MTAP

Chr 9AD

methylthioadenosine phosphorylase

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

NCBI Gene: 4507ENSG00000099810UniProt: Q13126

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]

Primary Disease Associations & Inheritance

Diaphyseal medullary stenosis with malignant fibrous histiocytomaMIM #112250
AD
277
ClinVar variants
79
Pathogenic / LP
0.00
pLI score
4
Active trials
Clinical Summary— MTAP
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
79 Pathogenic / Likely Pathogenic· 106 VUS of 277 total submissions
💊
Clinical Trials
4 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
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?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
-0.02Z-score
OE missense 1.00 (0.88–1.14)
167 obs / 166.4 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.86 (0.55–1.39)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.00 (0.88–1.14)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.25
0≤1.21.6
LoF obs/exp: 12 / 14.0Missense obs/exp: 167 / 166.4Syn Z: -1.54

ClinVar Variant Classifications

277 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic73
Likely Pathogenic6
VUS106
Likely Benign10
Benign71
Conflicting1
73
Pathogenic
6
Likely Pathogenic
106
VUS
10
Likely Benign
71
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
73
0
73
Likely Pathogenic
0
0
6
0
6
VUS
0
41
64
1
106
Likely Benign
0
3
3
4
10
Benign
0
3
65
3
71
Conflicting
—1
Total0472118267

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View 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.

Gene2Phenotype Curations

MTAP-related diaphyseal medullary stenosis with malignant fibrous histiocytoma

strong
ADLoss Of FunctionAbsent Gene Product, Altered Gene Product Structure
Cancer
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Diaphyseal medullary stenosis with malignant fibrous histiocytoma

MIM #112250

Molecular basis of disorder known

Autosomal dominant
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
MRTX1719 Is an MTA-Cooperative PRMT5 Inhibitor That Exhibits Synthetic Lethality in Preclinical Models and Patients with MTAP-Deleted Cancer.
Engstrom LD et al.·Cancer Discov
2023Clinical trial
The genomic and transcriptomic architecture of 2,000 breast tumours reveals novel subgroups.
Curtis C et al.·Nature
2012
MTAP as an emerging biomarker in thoracic malignancies.
Brune MM et al.·Lung Cancer
2024Review
AMG 193, a Clinical Stage MTA-Cooperative PRMT5 Inhibitor, Drives Antitumor Activity Preclinically and in Patients with MTAP-Deleted Cancers.
Belmontes B et al.·Cancer Discov
2025Cohort
MAT2A Inhibition Blocks the Growth of MTAP-Deleted Cancer Cells by Reducing PRMT5-Dependent mRNA Splicing and Inducing DNA Damage.
Kalev P et al.·Cancer Cell
2021
Identification of PRMT5 as a therapeutic target in cholangiocarcinoma.
Elurbide J et al.·Gut
2024
Pan-cancer clinical and molecular landscape of MTAP deletion in nationwide and international comprehensive genomic data.
Ikushima H et al.·ESMO Open
2025
Overview of Methionine Adenosyltransferase 2A (MAT2A) as an Anticancer Target: Structure, Function, and Inhibitors.
Li C et al.·J Med Chem
2022Review
MTAP deficiency confers resistance to cytosolic nucleic acid sensing and STING agonists.
Hsu JM et al.·Science
2025
Genomic landscape of non-small-cell lung cancer with methylthioadenosine phosphorylase (MTAP) deficiency.
Ashok Kumar P et al.·Cancer Med
2023
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Loss of Methylthioadenosine Phosphorylase (MTAP) Expression: A Potentially Useful Tool for Distinguishing Sarcomatoid Urothelial Carcinoma from Inflammatory Myofibroblastic Tumor.
Li H et al.·Mod Pathol
2026
Prognostic Significance of Abnormal MTAP and p16 Expression in Gastrointestinal Stromal Tumors (GISTs).
Neyaz A et al.·Appl Immunohistochem Mol Morphol
2026
The Diagnostic and Prognostic Role of Combined p16 and MTAP Immunohistochemistry in Melanocytic Tumors of Uncertain Malignant Potential: A Comprehensive Review and Clinical Practice Analysis.
Pepe L et al.·Int J Mol Sci
2026🔓 Open AccessReview
Utility of p53, p16, and MTAP Immunohistochemistry in Oral Epithelial Dysplasia With Concurrent Candidiasis: A Novel Pattern-based Approach.
Ji JX et al.·Mod Pathol
2026
Protective efficacy of the optimized GluB-MTAP fusion subunit vaccine against Nocardia seriolae infection in largemouth bass (Micropterus salmoides).
Pan K et al.·Fish Shellfish Immunol
2026
Top 5 resultsSearch Europe PMC ↗

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
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
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
Advanced Solid Tumor

Study of GS-5319 in Adults With Solid Tumors

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

External Resources

Links to major genomics databases and tools