NDUFV1

NADH:ubiquinone oxidoreductase core subunit V1, the group of NADH:ubiquinone oxidoreductase core subunits

Basic information

Region (hg38): 11:67605653-67612554

Links

ENSG00000167792 ∙ NCBI:4723 ∙ OMIM:161015 ∙ HGNC:7716 ∙ Uniprot:P49821 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• mitochondrial complex I deficiency, nuclear type 4 (Definitive), mode of inheritance: AR
• mitochondrial complex I deficiency, nuclear type 4 (Strong), mode of inheritance: AR
• mitochondrial complex I deficiency (Supportive), mode of inheritance: AR
• Leigh syndrome with leukodystrophy (Supportive), mode of inheritance: AR
• Leigh syndrome (Definitive), mode of inheritance: AR
• mitochondrial complex I deficiency, nuclear type 4 (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 4	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	10080174; 11743516; 18991197; 21696386
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 NDUFV1 gene.

• not_provided (416 variants)
• Inborn_genetic_diseases (65 variants)
• Mitochondrial_complex_I_deficiency,_nuclear_type_4 (57 variants)
• Leigh_syndrome (54 variants)
• Mitochondrial_complex_I_deficiency,_nuclear_type_1 (51 variants)
• not_specified (46 variants)
• NDUFV1-related_disorder (19 variants)
• Mitochondrial_complex_I_deficiency (12 variants)
• See_cases (2 variants)
• Mitochondrial_complex_V_(ATP_synthase)_deficiency,_nuclear_type_5 (1 variants)
• Mitochondrial_complex_I_deficiency,_nuclear_type (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NDUFV1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000007103.4. 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	2	135	3	141
missense	4	26	150	7		187
nonsense	7	6				13
start loss		3				3
frameshift	15	10				25
splice donor/acceptor (+/-2bp)	1	7			1	9
Total	27	53	152	142	4

Highest pathogenic variant AF is 0.000161705

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
NDUFV1	protein_coding	protein_coding	ENST00000322776	10	5684

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
6.36e-11	0.232	125689	0	59	125748	0.000235

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.282	281	295	0.954	0.0000212	2980
Missense in Polyphen		120	143.35	0.83713		1402
Synonymous	0.142	120	122	0.984	0.00000905	968
Loss of Function	0.799	18	22.0	0.816	0.00000121	241

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000452	0.000452
Ashkenazi Jewish	0.000198	0.000198
East Asian	0.00	0.00
Finnish	0.000282	0.000277
European (Non-Finnish)	0.000266	0.000264
Middle Eastern	0.00	0.00
South Asian	0.000394	0.000392
Other	0.00	0.00

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}.
• Disease: DISEASE: Leigh syndrome (LS) [MIM:256000]: An early-onset progressive neurodegenerative disorder characterized by the presence of focal, bilateral lesions in one or more areas of the central nervous system including the brainstem, thalamus, basal ganglia, cerebellum and spinal cord. Clinical features depend on which areas of the central nervous system are involved and include subacute onset of psychomotor retardation, hypotonia, ataxia, weakness, vision loss, eye movement abnormalities, seizures, and dysphagia. {ECO:0000269|PubMed:10080174}. Note=The disease is caused by mutations affecting the gene represented in this entry.; 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:10080174, ECO:0000269|PubMed:11349233}. 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: 0.260

Intolerance Scores

• loftool: 0.102
• rvis_EVS: -1.49
• rvis_percentile_EVS: 3.63

Haploinsufficiency Scores

• pHI: 0.154
• hipred: N
• hipred_score: 0.346
• ghis: 0.648

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.860

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Ndufv1

Gene ontology

• Biological process: mitochondrial electron transport, NADH to ubiquinone;mitochondrial respiratory chain complex I assembly;mitochondrial ATP synthesis coupled electron transport;cellular respiration
• Cellular component: mitochondrion;mitochondrial inner membrane;mitochondrial respiratory chain complex I;cytosol
• Molecular function: NADH dehydrogenase activity;NADH dehydrogenase (ubiquinone) activity;FMN binding;metal ion binding;NAD binding;4 iron, 4 sulfur cluster binding