MTAP

Chr 9AD

methylthioadenosine phosphorylase

Also known as: BDMF, DMSFH, DMSMFH, HEL-249, LGMBF, MSAP, c86fus

NCBI Gene: 4507 ENSG00000099810 UniProt: Q13126 OMIM: 156540

The protein catalyzes the reversible phosphorylation of S-methyl-5'-thioadenosine to adenine and 5-methylthioribose-1-phosphate, functioning in polyamine metabolism and the methionine salvage pathway. Mutations cause diaphyseal medullary stenosis with malignant fibrous histiocytoma, inherited in an autosomal dominant pattern. The gene shows very low constraint against loss-of-function variants (pLI near zero), suggesting tolerance to such mutations in the general population.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes an enzyme that plays a major role in polyamine metabolism and is important for the salvage pathway of both adenine and methionine. The encoded enzyme is deficient in many cancers. Multiple alternatively spliced transcript variants have been described for this gene. [provided by RefSeq, Sep 2021]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Diaphyseal medullary stenosis with malignant fibrous histiocytomaMIM #112250

Clinical highlights

Gene–disease validity (ClinGen)

Moderate · diaphyseal medullary stenosis-bone malignancy syndrome · AD · ClinGen 2021

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

289

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.39

LOEUF

LOF

Mechanism· G2P

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.39LOEUF

pLI 0.000

Z-score 0.49

OE 0.86 (0.55–1.39)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.02Z-score

OE missense 1.00 (0.88–1.14)

167 obs / 166.4 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.86 (0.55–1.39)

0≤0.351.4

Missense OE?1.00 (0.88–1.14)

0≤0.61.4

Synonymous OE?1.25

0≤1.21.6

LoF obs/exp: 12 / 14.0Missense obs/exp: 167 / 166.4Syn Z: -1.54

Background carrier burden — how many people carry a rare variant somewhere in MTAP?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 110

536 rare PASS variants

Rare truncating (LoF)

1 in 1,500

106 rare PASS variants

Rare synonymous (reference)

1 in 180

223 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for MTAP. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 170	1 in 1,900
South Asian	~43k	1 in 140	1 in 790
Remaining (unassigned)	~30k	1 in 97	1 in 2,100
European (Finnish)	~27k	1 in 300	1 in 2,300
Admixed American	~22k	1 in 110	1 in 1,300
African / African American	~21k	1 in 97	1 in 590
East Asian	~20k	1 in 170	1 in 1,100
Ashkenazi Jewish	~13k	1 in 430	1 in 1,600
Middle Eastern	~2,884	1 in 100	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 7 of 8 coding exons well covered in gnomAD exomes; exon 8 marginal. Genomes: all 8.? see exons ↓

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

MTAP · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

External Resources

Links to major genomics databases and tools

Franklin by Genoox

AI-powered variant curation and clinical analysis

DECIPHER

Genomic variants and phenotypes in rare disease patients

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

Metastatic Bladder Urothelial CarcinomaMetastatic Malignant Solid NeoplasmStage IV Bladder Cancer AJCC v8

Pemetrexed Response in Relation to Tumor Alterations of Gene Status for the Treatment of Patients With Metastatic Urothelial Bladder Cancer and Other Solid Tumors

RECRUITING

NCT06630416Phase PHASE2Northwestern UniversityStarted 2024-11-27

Biospecimen CollectionComputed TomographyPemetrexed

MesotheliomaNon Small Cell Lung CancerMalignant Peripheral Nerve Sheath Tumors

Phase 1 Study of MRTX1719 in Solid Tumors With MTAP Deletion

RECRUITING

NCT05245500Phase PHASE1Bristol-Myers SquibbStarted 2022-06-09

MRTX1719

Malignant Peripheral Nerve Sheath TumorsMPNST

Safety and Efficacy of BMS-986504 in Unresectable Malignant Peripheral Nerve Sheath Tumor

RECRUITING

NCT07549022Phase PHASE1, PHASE2Ankit Mangla, MDStarted 2026-08