TISIDB

Summary
Symbol	MTAP
Name	methylthioadenosine phosphorylase
Aliases	c86fus; S-methyl-5'-thioadenosine phosphorylase; BDMF; DMSFH; DMSMFH; HEL-249; LGMBF; 5'-methylthioadenosine ......
Chromosomal Location	9p21
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Basic function annotation. > Subcellular Location, Domain and Function > Gene Ontology > KEGG and Reactome Pathway

> Subcellular Location, Domain and Function [ TOP ]
Subcellular Location	Cytoplasm. Nucleus
Domain	PF01048 Phosphorylase superfamily
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.

> Gene Ontology [ TOP ]
Biological Process	GO:0006166 purine ribonucleoside salvage GO:0006520 cellular amino acid metabolic process GO:0006555 methionine metabolic process GO:0008652 cellular amino acid biosynthetic process GO:0009066 aspartate family amino acid metabolic process GO:0009067 aspartate family amino acid biosynthetic process GO:0009086 methionine biosynthetic process GO:0009116 nucleoside metabolic process GO:0009119 ribonucleoside metabolic process GO:0009163 nucleoside biosynthetic process GO:0016053 organic acid biosynthetic process GO:0019509 L-methionine biosynthetic process from methylthioadenosine GO:0032259 methylation GO:0033574 response to testosterone GO:0042278 purine nucleoside metabolic process GO:0042451 purine nucleoside biosynthetic process GO:0042455 ribonucleoside biosynthetic process GO:0043094 cellular metabolic compound salvage GO:0043101 purine-containing compound salvage GO:0043102 amino acid salvage GO:0043174 nucleoside salvage GO:0044283 small molecule biosynthetic process GO:0046128 purine ribonucleoside metabolic process GO:0046129 purine ribonucleoside biosynthetic process GO:0046394 carboxylic acid biosynthetic process GO:0071265 L-methionine biosynthetic process GO:0071267 L-methionine salvage GO:0072522 purine-containing compound biosynthetic process GO:1901605 alpha-amino acid metabolic process GO:1901607 alpha-amino acid biosynthetic process GO:1901654 response to ketone GO:1901657 glycosyl compound metabolic process GO:1901659 glycosyl compound biosynthetic process
Molecular Function	GO:0004645 phosphorylase activity GO:0004731 purine-nucleoside phosphorylase activity GO:0016757 transferase activity, transferring glycosyl groups GO:0016758 transferase activity, transferring hexosyl groups GO:0016763 transferase activity, transferring pentosyl groups GO:0017061 S-methyl-5-thioadenosine phosphorylase activity
Cellular Component	-

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa00270 Cysteine and methionine metabolism hsa01100 Metabolic pathways
Reactome	R-HSA-1430728: Metabolism R-HSA-71291: Metabolism of amino acids and derivatives R-HSA-351202: Metabolism of polyamines R-HSA-1237112: Methionine salvage pathway R-HSA-1614635: Sulfur amino acid metabolism

Summary
Symbol	MTAP
Name	methylthioadenosine phosphorylase
Aliases	c86fus; S-methyl-5'-thioadenosine phosphorylase; BDMF; DMSFH; DMSMFH; HEL-249; LGMBF; 5'-methylthioadenosine ......
Chromosomal Location	9p21
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between MTAP and anti-tumor immunity. The specific mechanism were also collected if the literature reports that a gene specifically promotes or inhibits the infiltration or function of T/NK cells.

> Text Mining [ TOP ]
There is no record.

Summary
Symbol	MTAP
Name	methylthioadenosine phosphorylase
Aliases	c86fus; S-methyl-5'-thioadenosine phosphorylase; BDMF; DMSFH; DMSMFH; HEL-249; LGMBF; 5'-methylthioadenosine ......
Chromosomal Location	9p21
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	High-throughput screening data (e.g. CRISPR-Cas9, shRNA and RNAi) for T cell-mediated killing. Genetic screen techniques can identify mechanisms of tumor cell resistance (e.g., PTPN2) and sensitivity (e.g., APLNR) to killing by cytotoxic T cells, the central effectors of anti-tumor immunity. After comprehensively searching, eight groups of screening data sets were collected in the current database. In this tab, users can check whether their selected genes cause resistance or increase sensitivity to T cell-mediated killing in various data sets.

> High-throughput Screening

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Statistical results of MTAP in screening data sets for detecting immune reponses.

PMID	Screening System	Cancer Type	Cell Line	Data Set	Statistical Results	Relation to immunity
29301958	CRISPR-Cas9	melanoma	B16F10	Pmel-1 T cell	NA/NS	NA/NS
29301958	CRISPR-Cas9	melanoma	B16F10	OT-1 T cell	NA/NS	NA/NS
28783722	CRISPR-Cas9	melanoma	Mel624	2CT-CRISPR	NA/NS	NA/NS
28723893	CRISPR-Cas9	melanoma	B16	GVAX+Anti-PD1	NA/NS	NA/NS
28723893	CRISPR-Cas9	melanoma	B16	GVAX	NA/NS	NA/NS
25691366	RNAi	Breast cancer	MCF7	Luc-CTL assay	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Primary screen	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Secondary screen	NA/NS	NA/NS

Summary
Symbol	MTAP
Name	methylthioadenosine phosphorylase
Aliases	c86fus; S-methyl-5'-thioadenosine phosphorylase; BDMF; DMSFH; DMSMFH; HEL-249; LGMBF; 5'-methylthioadenosine ......
Chromosomal Location	9p21
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Transcriptomic and genomic profiling of pre-treated tumor biopsies from responders and non-responders to immunotherapy. These data were used to identify signatures and mechanisms of response to checkpoint blockade (e.g., anti-PDL1 and anti-PD1). One example is that mutations in the gene PBRM1 benefit clinical survival of patients with clear cell renal cell carcinoma. After comprehensively searching, we collected 5 and 6 of transcriptomic and genomic data sets, respectively. In this tab, users can check whether their selected genes have significant difference of expression or mutation between responders and non-responders in various data sets. > Expression difference between responders and non-responders > Mutation difference between responders and non-responders

> Expression difference between responders and non-responders

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Points in the above scatter plot represent the expression difference of MTAP in various data sets.

No	PMID	Cancer type	Group	Drug	# Res	# NRes	Log2 (Fold Change)	P value
1	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	14	12	0.249	0.572
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	0.925	0.551
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	-0.231	0.816
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.97	0.0349
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0.867	0.651
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	1.107	0.667
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.261	0.604
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0.452	0.765
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0.04	0.981
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.68	0.592
11	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	2	0	0	1
12	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	2	8	1.693	0.333
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	0.616	0.0025

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of MTAP in various data sets.

No	PMID	Cancer type	Group	Drug	# Res	# NRes	% Mut/Res	% Diff (R vs NR)	Pval
1	25765070	Non-small cell lung cancer (NSCLC)	all	Anti-PD-1 (pembrolizumab)	14	17	0	0	1
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	0	0	1
3	25765070	Non-small cell lung cancer (NSCLC)	non-smoking	Anti-PD-1 (pembrolizumab)	4	14	0	0	1
4	26359337	Melanoma	all	Anti-CTLA-4 (ipilimumab)	27	73	0	0	1
5	26359337	Melanoma	BRAFi	Anti-CTLA-4 (ipilimumab)	0	14	0	0	1
6	26359337	Melanoma	non-BRAFi	Anti-CTLA-4 (ipilimumab)	27	59	0	0	1
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	0	0	1
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	0	0	1
9	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	13	11	0	0	1
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0	0	1
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0	0	1
12	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0	0	1
13	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	38	27	2.6	2.6	1
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	4.5	4.5	1
15	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	16	14	0	0	1
16	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	11	13	0	0	1
17	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	6	1	0	0	1
18	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	5	12	0	0	1

Summary
Symbol	MTAP
Name	methylthioadenosine phosphorylase
Aliases	c86fus; S-methyl-5'-thioadenosine phosphorylase; BDMF; DMSFH; DMSMFH; HEL-249; LGMBF; 5'-methylthioadenosine ......
Chromosomal Location	9p21
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of MTAP. The immune-related signatures of 28 TIL types from Charoentong's study, which can be viewed in the download page. For each cancer type, the relative abundance of TILs were inferred by using gene set variation analysis (GSVA) based on gene expression profile. In this tab, users can examine which kinds of TILs might be regulated by the current gene.

> Lymphocyte [ TOP ]

Summary
Symbol	MTAP
Name	methylthioadenosine phosphorylase
Aliases	c86fus; S-methyl-5'-thioadenosine phosphorylase; BDMF; DMSFH; DMSMFH; HEL-249; LGMBF; 5'-methylthioadenosine ......
Chromosomal Location	9p21
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of MTAP. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by MTAP. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	MTAP
Name	methylthioadenosine phosphorylase
Aliases	c86fus; S-methyl-5'-thioadenosine phosphorylase; BDMF; DMSFH; DMSMFH; HEL-249; LGMBF; 5'-methylthioadenosine ......
Chromosomal Location	9p21
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of MTAP. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene. > Chemokine > Receptor

> Chemokine [ TOP ]

> Receptor [ TOP ]

Summary
Symbol	MTAP
Name	methylthioadenosine phosphorylase
Aliases	c86fus; S-methyl-5'-thioadenosine phosphorylase; BDMF; DMSFH; DMSMFH; HEL-249; LGMBF; 5'-methylthioadenosine ......
Chromosomal Location	9p21
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of MTAP expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	MTAP
Name	methylthioadenosine phosphorylase
Aliases	c86fus; S-methyl-5'-thioadenosine phosphorylase; BDMF; DMSFH; DMSMFH; HEL-249; LGMBF; 5'-methylthioadenosine ......
Chromosomal Location	9p21
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between MTAP and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	MTAP
Name	methylthioadenosine phosphorylase
Aliases	c86fus; S-methyl-5'-thioadenosine phosphorylase; BDMF; DMSFH; DMSMFH; HEL-249; LGMBF; 5'-methylthioadenosine ......
Chromosomal Location	9p21
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting MTAP collected from DrugBank database.

> Drugs from DrugBank database

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Details on drugs targeting MTAP.

ID	Name	Drug Type	Targets	#Targets
DB00173	Adenine	Small Molecule	ACACB, ACP1, APRT, MTAP, PECR, SRPK2	6
DB02158	(1s)-1-(9-Deazaadenin-9-Yl)-1,4,5-Trideoxy-1,4-Imino-5-Methylthio-D-Ribitol	Small Molecule	MTAP	1
DB02281	Formycin	Small Molecule	MTAP	1
DB02282	5'-Deoxy-5'-Methylthioadenosine	Small Molecule	MTAP	1
DB02933	5'-Deoxy-5'-(Methylthio)-Tubercidin	Small Molecule	MTAP	1

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