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

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 (17 variants)
• Combined oxidative phosphorylation defect type 15 (5 variants)
• Inborn genetic diseases (2 variants)
• Mitochondrial complex 1 deficiency, nuclear type 27 (2 variants)
• 6 conditions (1 variants)
• Leigh syndrome (1 variants)
• Combined oxidative phosphorylation defect type 15;Mitochondrial complex 1 deficiency, nuclear type 27 (1 variants)
• See cases (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.

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			1	36	3	40
missense	1	2	73	6	5	87
nonsense	11	2	1			14
start loss	1	2				3
frameshift	5	3				8
inframe indel			3			3
splice donor/acceptor (+/-2bp)		2				2
splice region				2	2	4
non coding			1	33	20	54
Total	18	11	79	75	28

Highest pathogenic variant AF is 0.000571

Variants in MTFMT

This is a list of pathogenic ClinVar variants found in the MTFMT region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
15-65002769-C-G			Benign (Jul 31, 2018)
15-65002774-C-A			Likely benign (Jun 26, 2018)
15-65002962-C-A			Benign (Jul 30, 2020)
15-65002962-CA-C			Likely benign (Aug 13, 2019)
15-65002962-C-CA			Benign (Aug 06, 2019)
15-65003062-C-G			Uncertain significance (Sep 10, 2019)
15-65003069-A-C			Uncertain significance (Mar 08, 2023)
15-65003074-T-C			Likely benign (Aug 11, 2023)
15-65003084-G-C		Inborn genetic diseases	Uncertain significance (Nov 08, 2022)
15-65003100-GCTT-G		Combined oxidative phosphorylation defect type 15 • Mitochondrial complex 1 deficiency, nuclear type 27;Combined oxidative phosphorylation defect type 15	Uncertain significance (Jul 17, 2023)
15-65003103-T-G		Inborn genetic diseases	Conflicting classifications of pathogenicity (Feb 01, 2023)
15-65003112-T-C			Uncertain significance (Apr 17, 2023)
15-65003115-GA-G		Combined oxidative phosphorylation defect type 15	Likely pathogenic (Mar 29, 2024)
15-65003120-C-T		Inborn genetic diseases	Uncertain significance (Mar 01, 2024)
15-65003130-GAA-G		Mitochondrial oxidative phosphorylation disorder	Pathogenic/Likely pathogenic (Apr 23, 2021)
15-65003138-C-T		Microcephaly	Conflicting classifications of pathogenicity (Dec 13, 2023)
15-65003140-T-C			Benign/Likely benign (Nov 27, 2023)
15-65003159-G-C			Uncertain significance (May 18, 2022)
15-65003164-T-C			Benign (Jul 29, 2023)
15-65003167-C-T		not specified	Benign (Jan 29, 2024)
15-65003169-G-C			Uncertain significance (May 22, 2023)
15-65003183-A-T			Uncertain significance (Jul 18, 2022)
15-65003192-T-C		Microcephaly	Uncertain significance (-)
15-65003197-G-C			Uncertain significance (Jun 20, 2022)
15-65003222-T-C		Inborn genetic diseases	Uncertain significance (Oct 13, 2022)

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

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