MTAP

methylthioadenosine phosphorylase

Basic information

Region (hg38): 9:21802635-21937651

Links

ENSG00000099810 ∙ NCBI:4507 ∙ OMIM:156540 ∙ HGNC:7413 ∙ Uniprot:Q13126 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• diaphyseal medullary stenosis-bone malignancy syndrome (Strong), mode of inheritance: AD
• diaphyseal medullary stenosis-bone malignancy syndrome (Supportive), mode of inheritance: AD
• diaphyseal medullary stenosis-bone malignancy syndrome (Strong), mode of inheritance: AD
• diaphyseal medullary stenosis-bone malignancy syndrome (Moderate), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Diaphyseal medullary stenosis with malignant fibrous histiocytoma	AD	Oncologic	Individuals are at high risk for aggressive bone sarcoma, and surveillance and early treatment may be beneficial to reduce morbidity and mortality	Musculoskeletal; Oncologic	4713573; 3745248; 8680521; 8781110; 16244874; 22464254

ClinVar

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

• Diaphyseal medullary stenosis-bone malignancy syndrome (123 variants)
• not provided (29 variants)
• Inborn genetic diseases (11 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MTAP 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	3	3	7
missense			17	1	4	22
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				1		1
non coding			59	2	65	126
Total	0	0	77	6	72

Variants in MTAP

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

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

Position	Type	Phenotype	Significance	ClinVar
9-21802640-GCACTGC-G		Diaphyseal medullary stenosis-bone malignancy syndrome	Uncertain significance (Jun 14, 2016)
9-21802697-G-C		Diaphyseal medullary stenosis-bone malignancy syndrome	Uncertain significance (Jan 13, 2018)
9-21802744-C-G		Diaphyseal medullary stenosis-bone malignancy syndrome	Benign (Jan 12, 2018)
9-21802762-C-T		not specified	Uncertain significance (Aug 08, 2023)
9-21802923-C-G			Benign (Jun 21, 2021)
9-21815167-G-T			Benign (Jun 19, 2021)
9-21815438-A-C		Diaphyseal medullary stenosis-bone malignancy syndrome	Benign/Likely benign (Jul 01, 2022)
9-21815485-G-A		not specified	Uncertain significance (Jan 08, 2024)
9-21815510-A-G		Diaphyseal medullary stenosis-bone malignancy syndrome	Benign (Jan 12, 2018)
9-21815515-G-T		not specified	Uncertain significance (May 17, 2023)
9-21815517-A-C		not specified	Uncertain significance (Dec 13, 2021)
9-21815518-A-G		Diaphyseal medullary stenosis-bone malignancy syndrome	Uncertain significance (Jan 12, 2018)
9-21815590-T-TAA			Benign (Jun 20, 2021)
9-21815590-T-TAAA			Benign (Jun 20, 2021)
9-21815798-C-T			Benign (Jun 19, 2021)
9-21816529-A-G			Benign (Nov 12, 2018)
9-21816574-G-A			Benign (Nov 12, 2018)
9-21816638-T-C			Benign (Nov 12, 2018)
9-21816647-A-G			Benign (Jun 19, 2021)
9-21816704-T-C		Diaphyseal medullary stenosis-bone malignancy syndrome • MTAP-related disorder	Benign (Mar 25, 2019)
9-21816729-A-C		Diaphyseal medullary stenosis-bone malignancy syndrome • MTAP-related disorder	Benign/Likely benign (Jun 10, 2019)
9-21816747-A-G			Uncertain significance (Oct 01, 2023)
9-21816759-G-A		Diaphyseal medullary stenosis-bone malignancy syndrome	Benign (Jul 07, 2023)
9-21816784-T-A		Diaphyseal medullary stenosis-bone malignancy syndrome	Benign/Likely benign (Jul 07, 2023)
9-21817755-A-G			Benign (Nov 12, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MTAP	protein_coding	protein_coding	ENST00000380172	8	129105

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
7.60e-8	0.286	125722	0	24	125746	0.0000954

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.0176	167	166	1.00	0.00000888	1848
Missense in Polyphen		52	61.082	0.85132		708
Synonymous	-1.54	77	61.7	1.25	0.00000380	542
Loss of Function	0.489	12	14.0	0.859	5.91e-7	181

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000336	0.000335
Ashkenazi Jewish	0.000298	0.000298
East Asian	0.0000551	0.0000544
Finnish	0.0000533	0.0000462
European (Non-Finnish)	0.0000882	0.0000879
Middle Eastern	0.0000551	0.0000544
South Asian	0.0000327	0.0000327
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Catalyzes the reversible phosphorylation of S-methyl-5'- thioadenosine (MTA) to adenine and 5-methylthioribose-1-phosphate. Involved in the breakdown of MTA, a major by-product of polyamine biosynthesis. Responsible for the first step in the methionine salvage pathway after MTA has been generated from S- adenosylmethionine. Has broad substrate specificity with 6- aminopurine nucleosides as preferred substrates. {ECO:0000255|HAMAP-Rule:MF_03155, ECO:0000269|PubMed:3091600}.
• Disease: DISEASE: Note=Loss of MTAP activity may play a role in human cancer. MTAP loss has been reported in a number of cancers, including osteosarcoma, malignant melanoma and gastric cancer.
• Pathway: Cysteine and methionine metabolism - Homo sapiens (human);S-Adenosylhomocysteine (SAH) Hydrolase Deficiency;Methionine Metabolism;Methionine Adenosyltransferase Deficiency;Glycine N-methyltransferase Deficiency;Hypermethioninemia;Methylenetetrahydrofolate Reductase Deficiency (MTHFRD);Homocystinuria-megaloblastic anemia due to defect in cobalamin metabolism, cblG complementation type;Cystathionine Beta-Synthase Deficiency;Methionine De Novo and Salvage Pathway;Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulation;Metabolism of polyamines;Metabolism of amino acids and derivatives;Methionine salvage pathway;Metabolism;<i>S</i>-methyl-5,-thioadenosine degradation;methionine salvage cycle III;Sulfur amino acid metabolism (Consensus)

Recessive Scores

• pRec: 0.350

Intolerance Scores

• loftool: 0.376
• rvis_EVS: -0.38
• rvis_percentile_EVS: 27.69

Haploinsufficiency Scores

• pHI: 0.177
• hipred: N
• hipred_score: 0.112
• ghis: 0.624

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.832

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Mtap
• Phenotype: immune system phenotype; 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); 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); respiratory system phenotype; liver/biliary system phenotype

Gene ontology

• Biological process: nucleobase-containing compound metabolic process;purine ribonucleoside salvage;nicotinamide riboside catabolic process;L-methionine salvage from methylthioadenosine;interleukin-12-mediated signaling pathway
• Cellular component: nucleus;cytoplasm;cytosol;extracellular exosome
• Molecular function: phosphorylase activity;protein binding;S-methyl-5-thioadenosine phosphorylase activity