MTO1

mitochondrial tRNA translation optimization 1

Basic information

Region (hg38): 6:73461578-73509236

Links

ENSG00000135297

∙ NCBI:25821 ∙ OMIM:614667 ∙ HGNC:19261 ∙ Uniprot:Q9Y2Z2 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

mitochondrial hypertrophic cardiomyopathy with lactic acidosis due to MTO1 deficiency (Definitive), mode of inheritance: AR
mitochondrial hypertrophic cardiomyopathy with lactic acidosis due to MTO1 deficiency (Moderate), mode of inheritance: AR
mitochondrial hypertrophic cardiomyopathy with lactic acidosis due to MTO1 deficiency (Supportive), mode of inheritance: Unknown
mitochondrial hypertrophic cardiomyopathy with lactic acidosis due to MTO1 deficiency (Strong), mode of inheritance: AR
mitochondrial disease (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Combined oxidative phosphorylation deficiency 10	AR	Biochemical	The condition can include findings such as hypertrophic cardiomyopathy, hypoglycemia, and and lactic acidosis; Treatment with biotin, coenzyme Q10, thiamine, and dichloroacetate has been reported as beneficial in multiple individuals	Biochemical; Cardiovascular; Neurologic	22608499; 23929671; 29331171
Biochemical treatments (eg, with a mitochondrial cocktail) and ketogenic diet have been described, but the efficacy has been reported as unclear

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MTO1 gene.

Mitochondrial_hypertrophic_cardiomyopathy_with_lactic_acidosis_due_to_MTO1_deficiency (651 variants)
Inborn_genetic_diseases (100 variants)
not_provided (92 variants)
not_specified (22 variants)
MTO1-related_disorder (20 variants)
Abnormal_brain_morphology (2 variants)
Mitochondrial_oxidative_phosphorylation_disorder (1 variants)
Global_developmental_delay (1 variants)
Hereditary_motor_neuron_disease (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MTO1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000012123.4. Only rare variants are included in the table.

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.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous			3 clinvar	176 clinvar	2 clinvar	181
missense	3 clinvar	17 clinvar	305 clinvar	17 clinvar		342
nonsense	9 clinvar	4 clinvar	3 clinvar			16
start loss						0
frameshift	25 clinvar	7 clinvar	4 clinvar			36
splice donor/acceptor (+/-2bp)	1 clinvar	3 clinvar		1 clinvar		5
Total	38	31	315	194	2

Highest pathogenic variant AF is 0.0001480738

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MTO1	protein_coding	protein_coding	ENST00000415954	13	47659

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00000738	1.00	125644	0	103	125747	0.000410

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.650	373	410	0.910	0.0000225	4722
Missense in Polyphen		169	194.53	0.86877		2038
Synonymous	0.538	139	147	0.944	0.00000759	1472
Loss of Function	3.25	15	36.1	0.416	0.00000222	408

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000924	0.000924
Ashkenazi Jewish	0.00149	0.00149
East Asian	0.000435	0.000435
Finnish	0.000508	0.000508
European (Non-Finnish)	0.000229	0.000229
Middle Eastern	0.000435	0.000435
South Asian	0.000523	0.000523
Other	0.000489	0.000489

dbNSFP

Source: dbNSFP

Function: FUNCTION: Involved in the 5-carboxymethylaminomethyl modification (mnm(5)s(2)U34) of the wobble uridine base in mitochondrial tRNAs. {ECO:0000269|PubMed:12011058}.;

Recessive Scores

pRec: 0.161

Intolerance Scores

loftool: 0.0935
rvis_EVS: -0.2
rvis_percentile_EVS: 39.17

Haploinsufficiency Scores

pHI: 0.0662
hipred: N
hipred_score: 0.384
ghis: 0.593

Essentials

essential_gene_CRISPR: E
essential_gene_CRISPR2: S
essential_gene_gene_trap: N
gene_indispensability_pred: N
gene_indispensability_score: 0.154

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

Gene name: Mto1
Phenotype: behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); homeostasis/metabolism phenotype; growth/size/body region phenotype; muscle phenotype; cellular phenotype;

Gene ontology

Biological process: tRNA wobble uridine modification;tRNA methylation;mitochondrial tRNA wobble uridine modification
Cellular component: mitochondrion
Molecular function: RNA binding;flavin adenine dinucleotide binding