MTAP

Chr 9

methylthioadenosine phosphorylase

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

NCBI Gene: 4507 ENSG00000099810 UniProt: Q13126

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.

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]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtDiaphyseal medullary stenosis with malignant fibrous histiocytoma

Clinical highlights

Gene-disease validity (ClinGen)

diaphyseal medullary stenosis-bone malignancy syndrome · ADModerateconsider for supplementary testing

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

266

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.39

LOEUF

LOF

Mechanism· G2P

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

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

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

Metastatic Biliary Tract CarcinomaMetastatic Colon CarcinomaMetastatic Esophageal Carcinoma

BMS-986504 in Combination With Pemetrexed for the Treatment of Metastatic Solid Tumors With MTAP Deletion

RECRUITING

NCT07594626Phase PHASE1, PHASE2Northwestern UniversityStarted 2026-08-21

Biospecimen CollectionComputed TomographyPemetrexed

Advanced Solid Tumor

Study of GS-5319 Given Alone or in Combination in Adults With Solid Tumors

RECRUITING

NCT07128303Phase PHASE1Gilead SciencesStarted 2025-08-28