MTAP

Summary

MTAP (methylthioadenosine phosphorylase, HGNC:7413) is a protein-coding gene on chromosome 9p21.3, encoding S-methyl-5’-thioadenosine phosphorylase (Q13126). Catalyzes the reversible phosphorylation of S-methyl-5’-thioadenosine (MTA) to adenine and 5-methylthioribose-1-phosphate. In precision oncology, MTAP Deletion confers sensitivity to Anvumetostat in Solid Tumor (CIViC Level B); 2 further curated variant–drug associations are listed below.

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.

Source: NCBI Gene 4507 — RefSeq curated summary.

At a glance

• Gene–disease (curated): diaphyseal medullary stenosis-bone malignancy syndrome (Strong, GenCC)
• GWAS associations: 25
• Clinical variants (ClinVar): 184 total
• Phenotypes (HPO): 24
• Druggable target: yes
• Precision-oncology evidence (CIViC): 3 curated variant–drug associations
• Dosage sensitivity (ClinGen): haploinsufficiency little evidence, triplosensitivity no evidence
• MANE Select transcript: NM_002451

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7413
Approved symbol	MTAP
Name	methylthioadenosine phosphorylase
Location	9p21.3
Locus type	gene with protein product
Status	Approved
Aliases	MSAP, c86fus
Ensembl gene	ENSG00000099810
Ensembl biotype	protein_coding
OMIM	156540
Entrez	4507

Gene structure

Transcript identifiers

Ensembl transcripts: 17 — 9 protein_coding, 3 protein_coding_CDS_not_defined, 3 retained_intron, 2 nonsense_mediated_decay

ENST00000419385, ENST00000427788, ENST00000460874, ENST00000484957, ENST00000577563, ENST00000579422, ENST00000580675, ENST00000580718, ENST00000580900, ENST00000581962, ENST00000584988, ENST00000616982, ENST00000644715, ENST00000892659, ENST00000892660, ENST00000892661, ENST00000916854

RefSeq mRNA: 7 — MANE Select: NM_002451 NM_001396040, NM_001396041, NM_001396042, NM_001396043, NM_001396044, NM_001396045, NM_002451

CCDS: CCDS6509, CCDS94391, CCDS94392

Canonical transcript exons

ENST00000644715 — 8 exons

Exon	Start	End
ENSE00003480943	21818035	21818202
ENSE00003531693	21837908	21838010
ENSE00003598532	21815433	21815519
ENSE00003598545	21854631	21854870
ENSE00003682517	21816714	21816772
ENSE00003693437	21859303	21859425
ENSE00003823653	21861976	21867081
ENSE00003841538	21802636	21802781

Expression profiles

Bgee: expression breadth ubiquitous, 239 present calls, max score 92.05.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 36.5304 / max 709.1135, expressed in 1700 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
96288	34.8945	1698
96287	0.6824	449
96289	0.5966	346
96292	0.3568	128

Top tissues by expression

281 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
adrenal tissue	UBERON:0018303	92.05	gold quality
calcaneal tendon	UBERON:0003701	91.36	gold quality
colonic epithelium	UBERON:0000397	89.93	gold quality
sural nerve	UBERON:0015488	89.92	gold quality
stromal cell of endometrium	CL:0002255	88.27	gold quality
islet of Langerhans	UBERON:0000006	86.85	gold quality
rectum	UBERON:0001052	86.62	gold quality
ganglionic eminence	UBERON:0004023	85.90	gold quality
ventricular zone	UBERON:0003053	85.82	gold quality
body of pancreas	UBERON:0001150	85.43	gold quality
tibial nerve	UBERON:0001323	85.03	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	84.83	gold quality
esophagus mucosa	UBERON:0002469	84.80	gold quality
ectocervix	UBERON:0012249	84.51	gold quality
left ovary	UBERON:0002119	84.46	gold quality
pancreas	UBERON:0001264	84.44	gold quality
buccal mucosa cell	CL:0002336	84.30	silver quality
popliteal artery	UBERON:0002250	83.76	gold quality
tibial artery	UBERON:0007610	83.74	gold quality
right ovary	UBERON:0002118	83.69	gold quality
esophagus	UBERON:0001043	83.60	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.44	gold quality
minor salivary gland	UBERON:0001830	83.23	gold quality
left coronary artery	UBERON:0001626	83.16	gold quality
body of uterus	UBERON:0009853	83.03	gold quality
aorta	UBERON:0000947	82.95	gold quality
muscle layer of sigmoid colon	UBERON:0035805	82.93	gold quality
endocervix	UBERON:0000458	82.77	gold quality
monocyte	CL:0000576	82.66	gold quality
descending thoracic aorta	UBERON:0002345	82.61	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-MTAB-7249	yes	140.82
E-ANND-3	yes	5.90
E-CURD-112	yes	4.19

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CTNNB1, HAND1, HNF4A

miRNA regulators (miRDB)

118 targeting MTAP, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-4713-3P	100.00	65.92	505
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-188-3P	100.00	68.76	1240
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-146A-5P	99.96	68.93	988
HSA-MIR-146B-5P	99.96	69.13	977
HSA-MIR-7153-5P	99.94	68.89	1006
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805

Functional genomics

ClinGen dosage: haploinsufficiency 1 (little evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• Methylthioadenosine phosphorylase, a gene frequently codeleted with p16(cdkN2a/ARF), acts as a tumor suppressor in a breast cancer cell line. (PMID:12438261)
• Results suggest an important role of methylthioadenosine phosphorylase inactivation in the development of melanomas. (PMID:12875987)
• Methylthioadenosine phosphorylase regulates ornithine decarboxylase by production of downstream metabolites (PMID:14506228)
• MTAP is not expressed in normal human colonic epithelium but is strongly upregulated in colon carcinoma. (PMID:15492751)
• epigenetic mechanisms, involving DNA methylation and histone deacetylation, may play a role in the silencing of MTAP gene expression in hepatocarcinoma (PMID:15511635)
• MTAP activity is frequently lost, and ODC activity is frequently elevated in both pancreatic adenocarcinoma and neuroendocrine tumors (PMID:15534104)
• MTAP expression is lost in approximately 30% of infiltrating pancreatic cancers and in a lower percentage of other periampullary neoplasms; loss is a result of homozygous deletions encompassing both the MTAP and p16INK4A/CDKN2A genes (PMID:15662124)
• Results demonstrated concordant loss of MTAP and p16 protein expression in pancreatic intraepithelial neoplasia. (PMID:15832197)
• MTAP inactivation is associated with hepatocellular carcinoma development and invasiveness (PMID:16081515)
• Selective loss at the 3’ end of MTAP was observed in head and neck squamous cell carcinoma cell line UMSCC-11A. (PMID:16618910)
• The frequency of Methylthioadenosine phosphorylase (MTAP) deletions in conventional, grade II chondrosarcomas by fluorescence in situ hybridization (FISH) analysis was investigated. (PMID:16631464)
• Methylthioadenosine phosphorylase (MTAP) gene deletion and lack of protein expression are associated with poor prognosis in mantle cell lymphoma. (PMID:16778103)
• Regulation of MTAP by reactive oxygen species might participate in the redox regulation of the methionine catabolic pathway in the liver (PMID:18237276)
• analysis of methylthioadenosine phosphorylase (MTAP) deficiency in non-small cell lung carcinoma (PMID:18555557)
• This study demonstrates for the first time that polymorphisms in CDKN2B and MTAP gene may influence the risk of myocardial infarction in Chinese. (PMID:19272367)
• The G allele of rs10118757 was associated with an increased risk of stroke in Han Chinese even after controlling for confounding factors. The GA+GG genotype was associated with the increased risk of an undetermined subtype of ischemic stroke. (PMID:19427650)
• Expression of MTAP is significantly higher in human colorectal cancer than in normal colorectal tissues. Demethylation of MTAP promoter may play an important role in up-regulating MTAP expression. (PMID:19622299)
• MTAP homozygous deletion, the predominant mechanism to deplete protein expression, is present in 17% of gastrointestinal stromal tumors (PMID:19887491)
• Detection of CDKN2A-MTAP co-deletion in peritoneal mesotheliomas can help identify those patients who may have an unfavorable outcome (PMID:20081810)
• MTAP gene might be involved in the etiology of myocardial infarction in Chinese Han ethnicity. (PMID:20302706)
• Single nucleotide polymorphism in MTAP gene is associated with nevi. (PMID:20574843)
• CDKN2B (p15(INK4b)), CDKN2A (p16(INK4a), p14(ARF)), and MTAP are abundantly expressed in atherosclerotic lesions. (PMID:20637465)
• MTDIA antitumor activity in xenografts supports MTAP as a target for lung cancer therapy. (PMID:21135097)
• The expression of MTAP protein in non-small cell lung cancer tissue was significantly lower than that in paracarcinomous tissue and borderline lung tissue. (PMID:21342647)
• MTAP deficiency results in accumulation of 5’-deoxy-5’-methylthioadenosine, which is associated with increased tumorigenicity. (PMID:21356366)
• The present study suggests that MTAP plays an important role in the regulation of gastric carcinogenesis. (PMID:21412930)
• Polymorphisms in nevus-associated genes MTAP is associated with invasive cutaneous melanoma. (PMID:21962134)
• A large negative heat capacity change of -600 cal/(mol K) upon inhibitor binding to MTAP is consistent with altered hydrophobic interactions and release of water. (PMID:21985704)
• Data indicate that a signature of seven biomarkers (Bax, Bcl-X, PTEN, COX-2, beta-Catenin, MTAP and CD20) was found to be an independent negative predictor for overall and recurrence-free survival in cutaneous malignant melanoma (MM). (PMID:22685558)
• Letter: inactivation of MTAP expression seems to be an important step in the development and progression of malignant melanoma. of (PMID:23000879)
• Authors report here that a high percentage of t-cell lymphoma lack the enzyme methylthioadenosine phosphorylase (MTAP). (PMID:23040436)
• SNP rs10118757 was associated with CAD risk in a Chinese Han population, indicating that MTAP gene may play a potential role in the pathophysiological process of CAD. (PMID:23462334)
• Homozygous deletion of MTAP gene is associated with haploid lymphoblastic leukemia. (PMID:23508829)
• MTAP-mediated regulation of methylthioadenosine links polyamine metabolism with NF-kappaB activation and apoptosis in hepatic stellate cells. (PMID:24324622)
• MTAP expression is an independent prognostic factor and has greater prognostic significance than p16 expression in non-small cell lung cancer and concordant loss of MTAP and p16 expression indicates poor outcomes in lung cancer patients. (PMID:24969958)
• In the MTAP-deficient cases, the homozygous deletion of MTAP predicted adverse outcome. In MTAP-deficient cells, MTAP reexpression inhibited cell migration and invasion, proliferation and anchorage-independent colony formation and downregulated cyclin D1. (PMID:25426549)
• study to describe MTAP expression in a series of Pilocytic astrocytomas and relate it to the clinicopathological features of the patients; found MTAP expression is retained in Pilocytic astrocytomas and is not an outcome predictor for these tumors (PMID:26088413)
• MTAP deficiency was predictive of worse disease-specific survival and distant metastasis-free survival, suggesting its role in disease progression and as an independent prognostic biomarker of nasopharyngeal carcinoma (PMID:26656376)
• MTAP expression was significantly higher in Luminal-A breast tumors than in triple negative breast neoplasms, suggesting the lack of expression in more aggressive breast tumors. (PMID:26751376)
• Data demonstrate that MTAP deficiency leads to accumulation of MTA inducing deregulation of central cellular pathways that control cell fate and contributes to the onset of a proliferative and antiapoptotic phenotype in the liver. (PMID:26819315)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	mtap	ENSDARG00000037261
mus_musculus	Mtap	ENSMUSG00000062937
rattus_norvegicus	Mtap	ENSRNOG00000006615
drosophila_melanogaster	Mtap	FBGN0034215
drosophila_melanogaster	CG31115	FBGN0051115
caenorhabditis_elegans		WBGENE00015064

Paralogs (1): PNP (ENSG00000198805)

Protein

Protein identifiers

S-methyl-5’-thioadenosine phosphorylase — Q13126 (reviewed: Q13126)

Alternative names: 5’-methylthioadenosine phosphorylase

All UniProt accessions (7): Q13126, A0A2R8Y4K0, A0A384ME80, B4DUC8, F8WES2, J3KRN1, J3QSB7

UniProt curated annotations — full annotation on UniProt →

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.

Subunit / interactions. Homotrimer.

Subcellular location. Cytoplasm. Nucleus.

Tissue specificity. Ubiquitously expressed.

Disease relevance. Diaphyseal medullary stenosis with malignant fibrous histiocytoma (DMSMFH) [MIM:112250] An autosomal dominant bone dysplasia characterized by pathologic fractures due to abnormal cortical growth and diaphyseal medullary stenosis. The fractures heal poorly, and there is progressive bowing of the lower extremities. Some patients show a limb-girdle myopathy, with muscle weakness and atrophy. Approximately 35% of affected individuals develop an aggressive form of bone sarcoma consistent with malignant fibrous histiocytoma or osteosarcoma. The disease is caused by variants affecting the gene represented in this entry. DMSMFH causing mutations found in MTAP exon 9 result in exon skipping and dysregulated alternative splicing of all MTAP isoforms. 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.

Activity regulation. Inhibited by 5’-methylthiotubercin and 5’-chloroformycin.

Pathway. Amino-acid biosynthesis; L-methionine biosynthesis via salvage pathway; S-methyl-5-thio-alpha-D-ribose 1-phosphate from S-methyl-5’-thioadenosine (phosphorylase route): step 1/1.

Similarity. Belongs to the PNP/MTAP phosphorylase family. MTAP subfamily.

Isoforms (7)

UniProt ID	Names	Canonical?
Q13126-1	1	yes
Q13126-2	2, MTAP_v1
Q13126-3	3, MTAP_v2
Q13126-4	4, MTAP_v3
Q13126-5	5, MTAP_v4
Q13126-6	6, MTAP_v5
Q13126-7	7, MTAP_v6

RefSeq proteins (7): NP_001382969, NP_001382970, NP_001382971, NP_001382972, NP_001382973, NP_001382974, NP_002442* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000845	Nucleoside_phosphorylase_d	Domain
IPR010044	MTAP	Family
IPR018099	Purine_phosphorylase-2_CS	Conserved_site
IPR035994	Nucleoside_phosphorylase_sf	Homologous_superfamily

Pfam: PF01048

Enzyme classification (BRENDA):

• EC 2.4.2.28 — S-methyl-5’-thioadenosine phosphorylase (BRENDA: 23 organisms, 187 substrates, 154 inhibitors, 115 Km, 77 kcat entries)

Substrate kinetics (BRENDA)

44 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
5’-METHYLTHIOADENOSINE	0.0005–0.3	19
S-METHYL-5’-THIOADENOSINE	0.0001–8	15
PHOSPHATE	0.123–13.5	12
5’-DEOXY-5’-METHYLTHIOADENOSINE	—	10
ADENOSINE	0.0018–0.184	10
2’-DEOXYADENOSINE	0.001–0.0103	6
5’-DEOXYADENOSINE	0.0043–0.023	2
GUANOSINE	0.1136–0.916	2
INOSINE	0.084–0.963	2
2’-CHLORO-2’-DEOXYADENOSINE	0.032	1
2’-DEOXY-2’-AZIDO-5’-DEOXY-5’-METHYLTHIOADENOSIN	3.6	1
2’-DEOXY-5’-DEOXY-5’-METHYLTHIOADENOSINE	0.0031	1
2’-FLUORO-2’-DEOXYADENOSINE	0.005	1
3’-DEOXY-5’-DEOXY-5’-METHYLTHIOADENOSINE	0.0039	1
5’-DEOXY-5’-(1,3-THIAZOL)-2-YL-SULFANYLADENOSINE	0.009	1

Catalyzed reactions (Rhea), 1 shown:

• S-methyl-5’-thioadenosine + phosphate = 5-(methylsulfanyl)-alpha-D-ribose 1-phosphate + adenine (RHEA:11852)

UniProt features (44 total): strand 15, helix 9, binding site 6, splice variant 6, turn 2, site 2, chain 1, sequence variant 1, sequence conflict 1, modified residue 1

Structure

Experimental structures (PDB)

18 structures.

PDB	Method	Resolution (Å)
5TC6	X-RAY DIFFRACTION	1.48
6DYZ	X-RAY DIFFRACTION	1.62
6DZ0	X-RAY DIFFRACTION	1.62
1CB0	X-RAY DIFFRACTION	1.7
1CG6	X-RAY DIFFRACTION	1.7
5TC7	X-RAY DIFFRACTION	1.75
5TC8	X-RAY DIFFRACTION	1.8
5EUB	X-RAY DIFFRACTION	1.81
3LN5	X-RAY DIFFRACTION	1.9
6DZ3	X-RAY DIFFRACTION	1.91
3OZC	X-RAY DIFFRACTION	1.93
1K27	X-RAY DIFFRACTION	1.95
5TC5	X-RAY DIFFRACTION	1.96
6DZ2	X-RAY DIFFRACTION	1.99
3OZE	X-RAY DIFFRACTION	2
1SD1	X-RAY DIFFRACTION	2.03
1SD2	X-RAY DIFFRACTION	2.1
3OZD	X-RAY DIFFRACTION	2.1

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q13126-F1	92.99	0.84

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (2): 178 (important for substrate specificity); 233 (important for substrate specificity)

Ligand- & substrate-binding residues (6): 18; 60–61; 93–94; 196; 197; 220–222

Post-translational modifications (1): 51

Function

Pathways and Gene Ontology

Reactome pathways

10 pathways

ID	Pathway
R-HSA-1237112	Methionine salvage pathway
R-HSA-8950505	Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulation
R-HSA-1280215	Cytokine Signaling in Immune system
R-HSA-1430728	Metabolism
R-HSA-1614635	Sulfur amino acid metabolism
R-HSA-168256	Immune System
R-HSA-447115	Interleukin-12 family signaling
R-HSA-449147	Signaling by Interleukins
R-HSA-71291	Metabolism of amino acids and derivatives
R-HSA-9020591	Interleukin-12 signaling

MSigDB gene sets: 299 (showing top): RNGTGGGC_UNKNOWN, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, BROWNE_HCMV_INFECTION_6HR_DN, DACOSTA_UV_RESPONSE_VIA_ERCC3_XPCS_DN, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_ALPHA_AMINO_ACID_METABOLIC_PROCESS, XU_HGF_TARGETS_REPRESSED_BY_AKT1_DN, KEGG_CYSTEINE_AND_METHIONINE_METABOLISM, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, GOBP_CARBOHYDRATE_DERIVATIVE_CATABOLIC_PROCESS, GOBP_AMINO_ACID_BIOSYNTHETIC_PROCESS, TAKADA_GASTRIC_CANCER_COPY_NUMBER_DN, GOBP_ASPARTATE_FAMILY_AMINO_ACID_BIOSYNTHETIC_PROCESS, GOBP_ORGANIC_ACID_BIOSYNTHETIC_PROCESS

GO Biological Process (6): nucleobase-containing compound metabolic process (GO:0006139), purine ribonucleoside salvage (GO:0006166), obsolete L-methionine salvage from methylthioadenosine (GO:0019509), methylation (GO:0032259), response to testosterone (GO:0033574), nucleoside metabolic process (GO:0009116)

GO Molecular Function (8): 1,4-alpha-oligoglucan phosphorylase activity (GO:0004645), S-methyl-5-thioadenosine phosphorylase activity (GO:0017061), catalytic activity (GO:0003824), purine-nucleoside phosphorylase activity (GO:0004731), protein binding (GO:0005515), transferase activity (GO:0016740), glycosyltransferase activity (GO:0016757), pentosyltransferase activity (GO:0016763)

GO Cellular Component (5): nucleoplasm (GO:0005654), cytosol (GO:0005829), extracellular exosome (GO:0070062), nucleus (GO:0005634), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-8 pathways:

Category	Pathways
Sulfur amino acid metabolism	1
Interleukin-12 signaling	1
Immune System	1
Metabolism of amino acids and derivatives	1
Signaling by Interleukins	1
Cytokine Signaling in Immune system	1
Metabolism	1
Interleukin-12 family signaling	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
primary metabolic process	1
purine-containing compound salvage	1
nucleoside salvage	1
purine ribonucleoside biosynthetic process	1
metabolic process	1
response to lipid	1
response to ketone	1
nucleobase-containing small molecule metabolic process	1
carbohydrate derivative metabolic process	1
hexosyltransferase activity	1
purine-nucleoside phosphorylase activity	1
molecular_function	1
pentosyltransferase activity	1
binding	1
catalytic activity	1
transferase activity	1
glycosyltransferase activity	1
nuclear lumen	1
cytoplasm	1
extracellular vesicle	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1932 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MTAP	CDKN2A	P42771	918
MTAP	MC1R	Q01726	822
MTAP	CDKN2B	P42772	807
MTAP	PLA2G6	O60733	771
MTAP	PRMT5	O14744	770
MTAP	TYR	P14679	720
MTAP	ADAMTSL1	Q8N6G6	676
MTAP	MAT2A	P31153	665
MTAP	RIOK1	Q9BRS2	665
MTAP	TYRP1	P17643	663
MTAP	IFNW1	P05000	657
MTAP	SLC45A2	Q9UMX9	646
MTAP	APRT	P07741	643
MTAP	SMS	P52788	641
MTAP	SRM	P19623	625

IntAct

38 interactions, top by confidence:

A	B	Type	Score
CENPH	MTAP	psi-mi:“MI:0915”(physical association)	0.560
MTAP	CENPH	psi-mi:“MI:0915”(physical association)	0.560
MTAP	EMC3	psi-mi:“MI:0915”(physical association)	0.560
NEURL4	APBB1	psi-mi:“MI:0914”(association)	0.530
GPSM3	ATE1	psi-mi:“MI:0914”(association)	0.530
UBE3A	HERC2	psi-mi:“MI:0914”(association)	0.500
MTAP	NT5C3A	psi-mi:“MI:0915”(physical association)	0.400
NP	MTAP	psi-mi:“MI:0915”(physical association)	0.370
CDC25A	MTAP	psi-mi:“MI:0915”(physical association)	0.370
FOLH1	MTAP	psi-mi:“MI:0915”(physical association)	0.370
MTAP	RELB	psi-mi:“MI:0915”(physical association)	0.370
LYRM1	MTAP	psi-mi:“MI:0915”(physical association)	0.370
JUN	TPM3	psi-mi:“MI:0914”(association)	0.350
UBE3A	IGLC7	psi-mi:“MI:0914”(association)	0.350
UBE3A	TXNL1	psi-mi:“MI:0914”(association)	0.350
UBE3A	POTEF	psi-mi:“MI:0914”(association)	0.350
NEURL4	CCDC85C	psi-mi:“MI:0914”(association)	0.350
	EI24	psi-mi:“MI:0914”(association)	0.350
PRNP	WDR91	psi-mi:“MI:0914”(association)	0.350
SH3GL3	HMGB1P1	psi-mi:“MI:0914”(association)	0.350
CAV1	PPM1G	psi-mi:“MI:0914”(association)	0.350
ARID3A	PTMA	psi-mi:“MI:0914”(association)	0.350
KDM4C	SMCHD1	psi-mi:“MI:0914”(association)	0.350
P/V/C	BCAS2	psi-mi:“MI:0914”(association)	0.350
MAP1LC3A		psi-mi:“MI:0914”(association)	0.350
MTAP	KLK7	psi-mi:“MI:0914”(association)	0.350
DDX28	UBA6	psi-mi:“MI:0914”(association)	0.350
PEX7	UBA6	psi-mi:“MI:0914”(association)	0.350
RBPMS	CA2	psi-mi:“MI:0914”(association)	0.350

BioGRID (116): MTAP (Affinity Capture-MS), CENPH (Two-hybrid), ARF4 (Co-fractionation), ASS1 (Co-fractionation), CARKD (Co-fractionation), CSE1L (Co-fractionation), EIF2B1 (Co-fractionation), FAM49B (Co-fractionation), GLRX (Co-fractionation), GNPDA2 (Co-fractionation), HINT1 (Co-fractionation), LYPLA2 (Co-fractionation), MTAP (Co-fractionation), MTAP (Co-fractionation), PCMT1 (Co-fractionation)

ESM2 similar proteins: A0A1L8EV45, C9WPN6, F1QGW6, F6RQL9, O73723, O77676, P00516, P0C605, P20461, P23258, P23330, P31321, P32392, P35250, P41091, P53033, P61157, P61158, P62482, P62483, P81795, P83887, P83888, Q05B83, Q0VCD2, Q13126, Q13303, Q13976, Q27955, Q2KHU8, Q2KJ81, Q2VIR3, Q32KM1, Q4V7C7, Q5R797, Q5R8R1, Q5ZHS1, Q5ZMS3, Q641P0, Q641W4

Diamond homologs: A0QR54, A0RVQ7, A1RXU2, A2BIU4, A7EAA1, A7SN31, A8P7Y3, A8XGS6, A9A3N5, A9WAL0, B1L719, B5YKP5, B8E181, C0NRX4, C4YQD9, C7YLQ3, C8VP37, D5GFR0, E3K7C1, E3K7C3, E3XFR6, F6RQL9, F6V515, F6X2V8, O06401, O27633, O28486, O57865, O66839, P0DJF8, P0DJF9, P23139, Q07938, Q09438, Q09816, Q0U796, Q13126, Q16MW6, Q1INC3, Q291H4

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
MTAP	“up-regulates quantity”	adenine	“chemical modification”

Disease & clinical

Cancer significance

Clinical variants and AI predictions

ClinVar

184 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	99
Likely benign	2
Benign	70

Top pathogenic / likely-pathogenic (0)

SpliceAI

2805 predictions. Top by Δscore:

Variant	Effect	Δscore
9:21815429:TTAG:T	acceptor_loss	1.0000
9:21815430:TA:T	acceptor_loss	1.0000
9:21815430:TAG:T	acceptor_loss	1.0000
9:21815431:A:AG	acceptor_gain	1.0000
9:21815431:AGATT:A	acceptor_gain	1.0000
9:21815432:G:GG	acceptor_gain	1.0000
9:21815432:G:GT	acceptor_gain	1.0000
9:21815432:GA:G	acceptor_gain	1.0000
9:21815432:GAT:G	acceptor_gain	1.0000
9:21815432:GATT:G	acceptor_gain	1.0000
9:21815432:GATTG:G	acceptor_gain	1.0000
9:21815482:G:GT	donor_gain	1.0000
9:21815518:AGG:A	donor_loss	1.0000
9:21815519:GG:G	donor_loss	1.0000
9:21815520:GTT:G	donor_loss	1.0000
9:21816708:A:AG	acceptor_gain	1.0000
9:21816708:AT:A	acceptor_gain	1.0000
9:21816709:T:G	acceptor_gain	1.0000
9:21818031:A:AG	acceptor_gain	1.0000
9:21818031:ATAG:A	acceptor_gain	1.0000
9:21818032:T:G	acceptor_gain	1.0000
9:21818033:A:AG	acceptor_gain	1.0000
9:21818033:AG:A	acceptor_gain	1.0000
9:21818034:G:GA	acceptor_gain	1.0000
9:21818034:G:GG	acceptor_gain	1.0000
9:21818034:GG:G	acceptor_gain	1.0000
9:21818034:GGC:G	acceptor_gain	1.0000
9:21818034:GGCA:G	acceptor_gain	1.0000
9:21818034:GGCAT:G	acceptor_gain	1.0000
9:21818200:CAGGT:C	donor_loss	1.0000

AlphaMissense

1856 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:21816772:G:T	R60M	0.997
9:21854712:A:C	S178R	0.997
9:21854714:C:A	S178R	0.997
9:21854714:C:G	S178R	0.997
9:21854709:T:C	F177L	0.996
9:21854711:T:A	F177L	0.996
9:21854711:T:G	F177L	0.996
9:21854768:G:A	M196I	0.996
9:21854768:G:C	M196I	0.996
9:21854768:G:T	M196I	0.996
9:21859376:T:A	I255K	0.996
9:21815437:G:A	G13E	0.995
9:21815440:T:A	I14K	0.995
9:21816772:G:C	R60T	0.995
9:21818113:T:G	C86W	0.995
9:21854727:A:C	S183R	0.995
9:21854729:C:A	S183R	0.995
9:21854729:C:G	S183R	0.995
9:21816756:T:C	C55R	0.994
9:21859376:T:G	I255R	0.994
9:21816760:T:A	V56D	0.993
9:21818086:C:A	N77K	0.993
9:21818086:C:G	N77K	0.993
9:21818140:T:G	C95W	0.993
9:21854794:C:A	A205D	0.993
9:21854802:G:C	A208P	0.993
9:21854820:A:C	S214R	0.993
9:21854822:T:A	S214R	0.993
9:21854822:T:G	S214R	0.993
9:21854850:T:A	W224R	0.993

dbSNP variants (sampled 300 via entrez): RS1000006624 (9:21873614 C>A,G), RS1000007383 (9:21898857 A>T), RS1000025402 (9:21834161 A>G,T), RS1000042096 (9:21939479 T>C), RS1000044726 (9:21829130 A>C,G), RS1000047679 (9:21910451 T>C), RS1000064089 (9:21817915 G>C,T), RS1000067022 (9:21904343 A>T), RS1000097877 (9:21921109 T>C), RS1000099915 (9:21869967 A>G), RS1000103198 (9:21904328 C>A,G,T), RS1000140684 (9:21864362 T>A,G), RS1000142862 (9:21834344 T>A), RS1000165706 (9:21917981 A>G), RS1000176285 (9:21856013 C>G)

Disease associations

OMIM: gene MIM:156540 | disease phenotypes: MIM:112250

GenCC curated gene-disease

Disease	Classification	Inheritance
diaphyseal medullary stenosis-bone malignancy syndrome	Strong	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
diaphyseal medullary stenosis-bone malignancy syndrome	Moderate	AD

Mondo (1): diaphyseal medullary stenosis-bone malignancy syndrome (MONDO:0007205)

Orphanet (1): Diaphyseal medullary stenosis-bone malignancy syndrome (Orphanet:85182)

HPO phenotypes

24 total (24 of 24 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000938	Osteopenia
HP:0000963	Thin skin
HP:0000977	Soft skin
HP:0000978	Bruising susceptibility
HP:0002216	Premature graying of hair
HP:0002669	Osteosarcoma
HP:0002756	Pathologic fracture
HP:0002979	Bowing of the legs
HP:0003084	Recurrent long bone fractures
HP:0003198	Myopathy
HP:0003202	Skeletal muscle atrophy
HP:0003325	Limb-girdle muscle weakness
HP:0003676	Progressive
HP:0003690	Limb muscle weakness
HP:0003701	Proximal muscle weakness
HP:0005010	Osteomyelitis leading to amputation due to slow healing fractures
HP:0005045	Diaphyseal cortical sclerosis
HP:0005686	Patchy osteosclerosis
HP:0007819	Presenile cataracts
HP:0012315	Histiocytoma
HP:0031367	Metaphyseal striations
HP:0100244	Fibrosarcoma
HP:0100254	Stenosis of the medullary cavity of the long bones

GWAS associations

25 associations (top):

Study	Trait	p-value
GCST000438_1	Cutaneous nevi	3.000000e-15
GCST001079_5	Coronary heart disease	2.000000e-27
GCST001267_6	Melanoma	7.000000e-09
GCST002952_1	Pediatric bone mineral content (radius)	1.000000e-08
GCST003805_6	Diastolic blood pressure response to hydrochlorothiazide in hypertension	6.000000e-06
GCST004142_12	Melanoma	3.000000e-17
GCST004142_26	Melanoma	7.000000e-09
GCST004278_94	Pulse pressure	1.000000e-07
GCST004280_77	Diastolic blood pressure	1.000000e-10
GCST004744_60	Lung adenocarcinoma	1.000000e-09
GCST004747_2	Lung cancer in never smokers	2.000000e-06
GCST004748_13	Lung cancer	2.000000e-06
GCST004748_14	Lung cancer	9.000000e-06
GCST005173_76	Coronary artery calcified atherosclerotic plaque (130 HU threshold) in type 2 diabetes	4.000000e-06
GCST006976_16	Macular thickness	8.000000e-26
GCST007504_9	Nevus count	2.000000e-37
GCST007505_30	Nevus count or cutaneous melanoma	7.000000e-67
GCST007505_4	Nevus count or cutaneous melanoma	2.000000e-34
GCST007954_2	Glycated hemoglobin levels	7.000000e-12
GCST008659_2	Lung function in heavy smokers (low FEV1 vs high FEV1)	2.000000e-07
GCST009028_43	Adverse response to drug	7.000000e-07
GCST010303_1	Nevus count or cutaneous melanoma	6.000000e-113
GCST010304_43	Cutaneous malignant melanoma	3.000000e-65
GCST010463_17	Childhood ALL/LBL (acute lymphoblastic leukemia/lymphoblastic lymphoma) treatment-related venous thromboembolism	4.000000e-06
GCST90002397_676	Mean spheric corpuscular volume	5.000000e-12

EFO canonical traits (10, from GWAS)

EFO ID	Trait name
EFO:0000625	nevus
EFO:0007621	bone mineral content measurement
EFO:0006945	diastolic blood pressure change measurement
EFO:0005763	pulse pressure measurement
EFO:0006336	diastolic blood pressure
EFO:0004723	coronary artery calcification
EFO:0004632	nevus count
EFO:0004541	HbA1c measurement
EFO:0004314	forced expiratory volume
EFO:0009658	adverse effect

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4941 (SINGLE PROTEIN)

Clinical evidence (CIViC)

Drug × variant × indication: 3 predictive associations from 3 curated evidence items.

Variant	Therapy	Indication	Effect	Level	CIViC
MTAP Deletion	Anvumetostat	Solid Tumor	Sensitivity/Response	CIViC B	EID12158
MTAP Deletion	Pemetrexed	Bladder Urothelial Carcinoma	Sensitivity/Response	CIViC B	EID12722
MTAP Underexpression	Pyrimidine Antagonist	Breast Cancer	Sensitivity/Response	CIViC D	EID1980

PharmGKB: 1 entry (VIP=true, CPIC=false)

ChEMBL bioactivities

112 potent at pChembl≥5 of 112 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
11.00	Ki	0.01	nM	CHEMBL365813
10.47	Ki	0.034	nM	CHEMBL191544
10.11	Ki	0.078	nM	CHEMBL405346
10.05	Ki	0.09	nM	CHEMBL405346
10.05	Ki	0.09	nM	CHEMBL188375
9.96	Ki	0.11	nM	CHEMBL365378
9.92	Ki	0.12	nM	CHEMBL425188
9.80	Ki	0.16	nM	CHEMBL190216
9.80	Ki	0.16	nM	CHEMBL190139
9.78	Ki	0.166	nM	CHEMBL552894
9.77	Ki	0.17	nM	CHEMBL188034
9.67	Ki	0.214	nM	CHEMBL544806
9.59	Ki	0.26	nM	CHEMBL191281
9.57	Ki	0.27	nM	CHEMBL191177
9.57	Ki	0.266	nM	CHEMBL554965
9.55	Ki	0.28	nM	CHEMBL365378
9.44	Ki	0.36	nM	CHEMBL365813
9.43	Ki	0.37	nM	CHEMBL190867
9.28	Ki	0.53	nM	CHEMBL405346
9.26	Ki	0.55	nM	CHEMBL1243249
9.24	Ki	0.576	nM	CHEMBL552894
9.20	Kd	0.63	nM	CHEMBL4445386
9.20	Ki	0.628	nM	CHEMBL542449
9.19	Ki	0.65	nM	CHEMBL191544
9.19	Ki	0.64	nM	CHEMBL544110
9.15	Ki	0.7	nM	CHEMBL191436
9.15	Ki	0.7	nM	CHEMBL1241349
9.12	Ki	0.76	nM	CHEMBL190867
9.10	Ki	0.8	nM	CHEMBL1243249
9.09	Ki	0.81	nM	CHEMBL190216
9.05	Ki	0.9	nM	CHEMBL191281
9.03	Kd	0.94	nM	CHEMBL4465346
9.00	Ki	1	nM	CHEMBL1195586
9.00	Ki	1	nM	CHEMBL1161749
9.00	Ki	1	nM	CHEMBL545042
9.00	Ki	1	nM	CHEMBL554322
8.92	IC50	1.2	nM	CHEMBL554896
8.89	Ki	1.3	nM	CHEMBL425188
8.89	Kd	1.3	nM	CHEMBL4450105
8.86	Ki	1.39	nM	CHEMBL542449
8.85	Ki	1.4	nM	CHEMBL191436
8.85	Kd	1.4	nM	CHEMBL4439603
8.82	Ki	1.5	nM	CHEMBL188034
8.77	Ki	1.7	nM	CHEMBL188375
8.77	Ki	1.7	nM	CHEMBL1243250
8.70	Ki	2	nM	CHEMBL191177
8.70	Ki	2	nM	CHEMBL190139
8.70	Ki	2	nM	CHEMBL405371
8.70	Ki	2	nM	CHEMBL545740
8.68	Ki	2.1	nM	CHEMBL1241380

PubChem BioAssay actives

123 with measured affinity, of 244 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
1-[(4-amino-4,5-dihydro-1H-pyrrolo[3,2-d]pyrimidin-7-yl)methyl]-4-(ethylsulfanylmethyl)pyrrolidin-3-ol	239814: Inhibition of human MTAP as equilibrium dissociation constant	ki	<0.0001	uM
1-[(4-amino-4,5-dihydro-1H-pyrrolo[3,2-d]pyrimidin-7-yl)methyl]-4-[(4-chlorophenyl)sulfanylmethyl]pyrrolidin-3-ol	239814: Inhibition of human MTAP as equilibrium dissociation constant	ki	<0.0001	uM
1-[(4-amino-5H-pyrrolo[3,2-d]pyrimidin-7-yl)methyl]-4-[(4-chlorophenyl)sulfanylmethyl]pyrrolidin-3-ol	1799419: Enzyme Activity Assay from Article 10.1021/cb700166z: “Picomolar inhibitors as transition-state probes of 5’-methylthioadenosine nucleosidases.”	kd	<0.0001	uM
(3R,4S)-1-[(4-amino-5H-pyrrolo[3,2-d]pyrimidin-7-yl)methyl]-4-(methylsulfanylmethyl)pyrrolidin-3-ol	1799419: Enzyme Activity Assay from Article 10.1021/cb700166z: “Picomolar inhibitors as transition-state probes of 5’-methylthioadenosine nucleosidases.”	kd	<0.0001	uM
1-[(4-amino-4,5-dihydro-1H-pyrrolo[3,2-d]pyrimidin-7-yl)methyl]-4-(butylsulfanylmethyl)pyrrolidin-3-ol	239814: Inhibition of human MTAP as equilibrium dissociation constant	ki	0.0001	uM
1-[(4-amino-4,5-dihydro-1H-pyrrolo[3,2-d]pyrimidin-7-yl)methyl]-4-(propylsulfanylmethyl)pyrrolidin-3-ol	239814: Inhibition of human MTAP as equilibrium dissociation constant	ki	0.0001	uM
1-[(4-amino-5H-pyrrolo[3,2-d]pyrimidin-7-yl)methyl]-4-(methylsulfanylmethyl)pyrrolidin-3-ol	239814: Inhibition of human MTAP as equilibrium dissociation constant	ki	0.0001	uM
2-(4-amino-5H-pyrrolo[3,2-d]pyrimidin-7-yl)-5-[(4-chlorophenyl)sulfanylmethyl]pyrrolidine-3,4-diol	1799419: Enzyme Activity Assay from Article 10.1021/cb700166z: “Picomolar inhibitors as transition-state probes of 5’-methylthioadenosine nucleosidases.”	kd	0.0002	uM
1-[(4-amino-4,5-dihydro-1H-pyrrolo[3,2-d]pyrimidin-7-yl)methyl]-4-(pyridin-4-ylsulfanylmethyl)pyrrolidin-3-ol	239814: Inhibition of human MTAP as equilibrium dissociation constant	ki	0.0002	uM
1-[(4-amino-4,5-dihydro-1H-pyrrolo[3,2-d]pyrimidin-7-yl)methyl]-4-[(4-fluorophenyl)sulfanylmethyl]pyrrolidin-3-ol	239814: Inhibition of human MTAP as equilibrium dissociation constant	ki	0.0002	uM
1-[(4-amino-4,5-dihydro-1H-pyrrolo[3,2-d]pyrimidin-7-yl)methyl]-4-(phenylsulfanylmethyl)pyrrolidin-3-ol	239814: Inhibition of human MTAP as equilibrium dissociation constant	ki	0.0002	uM
2-(4-amino-5H-pyrrolo[3,2-d]pyrimidin-7-yl)-5-(propylsulfanylmethyl)pyrrolidine-3,4-diol;hydrochloride	3135: Equilibrium dissociation constant towards human 5’-methylthioadenosine phosphorylase	ki	0.0002	uM
2-(4-amino-5H-pyrrolo[3,2-d]pyrimidin-7-yl)-5-[(4-chlorophenyl)sulfanylmethyl]pyrrolidine-3,4-diol;hydrochloride	3135: Equilibrium dissociation constant towards human 5’-methylthioadenosine phosphorylase	ki	0.0002	uM
2-(4-amino-5H-pyrrolo[3,2-d]pyrimidin-7-yl)-5-(ethylsulfanylmethyl)pyrrolidine-3,4-diol	1799419: Enzyme Activity Assay from Article 10.1021/cb700166z: “Picomolar inhibitors as transition-state probes of 5’-methylthioadenosine nucleosidases.”	kd	0.0003	uM
1-[(4-amino-4,5-dihydro-1H-pyrrolo[3,2-d]pyrimidin-7-yl)methyl]-4-[(3-chlorophenyl)sulfanylmethyl]pyrrolidin-3-ol	239814: Inhibition of human MTAP as equilibrium dissociation constant	ki	0.0003	uM
1-[(4-amino-4,5-dihydro-1H-pyrrolo[3,2-d]pyrimidin-7-yl)methyl]-4-(propan-2-ylsulfanylmethyl)pyrrolidin-3-ol	239814: Inhibition of human MTAP as equilibrium dissociation constant	ki	0.0003	uM
2-(4-amino-5H-pyrrolo[3,2-d]pyrimidin-7-yl)-5-(ethylsulfanylmethyl)pyrrolidine-3,4-diol;hydrochloride	3135: Equilibrium dissociation constant towards human 5’-methylthioadenosine phosphorylase	ki	0.0003	uM
1-[(4-amino-4,5-dihydro-1H-pyrrolo[3,2-d]pyrimidin-7-yl)methyl]-4-(cyclohexylsulfanylmethyl)pyrrolidin-3-ol	239814: Inhibition of human MTAP as equilibrium dissociation constant	ki	0.0004	uM
(3R,4S)-1-[(4-amino-5H-pyrrolo[3,2-d]pyrimidin-7-yl)methyl]-4-(prop-2-ynylsulfanylmethyl)pyrrolidin-3-ol	1543976: Binding affinity to recombinant human N-terminal TEV cleavage site-fused-His6-tagged MTAP expressed in Escherichia coli BL21-CodonPlus(DE3)-RIPL competent cells assessed as reduction in MTA hydrolysis measured after 40 mins in presence of xanthine oxidase	kd	0.0006	uM
2-(4-amino-5H-pyrrolo[3,2-d]pyrimidin-7-yl)-5-[(4-methylphenyl)sulfanylmethyl]pyrrolidine-3,4-diol;hydrochloride	3135: Equilibrium dissociation constant towards human 5’-methylthioadenosine phosphorylase	ki	0.0006	uM
2-(4-amino-5H-pyrrolo[3,2-d]pyrimidin-7-yl)-5-[(3-methylphenyl)sulfanylmethyl]pyrrolidine-3,4-diol;hydrochloride	3135: Equilibrium dissociation constant towards human 5’-methylthioadenosine phosphorylase	ki	0.0006	uM
(3R,4S)-1-[(4-amino-5H-pyrrolo[3,2-d]pyrimidin-7-yl)methyl]-4-butylpyrrolidin-3-ol	509579: Inhibition of His-tagged human MTAP	ki	0.0006	uM
1-[(4-amino-5H-pyrrolo[3,2-d]pyrimidin-7-yl)methyl]-4-(benzylsulfanylmethyl)pyrrolidin-3-ol	1799419: Enzyme Activity Assay from Article 10.1021/cb700166z: “Picomolar inhibitors as transition-state probes of 5’-methylthioadenosine nucleosidases.”	kd	0.0007	uM
(3R,4S)-1-[(4-amino-5H-pyrrolo[3,2-d]pyrimidin-7-yl)methyl]-4-ethylpyrrolidin-3-ol	509579: Inhibition of His-tagged human MTAP	ki	0.0007	uM
(3R,4S)-1-[(4-amino-5H-pyrrolo[3,2-d]pyrimidin-7-yl)methyl]-4-(pent-4-ynylsulfanylmethyl)pyrrolidin-3-ol	1543976: Binding affinity to recombinant human N-terminal TEV cleavage site-fused-His6-tagged MTAP expressed in Escherichia coli BL21-CodonPlus(DE3)-RIPL competent cells assessed as reduction in MTA hydrolysis measured after 40 mins in presence of xanthine oxidase	kd	0.0009	uM
2-(4-amino-5H-pyrrolo[3,2-d]pyrimidin-7-yl)-5-(methylsulfanylmethyl)pyrrolidine-3,4-diol	239814: Inhibition of human MTAP as equilibrium dissociation constant	ki	0.0010	uM
2-(4-amino-5H-pyrrolo[3,2-d]pyrimidin-7-yl)-5-(methylsulfanylmethyl)pyrrolidin-1-ium-3,4-diol	1799419: Enzyme Activity Assay from Article 10.1021/cb700166z: “Picomolar inhibitors as transition-state probes of 5’-methylthioadenosine nucleosidases.”	kd	0.0010	uM
(2S,3S,4R,5S)-2-(4-amino-5H-pyrrolo[3,2-d]pyrimidin-7-yl)-5-(methylsulfanylmethyl)pyrrolidine-3,4-diol	677808: Inhibition of human MTAP assessed as reduction in methylthioadenosine phosphorolysis/hydrolysis	ki	0.0010	uM
2-(4-amino-5H-pyrrolo[3,2-d]pyrimidin-7-yl)-5-(phenylsulfanylmethyl)pyrrolidine-3,4-diol;hydrochloride	3135: Equilibrium dissociation constant towards human 5’-methylthioadenosine phosphorylase	ki	0.0010	uM
2-(4-amino-5H-pyrrolo[3,2-d]pyrimidin-7-yl)-5-(methylsulfanylmethyl)pyrrolidine-3,4-diol;hydrochloride	3135: Equilibrium dissociation constant towards human 5’-methylthioadenosine phosphorylase	ki	0.0010	uM
(2S,3S,4R,5S)-2-(4-amino-5H-pyrrolo[3,2-d]pyrimidin-7-yl)-5-(methylsulfanylmethyl)pyrrolidine-3,4-diol;hydrochloride	108077: Inhibitory concentration against Methylthioadenosine phosphorylase	ic50	0.0012	uM
(3R,4S)-1-[(4-amino-5H-pyrrolo[3,2-d]pyrimidin-7-yl)methyl]-4-[3-(1-butyltriazol-4-yl)propylsulfanylmethyl]pyrrolidin-3-ol	1543976: Binding affinity to recombinant human N-terminal TEV cleavage site-fused-His6-tagged MTAP expressed in Escherichia coli BL21-CodonPlus(DE3)-RIPL competent cells assessed as reduction in MTA hydrolysis measured after 40 mins in presence of xanthine oxidase	kd	0.0013	uM
(3R,4S)-1-[(4-amino-5H-pyrrolo[3,2-d]pyrimidin-7-yl)methyl]-4-[3-(1-benzyltriazol-4-yl)propylsulfanylmethyl]pyrrolidin-3-ol	1543976: Binding affinity to recombinant human N-terminal TEV cleavage site-fused-His6-tagged MTAP expressed in Escherichia coli BL21-CodonPlus(DE3)-RIPL competent cells assessed as reduction in MTA hydrolysis measured after 40 mins in presence of xanthine oxidase	kd	0.0014	uM
(3R,4S)-1-[(4-amino-5H-pyrrolo[3,2-d]pyrimidin-7-yl)methyl]-4-(2-methylpropyl)pyrrolidin-3-ol	509579: Inhibition of His-tagged human MTAP	ki	0.0017	uM
7-[[3-(methylsulfanylmethyl)azetidin-1-yl]methyl]-5H-pyrrolo[3,2-d]pyrimidin-4-amine	1798157: MTAP/MTAN Inhibition Assay from Article 10.1021/jm701265n: “Azetidine based transition state analogue inhibitors of N-ribosyl hydrolases and phosphorylases.”	ki	0.0020	uM
2-(4-amino-5H-pyrrolo[3,2-d]pyrimidin-7-yl)-5-[(4-fluorophenyl)sulfanylmethyl]pyrrolidine-3,4-diol;hydrochloride	3135: Equilibrium dissociation constant towards human 5’-methylthioadenosine phosphorylase	ki	0.0020	uM
(3R,4S)-1-[(4-amino-5H-pyrrolo[3,2-d]pyrimidin-7-yl)methyl]-4-cyclopropylpyrrolidin-3-ol	509579: Inhibition of His-tagged human MTAP	ki	0.0021	uM
(3R,4S)-1-[(4-amino-5H-pyrrolo[3,2-d]pyrimidin-7-yl)methyl]-4-[3-(1-prop-2-enyltriazol-4-yl)propylsulfanylmethyl]pyrrolidin-3-ol	1543976: Binding affinity to recombinant human N-terminal TEV cleavage site-fused-His6-tagged MTAP expressed in Escherichia coli BL21-CodonPlus(DE3)-RIPL competent cells assessed as reduction in MTA hydrolysis measured after 40 mins in presence of xanthine oxidase	kd	0.0024	uM
(3R,4S)-1-[(4-amino-5H-pyrrolo[3,2-d]pyrimidin-7-yl)methyl]-4-cyclopentylpyrrolidin-3-ol	509579: Inhibition of His-tagged human MTAP	ki	0.0026	uM
(3R,4S)-1-[(4-amino-5H-pyrrolo[3,2-d]pyrimidin-7-yl)methyl]-4-[3-(1-methyltriazol-4-yl)propylsulfanylmethyl]pyrrolidin-3-ol	1543976: Binding affinity to recombinant human N-terminal TEV cleavage site-fused-His6-tagged MTAP expressed in Escherichia coli BL21-CodonPlus(DE3)-RIPL competent cells assessed as reduction in MTA hydrolysis measured after 40 mins in presence of xanthine oxidase	kd	0.0030	uM
1-[(4-amino-4,5-dihydro-1H-pyrrolo[3,2-d]pyrimidin-7-yl)methyl]-4-propylpyrrolidin-3-ol	239814: Inhibition of human MTAP as equilibrium dissociation constant	ki	0.0030	uM
(3R,4S)-1-[(4-amino-5H-pyrrolo[3,2-d]pyrimidin-7-yl)methyl]-4-prop-2-enylpyrrolidin-3-ol	509579: Inhibition of His-tagged human MTAP	ki	0.0030	uM
2-(4-amino-5H-pyrrolo[3,2-d]pyrimidin-7-yl)-5-(2-fluoroethylsulfanylmethyl)pyrrolidine-3,4-diol;hydrochloride	3135: Equilibrium dissociation constant towards human 5’-methylthioadenosine phosphorylase	ki	0.0032	uM
(3R,4S)-1-[(4-amino-5H-pyrrolo[3,2-d]pyrimidin-7-yl)methyl]-4-ethenylpyrrolidin-3-ol	509579: Inhibition of His-tagged human MTAP	ki	0.0032	uM
(2R)-2-[(4-amino-5H-pyrrolo[3,2-d]pyrimidin-7-yl)methylamino]-3-methylsulfanylpropan-1-ol	677808: Inhibition of human MTAP assessed as reduction in methylthioadenosine phosphorolysis/hydrolysis	ki	0.0044	uM
(2R,3S)-2-[(4-amino-5H-pyrrolo[3,2-d]pyrimidin-7-yl)methylamino]-4-methylsulfanylbutane-1,3-diol	677808: Inhibition of human MTAP assessed as reduction in methylthioadenosine phosphorolysis/hydrolysis	ki	0.0052	uM
2-(4-amino-5H-pyrrolo[3,2-d]pyrimidin-7-yl)-5-[(3-chlorophenyl)sulfanylmethyl]pyrrolidine-3,4-diol;hydrochloride	3137: Initial dissociation constant towards human 5’-methylthioadenosine phosphorylase	ki	0.0064	uM
1-[(4-amino-4,5-dihydro-1H-pyrrolo[3,2-d]pyrimidin-7-yl)methyl]-4-(methoxymethyl)pyrrolidin-3-ol	239814: Inhibition of human MTAP as equilibrium dissociation constant	ki	0.0080	uM
(3R,4S)-1-[(4-amino-5H-pyrrolo[3,2-d]pyrimidin-7-yl)methyl]-4-phenylpyrrolidin-3-ol	509579: Inhibition of His-tagged human MTAP	ki	0.0080	uM
2-[[(4-amino-5H-pyrrolo[3,2-d]pyrimidin-7-yl)methylamino]methyl]-3-methylsulfanylpropan-1-ol	677808: Inhibition of human MTAP assessed as reduction in methylthioadenosine phosphorolysis/hydrolysis	ki	0.0100	uM

CTD chemical–gene interactions

57 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, decreases expression, decreases methylation	4
trichostatin A	affects cotreatment, increases expression	3
Arsenic Trioxide	affects binding, decreases reaction, decreases expression, increases expression	3
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression, increases expression	2
Benzo(a)pyrene	affects methylation, decreases expression	2
aristolochic acid I	decreases expression	1
bisphenol F	increases expression	1
TAK-243	increases sumoylation	1
bismuth tripotassium dicitrate	decreases expression	1
methylmercuric chloride	increases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, decreases expression, increases abundance	1
bisphenol A	decreases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, decreases expression	1
beta-lapachone	increases expression	1
sodium arsenite	affects binding, increases reaction	1
4-aminophenylarsenoxide	affects binding, decreases reaction	1
methacrylaldehyde	affects cotreatment, decreases expression, increases abundance	1
beta-methylcholine	affects expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
tanespimycin	decreases expression, affects cotreatment	1
K 7174	decreases expression	1
ICG 001	decreases expression	1
bisphenol B	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
jinfukang	increases expression	1
VER 155008	affects cotreatment, decreases expression	1
LDN 193189	affects cotreatment, decreases expression	1

ChEMBL screening assays

24 unique, capped per target: 23 binding, 1 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1244606	Binding	Inhibition of MTAP in human FaDu cells by ESI-MS analysis	Transition state analogs of 5’-methylthioadenosine nucleosidase disrupt quorum sensing. — Nat Chem Biol
CHEMBL3755835	ADMET	Prodrug activation assessed as recombinant human MTAP-mediated compound cleavage at 100 uM by reverse phase HPLC analysis	6-Methylpurine derived sugar modified nucleosides: Synthesis and in vivo antitumor activity in D54 tumor expressing M64V-Escherichia coli purine nucleoside phosphorylase. — Eur J Med Chem

Cellosaurus cell lines

28 cell lines: 21 cancer cell line, 5 telomerase immortalized cell line, 2 spontaneously immortalized cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_A121	Ma-Mel-08a	Cancer cell line	Male
CVCL_A124	Ma-Mel-100a	Cancer cell line	Male
CVCL_A127	Ma-Mel-103a	Cancer cell line	Female
CVCL_A142	Ma-Mel-122	Cancer cell line	Male
CVCL_A146	Ma-Mel-13	Cancer cell line	Male
CVCL_A156	Ma-Mel-19	Cancer cell line	Female
CVCL_A165	Ma-Mel-30	Cancer cell line	Male
CVCL_A201	Ma-Mel-66a	Cancer cell line	Female
CVCL_A218	Ma-Mel-83	Cancer cell line	Female
CVCL_A229	Ma-Mel-95	Cancer cell line	Sex unspecified

Clinical trials (associated diseases)

1 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT05523076	Not specified	COMPLETED	Transdiagnostic Markers of Cognitive Symptoms in Disorders Affective.