MT-ND4
mitochondrially encoded NADH:ubiquinone oxidoreductase core subunit 4, the group of Mitochondrially encoded protein coding genes|NADH:ubiquinone oxidoreductase core subunits
Basic information
Region (hg38): M:10759-12137
Previous symbols: [ "MTND4", "LHON" ]
Links
Phenotypes
GenCC
Source:
- MELAS syndrome (Supportive), mode of inheritance: Mitochondrial
- Leber hereditary optic neuropathy (Supportive), mode of inheritance: Mitochondrial
- Leber plus disease (Supportive), mode of inheritance: Mitochondrial
- 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:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Leber hereditary optic neuropathy; Leber optic atrophy and dystonia; 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 | 201231; 2566116; 1763894; 2039048; 8644732; 18216301; 32516135 |
| Mitochondrial variants may involve a variety of sequelae, including hearing impairment; Variants in genes such as PRICKLE3 may modify the condition |
ClinVar
This is a list of variants' phenotypes submitted to
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the MT-ND4 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-ND4
This is a list of pathogenic ClinVar variants found in the MT-ND4 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
GnomAD
Source:
dbNSFP
Source:
- 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:1959619, ECO:0000269|PubMed:1959931, ECO:0000269|PubMed:3201231, ECO:0000269|PubMed:9452107}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Leber hereditary optic neuropathy with dystonia (LDYT) [MIM:500001]: Part of a spectrum of Leber hereditary optic neuropathy. It is characterized by the association of optic atrophy and central vision loss with dystonia. {ECO:0000269|PubMed:8644732}. 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:1323207}. 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
- 0.129
- hipred
- hipred_score
- ghis
- 0.397
Essentials
- essential_gene_CRISPR
- essential_gene_CRISPR2
- essential_gene_gene_trap
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.613
Mouse Genome Informatics
- Gene name
- mt-Nd4
- Phenotype
Gene ontology
- Biological process
- response to hypoxia;in utero embryonic development;mitochondrial electron transport, NADH to ubiquinone;aging;aerobic respiration;electron transport coupled proton transport;cerebellum development;mitochondrial respiratory chain complex I assembly;response to nicotine;response to ethanol
- Cellular component
- mitochondrial inner membrane;mitochondrial respiratory chain complex I;integral component of membrane
- Molecular function
- NADH dehydrogenase activity;NADH dehydrogenase (ubiquinone) activity;ubiquinone binding