MT-ND5

mitochondrially encoded NADH:ubiquinone oxidoreductase core subunit 5, the group of Mitochondrially encoded protein coding genes|NADH:ubiquinone oxidoreductase core subunits

Basic information

Region (hg38): M:12336-14148

Previous symbols: [ "MTND5" ]

Links

ENSG00000198786 ∙ NCBI:4540 ∙ OMIM:516005 ∙ HGNC:7461 ∙ Uniprot:P03915 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• MELAS syndrome (Supportive), mode of inheritance: Mitochondrial
• MERRF syndrome (Supportive), mode of inheritance: Mitochondrial
• Leber hereditary optic neuropathy (Supportive), mode of inheritance: Mitochondrial
• maternally-inherited Leigh syndrome (Supportive), mode of inheritance: Mitochondrial
• Leber hereditary optic neuropathy (Strong), mode of inheritance: Mitochondrial
• mitochondrial disease (Definitive), mode of inheritance: Mitochondrial
• Leigh syndrome (Definitive), mode of inheritance: Mitochondrial

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Myoclonic epilepsy with ragged red fibers; Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes; Leber hereditary optic neuropathy; Mitochondrial complex I deficiency	Maternal	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; Musculoskeletal; Neurologic; Ophthalmologic	1900003; 1732158; 8213825; 8016139; 18524835
Mitochondrial variants may involve a variety of sequelae, including hearing impairment

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MT-ND5 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MT-ND5 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						0
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	0	0	0

Variants in MT-ND5

This is a list of pathogenic ClinVar variants found in the MT-ND5 region.

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

Position	Type	Phenotype	Significance	ClinVar
M-12338-T-C		Leber optic atrophy • Leigh syndrome	Benign (Oct 17, 2019)
M-12340-A-G		Leigh syndrome	Likely benign (Oct 17, 2019)
M-12341-C-T		Leigh syndrome	Likely benign (Oct 17, 2019)
M-12344-T-C		Leigh syndrome	Uncertain significance (Oct 17, 2019)
M-12346-C-T		Leigh syndrome	Benign/Likely benign (Oct 17, 2019)
M-12349-A-G		Leigh syndrome	Uncertain significance (Oct 17, 2019)
M-12352-A-G		Leigh syndrome	Likely benign (Oct 17, 2019)
M-12358-A-G		Leigh syndrome	Benign (Oct 17, 2019)
M-12361-A-G		Leigh syndrome	Benign (Oct 17, 2019)
M-12362-C-T		Leigh syndrome	Benign (Oct 17, 2019)
M-12367-A-G		Leigh syndrome	Likely benign (Oct 17, 2019)
M-12372-G-A		Mitochondrial disease • not specified	Benign (Jul 20, 2024)
M-12373-A-G		Leigh syndrome	Benign (Oct 17, 2019)
M-12382-A-G		Leigh syndrome	Uncertain significance (Oct 17, 2019)
M-12383-T-C		Leigh syndrome	Uncertain significance (Oct 17, 2019)
M-12386-C-T		Leigh syndrome	Uncertain significance (Oct 17, 2019)
M-12389-C-T		Leigh syndrome	Uncertain significance (Oct 17, 2019)
M-12397-A-G		Autosomal recessive early-onset Parkinson disease 6 • Leigh syndrome	Benign (Oct 17, 2019)
M-12400-A-G		Leigh syndrome	Benign (Oct 17, 2019)
M-12401-C-T		Leigh syndrome	Likely benign (Oct 17, 2019)
M-12403-C-T		Leigh syndrome	Benign (Oct 17, 2019)
M-12406-G-A		Leigh syndrome	Benign (Oct 17, 2019)
M-12410-A-G		Leigh syndrome	Uncertain significance (Oct 17, 2019)
M-12417-CA-C		Mitochondrial myopathy with reversible cytochrome C oxidase deficiency • Juvenile myopathy, encephalopathy, lactic acidosis AND stroke • Leber optic atrophy • Mitochondrial disease	Likely pathogenic (Nov 28, 2023)
M-12424-A-G		Leigh syndrome	Likely benign (Oct 17, 2019)

GnomAD

Source: gnomAD

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: Leber hereditary optic neuropathy (LHON) [MIM:535000]: A maternally inherited disease resulting in acute or subacute loss of central vision, due to optic nerve dysfunction. Cardiac conduction defects and neurological defects have also been described in some patients. LHON results from primary mitochondrial DNA mutations affecting the respiratory chain complexes. {ECO:0000269|PubMed:16240359, ECO:0000269|PubMed:1732158, ECO:0000269|PubMed:1900003, ECO:0000269|PubMed:8213825}. Note=The disease is caused by mutations affecting the gene represented in this entry.; 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:11938446, ECO:0000269|PubMed:12796552, ECO:0000269|PubMed:17400793}. 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:12509858, ECO:0000269|PubMed:15767514, ECO:0000269|PubMed:17400793, ECO:0000269|PubMed:20818383}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes syndrome (MELAS) [MIM:540000]: Genetically heterogeneous disorder, characterized by episodic vomiting, seizures, and recurrent cerebral insults resembling strokes and causing hemiparesis, hemianopsia, or cortical blindness. {ECO:0000269|PubMed:12509858, ECO:0000269|PubMed:15767514, ECO:0000269|PubMed:17400793, ECO:0000269|PubMed:9299505}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Retrograde endocannabinoid signaling - 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)

Haploinsufficiency Scores

• ghis: 0.452

Essentials

• gene_indispensability_pred: E
• gene_indispensability_score: 0.613

Mouse Genome Informatics

• Gene name: mt-Nd5

Gene ontology

• Biological process: response to hypoxia;mitochondrial electron transport, NADH to ubiquinone;response to organonitrogen compound;mitochondrial respiratory chain complex I assembly;response to hydrogen peroxide
• Cellular component: mitochondrial inner membrane;mitochondrial respiratory chain complex I;integral component of membrane;neuron projection
• Molecular function: NADH dehydrogenase (ubiquinone) activity