MT-ND2

mitochondrially encoded NADH:ubiquinone oxidoreductase core subunit 2, the group of Mitochondrially encoded protein coding genes|NADH:ubiquinone oxidoreductase core subunits

Basic information

Region (hg38): M:4469-5511

Previous symbols: [ "MTND2" ]

Links

ENSG00000198763 ∙ NCBI:4536 ∙ OMIM:516001 ∙ HGNC:7456 ∙ Uniprot:P03891 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Leber hereditary optic neuropathy (Supportive), mode of inheritance: Mitochondrial
• mitochondrial complex I deficiency (Supportive), mode of inheritance: AR
• maternally-inherited Leigh syndrome (Supportive), mode of inheritance: Mitochondrial
• Leigh syndrome (Limited), mode of inheritance: Mitochondrial
• mitochondrial disease (Moderate), mode of inheritance: Mitochondrial

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
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	1732158; 20454697; 21145289
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-ND2 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MT-ND2 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-ND2

This is a list of pathogenic ClinVar variants found in the MT-ND2 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-4472-T-C			Uncertain significance (Jan 02, 2017)
M-4480-T-C		Leigh syndrome	Uncertain significance (Oct 17, 2019)
M-4482-G-A		Leigh syndrome	Uncertain significance (Oct 17, 2019)
M-4488-C-T		Leigh syndrome	Uncertain significance (Oct 17, 2019)
M-4491-G-A		Leigh syndrome	Benign (Oct 17, 2019)
M-4494-A-G		Leigh syndrome	Uncertain significance (Oct 17, 2019)
M-4495-T-C		Leigh syndrome	Uncertain significance (Oct 17, 2019)
M-4497-T-C		Leigh syndrome	Uncertain significance (Oct 17, 2019)
M-4500-T-C		Leigh syndrome	Likely benign (Oct 17, 2019)
M-4501-C-T		Leigh syndrome	Benign (Oct 17, 2019)
M-4503-A-T		Leigh syndrome	Uncertain significance (Oct 17, 2019)
M-4506-A-G		Leigh syndrome	Benign (Oct 17, 2019)
M-4509-T-C		Leigh syndrome	Uncertain significance (Oct 17, 2019)
M-4512-G-A		Leigh syndrome	Benign (Oct 17, 2019)
M-4513-C-T		Leigh syndrome	Uncertain significance (Oct 17, 2019)
M-4531-C-T		Leigh syndrome	Likely benign (Oct 17, 2019)
M-4548-T-C		Leigh syndrome	Uncertain significance (Oct 17, 2019)
M-4554-A-G		Leigh syndrome	Uncertain significance (Oct 17, 2019)
M-4560-G-A		Leigh syndrome	Benign (Oct 17, 2019)
M-4561-T-C		Leigh syndrome	Benign (Oct 17, 2019)
M-4579-T-C		Leigh syndrome	Uncertain significance (Oct 17, 2019)
M-4596-G-A		Leigh syndrome	Benign (Oct 17, 2019)
M-4597-T-C			Uncertain significance (Feb 18, 2018)
M-4604-CA-C		Leigh syndrome	Likely pathogenic (Oct 17, 2019)
M-4612-T-C		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:1732158, ECO:0000269|PubMed:1900003}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Alzheimer disease mitochondrial (AD-MT) [MIM:502500]: Alzheimer disease is a neurodegenerative disorder characterized by progressive dementia, loss of cognitive abilities, and deposition of fibrillar amyloid proteins as intraneuronal neurofibrillary tangles, extracellular amyloid plaques and vascular amyloid deposits. The major constituents of these plaques are neurotoxic amyloid-beta protein 40 and amyloid-beta protein 42, that are produced by the proteolysis of the transmembrane APP protein. The cytotoxic C-terminal fragments (CTFs) and the caspase-cleaved products, such as C31, are also implicated in neuronal death. {ECO:0000269|PubMed:1370613}. Note=Disease susceptibility may be associated with variations 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

• pHI: 0.137
• ghis: 0.436

Essentials

• gene_indispensability_pred: E
• gene_indispensability_score: 0.613

Mouse Genome Informatics

• Gene name: mt-Nd2
• Phenotype: immune system phenotype; cellular phenotype

Gene ontology

• Biological process: mitochondrial electron transport, NADH to ubiquinone;mitochondrial respiratory chain complex I assembly;reactive oxygen species metabolic process
• Cellular component: mitochondrial inner membrane;mitochondrial respiratory chain complex I;postsynaptic density;integral component of membrane
• Molecular function: NADH dehydrogenase (ubiquinone) activity;protein kinase binding;ionotropic glutamate receptor binding