MTFMT

mitochondrial methionyl-tRNA formyltransferase

Basic information

Region (hg38): 15:65001512-65029639

Links

ENSG00000103707

∙ NCBI:123263 ∙ OMIM:611766 ∙ HGNC:29666 ∙ Uniprot:Q96DP5 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

combined oxidative phosphorylation defect type 15 (Moderate), mode of inheritance: AR
Leigh syndrome with leukodystrophy (Supportive), mode of inheritance: AR
combined oxidative phosphorylation defect type 15 (Strong), mode of inheritance: AR
Leigh syndrome (Definitive), mode of inheritance: AR
combined oxidative phosphorylation defect type 15 (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Combined oxidative phosphorylation deficiency 15	AR	Cardiovascular	Among other multi-systemic manifestations, the condition may include cardiac manifestations such as Wolff-Parkinson-White syndrome, and surveillance may allow early diagnosis and management	Biochemical; Cardiovascular; Neurologic; Ophthalmologic	21907147; 22499348; 23499752; 24461907

ClinVar

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

not_provided (184 variants)
Inborn_genetic_diseases (70 variants)
Combined_oxidative_phosphorylation_defect_type_15 (24 variants)
not_specified (15 variants)
MTFMT-related_disorder (11 variants)
Mitochondrial_complex_I_deficiency,_nuclear_type_27 (6 variants)
MTFMT-Related_Disorders (3 variants)
Microcephaly (2 variants)
Leigh_syndrome (2 variants)
Decreased_activity_of_mitochondrial_complex_I (1 variants)
Mitochondrial_oxidative_phosphorylation_disorder (1 variants)
Cytochrome_C_oxidase-negative_muscle_fibers (1 variants)
Inability_to_walk_by_childhood/adolescence (1 variants)
See_cases (1 variants)
Short_stature (1 variants)
Poor_speech (1 variants)
Abnormal_facial_shape (1 variants)
Waardenburg_syndrome,_IIa_2F (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MTFMT gene is commonly pathogenic or not. These statistics are base on transcript: NM_000139242.4. 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				39 clinvar	3 clinvar	42
missense	4 clinvar	4 clinvar	103 clinvar	12 clinvar	4 clinvar	127
nonsense	11 clinvar	2 clinvar	1 clinvar			14
start loss	1	1	1			3
frameshift	6 clinvar	4 clinvar				10
splice donor/acceptor (+/-2bp)		2 clinvar				2
Total	22	13	105	51	7

Highest pathogenic variant AF is 0.000696738

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MTFMT	protein_coding	protein_coding	ENST00000220058	9	27133

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.50e-7	0.846	124614	0	47	124661	0.000189

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.462	214	196	1.09	0.00000987	2467
Missense in Polyphen		70	69.718	1.004		810
Synonymous	-0.381	76	71.9	1.06	0.00000399	768
Loss of Function	1.53	14	21.7	0.645	0.00000107	252

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000175	0.000175
Ashkenazi Jewish	0.00	0.00
East Asian	0.000112	0.000111
Finnish	0.000186	0.000186
European (Non-Finnish)	0.000313	0.000310
Middle Eastern	0.000112	0.000111
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

Function: FUNCTION: Formylates methionyl-tRNA in mitochondria. A single tRNA(Met) gene gives rise to both an initiator and an elongator species via an unknown mechanism (By similarity). {ECO:0000250}.;
Disease: DISEASE: Combined oxidative phosphorylation deficiency 15 (COXPD15) [MIM:614947]: An autosomal recessive, mitochondrial, neurologic disorder characterized by features of Leigh syndrome and combined oxidative phosphorylation deficiency. Clinical features include mild global developmental delay, white matter abnormalities, ataxia, incoordination, speech and reading difficulties, T2-weighted hyperintensities in the basal ganglia, corpus callosum, and brainstem. {ECO:0000269|PubMed:21907147}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Leigh syndrome (LS) [MIM:256000]: An early-onset progressive neurodegenerative disorder characterized by the presence of focal, bilateral lesions in one or more areas of the central nervous system including the brainstem, thalamus, basal ganglia, cerebellum and spinal cord. Clinical features depend on which areas of the central nervous system are involved and include subacute onset of psychomotor retardation, hypotonia, ataxia, weakness, vision loss, eye movement abnormalities, seizures, and dysphagia. {ECO:0000269|PubMed:22499348}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway: One carbon pool by folate - Homo sapiens (human);Aminoacyl-tRNA biosynthesis - Homo sapiens (human);S-Adenosylhomocysteine (SAH) Hydrolase Deficiency;Methionine Metabolism;Folate malabsorption, hereditary;Methionine Adenosyltransferase Deficiency;Glycine N-methyltransferase Deficiency;Methylenetetrahydrofolate Reductase Deficiency (MTHFRD);Hypermethioninemia;Methylenetetrahydrofolate Reductase Deficiency (MTHFRD);Methotrexate Action Pathway;Folate Metabolism;Homocystinuria-megaloblastic anemia due to defect in cobalamin metabolism, cblG complementation type;Cystathionine Beta-Synthase Deficiency;One Carbon Metabolism;Mitochondrial translation initiation;Translation;Metabolism of proteins;Methionine and cysteine metabolism;Mitochondrial translation (Consensus)

Recessive Scores

pRec: 0.121

Intolerance Scores

loftool: 0.817
rvis_EVS: 0.71
rvis_percentile_EVS: 85.53

Haploinsufficiency Scores

pHI: 0.824
hipred: N
hipred_score: 0.229
ghis

Essentials

essential_gene_CRISPR: E
essential_gene_CRISPR2: S
essential_gene_gene_trap: N
gene_indispensability_pred: E
gene_indispensability_score: 0.960

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Mtfmt
Phenotype: 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);

Gene ontology

Biological process: translational initiation;conversion of methionyl-tRNA to N-formyl-methionyl-tRNA
Cellular component: mitochondrion
Molecular function: methionyl-tRNA formyltransferase activity