙ HGNC:7717 ∙ Uniprot:P19404 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• mitochondrial complex I deficiency, nuclear type 7 (Moderate), mode of inheritance: AR
• mitochondrial complex I deficiency, nuclear type 7 (Strong), mode of inheritance: AR
• mitochondrial complex I deficiency (Supportive), mode of inheritance: AR
• Leigh syndrome with leukodystrophy (Supportive), mode of inheritance: AR
• mitochondrial complex I deficiency, nuclear type 7 (Moderate), mode of inheritance: AR
• mitochondrial disease (Definitive), mode of inheritance: AR
• Leigh syndrome (Limited), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Mitochondrial complex I deficiency, nuclear type 7	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; 12754703; 21548921
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 NDUFV2 gene.

• not_provided (91 variants)
• Inborn_genetic_diseases (32 variants)
• Mitochondrial_complex_I_deficiency,_nuclear_type_7 (17 variants)
• Mitochondrial_complex_I_deficiency,_nuclear_type_1 (12 variants)
• not_specified (7 variants)
• NDUFV2-related_disorder (4 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NDUFV2 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000021074.5. 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	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	14		15
missense		3	57	2	1	63
nonsense			1			1
start loss		1				1
frameshift	6	4				10
splice donor/acceptor (+/-2bp)		1	1			2
Total	6	9	60	16	1

Highest pathogenic variant AF is 0.00013833659

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
NDUFV2	protein_coding	protein_coding	ENST00000318388	8	31716

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00558	0.973	125685	0	63	125748	0.000251

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.555	149	131	1.14	0.00000603	1608
Missense in Polyphen		51	47.298	1.0783		578
Synonymous	0.0650	42	42.5	0.987	0.00000194	477
Loss of Function	2.02	6	14.2	0.422	7.30e-7	172

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000868	0.0000868
Ashkenazi Jewish	0.00	0.00
East Asian	0.000381	0.000381
Finnish	0.000416	0.000416
European (Non-Finnish)	0.000299	0.000299
Middle Eastern	0.000381	0.000381
South Asian	0.000229	0.000229
Other	0.000491	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);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: 0.216

Intolerance Scores

• loftool: 0.814
• rvis_EVS: 0.13
• rvis_percentile_EVS: 63

Haploinsufficiency Scores

• pHI: 0.321
• hipred: N
• hipred_score: 0.287
• ghis: 0.542

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.553

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Ndufv2
• 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)

Gene ontology

• Biological process: mitochondrial electron transport, NADH to ubiquinone;nervous system development;mitochondrial respiratory chain complex I assembly;cardiac muscle tissue development
• Cellular component: mitochondrion;mitochondrial inner membrane;mitochondrial respiratory chain complex I;myelin sheath
• Molecular function: NADH dehydrogenase activity;protein binding;NADH dehydrogenase (ubiquinone) activity;electron transfer activity;metal ion binding;2 iron, 2 sulfur cluster binding