MTAP

Chr 9AD

methylthioadenosine phosphorylase

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

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]

OMIMResearchGenerating clinical summary…
LOFmechanismADLOEUF 1.391 OMIM phenotype
Clinical SummaryMTAP
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Gene-Disease Validity (ClinGen)
diaphyseal medullary stenosis-bone malignancy syndrome · ADModerate

Moderate evidence — consider for supplementary testing

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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Clinical Trials
7 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint?
1.39LOEUF
pLI 0.000
Z-score 0.49
OE 0.86 (0.551.39)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?
-0.02Z-score
OE missense 1.00 (0.881.14)
167 obs / 166.4 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?
LoF OE?0.86 (0.551.39)
00.351.4
Missense OE?1.00 (0.881.14)
00.61.4
Synonymous OE?1.25
01.21.6
LoF obs/exp: 12 / 14.0Missense obs/exp: 167 / 166.4Syn Z: -1.54
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongMTAP-related diaphyseal medullary stenosis with malignant fibrous histiocytomaLOFAD

This gene — mechanism propensity

DN
0.6455th %ile
GOF
0.5562th %ile
LOF
0.4332th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in 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.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

Advanced Solid Tumors With MTAP Gene Deletion

A Phase Ia/Ib Clinical Study of GH56 Capsules in Subjects With MTAP-Deleted Advanced Solid Tumors

RECRUITING
NCT06796699Phase PHASE1Suzhou Genhouse Bio Co., Ltd.Started 2025-03-07
GH56 Capsule
Advanced Solid Tumor

Study of GS-5319 in Adults With Solid Tumors

RECRUITING
NCT07128303Phase PHASE1Gilead SciencesStarted 2025-08-28
GS-5319
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

NOT YET RECRUITING
NCT07549022Phase PHASE1, PHASE2Ankit Mangla, MDStarted 2026-08
BMS-986504
Metastatic Biliary Tract CarcinomaMetastatic Colon CarcinomaMetastatic Esophageal Carcinoma

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

NOT YET RECRUITING
NCT07594626Phase PHASE1, PHASE2Northwestern UniversityStarted 2027-12-09
Biospecimen CollectionComputed TomographyPemetrexed
OsteosarcomaMTAP DeletionImmunohistochemistry

the Exploration of MTAP Deletion in Osteosarcoma by Immunohistochemistry

ACTIVE NOT RECRUITING
NCT07593573Peking University People's HospitalStarted 2025-12-15
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