MT-ND4L

mitochondrially encoded NADH:ubiquinone oxidoreductase core subunit 4L, the group of NADH:ubiquinone oxidoreductase core subunits|Mitochondrially encoded protein coding genes

Basic information

Region (hg38): M:10470-10766

Previous symbols: [ "MTND4L" ]

Links

ENSG00000212907 ∙ NCBI:4539 ∙ OMIM:516004 ∙ HGNC:7460 ∙ Uniprot:P03901 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Leber hereditary optic neuropathy (Supportive), mode of inheritance: Mitochondrial
• mitochondrial disease (Limited), mode of inheritance: Mitochondrial

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Leber hereditary optic neuropathy	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; Ophthalmologic	11935318
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-ND4L gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MT-ND4L 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-ND4L

This is a list of pathogenic ClinVar variants found in the MT-ND4L 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-10489-A-G		Leigh syndrome	Uncertain significance (Oct 17, 2019)
M-10491-A-G			not provided (-)
M-10492-T-C		Leigh syndrome	Uncertain significance (Oct 17, 2019)
M-10499-A-G			Benign (Jan 26, 2017)
M-10506-A-G		Leigh syndrome	Benign (Oct 17, 2019)
M-10507-C-T		Leigh syndrome	Likely benign (Oct 17, 2019)
M-10522-G-A		Leigh syndrome	Uncertain significance (Oct 17, 2019)
M-10524-A-G		Leigh syndrome	Uncertain significance (Oct 17, 2019)
M-10530-G-A		Leigh syndrome	Benign (Oct 17, 2019)
M-10563-T-C		Familial colorectal cancer	Pathogenic (Nov 01, 1998)
M-10579-T-C		Leigh syndrome	Uncertain significance (Oct 17, 2019)
M-10599-G-A		Leigh syndrome	Likely benign (Oct 17, 2019)
M-10600-C-T		Leigh syndrome	Uncertain significance (Oct 17, 2019)
M-10602-A-G		Leigh syndrome	Uncertain significance (Oct 17, 2019)
M-10609-T-C		Leigh syndrome	Benign (Oct 17, 2019)
M-10620-A-G		Leigh syndrome	Uncertain significance (Oct 17, 2019)
M-10630-T-C		Leigh syndrome	Uncertain significance (Oct 17, 2019)
M-10632-T-C			Likely benign (Sep 14, 2016)
M-10635-G-A		Leigh syndrome	Likely benign (Oct 17, 2019)
M-10639-A-G		Leigh syndrome	Likely benign (Oct 17, 2019)
M-10644-G-A		Leigh syndrome	Conflicting classifications of pathogenicity (Oct 17, 2019)
M-10653-G-A		Leigh syndrome	Benign (Oct 17, 2019)
M-10654-C-T		Leigh syndrome	Benign (Oct 17, 2019)
M-10663-T-C		Leber optic atrophy • Mitochondrial disease	Likely pathogenic (Jun 13, 2022)
M-10677-G-A		Leigh syndrome	Uncertain significance (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:8680405}. 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 (Consensus)

Haploinsufficiency Scores

• pHI: 0.139
• ghis: 0.414

Essentials

• gene_indispensability_pred: E
• gene_indispensability_score: 0.613

Mouse Genome Informatics

• Gene name: mt-Nd4l

Gene ontology

• Biological process: mitochondrial electron transport, NADH to ubiquinone
• Cellular component: mitochondrial respiratory chain complex I;integral component of membrane;NADH dehydrogenase complex
• Molecular function: NADH dehydrogenase (ubiquinone) activity