MT-TL1

Chr MT

tRNA-Leu

Also known as: MTTL1

NCBI Gene: 4567 ENSG00000209082 OMIM: 590050

This gene encodes mitochondrial tRNA-Leucine (UUR), which is required for translation of all 13 mtDNA-encoded proteins involved in oxidative phosphorylation. Mutations cause MELAS syndrome (with m.3243A>G accounting for approximately 80% of cases), maternally inherited diabetes and deafness (MIDD), and progressive external ophthalmoplegia. Inheritance is maternal through the mitochondrial genome, with clinical severity often correlating with heteroplasmy levels.

GeneReviews OMIM ResearchSummary from Curated mito context

Predicted to enable triplet codon-amino acid adaptor activity. Predicted to be involved in translation. Implicated in cardiomyopathy. [provided by Alliance of Genome Resources, Jul 2025]

GeneReviews OMIM ResearchGenerating clinical summary…

Clinical highlights

Management implications

Nitric-oxide precursors (L-arginine) are recommended for stroke-like episodes in MELAS; dosing and timing evidence is still limited.Treat stroke-like episodes as an emergency with nitric-oxide precursors; applies to MT-TL1 variants causing MELAS (e.g. m.3243A>G).

MT-TL1: treatable — urgent IV L-arginine during a stroke-like episode; arginine/citrulline prophylaxis considered

Gene–disease validity (ClinGen)

Active trials

Pubs (1 yr)

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P/LP submissions

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P/LP missense

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LOEUF

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Mechanism

📖

GeneReview available — MT-TL1

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Treatment implicationsTreatable

MELAS (stroke-like episodes)

Treat stroke-like episodes as an emergency with nitric-oxide precursors; applies to MT-TL1 variants causing MELAS (e.g. m.3243A>G).

Nitric-oxide precursors (L-arginine) are recommended for stroke-like episodes in MELAS; dosing and timing evidence is still limited.

Treatment of choice

urgent IV L-arginine during a stroke-like episodearginine/citrulline prophylaxis considered

Koenig et al. 2016, JAMA Neurol (PMID 26954033). Confirm with a neurologist and current guidelines. Functional class (GOF/LOF) is from published functional/segregation data, never inferred from the variant. As of 2026-10. Curated from the clinical genetics/neurology literature (cited per gene). Decision-support, not prescribing.

Nuclear-gene analyses omitted

MT-TL1 is a mitochondrial tRNA gene. gnomAD constraint, carrier burden and exome coverage, the ClinVar type breakdown, the protein lollipop, AlphaFold and transcript-architecture views are built for nuclear genes and are not shown. Population data for mtDNA variants (gnomAD v3.1, homoplasmy and heteroplasmy) is on each variant page.

Where it sits in the mitochondrial genome

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proteinrRNAtRNAouter ring H-strand · inner L-strandMITOMAP confirmedreported (as of 2026-10-07)

37 genes from Ensembl (rCRS numbering, matched to MITOMAP’s Gene Loci); landmarks and disease alleles from MITOMAP (CC BY 3.0). Circular layout after MitoWheel.

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

MITOMAP Disease Variants — MT-TL1

Live table ↗

Variant	Disease	Status	GenBank seqs
m.3236A>G	Sporadic bilateral optic neuropathy / hearing loss	Reported	4
m.3242G>A	MM / HCM+renal tubular dysfunction	Likely pathogenic · confirmed	0
m.3243A>G	MELAS / Leigh Syndrome / DMDF / MIDD / SNHL / CPEO / MM / FSGS / ASD / Cardiac+multi-organ dysfunction	Pathogenic · confirmed	10
m.3243A>T	MM / MELAS / SNHL / CPEO	Likely pathogenic · confirmed	0
m.3244G>A	MELAS	Reported	4
m.3249G>A	KSS	Uncertain significance · reported	0
m.3250T>C	MM / CPEO / cardiomyopathy	Reported	1
m.3251A>G	MM / MELAS	Likely pathogenic · confirmed	0
m.3252A>G	MELAS	Likely pathogenic · confirmed	0
m.3252A>T	EXIT	Reported	0
m.3253T>C	Maternally inherited hypertension	Reported	8
m.3254C>A	Gestational Diabetes (GDM)	Reported	44
m.3254C>G	MM	Reported	0
m.3254C>T	CPEO / diabetes / poss. hypertension factor	Reported	22
m.3255G>A	MERRF / KSS overlap	Likely pathogenic · confirmed	0
m.3256C>T	MELAS; possible atherosclerosis risk	Likely pathogenic · confirmed	0
m.3258T>C	MELAS / Myopathy	Likely pathogenic · confirmed	1
m.3260A>G	MMC / MELAS	Likely pathogenic · confirmed	0
m.3261A>G	Essential hypertension	Reported	7
m.3264T>C	DM	Reported	0
m.3271T>C	MELAS / DM / MERRF-like	Pathogenic · confirmed	0
m.3273T>C	Ocular myopathy	Reported	0
m.3273T>-	PEM / retinal dystrophy in MELAS	Uncertain significance · confirmed	0
m.3274A>G	Neuropsychiatric syndrome + cataract	Uncertain significance · reported	0
m.3274AC>-	Encephalomyopathy with proteinuric kidney disease	Reported	0
m.3275C>T	Metabolic syndrome and polycystic ovary syndrome / LHON	Reported	2
m.3275C>A	LHON	Reported	4
m.3277G>A	Poss. hypertension factor	Reported	52
m.3278T>C	Poss. hypertension factor	Reported	19
m.3280A>G	Myopathy	Uncertain significance · confirmed	0
m.3283G>A	Late onset ocular myopathy	Reported	0
m.3287C>A	Encephalomyopathy	Reported	0
m.3288A>G	Myopathy	Uncertain significance · reported	0
m.3290T>C	Poss. hypertension factor / 3243G-protective	Reported	142
m.3291T>C	MELAS / Myopathy / Deafness+Cognitive Impairment	Likely pathogenic · confirmed	0
m.3302A>G	MM	Likely pathogenic · confirmed	0
m.3303C>T	MMC	Likely pathogenic · confirmed	0