MT-ND1

mitochondrially encoded NADH:ubiquinone oxidoreductase core subunit 1, the group of NADH:ubiquinone oxidoreductase core subunits|Mitochondrially encoded protein coding genes

Basic information

Region (hg38): M:3306-4262

Previous symbols: [ "MTND1" ]

Links

ENSG00000198888 ∙ NCBI:4535 ∙ OMIM:516000 ∙ HGNC:7455 ∙ Uniprot:P03886 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• MELAS syndrome (Supportive), mode of inheritance: Mitochondrial
• 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
• Leber hereditary optic neuropathy (Definitive), 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
Deafness, mitochondrial	Maternal	Audiologic/Otolaryngologic	Mitochondrial variants may involve a variety of sequelae, including hearing impairment, with highly variable age of onset, and for individuals with early-onset hearing impairment, early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	Audiologic/Otolaryngologic; Biochemical; Musculoskeletal; Neurologic; Ophthalmologic	1928099; 2018041; 1674640; 1732158; 10519336; 15466014; 15505787; 17562939; 18216301; 21625124; 21723259; 21968326; 22079202; 22241583; 22577081
As with other forms of epilepsy, optimal seizure control is advantageous, and genetic diagnosis may aid with medication selection

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MT-ND1 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MT-ND1 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-ND1

This is a list of pathogenic ClinVar variants found in the MT-ND1 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-3307-A-T		Leigh syndrome	Uncertain significance (Oct 17, 2019)
M-3308-T-C		Carcinoma of colon • SUDDEN INFANT DEATH SYNDROME • not specified • Leigh syndrome	Benign/Likely benign (Feb 04, 2020)
M-3308-T-G		SUDDEN INFANT DEATH SYNDROME • Leigh syndrome	Likely benign (Oct 17, 2019)
M-3308-T-AC		Leigh syndrome	Uncertain significance (Oct 17, 2019)
M-3310-C-T		Leigh syndrome	Uncertain significance (Oct 17, 2019)
M-3313-A-G		Leigh syndrome	Uncertain significance (Oct 17, 2019)
M-3316-G-A		Leigh syndrome	Benign (Oct 17, 2019)
M-3316-G-C		Leigh syndrome	Uncertain significance (Oct 17, 2019)
M-3320-A-G		Leigh syndrome	Uncertain significance (Oct 17, 2019)
M-3328-C-T		Leigh syndrome	Uncertain significance (Oct 17, 2019)
M-3335-T-C		Leigh syndrome	Benign (Oct 17, 2019)
M-3337-G-A		Leigh syndrome	Benign (Oct 17, 2019)
M-3338-T-C		Leigh syndrome	Benign (Oct 17, 2019)
M-3340-C-T		Leigh syndrome	Likely benign (Oct 17, 2019)
M-3344-T-C		Leigh syndrome	Likely benign (Oct 17, 2019)
M-3349-A-G		Leigh syndrome	Benign (Oct 17, 2019)
M-3350-T-C		Leigh syndrome	Benign (Oct 17, 2019)
M-3357-G-C		Leigh syndrome • Mitochondrial disease	Uncertain significance (Dec 10, 2021)
M-3358-G-A		Leigh syndrome	Uncertain significance (Oct 17, 2019)
M-3368-T-C		Leigh syndrome	Likely benign (Oct 17, 2019)
M-3376-G-A		Leber optic atrophy • Mitochondrial disease	Uncertain significance (Jun 30, 2022)
M-3380-G-A		Juvenile myopathy, encephalopathy, lactic acidosis AND stroke	Pathogenic (Oct 17, 2019)
M-3385-A-G		Leigh syndrome	Likely benign (Oct 17, 2019)
M-3388-C-A		Mitochondrial non-syndromic sensorineural hearing loss • Leigh syndrome	Benign (Oct 17, 2019)
M-3391-G-A		Leigh syndrome	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:1417830, ECO:0000269|PubMed:1674640, ECO:0000269|PubMed:1900003, ECO:0000269|PubMed:1928099, ECO:0000269|PubMed:1959619, ECO:0000269|PubMed:2018041}. 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:8723687}. 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:8104867}. Note=Disease susceptibility may be associated with variations affecting the gene represented in this entry.; DISEASE: Diabetes mellitus, non-insulin-dependent (NIDDM) [MIM:125853]: A multifactorial disorder of glucose homeostasis caused by a lack of sensitivity to the body's own insulin. Affected individuals usually have an obese body habitus and manifestations of a metabolic syndrome characterized by diabetes, insulin resistance, hypertension and hypertriglyceridemia. The disease results in long-term complications that affect the eyes, kidneys, nerves, and blood vessels. {ECO:0000269|PubMed:15265369, ECO:0000269|PubMed:7733935}. Note=The gene represented in this entry may be involved in disease pathogenesis.; 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:24105702}. 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

• pHI: 0.176
• ghis: 0.471

Essentials

• gene_indispensability_pred: E
• gene_indispensability_score: 0.613

Mouse Genome Informatics

• Gene name: mt-Nd1

Gene ontology

• Biological process: mitochondrial electron transport, NADH to ubiquinone;aerobic respiration;response to organic cyclic compound;mitochondrial respiratory chain complex I assembly;response to hydroperoxide;response to drug
• Cellular component: mitochondrial inner membrane;mitochondrial respiratory chain complex I;integral component of membrane;dendrite;mitochondrial membrane;neuronal cell body
• Molecular function: NADH dehydrogenase activity;protein binding;NADH dehydrogenase (ubiquinone) activity