MAT2A

Summary

MAT2A (methionine adenosyltransferase 2A, HGNC:6904) is a protein-coding gene on chromosome 2p11.2, encoding S-adenosylmethionine synthase isoform type-2 (P31153). Catalyzes the formation of S-adenosylmethionine from methionine and ATP. It is a common-essential gene (DepMap: required in 95.0% of cancer cell lines).

The protein encoded by this gene catalyzes the production of S-adenosylmethionine (AdoMet) from methionine and ATP. AdoMet is the key methyl donor in cellular processes.

Source: NCBI Gene 4144 — RefSeq curated summary.

At a glance

• Gene–disease (curated): thoracic aortic aneurysm (Moderate, GenCC) — +1 more curated relationship
• GWAS associations: 5
• Clinical variants (ClinVar): 332 total — 2 pathogenic
• Phenotypes (HPO): 42
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 95.0% of screened cell lines (common-essential)
• MANE Select transcript: NM_005911

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6904
Approved symbol	MAT2A
Name	methionine adenosyltransferase 2A
Location	2p11.2
Locus type	gene with protein product
Status	Approved
Aliases	SAMS2, MATA2, MATII, MAT-II
Ensembl gene	ENSG00000168906
Ensembl biotype	protein_coding
OMIM	601468
Entrez	4144

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 8 protein_coding, 3 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000306434, ENST00000409017, ENST00000465151, ENST00000469221, ENST00000481412, ENST00000490878, ENST00000881371, ENST00000881372, ENST00000881373, ENST00000881374, ENST00000881375, ENST00000881376

RefSeq mRNA: 1 — MANE Select: NM_005911 NM_005911

CCDS: CCDS1977

Canonical transcript exons

ENST00000306434 — 9 exons

Exon	Start	End
ENSE00001135603	85542901	85543034
ENSE00001135613	85542565	85542747
ENSE00001135625	85542155	85542373
ENSE00001155028	85539168	85539378
ENSE00001880464	85543670	85545281
ENSE00003468328	85541255	85541377
ENSE00003544727	85541083	85541160
ENSE00003667793	85541829	85541972
ENSE00003691165	85541633	85541745

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 99.54.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 193.1528 / max 1817.9403, expressed in 1828 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
21215	193.1528	1828

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
body of pancreas	UBERON:0001150	99.54	gold quality
right lobe of thyroid gland	UBERON:0001119	99.52	gold quality
left lobe of thyroid gland	UBERON:0001120	99.50	gold quality
mucosa of stomach	UBERON:0001199	99.49	gold quality
left uterine tube	UBERON:0001303	99.46	gold quality
thyroid gland	UBERON:0002046	99.44	gold quality
adenohypophysis	UBERON:0002196	99.36	gold quality
gall bladder	UBERON:0002110	99.28	gold quality
body of stomach	UBERON:0001161	99.18	gold quality
right ovary	UBERON:0002118	99.16	gold quality
pituitary gland	UBERON:0000007	99.15	gold quality
muscle layer of sigmoid colon	UBERON:0035805	99.02	gold quality
popliteal artery	UBERON:0002250	98.96	gold quality
tibial artery	UBERON:0007610	98.96	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	98.94	gold quality
vagina	UBERON:0000996	98.92	gold quality
ectocervix	UBERON:0012249	98.91	gold quality
aorta	UBERON:0000947	98.90	gold quality
right coronary artery	UBERON:0001625	98.90	gold quality
left coronary artery	UBERON:0001626	98.89	gold quality
transverse colon	UBERON:0001157	98.87	gold quality
small intestine Peyer’s patch	UBERON:0003454	98.87	gold quality
right lung	UBERON:0002167	98.86	gold quality
lower esophagus muscularis layer	UBERON:0035833	98.86	gold quality
ascending aorta	UBERON:0001496	98.85	gold quality
lower esophagus	UBERON:0013473	98.85	gold quality
coronary artery	UBERON:0001621	98.84	gold quality
body of uterus	UBERON:0009853	98.84	gold quality
thoracic aorta	UBERON:0001515	98.83	gold quality
left ovary	UBERON:0002119	98.83	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-MTAB-10137	no	546.03
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, CEBPA, CREB1, E2F1, E2F3, E2F4, FOS, HIF1A, JUN, MYB, NFKB1, NFKB, PPARA, PPARD, PPARG, RELA, SP1, SP2, SP3, STAT1, USF1, YY1, ZBTB16

miRNA regulators (miRDB)

122 targeting MAT2A, 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-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-512-3P	99.97	67.35	1049
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-22-3P	99.93	68.13	917
HSA-MIR-4760-3P	99.93	70.50	2385
HSA-MIR-338-5P	99.92	72.34	2951
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-498-3P	99.91	71.27	1114
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-6499-3P	99.90	66.38	1212
HSA-MIR-4302	99.89	67.94	1187
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-7162-3P	99.89	68.16	1682
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-7845-5P	99.88	64.88	771
HSA-MIR-221-3P	99.86	71.56	1329
HSA-MIR-222-3P	99.86	71.35	1337

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 95.0% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 40)

• regulation of expression in hepatocarcinoma cells by L-methionine availability (PMID:12660248)
• beta subunit associates with cirrhosis and cancer providing a proliferative advantage in hepatoma cells through its interaction with methionine adenosyltransferase II alpha2 and down-regulation of S-adenosylmethionine levels. (PMID:12671891)
• NF-kappa B and AP-1 are required for basal MAT2A expression in HepG2 cells and mediate the increase in MAT2A expression in response to TNF-alpha (PMID:14530285)
• up-regulation of MAT2A also provides a growth advantage and s-adenosylmethionine and methylthioadenosine can block mitogenic signaling in colon cancer cells (PMID:17631143)
• Lower expression of both MAT2A and MAT2beta and interfere with leptin signaling in liver cancer cells. (PMID:18041713)
• This work was carried out to examine the role of MAT II activity and S-adenosylmethionine biosynthesis in the survival of leukemic T cells. (PMID:19048023)
• X protein of hepatitis B virus inhibits apoptosis in hepatoma cells through enhancing the methionine adenosyltransferase 2A gene expression and reducing S-adenosylmethionine production (PMID:21247894)
• Methionine adenosyltransferase II serves as a transcriptional corepressor of Maf oncoprotein (PMID:21362551)
• Insulin-like growth factor 1 (IGF1) activates methionine adenosyltransferase 2A MAT2A) transcription by both known and novel pathways in colon cancer cells. (PMID:21406062)
• hypoxia-induced MAT2A expression is HIF-1alpha dependent (PMID:21460102)
• we found for the first time a post-transcriptional regulation of MAT1A and MAT2A by AUF1 and HuR in hepatocellular carcinoma. (PMID:22318685)
• Differential gene expression of BACE1 and PSEN1 in the knockdown cells, which is possibly a consequence of MAT2A deregulation and may indicate a self regulatory mechanism. (PMID:22879628)
• Liver-specific isoenzyme MAT1A is genetically linked with an inborn metabolic disorder of hypermethioninemia, as well as a ubiquitously expressed isoenzyme MAT2A, whose enzymatic activity is regulated by an associated subunit MAT2B. (PMID:23425511)
• Results suggest that MAT2A is downregulated in cancer tissues of renal cell carcinomas patients and has function of tumor suppressor though repressing the expression of heme oxygenase-1. (PMID:24636201)
• Mutagenesis of MATalpha2 and MATbeta phospho-sites destabilized them and prevented hepatic stellate cell trans-differentiation. (PMID:25294683)
• The data presented here support the conclusion that rare genetic variants in MAT2A predispose individuals to thoracic aortic disease. (PMID:25557781)
• acetylation decreased in hepatocellular cancer (PMID:25925782)
• High MAT2A expression is associated with tamoxifen-resistant breast cancer. (PMID:26418898)
• crystal structures of human MATalpha2 containing various bound ligands. (PMID:26858410)
• methionine adenosyltransferase II alpha (MAT2A), and the arginine methyltransferase, PRMT5, as vulnerable enzymes in cells with MTAP deletion. (PMID:27068473)
• S-adenosyl-L-methionine diminishes hepatitis C virus expression by altering MAT1A/2A signaling in hepatocytes. (PMID:27076759)
• METTL16 that controls MAT2A intron retention in response to intracellular SAM levels; splicing of the MAT2A retained intron is rapidly induced upon Met depletion, and this effect requires a conserved hairpin which is a METTL16 m6A substrate. (PMID:28525753)
• MAT2A expression is upregulated through mRNA stabilization upon SAM depletion. (PMID:29262316)
• Increased MAT2A expression is associated with recurrence in hepatocellular carcinoma. (PMID:29448301)
• The simultaneous downregulation of MAT1A and upregulation of MAT2A are necessary and sufficient for hepatocellular carcinoma metastasis in the process of M1-M2 switch. (PMID:29749642)
• the protein-protein interacting surface formed in MATa2:MATbeta complexes is explored to demonstrate that several quinolone-based compounds modulate the activity of MATa2 and its mutants, providing a rational for chemical design/intervention responsive to the level of S-Adenosylmethionine in the cellular environment (PMID:30776190)
• Methionine Adenosyltransferase Engineering to Enable Bioorthogonal Platforms for AdoMet-Utilizing Enzymes. (PMID:32091873)
• Genetic variants in S-adenosyl-methionine synthesis pathway and nonsyndromic cleft lip with or without cleft palate in Chile. (PMID:32492698)
• Hsa_circ_0000337 promotes proliferation, migration and invasion in glioma by competitively binding miRNA-942-5p and thus upregulates MAT2A. (PMID:33336744)
• MAT2A Inhibition Blocks the Growth of MTAP-Deleted Cancer Cells by Reducing PRMT5-Dependent mRNA Splicing and Inducing DNA Damage. (PMID:33450196)
• Activation of MAT2A-RIP1 signaling axis reprograms monocytes in gastric cancer. (PMID:33593829)
• SAM homeostasis is regulated by CFIm-mediated splicing of MAT2A. (PMID:33949310)
• MAT2A Localization and Its Independently Prognostic Relevance in Breast Cancer Patients. (PMID:34065390)
• Circ_0044516 Regulates miR-136/MAT2A Pathway to Facilitate Lung Cancer Development. (PMID:34258296)
• Genomic and transcriptomic profiling of hepatoid adenocarcinoma of the stomach. (PMID:34326469)
• MALAT1 Inhibits Proliferation of HPV16-Positive Cervical Cancer by Sponging miR-485-5p to Promote Expression of MAT2A. (PMID:34610246)
• MAT2A-Mediated S-Adenosylmethionine Level in CD4(+) T Cells Regulates HIV-1 Latent Infection. (PMID:34616406)
• Human Mat2A Uses an Ordered Kinetic Mechanism and Is Stabilized but Not Regulated by Mat2B. (PMID:34780697)
• Activation of MAT2A-ACSL3 pathway protects cells from ferroptosis in gastric cancer. (PMID:35182729)
• Expression of vimentin, TPI and MAT2A in human dermal microvascular endothelial cells during angiogenesis in vitro. (PMID:35482724)

Cross-species orthologs

10 orthologs

Organism	Symbol	Gene ID
danio_rerio	mat2ab	ENSDARG00000037121
danio_rerio	mat2aa	ENSDARG00000040334
mus_musculus	Mat2a	ENSMUSG00000053907
rattus_norvegicus	Mat2a	ENSRNOG00000013520
rattus_norvegicus	Mat2al1	ENSRNOG00000028513
drosophila_melanogaster	Sam-S	FBGN0005278
caenorhabditis_elegans		WBGENE00006416
caenorhabditis_elegans		WBGENE00008205
caenorhabditis_elegans		WBGENE00015538
caenorhabditis_elegans		WBGENE00015540

Paralogs (1): MAT1A (ENSG00000151224)

Protein

Protein identifiers

S-adenosylmethionine synthase isoform type-2 — P31153 (reviewed: P31153)

Alternative names: Methionine adenosyltransferase 2, Methionine adenosyltransferase II

All UniProt accessions (2): P31153, A0A140VJP5

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the formation of S-adenosylmethionine from methionine and ATP. The reaction comprises two steps that are both catalyzed by the same enzyme: formation of S-adenosylmethionine (AdoMet) and triphosphate, and subsequent hydrolysis of the triphosphate.

Subunit / interactions. Heterotrimer; composed of a catalytic MAT2A homodimer that binds one regulatory MAT2B chain. Heterohexamer; composed of a central, catalytic MAT2A homotetramer flanked on either side by a regulatory MAT2B chain.

Tissue specificity. Detected in kidney.

Cofactor. Binds 2 magnesium ions per subunit. The magnesium ions interact primarily with the substrate. Binds 1 potassium ion per subunit. The potassium ion interacts primarily with the substrate.

Pathway. Amino-acid biosynthesis; S-adenosyl-L-methionine biosynthesis; S-adenosyl-L-methionine from L-methionine: step 1/1.

Miscellaneous. Protein expression is regulated by post-transcriptional regulation: in presence of S-adenosyl-L-methionine, METTL16 binds and methylates the first hairpin of the 3’-UTR region of MAT2A mRNA, preventing recognition of their 3’-splice site by U2AF1/U2AF35, thereby inhibiting splicing and protein production of S-adenosylmethionine synthase. In S-adenosyl-L-methionine-limiting conditions, METTL16 binds the 3’-UTR region of MAT2A mRNA without methylating it due to the lack of a methyl donor, preventing N6-methylation and promoting expression of MAT2A.

Similarity. Belongs to the AdoMet synthase family.

Isoforms (2)

UniProt ID	Names	Canonical?
P31153-1	1	yes
P31153-2	2

RefSeq proteins (1): NP_005902* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002133	S-AdoMet_synthetase	Family
IPR022628	S-AdoMet_synt_N	Domain
IPR022629	S-AdoMet_synt_central	Domain
IPR022630	S-AdoMet_synt_C	Domain
IPR022631	ADOMET_SYNTHASE_CS	Conserved_site
IPR022636	S-AdoMet_synthetase_sfam	Homologous_superfamily

Pfam: PF00438, PF02772, PF02773

Enzyme classification (BRENDA):

• EC 2.5.1.6 — methionine adenosyltransferase (BRENDA: 64 organisms, 105 substrates, 289 inhibitors, 269 Km, 118 kcat entries)

Substrate kinetics (BRENDA)

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

Substrate	Km (mM)	Measurements
L-METHIONINE	0.0023–3.3	118
ATP	0.002–6.54	93
TRIPOLYPHOSPHATE	0.0013–0.026	12
METHIONINE	0.0083–1.12	9
S-ADENOSYL-L-METHIONINE	0.32–0.45	6
S-(6-AZIDOHEX-2-YNYL)-L-HOMOCYSTEINE	0.92–1.518	4
L-ETHIONINE	0.0056–0.74	3
S-(-)-METHIONINOL	0.39–2.4	3
CTP	0.4	2
GTP	0.62	2
MG2+	0.006–0.007	2
UTP	2.2	2
D-METHIONINE	3.5	1
ITP	1.4	1
L-METHIONINE METHYL ESTHER	2.6	1

Catalyzed reactions (Rhea), 1 shown:

• L-methionine + ATP + H2O = S-adenosyl-L-methionine + phosphate + diphosphate (RHEA:21080)

UniProt features (61 total): strand 18, helix 16, binding site 14, turn 4, modified residue 3, cross-link 2, splice variant 2, chain 1, region of interest 1

Structure

Experimental structures (PDB)

59 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
7RWG	X-RAY DIFFRACTION	0.97
7BHS	X-RAY DIFFRACTION	1.05
7BHT	X-RAY DIFFRACTION	1.05
7RXV	X-RAY DIFFRACTION	1.07
7RXW	X-RAY DIFFRACTION	1.07
7BHR	X-RAY DIFFRACTION	1.08
7BHX	X-RAY DIFFRACTION	1.08
8QE3	X-RAY DIFFRACTION	1.09
5A1I	X-RAY DIFFRACTION	1.09
8QE1	X-RAY DIFFRACTION	1.09
7KCF	X-RAY DIFFRACTION	1.1
8QE2	X-RAY DIFFRACTION	1.11
8QE0	X-RAY DIFFRACTION	1.12
8XB0	X-RAY DIFFRACTION	1.12
7KCE	X-RAY DIFFRACTION	1.14
7BHU	X-RAY DIFFRACTION	1.15
7BHW	X-RAY DIFFRACTION	1.15
8P1W	X-RAY DIFFRACTION	1.15
8AXZ	X-RAY DIFFRACTION	1.15
7BHV	X-RAY DIFFRACTION	1.16
8QDZ	X-RAY DIFFRACTION	1.16
7RWH	X-RAY DIFFRACTION	1.17
7RW7	X-RAY DIFFRACTION	1.19
8QDY	X-RAY DIFFRACTION	1.19
8XAR	X-RAY DIFFRACTION	1.19
2P02	X-RAY DIFFRACTION	1.21
7KDA	X-RAY DIFFRACTION	1.24
7KDB	X-RAY DIFFRACTION	1.24
7L1A	X-RAY DIFFRACTION	1.25
7RXX	X-RAY DIFFRACTION	1.25

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P31153-F1	96.08	0.93

Functional residue map

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

Ligand- & substrate-binding residues (14): 258; 264–265 (in other chain); 281; 285; 289 (in other chain); 291; 29 (in other chain); 31; 57; 70 (in other chain); 113 (in other chain); 179–181 (in other chain) …

Post-translational modifications (5): 81, 114, 384, 228, 234

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-156581	Methylation
R-HSA-1430728	Metabolism
R-HSA-156580	Phase II - Conjugation of compounds
R-HSA-211859	Biological oxidations

MSigDB gene sets: 464 (showing top): GSE45365_NK_CELL_VS_CD11B_DC_DN, GSE45365_NK_CELL_VS_BCELL_UP, TGGTGCT_MIR29A_MIR29B_MIR29C, E2F_Q4_01, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, REACTOME_BIOLOGICAL_OXIDATIONS, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, GRUETZMANN_PANCREATIC_CANCER_DN, E2F4DP1_01, GOBP_RESPONSE_TO_ACID_CHEMICAL, GOBP_RESPONSE_TO_PEPTIDE, KEGG_CYSTEINE_AND_METHIONINE_METABOLISM, AAGCCAT_MIR135A_MIR135B, GOBP_POSITIVE_REGULATION_OF_TOR_SIGNALING, DACOSTA_UV_RESPONSE_VIA_ERCC3_UP

GO Biological Process (14): S-adenosylmethionine biosynthetic process (GO:0006556), one-carbon metabolic process (GO:0006730), protein hexamerization (GO:0034214), protein heterooligomerization (GO:0051291), cellular response to methionine (GO:0061431), positive regulation of TORC1 signaling (GO:1904263), cellular response to leukemia inhibitory factor (GO:1990830), protein-containing complex localization (GO:0031503), cellular response to nutrient levels (GO:0031669), cellular response to amino acid starvation (GO:0034198), TORC1 signaling (GO:0038202), protein complex oligomerization (GO:0051259), protein localization to lysosome (GO:0061462), negative regulation of TORC1 signaling (GO:1904262)

GO Molecular Function (8): methionine adenosyltransferase activity (GO:0004478), ATP binding (GO:0005524), small molecule binding (GO:0036094), identical protein binding (GO:0042802), metal ion binding (GO:0046872), nucleotide binding (GO:0000166), protein binding (GO:0005515), transferase activity (GO:0016740)

GO Cellular Component (2): cytosol (GO:0005829), methionine adenosyltransferase complex (GO:0048269)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Phase II - Conjugation of compounds	1
Biological oxidations	1
Metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein complex oligomerization	2
TORC1 signaling	2
regulation of TORC1 signaling	2
binding	2
sulfur compound biosynthetic process	1
S-adenosylmethionine metabolic process	1
small molecule metabolic process	1
cellular response to nutrient	1
cellular response to amino acid stimulus	1
cellular response to nitrogen compound	1
cellular response to oxygen-containing compound	1
response to methionine	1
positive regulation of TOR signaling	1
cellular response to cytokine stimulus	1
response to leukemia inhibitory factor	1
macromolecule localization	1
response to nutrient levels	1
cellular response to stimulus	1
cellular response to starvation	1
response to amino acid starvation	1
TOR signaling	1
protein-containing complex assembly	1
protein localization to vacuole	1
negative regulation of TOR signaling	1
transferase activity, transferring alkyl or aryl (other than methyl) groups	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
protein binding	1
cation binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
catalytic activity	1
cytoplasm	1
cellular anatomical structure	1
intracellular protein-containing complex	1
transferase complex	1

Protein interactions and networks

STRING

3425 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MAT2A	MAT2B	Q9NZL9	992
MAT2A	EMG1	Q92979	840
MAT2A	NOP14	P78316	828
MAT2A	METTL16	Q86W50	798
MAT2A	AHCY	P23526	720
MAT2A	MYB	P10242	690
MAT2A	BHMT	Q93088	681
MAT2A	MTR	Q99707	670
MAT2A	MTAP	Q13126	665
MAT2A	MTHFR	P42898	645
MAT2A	ELAVL1	Q15717	634
MAT2A	H7C2H4	H7C2H4	630
MAT2A	P0DN79	P0DN79	630
MAT2A	GNMT	Q14749	620
MAT2A	MTHFD1L	Q6UB35	603

IntAct

208 interactions, top by confidence:

A	B	Type	Score
MAT1A	MAT2A	psi-mi:“MI:0914”(association)	0.800
MAT2A	MAT1A	psi-mi:“MI:0915”(physical association)	0.800
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
VCP	UBXN8	psi-mi:“MI:0914”(association)	0.690
MAT2A	MAT2B	psi-mi:“MI:0915”(physical association)	0.680
MAT2B	MAT2A	psi-mi:“MI:0915”(physical association)	0.680
MAT2A	MAT2A	psi-mi:“MI:0915”(physical association)	0.670
CFTR	HAX1	psi-mi:“MI:0914”(association)	0.610
	MAT2A	psi-mi:“MI:0915”(physical association)	0.560
MAT2A		psi-mi:“MI:0915”(physical association)	0.560
SAM1	MAT2A	psi-mi:“MI:0915”(physical association)	0.560
SAM2	MAT2A	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (291): MAT2A (Affinity Capture-MS), MAT2A (Two-hybrid), MAT2B (Two-hybrid), TMEM213 (Two-hybrid), MAT2A (Affinity Capture-MS), MAT2A (Affinity Capture-MS), ABCB7 (Co-fractionation), ACSS2 (Co-fractionation), ASNS (Co-fractionation), MAT2A (Co-fractionation), MAT2A (Co-fractionation), NMD3 (Co-fractionation), SDHB (Co-fractionation), TUBB (Co-fractionation), MAT2A (Affinity Capture-MS)

ESM2 similar proteins: A1JPS4, A1K301, A2SKW6, A4G977, A4TI83, A5CYJ7, A5EY13, A6T2Z1, A7FEZ7, A7H6N1, A7HZ88, A9EXT3, A9WGQ3, B0U4E7, B0UPH0, B1I6C4, B1YPQ4, B2FPC7, B2K0S7, B4SK03, B4ULF7, B8FSB9, B8IST7, B8J8T3, B9LBJ9, P31153, Q0A6D3, Q0AXL1, Q0BAY8, Q12FG9, Q1CB69, Q1CEX6, Q1CY83, Q1LS34, Q2IM98, Q2RK28, Q2RMS5, Q2Y5Z1, Q39BZ1, Q3A388

Diamond homologs: A0A9E8G339, A2Y053, A4PU48, A4S779, A4ULF8, A6XMY9, A7L2Z6, A7NVX9, A7PQS0, A7PRJ6, A7Q0V4, A7QJG1, A8HYU5, A9NUH8, A9NYY0, A9P2P4, A9P822, A9PDZ7, A9PEK8, A9PHC5, A9PHE9, B0LXM0, O17680, O22338, O43938, O60198, P13444, P17562, P18298, P23686, P24260, P31153, P31155, P43280, P43281, P43282, P47916, P48466, P48498, P49611

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 144 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

GO biological processes:

GO term	Partners	Fold	FDR
negative regulation of apoptotic process	14	4.3×	6e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	0
Uncertain significance	105
Likely benign	184
Benign	14

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
1180533	GRCh37/hg19 2p12-11.2(chr2:81209244-86688030)x1	Pathogenic
265866	NM_005911.6(MAT2A):c.1031A>C (p.Glu344Ala)	Pathogenic

SpliceAI

1405 predictions. Top by Δscore:

Variant	Effect	Δscore
2:85539330:G:GT	donor_gain	1.0000
2:85539375:CCAG:C	donor_loss	1.0000
2:85539377:AGG:A	donor_loss	1.0000
2:85539379:GTGA:G	donor_loss	1.0000
2:85539380:T:A	donor_loss	1.0000
2:85541081:A:AG	acceptor_gain	1.0000
2:85541082:G:GG	acceptor_gain	1.0000
2:85541082:GATAA:G	acceptor_gain	1.0000
2:85541249:TATTA:T	acceptor_loss	1.0000
2:85541250:ATTAG:A	acceptor_loss	1.0000
2:85541251:TTA:T	acceptor_loss	1.0000
2:85541252:TAG:T	acceptor_loss	1.0000
2:85541253:A:AG	acceptor_gain	1.0000
2:85541253:AG:A	acceptor_loss	1.0000
2:85541254:G:GG	acceptor_gain	1.0000
2:85541289:T:A	acceptor_gain	1.0000
2:85541377:GGTG:G	donor_loss	1.0000
2:85541379:T:A	donor_loss	1.0000
2:85541624:T:A	acceptor_gain	1.0000
2:85541629:ATAG:A	acceptor_gain	1.0000
2:85541630:TA:T	acceptor_loss	1.0000
2:85541631:A:AG	acceptor_gain	1.0000
2:85541631:AG:A	acceptor_gain	1.0000
2:85541631:AGGT:A	acceptor_loss	1.0000
2:85541632:G:GA	acceptor_gain	1.0000
2:85541632:GG:G	acceptor_gain	1.0000
2:85541632:GGT:G	acceptor_gain	1.0000
2:85541632:GGTT:G	acceptor_gain	1.0000
2:85541632:GGTTT:G	acceptor_gain	1.0000
2:85541744:AGGTA:A	donor_loss	1.0000

AlphaMissense

2581 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:85541965:A:T	K181I	1.000
2:85542590:A:T	K265I	1.000
2:85542629:G:A	G278E	1.000
2:85539357:T:C	S24P	0.999
2:85541092:G:A	C34Y	0.999
2:85541093:T:G	C34W	0.999
2:85541291:G:A	G69E	0.999
2:85541741:A:C	D134A	0.999
2:85541741:A:T	D134V	0.999
2:85541829:G:C	G136R	0.999
2:85541838:T:C	F139L	0.999
2:85541840:T:A	F139L	0.999
2:85541840:T:G	F139L	0.999
2:85541841:G:C	G140R	0.999
2:85541842:G:A	G140D	0.999
2:85541966:A:C	K181N	0.999
2:85541966:A:T	K181N	0.999
2:85542353:T:C	F250L	0.999
2:85542355:T:A	F250L	0.999
2:85542355:T:G	F250L	0.999
2:85542584:G:A	G263E	0.999
2:85542586:C:A	R264S	0.999
2:85542587:G:C	R264P	0.999
2:85542602:A:T	D269V	0.999
2:85542611:G:A	G272D	0.999
2:85542647:G:A	G284E	0.999
2:85542647:G:T	G284V	0.999
2:85542651:G:C	K285N	0.999
2:85542651:G:T	K285N	0.999
2:85542668:A:T	D291V	0.999

dbSNP variants (sampled 300 via entrez): RS1000009714 (2:85542440 T>C,G), RS1000077643 (2:85537943 C>T), RS1000213783 (2:85538478 C>A), RS1000712564 (2:85538670 A>C), RS1000718818 (2:85543185 G>C), RS1001214458 (2:85537538 A>C,T), RS1001313002 (2:85539410 C>A,T), RS1001663814 (2:85537863 T>C), RS1001721327 (2:85544729 CTTTGT>C), RS1001773700 (2:85545023 A>G), RS1002247010 (2:85540645 A>G), RS1002722824 (2:85540229 C>T), RS1003250554 (2:85539726 C>T), RS1003321942 (2:85541505 C>A,T), RS1003420457 (2:85539587 C>T)

Disease associations

OMIM: gene MIM:601468 | disease phenotypes: MIM:607086, MIM:277450

GenCC curated gene-disease

Disease	Classification	Inheritance
thoracic aortic aneurysm	Moderate	Autosomal dominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
familial thoracic aortic aneurysm and aortic dissection	Limited	AD

Mondo (3): familial thoracic aortic aneurysm and aortic dissection (MONDO:0019625), vitamin K-dependent clotting factors, combined deficiency of, type 1 (MONDO:0010187), thoracic aortic aneurysm (MONDO:0005396)

Orphanet (2): Familial thoracic aortic aneurysm and aortic dissection (Orphanet:91387), Hereditary combined deficiency of vitamin K-dependent clotting factors (Orphanet:98434)

HPO phenotypes

42 total (30 of 42 shown, HPO-id order):

HPO	Term
HP:0000023	Inguinal hernia
HP:0000098	Tall stature
HP:0000278	Retrognathia
HP:0000316	Hypertelorism
HP:0000525	Abnormality iris morphology
HP:0000766	Abnormal sternum morphology
HP:0000822	Hypertension
HP:0000965	Cutis marmorata
HP:0000978	Bruising susceptibility
HP:0001166	Arachnodactyly
HP:0001297	Stroke
HP:0001640	Cardiomegaly
HP:0001643	Patent ductus arteriosus
HP:0001647	Bicuspid aortic valve
HP:0001659	Aortic regurgitation
HP:0001677	Coronary artery atherosclerosis
HP:0001763	Pes planus
HP:0002105	Hemoptysis
HP:0002107	Pneumothorax
HP:0002138	Subarachnoid hemorrhage
HP:0002140	Ischemic stroke
HP:0002326	Transient ischemic attack
HP:0002616	Aortic root aneurysm
HP:0002647	Aortic dissection
HP:0002650	Scoliosis
HP:0002686	Pregnancy history
HP:0002705	High, narrow palate
HP:0002875	Exertional dyspnea
HP:0003549	Abnormality of connective tissue
HP:0004933	Ascending aortic dissection

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST003927_6	Dysmenorrheic pain	8.000000e-07
GCST005195_43	Coronary artery disease	2.000000e-23
GCST006586_4	Urinary albumin excretion	4.000000e-10
GCST011364_4	Myocardial infarction	1.000000e-09
GCST011365_41	Myocardial infarction	9.000000e-18

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0007889	dysmenorrheic pain measurement
EFO:0004285	albuminuria

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D017545	Aortic Aneurysm, Thoracic	C14.907.055.239.125; C14.907.109.139.125
C564741	Vitamin K-Dependent Clotting Factors, Combined Deficiency Of, 1 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3313835 (SINGLE PROTEIN)

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

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — Methionine turnover

Most potent curated ligand interactions (5 total), top 5:

Ligand	Action	Affinity	Parameter
ZS34	Inhibition	7.86	pIC50
SCR‐7952	Inhibition	7.73	pIC50
compound 28 [PMID: 33900758]	Inhibition	7.66	pIC50
AG-270	Inhibition	7.17	pIC50
IDE397	Inhibition	6.7	pIC50

Binding affinities (BindingDB)

187 measured of 199 human assays (199 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
US20250221979, Example 252	IC50	0.14 nM	US-20250221979: NOVEL HETEROCYCLIC COMPOUND
US20250221979, Example 275	IC50	0.15 nM	US-20250221979: NOVEL HETEROCYCLIC COMPOUND
US20250221979, Example 189	IC50	0.32 nM	US-20250221979: NOVEL HETEROCYCLIC COMPOUND
US20250221979, Example 25	IC50	0.43 nM	US-20250221979: NOVEL HETEROCYCLIC COMPOUND
US20250221979, Example 298	IC50	0.43 nM	US-20250221979: NOVEL HETEROCYCLIC COMPOUND
US20250221979, Example 354	IC50	0.46 nM	US-20250221979: NOVEL HETEROCYCLIC COMPOUND
US20250221979, Example 274	IC50	0.53 nM	US-20250221979: NOVEL HETEROCYCLIC COMPOUND
US20250221979, Example 22	IC50	0.54 nM	US-20250221979: NOVEL HETEROCYCLIC COMPOUND
US20250221979, Example 357	IC50	0.54 nM	US-20250221979: NOVEL HETEROCYCLIC COMPOUND
US20250221979, Example 101	IC50	0.59 nM	US-20250221979: NOVEL HETEROCYCLIC COMPOUND
US20250221979, Example 311	IC50	0.6 nM	US-20250221979: NOVEL HETEROCYCLIC COMPOUND
US20250221979, Example 79	IC50	0.61 nM	US-20250221979: NOVEL HETEROCYCLIC COMPOUND
US20250221979, Example 283	IC50	0.7 nM	US-20250221979: NOVEL HETEROCYCLIC COMPOUND
US20250221979, Example 310	IC50	0.74 nM	US-20250221979: NOVEL HETEROCYCLIC COMPOUND
US20250221979, Example 180	IC50	0.76 nM	US-20250221979: NOVEL HETEROCYCLIC COMPOUND
US20250221979, Example 187	IC50	0.76 nM	US-20250221979: NOVEL HETEROCYCLIC COMPOUND
US20250221979, Example 147	IC50	0.78 nM	US-20250221979: NOVEL HETEROCYCLIC COMPOUND
US20250221979, Example 272	IC50	0.78 nM	US-20250221979: NOVEL HETEROCYCLIC COMPOUND
US20250221979, Example 290	IC50	0.79 nM	US-20250221979: NOVEL HETEROCYCLIC COMPOUND
US20250221979, Example 196	IC50	0.81 nM	US-20250221979: NOVEL HETEROCYCLIC COMPOUND
US20250221979, Example 92	IC50	0.83 nM	US-20250221979: NOVEL HETEROCYCLIC COMPOUND
US20250221979, Example 244	IC50	0.86 nM	US-20250221979: NOVEL HETEROCYCLIC COMPOUND
US20250221979, Example 295	IC50	0.89 nM	US-20250221979: NOVEL HETEROCYCLIC COMPOUND
US20250221979, Example 23	IC50	0.91 nM	US-20250221979: NOVEL HETEROCYCLIC COMPOUND
US20250221979, Example 273	IC50	0.92 nM	US-20250221979: NOVEL HETEROCYCLIC COMPOUND
US20250221979, Example 303	IC50	0.92 nM	US-20250221979: NOVEL HETEROCYCLIC COMPOUND
US20250221979, Example 330	IC50	0.92 nM	US-20250221979: NOVEL HETEROCYCLIC COMPOUND
US20250221979, Example 91	IC50	0.93 nM	US-20250221979: NOVEL HETEROCYCLIC COMPOUND
US20250221979, Example 265	IC50	0.94 nM	US-20250221979: NOVEL HETEROCYCLIC COMPOUND
US20250221979, Example 412	IC50	0.97 nM	US-20250221979: NOVEL HETEROCYCLIC COMPOUND
US20250221979, Example 366	IC50	1 nM	US-20250221979: NOVEL HETEROCYCLIC COMPOUND
US20250221979, Example 26	IC50	1.04 nM	US-20250221979: NOVEL HETEROCYCLIC COMPOUND
US20250221979, Example 289	IC50	1.04 nM	US-20250221979: NOVEL HETEROCYCLIC COMPOUND
US20250221979, Example 351	IC50	1.05 nM	US-20250221979: NOVEL HETEROCYCLIC COMPOUND
US20250221979, Example 373	IC50	1.05 nM	US-20250221979: NOVEL HETEROCYCLIC COMPOUND
US20250221979, Example 259	IC50	1.08 nM	US-20250221979: NOVEL HETEROCYCLIC COMPOUND
US20250221979, Example 294	IC50	1.08 nM	US-20250221979: NOVEL HETEROCYCLIC COMPOUND
US20250221979, Example 307	IC50	1.14 nM	US-20250221979: NOVEL HETEROCYCLIC COMPOUND
US20250221979, Example 429	IC50	1.15 nM	US-20250221979: NOVEL HETEROCYCLIC COMPOUND
US20250221979, Example 182	IC50	1.16 nM	US-20250221979: NOVEL HETEROCYCLIC COMPOUND
US20250221979, Example 173	IC50	1.18 nM	US-20250221979: NOVEL HETEROCYCLIC COMPOUND
US20250221979, Example 320	IC50	1.19 nM	US-20250221979: NOVEL HETEROCYCLIC COMPOUND
US20250221979, Example 356	IC50	1.19 nM	US-20250221979: NOVEL HETEROCYCLIC COMPOUND
US20250221979, Example 319	IC50	1.2 nM	US-20250221979: NOVEL HETEROCYCLIC COMPOUND
US20250221979, Example 378	IC50	1.2 nM	US-20250221979: NOVEL HETEROCYCLIC COMPOUND
US20250221979, Example 83	IC50	1.21 nM	US-20250221979: NOVEL HETEROCYCLIC COMPOUND
US20250221979, Example 16	IC50	1.23 nM	US-20250221979: NOVEL HETEROCYCLIC COMPOUND
US20250221979, Example 238	IC50	1.24 nM	US-20250221979: NOVEL HETEROCYCLIC COMPOUND
US20250221979, Example 327	IC50	1.25 nM	US-20250221979: NOVEL HETEROCYCLIC COMPOUND
US20250221979, Example 353	IC50	1.25 nM	US-20250221979: NOVEL HETEROCYCLIC COMPOUND

ChEMBL bioactivities

552 potent at pChembl≥5 of 569 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.40	IC50	0.3981	nM	CHEMBL4573938
9.30	IC50	0.5012	nM	CHEMBL5561157
9.10	IC50	0.7943	nM	CHEMBL5560496
9.00	IC50	1	nM	CHEMBL6174106
8.90	IC50	1.259	nM	CHEMBL5555241
8.90	IC50	1.259	nM	CHEMBL5560496
8.80	IC50	1.585	nM	CHEMBL5566482
8.70	IC50	2	nM	CHEMBL6146713
8.60	IC50	2.512	nM	CHEMBL5560496
8.52	IC50	3	nM	CHEMBL5782897
8.52	IC50	3	nM	CHEMBL6058362
8.52	IC50	3	nM	CHEMBL6174106
8.50	IC50	3.162	nM	CHEMBL5562188
8.50	IC50	3.162	nM	CHEMBL5558104
8.40	IC50	4	nM	CHEMBL4521249
8.40	IC50	4	nM	CHEMBL4552959
8.40	IC50	3.981	nM	CHEMBL5558255
8.40	IC50	3.981	nM	CHEMBL5566207
8.40	IC50	3.981	nM	CHEMBL5559030
8.40	IC50	4	nM	CHEMBL6133791
8.40	IC50	4	nM	CHEMBL6175100
8.40	IC50	4	nM	CHEMBL6174106
8.40	IC50	4	nM	CHEMBL6167341
8.40	IC50	4	nM	CHEMBL6146713
8.40	IC50	4	nM	CHEMBL6176849
8.40	IC50	4	nM	CHEMBL6176021
8.40	IC50	4	nM	CHEMBL6164002
8.33	IC50	4.7	nM	CHEMBL5199008
8.30	IC50	5	nM	CHEMBL4558617
8.30	IC50	5	nM	CHEMBL6159771
8.22	IC50	6	nM	CHEMBL5549959
8.22	IC50	6	nM	CHEMBL6176268
8.22	IC50	6	nM	CHEMBL6177194
8.20	IC50	6.31	nM	CHEMBL5561157
8.20	IC50	6.31	nM	CHEMBL5523635
8.20	IC50	6.31	nM	CHEMBL5566518
8.15	IC50	7	nM	CHEMBL4514699
8.15	IC50	7	nM	CHEMBL4582312
8.15	IC50	7	nM	CHEMBL4568226
8.15	IC50	7	nM	CHEMBL6176153
8.10	IC50	8	nM	CHEMBL4870597
8.10	IC50	8	nM	CHEMBL4860456
8.10	IC50	8	nM	CHEMBL6145910
8.10	IC50	8	nM	CHEMBL6174062
8.05	IC50	9	nM	CHEMBL6176895
8.05	IC50	9	nM	CHEMBL6152324
8.00	IC50	10	nM	CHEMBL4585665
8.00	IC50	10	nM	CHEMBL5185760
8.00	IC50	10	nM	CHEMBL5562574
8.00	IC50	10	nM	CHEMBL5568378

PubChem BioAssay actives

304 with measured affinity, of 697 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
3-(cyclohexen-1-yl)-6-(4-methoxyphenyl)-2-phenyl-5-(pyridin-2-ylamino)-1H-pyrazolo[1,5-a]pyrimidin-7-one	2081348: Inhibition of MAT2a (unknown origin) using methionine and ATP as substrate assessed as reduction in S-adenosyl-L-methionine formation incubated for 300 mins by RapidFire-Mass Spectrometry analysis	ic50	0.0004	uM
3-cyclopropyl-4-[4-(difluoromethoxy)phenyl]-6-(4-methoxyphenyl)-2H-pyrazolo[4,3-b]pyridin-5-one	2081348: Inhibition of MAT2a (unknown origin) using methionine and ATP as substrate assessed as reduction in S-adenosyl-L-methionine formation incubated for 300 mins by RapidFire-Mass Spectrometry analysis	ic50	0.0005	uM
3-cyclopropyl-4-[4-(difluoromethoxy)phenyl]-6-(2-methylindazol-5-yl)-2H-pyrazolo[4,3-b]pyridin-5-one	2081348: Inhibition of MAT2a (unknown origin) using methionine and ATP as substrate assessed as reduction in S-adenosyl-L-methionine formation incubated for 300 mins by RapidFire-Mass Spectrometry analysis	ic50	0.0008	uM
4-(4-chlorophenyl)-3-cyclopropyl-6-(2-methylindazol-5-yl)-2H-pyrazolo[4,3-b]pyridin-5-one	2081349: Inhibition of MAT2a in human HCT116- MTAP null cells assessed as reduction in symmetric dimethyl arginine formation incubated for 48 hrs by Hoechst 33342 staining based fluorescence analysis	ic50	0.0013	uM
3-cyclopropyl-4-[4-(difluoromethoxy)phenyl]-6-(4-hydroxyphenyl)-2H-pyrazolo[4,3-b]pyridin-5-one	2081349: Inhibition of MAT2a in human HCT116- MTAP null cells assessed as reduction in symmetric dimethyl arginine formation incubated for 48 hrs by Hoechst 33342 staining based fluorescence analysis	ic50	0.0016	uM
3-cyclopropyl-4-[4-(difluoromethoxy)phenyl]-6-(3-methylbenzotriazol-5-yl)-2H-pyrazolo[4,3-b]pyridin-5-one	2081349: Inhibition of MAT2a in human HCT116- MTAP null cells assessed as reduction in symmetric dimethyl arginine formation incubated for 48 hrs by Hoechst 33342 staining based fluorescence analysis	ic50	0.0032	uM
3-cyclopropyl-6-(2-methylindazol-5-yl)-4-(4-methylphenyl)-2H-pyrazolo[4,3-b]pyridin-5-one	2081349: Inhibition of MAT2a in human HCT116- MTAP null cells assessed as reduction in symmetric dimethyl arginine formation incubated for 48 hrs by Hoechst 33342 staining based fluorescence analysis	ic50	0.0032	uM
3-(cyclohexen-1-yl)-2-phenyl-5-(1H-pyrazol-5-ylamino)-6-quinolin-6-yl-1H-pyrazolo[1,5-a]pyrimidin-7-one	1776047: Inhibition of recombinant human MAT2A expressed in baculovirus infected Sf9 cells assessed as S-adenosyl methionine production using L-methionine as substrate incubated for 60 mins followed by substrate addition and measured after 60 mins	ic50	0.0040	uM
ethyl 5-[(7-oxo-2,3-diphenyl-6-quinolin-6-yl-4H-pyrazolo[1,5-a]pyrimidin-5-yl)amino]-1,3,4-oxadiazole-2-carboxylate	1776047: Inhibition of recombinant human MAT2A expressed in baculovirus infected Sf9 cells assessed as S-adenosyl methionine production using L-methionine as substrate incubated for 60 mins followed by substrate addition and measured after 60 mins	ic50	0.0040	uM
3-cyclopropyl-4-[4-(difluoromethoxy)phenyl]-6-(2,3-dimethylbenzimidazol-5-yl)-2H-pyrazolo[4,3-b]pyridin-5-one	2081349: Inhibition of MAT2a in human HCT116- MTAP null cells assessed as reduction in symmetric dimethyl arginine formation incubated for 48 hrs by Hoechst 33342 staining based fluorescence analysis	ic50	0.0040	uM
3-cyclopropyl-4-(4-methoxyphenyl)-6-(2-methylindazol-5-yl)-2H-pyrazolo[4,3-b]pyridin-5-one	2081349: Inhibition of MAT2a in human HCT116- MTAP null cells assessed as reduction in symmetric dimethyl arginine formation incubated for 48 hrs by Hoechst 33342 staining based fluorescence analysis	ic50	0.0040	uM
3-cyclopropyl-4-[4-[(1R)-1-hydroxyethyl]phenyl]-6-(2-methylindazol-5-yl)-2H-pyrazolo[4,3-b]pyridin-5-one	2081349: Inhibition of MAT2a in human HCT116- MTAP null cells assessed as reduction in symmetric dimethyl arginine formation incubated for 48 hrs by Hoechst 33342 staining based fluorescence analysis	ic50	0.0040	uM
8-[4-(difluoromethoxy)phenyl]-2-ethoxy-6-[2-[2-(3-hydroxypyrrolidin-1-yl)ethyl]-1-methyl-3a,7a-dihydrobenzimidazol-5-yl]pyrido[2,3-d]pyrimidin-7-one	1885194: Inhibition of MAT2A (unknown origin) assessed as S-adenosyl methionine production using L-methionine as substrate pretreated for 60 mins followed by L-methionine and ATP addition	ic50	0.0047	uM
3-(cyclohexen-1-yl)-6-(4-methoxyphenyl)-2-phenyl-5-(1H-pyrazol-5-ylamino)-1H-pyrazolo[1,5-a]pyrimidin-7-one	1776047: Inhibition of recombinant human MAT2A expressed in baculovirus infected Sf9 cells assessed as S-adenosyl methionine production using L-methionine as substrate incubated for 60 mins followed by substrate addition and measured after 60 mins	ic50	0.0050	uM
2-methyl-5-(2-methyl-3-pyridinyl)-7-(trifluoromethyl)pyrazolo[3,4-c][1,8]naphthyridin-4-one	2073047: Inhibition of MAT2A in MTAP-knock out human HCT-116 cells assessed as reduction in PRMT5-mediated symmetrical demethylation of arginine (SDMA) measured after 96 hrs	ic50	0.0060	uM
4-[4-(difluoromethoxy)phenyl]-3-ethyl-6-(2-methylindazol-5-yl)-2H-pyrazolo[4,3-b]pyridin-5-one	2081349: Inhibition of MAT2a in human HCT116- MTAP null cells assessed as reduction in symmetric dimethyl arginine formation incubated for 48 hrs by Hoechst 33342 staining based fluorescence analysis	ic50	0.0063	uM
4-[4-(difluoromethoxy)phenyl]-6-(2-methylindazol-5-yl)-3-[(3S)-oxolan-3-yl]-2H-pyrazolo[4,3-b]pyridin-5-one	2081349: Inhibition of MAT2a in human HCT116- MTAP null cells assessed as reduction in symmetric dimethyl arginine formation incubated for 48 hrs by Hoechst 33342 staining based fluorescence analysis	ic50	0.0063	uM
6-(4-hydroxyphenyl)-2,3-diphenyl-5-(1H-pyrazol-5-ylamino)-1H-pyrazolo[1,5-a]pyrimidin-7-one	1776047: Inhibition of recombinant human MAT2A expressed in baculovirus infected Sf9 cells assessed as S-adenosyl methionine production using L-methionine as substrate incubated for 60 mins followed by substrate addition and measured after 60 mins	ic50	0.0070	uM
6-(4-methoxyphenyl)-2,3-diphenyl-5-(pyridin-2-ylamino)-1H-pyrazolo[1,5-a]pyrimidin-7-one	1776047: Inhibition of recombinant human MAT2A expressed in baculovirus infected Sf9 cells assessed as S-adenosyl methionine production using L-methionine as substrate incubated for 60 mins followed by substrate addition and measured after 60 mins	ic50	0.0070	uM
2,3-diphenyl-5-(1H-pyrazol-3-ylamino)-6-quinolin-6-yl-4H-pyrazolo[1,5-a]pyrimidin-7-one	1776047: Inhibition of recombinant human MAT2A expressed in baculovirus infected Sf9 cells assessed as S-adenosyl methionine production using L-methionine as substrate incubated for 60 mins followed by substrate addition and measured after 60 mins	ic50	0.0070	uM
6-(1,3-benzodioxol-5-yl)-5-methyl-2-phenyl-3-piperidin-1-yl-1H-pyrazolo[1,5-a]pyrimidin-7-one	1776047: Inhibition of recombinant human MAT2A expressed in baculovirus infected Sf9 cells assessed as S-adenosyl methionine production using L-methionine as substrate incubated for 60 mins followed by substrate addition and measured after 60 mins	ic50	0.0080	uM
2,5-dimethyl-3-phenyl-1H-pyrazolo[1,5-a]pyrimidin-7-one	1885191: Inhibition of human MAT2A expressed in baculovirus infected Sf9 cells expression system assessed as S-adenosyl methionine production using L-methionine as substrate pretreated for 60 mins followed by L-methionine and ATP addition	ic50	0.0080	uM
3-(cyclohexen-1-yl)-6-(4-methoxyphenyl)-5-(1,2-oxazol-3-ylamino)-2-phenyl-1H-pyrazolo[1,5-a]pyrimidin-7-one	1776047: Inhibition of recombinant human MAT2A expressed in baculovirus infected Sf9 cells assessed as S-adenosyl methionine production using L-methionine as substrate incubated for 60 mins followed by substrate addition and measured after 60 mins	ic50	0.0100	uM
8-(4-chlorophenyl)-2-(ethylamino)-6-(2-methylindazol-5-yl)-1,6-naphthyridin-7-one	1905161: Inhibition of MT2A in MTAP-null human HCT-116 cells after 72 hrs by LC-MS/MS analysis	ic50	0.0100	uM
3-cyclopropyl-4-[4-(difluoromethoxy)phenyl]-6-(4-methoxyphenyl)-2H-pyrazolo[4,3-c]pyridine	2081348: Inhibition of MAT2a (unknown origin) using methionine and ATP as substrate assessed as reduction in S-adenosyl-L-methionine formation incubated for 300 mins by RapidFire-Mass Spectrometry analysis	ic50	0.0100	uM
3-cyclopropyl-4-[4-(2-hydroxyethyl)phenyl]-6-(2-methylindazol-5-yl)-2H-pyrazolo[4,3-b]pyridin-5-one	2081349: Inhibition of MAT2a in human HCT116- MTAP null cells assessed as reduction in symmetric dimethyl arginine formation incubated for 48 hrs by Hoechst 33342 staining based fluorescence analysis	ic50	0.0100	uM
3-cyclopropyl-4-[4-(hydroxymethyl)phenyl]-6-(2-methylindazol-5-yl)-2H-pyrazolo[4,3-b]pyridin-5-one	2081349: Inhibition of MAT2a in human HCT116- MTAP null cells assessed as reduction in symmetric dimethyl arginine formation incubated for 48 hrs by Hoechst 33342 staining based fluorescence analysis	ic50	0.0100	uM
ethyl 3-[[6-(4-methoxyphenyl)-7-oxo-2,3-diphenyl-4H-pyrazolo[1,5-a]pyrimidin-5-yl]amino]pyrazole-1-carboxylate	1776047: Inhibition of recombinant human MAT2A expressed in baculovirus infected Sf9 cells assessed as S-adenosyl methionine production using L-methionine as substrate incubated for 60 mins followed by substrate addition and measured after 60 mins	ic50	0.0110	uM
8-(4-chlorophenyl)-6-(2-methylindazol-5-yl)-2-(2,2,2-trifluoroethylamino)-1,6-naphthyridin-7-one	1905161: Inhibition of MT2A in MTAP-null human HCT-116 cells after 72 hrs by LC-MS/MS analysis	ic50	0.0110	uM
7-chloro-5-(2-cyclopropyl-3-pyridinyl)-8-fluoro-2-methylpyrazolo[3,4-c]quinolin-4-one	2073045: Inhibition of MAT2A (unknown origin) assessed as release of inorganic phosphate using ATP/L-methionine incubated for 30 mins by colorimetric phosphate assay	ic50	0.0111	uM
7-chloro-2-methyl-5-(2-methyl-3-pyridinyl)pyrazolo[3,4-c]quinolin-4-one	2073047: Inhibition of MAT2A in MTAP-knock out human HCT-116 cells assessed as reduction in PRMT5-mediated symmetrical demethylation of arginine (SDMA) measured after 96 hrs	ic50	0.0121	uM
7-chloro-4-(dimethylamino)-1-phenylquinazolin-2-one	2073045: Inhibition of MAT2A (unknown origin) assessed as release of inorganic phosphate using ATP/L-methionine incubated for 30 mins by colorimetric phosphate assay	ic50	0.0124	uM
3-cyclopropyl-4-[4-(difluoromethoxy)phenyl]-2H-pyrazolo[4,3-c]pyridine-6-carbonitrile	2081348: Inhibition of MAT2a (unknown origin) using methionine and ATP as substrate assessed as reduction in S-adenosyl-L-methionine formation incubated for 300 mins by RapidFire-Mass Spectrometry analysis	ic50	0.0126	uM
6-(4-methoxyphenyl)-2,3-diphenyl-5-(1H-pyrazol-5-ylamino)-1H-pyrazolo[1,5-a]pyrimidin-7-one	1776047: Inhibition of recombinant human MAT2A expressed in baculovirus infected Sf9 cells assessed as S-adenosyl methionine production using L-methionine as substrate incubated for 60 mins followed by substrate addition and measured after 60 mins	ic50	0.0130	uM
7-chloro-4-[ethyl(methyl)amino]-1-phenylquinazolin-2-one	1814115: Inhibition of full length recombinant human N-terminal His6-tagged MAT2A expressed in Escherichia coli using methionine and ATP as substrate incubated for 90 mins by biomol green reagent based assay	ic50	0.0130	uM
8-(4-chlorophenyl)-2-(2,2-difluoroethoxy)-6-(2-methylindazol-5-yl)-1,6-naphthyridin-7-one	1905161: Inhibition of MT2A in MTAP-null human HCT-116 cells after 72 hrs by LC-MS/MS analysis	ic50	0.0130	uM
8-(4-chlorophenyl)-6-(2-methylindazol-5-yl)-2-(2,2,2-trifluoroethylamino)pyrido[4,3-d]pyrimidin-7-one	1905161: Inhibition of MT2A in MTAP-null human HCT-116 cells after 72 hrs by LC-MS/MS analysis	ic50	0.0140	uM
2-cyclopropyl-8-[4-(difluoromethoxy)phenyl]-6-(2-methyl-3,4-dihydro-1H-pyrazino[1,2-a]benzimidazol-7-yl)pyrido[2,3-d]pyrimidin-7-one	2029870: Inhibition of recombinant MAT2A (unknown origin) expressed in baculovirus infected Sf9 insect cells using L-methionine as substrate preincubated for 15 mins followed by substrate addition measured after 60 mins by Kinase-Glo Luminescent assay	ic50	0.0140	uM
8-[4-(difluoromethoxy)phenyl]-2-(ethylamino)-6-(2-methyl-3,4-dihydro-1H-pyrazino[1,2-a]benzimidazol-7-yl)pyrido[2,3-d]pyrimidin-7-one	2029870: Inhibition of recombinant MAT2A (unknown origin) expressed in baculovirus infected Sf9 insect cells using L-methionine as substrate preincubated for 15 mins followed by substrate addition measured after 60 mins by Kinase-Glo Luminescent assay	ic50	0.0140	uM
7-chloro-2-ethyl-5-pyridin-3-ylpyrazolo[3,4-c]quinolin-4-one	2073045: Inhibition of MAT2A (unknown origin) assessed as release of inorganic phosphate using ATP/L-methionine incubated for 30 mins by colorimetric phosphate assay	ic50	0.0142	uM
3-cyclopropyl-4-[4-(difluoromethoxy)phenyl]-6-(1-methyl-6-oxo-3-pyridinyl)-2H-pyrazolo[4,3-b]pyridin-5-one	2081349: Inhibition of MAT2a in human HCT116- MTAP null cells assessed as reduction in symmetric dimethyl arginine formation incubated for 48 hrs by Hoechst 33342 staining based fluorescence analysis	ic50	0.0158	uM
7-chloro-4-(dimethylamino)-1-(3-methylphenyl)quinazolin-2-one	1814115: Inhibition of full length recombinant human N-terminal His6-tagged MAT2A expressed in Escherichia coli using methionine and ATP as substrate incubated for 90 mins by biomol green reagent based assay	ic50	0.0160	uM
7-chloro-8-fluoro-2-methyl-5-[2-(trifluoromethyl)-3-pyridinyl]pyrazolo[3,4-c]quinolin-4-one	2073045: Inhibition of MAT2A (unknown origin) assessed as release of inorganic phosphate using ATP/L-methionine incubated for 30 mins by colorimetric phosphate assay	ic50	0.0162	uM
8-[4-(difluoromethoxy)phenyl]-2-ethoxy-6-(2-propan-2-yl-3,4-dihydro-1H-pyrazino[1,2-a]benzimidazol-7-yl)pyrido[2,3-d]pyrimidin-7-one	2029870: Inhibition of recombinant MAT2A (unknown origin) expressed in baculovirus infected Sf9 insect cells using L-methionine as substrate preincubated for 15 mins followed by substrate addition measured after 60 mins by Kinase-Glo Luminescent assay	ic50	0.0170	uM
8-[4-(difluoromethoxy)phenyl]-2-ethoxy-6-[2-(2-methoxyethyl)-3,4-dihydro-1H-pyrazino[1,2-a]benzimidazol-7-yl]pyrido[2,3-d]pyrimidin-7-one	2029870: Inhibition of recombinant MAT2A (unknown origin) expressed in baculovirus infected Sf9 insect cells using L-methionine as substrate preincubated for 15 mins followed by substrate addition measured after 60 mins by Kinase-Glo Luminescent assay	ic50	0.0170	uM
7-chloro-5-(2-cyclopropyl-3-pyridinyl)-2-(difluoromethyl)-8-fluoropyrazolo[3,4-c]quinolin-4-one	2073045: Inhibition of MAT2A (unknown origin) assessed as release of inorganic phosphate using ATP/L-methionine incubated for 30 mins by colorimetric phosphate assay	ic50	0.0170	uM
7-chloro-4-[ethyl(methyl)amino]-1-pyridin-3-ylquinazolin-2-one	1814115: Inhibition of full length recombinant human N-terminal His6-tagged MAT2A expressed in Escherichia coli using methionine and ATP as substrate incubated for 90 mins by biomol green reagent based assay	ic50	0.0180	uM
8-[4-(difluoromethoxy)phenyl]-2-ethoxy-6-(2-methyl-3,4-dihydro-1H-pyrazino[1,2-a]benzimidazol-7-yl)pyrido[2,3-d]pyrimidin-7-one	2029870: Inhibition of recombinant MAT2A (unknown origin) expressed in baculovirus infected Sf9 insect cells using L-methionine as substrate preincubated for 15 mins followed by substrate addition measured after 60 mins by Kinase-Glo Luminescent assay	ic50	0.0180	uM
2-methyl-5-pyridin-3-yl-7-(trifluoromethyl)pyrazolo[3,4-c][1,8]naphthyridin-4-one	2073045: Inhibition of MAT2A (unknown origin) assessed as release of inorganic phosphate using ATP/L-methionine incubated for 30 mins by colorimetric phosphate assay	ic50	0.0181	uM
7-chloro-2-methyl-5-pyridin-3-ylpyrazolo[3,4-c]quinolin-4-one	2073045: Inhibition of MAT2A (unknown origin) assessed as release of inorganic phosphate using ATP/L-methionine incubated for 30 mins by colorimetric phosphate assay	ic50	0.0182	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression	3
cadmium sulfate	decreases expression	3
Estradiol	increases expression	3
Tobacco Smoke Pollution	affects expression, increases expression	3
sodium arsenite	affects cotreatment, increases abundance, increases expression, decreases expression	2
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	2
Resveratrol	increases expression, affects binding, decreases reaction	2
Arsenic	affects expression, affects cotreatment, increases abundance, increases expression	2
Benzo(a)pyrene	increases expression	2
Cisplatin	increases expression, decreases expression, affects cotreatment	2
Formaldehyde	decreases expression	2
Rotenone	decreases expression, increases expression	2
Tretinoin	decreases expression	2
Valproic Acid	decreases methylation, increases expression	2
aristolochic acid I	decreases expression	1
TAK-243	increases sumoylation	1
dicrotophos	increases expression	1
bismuth tripotassium dicitrate	increases expression	1
2,4,6-tribromophenol	decreases expression	1
quinomethionate	affects expression	1
alpha phellandrene	decreases expression	1
pirinixic acid	increases activity, affects binding, decreases expression	1
sodium arsenate	decreases expression	1
decabromobiphenyl ether	decreases expression	1
quercitrin	increases expression	1
2-butenal	decreases expression	1
methylparaben	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
cobaltous chloride	decreases expression	1
tetrabromobisphenol A	decreases expression	1

ChEMBL screening assays

64 unique, capped per target: 64 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3378077	Binding	Inhibition of recombinant His-tagged MAT2A (unknown origin) using L-methionine and ATP at 30 uM	2’,6’-Dihalostyrylanilines, pyridines, and pyrimidines for the inhibition of the catalytic subunit of methionine S-adenosyltransferase-2. — J Med Chem

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_E0UI	Ubigene Hep G2 MAT2A KO	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00339053	PHASE4	UNKNOWN	Immunonutrition and Thoracoabdominal Aorta Aneurysm Repair
NCT02291718	PHASE4	COMPLETED	Thoracoabdominal Arortic CTA Study
NCT01033214	PHASE1	UNKNOWN	ENTRUST - TAArget® Thoracic Stent Graft Clinical Trial
NCT03998631	PHASE1	UNKNOWN	Comparison of Carbon Dioxide and Saline Flush to Saline Flush in TEVAR and TAVI Procedures to Reduce Cerebral Ischemia
NCT00604799	PHASE2/PHASE3	COMPLETED	VALOR: The Talent Thoracic Stent Graft System Clinical Study
NCT07483177	PHASE1/PHASE2	NOT_YET_RECRUITING	HEART: Pilot Randomized Controlled Trial
NCT00111176	Not specified	COMPLETED	STARZ-TX2 Clinical Study: Study of Thoracic Aortic Aneurysm Repair With the Zenith TX2 Endovascular Graft
NCT00413231	Not specified	COMPLETED	Valor II: The Valiant Thoracic Stent Graft System Clinical Study
NCT00435942	Not specified	COMPLETED	Phase II Study of the Safety and Efficacy of the Relay Thoracic Stent-Graft
NCT00549315	Not specified	UNKNOWN	Clinical Study of Thoracic Aortic Aneurysm Exclusion
NCT00583817	Not specified	ENROLLING_BY_INVITATION	Endovascular Treatment of Thoracic Aortic Disease
NCT00597870	Not specified	COMPLETED	Physician-Sponsored IDE for the Talent Endoluminal Stent Graft System for the Treatment of Thoracic Lesions
NCT00805948	Not specified	TERMINATED	Post-Approval Clinical Study of the Talent Thoracic Stent Graft to Treat Thoracic Aortic Aneurysms (THRIVE)
NCT01082172	Not specified	COMPLETED	South American Thoracic Stent-Graft Study
NCT01327742	Not specified	APPROVED_FOR_MARKETING	Phase II Clinical Study of the Safety and Efficacy of the Relay Thoracic Stent-Graft
NCT01390181	Not specified	TERMINATED	The Effect of Losartan in Bicuspid Aortic Valve Patients
NCT01480206	Not specified	COMPLETED	Overlay of 3D Scans on Live Fluoroscopy for Endovascular Procedures in the Hybrid OR
NCT01839695	Not specified	COMPLETED	Safety and Efficacy of Valiant Mona LSA Stent Graft System
NCT02010892	Not specified	UNKNOWN	Effective Treatments for Thoracic Aortic Aneurysms (ETTAA Study): A Prospective Cohort Study
NCT02164201	Not specified	COMPLETED	Post Market Surveillance Study Evaluating BioFoam Surgical Matrix in Cardiovascular Surgery
NCT02256163	Not specified	COMPLETED	Identification of Genes and Pathogenesis Involved in Familial Thoracic Aortic Aneurysm
NCT02365454	Not specified	COMPLETED	NEXUS™ Aortic Arch Stent Graft System First In Man Study
NCT02735720	Not specified	TERMINATED	The CardiOvascular Remodeling Following Endovascular Aortic Repair (CORE) Study
NCT03142074	Not specified	RECRUITING	Biomechanical and Microstructural Properties of Ascending Aortic Aneurysms
NCT03440697	Not specified	ACTIVE_NOT_RECRUITING	Pathogenetic Basis of Aortopathy and Aortic Valve Disease
NCT03824626	Not specified	UNKNOWN	Biomechanical Reappraisal of Planning for Thoracic Endovascular Aortic Repair
NCT04083118	Not specified	COMPLETED	Assessment of Risk in Thoracic Aortopathy Using 18F-Sodium Fluoride
NCT04100499	Not specified	UNKNOWN	Evaluation of Adjunctive EndoAnchors for EVAR and TEVAR
NCT04197648	Not specified	RECRUITING	Effects of Exercise on Thoracic Aneurysms
NCT04246463	Not specified	RECRUITING	Terumo Aortic Global Endovascular Registry
NCT04523909	Not specified	RECRUITING	Trajectory of Neuroinflammatory Markers in Cerebrospinal Fluid Prior to and After Thoracic Aortic Surgery
NCT04663074	Not specified	COMPLETED	Intravascular Ultrasound (IVUS) in Complex Aortic Endovascular Interventions
NCT04747626	Not specified	RECRUITING	B-SAFER: Branched Stented Anastomosis Frozen Elephant Trunk Repair
NCT04756778	Not specified	COMPLETED	Indexed Aortic Area in Bicuspid Aortic Valve Aortopathy
NCT05137366	Not specified	UNKNOWN	Transthoracic Ultrasound Evaluation of Thoracic Aortic Aneurysms
NCT05143138	Not specified	ACTIVE_NOT_RECRUITING	Real-World Data Collection of the GORE® VIABAHN® VBX Balloon Expandable Endoprosthesis When Used as a Bridging Stent With Branched and Fenestrated Endografts in the Treatment of Aortic Aneurysms Involving the Renal-Mesenteric Arteries
NCT05146375	Not specified	UNKNOWN	Genes Modulating the Severity of Aortic Aneurysms (MSF1-TGFBR2)
NCT05155956	Not specified	ACTIVE_NOT_RECRUITING	Cerebral Hemodynamics and Microemboli During Placement of Relay®Branch Thoracic Stent-Graft System
NCT05309707	Not specified	RECRUITING	ENDOBARC-S Study: Endovascular Branched Stent-grafts for Aortic ARCh Pathologies in Spain
NCT05395598	Not specified	RECRUITING	Incidence of Major Complication in Case of Thoracic Aortic Aneurysm