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): 341 total — 2 pathogenic (top 10% of genes corpus-wide)
• Regional missense constraint (gnomAD): 3 of 6 regions constrained (≈27% of expected missense variation)
• GTEx eGene: eQTL in 12 tissues, sQTL in 1 (q < 0.05)
• Phenotypes (HPO): 42
• Cancer dependency (DepMap): dependent in 95.0% of screened cell lines (common-essential)
• Constraint (gnomAD): pLI 1.00 (loss-of-function intolerant), LOEUF 0.16 (highly constrained)
• MANE Select transcript: NM_005911
• Interaction hub: 2,411 STRING partners (top 5% of genes corpus-wide)
• Notable: 341 clinical variants but no curated precision-oncology (CIViC) evidence yet

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: 24 — 13 protein_coding, 7 nonsense_mediated_decay, 3 retained_intron, 1 protein_coding_CDS_not_defined

MANE Select: ENST00000306434

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 3, TSL 2: 2, TSL 3: 1

ENST00000306434, ENST00000409017, ENST00000465151, ENST00000469221, ENST00000481412, ENST00000490878, ENST00000881371, ENST00000881372, ENST00000881373, ENST00000881374, ENST00000881375, ENST00000881376, ENST00000986421, ENST00001015751, ENST00001015752, ENST00001015754, ENST00001015755, ENST00001078791, ENST00001078795, ENST00001102368, ENST00001102369, ENST00001102370, ENST00001102371, ENST00001143016

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.

Highest expression (Bgee): body of pancreas, lobe of thyroid gland, mucosa of stomach, uterine tube, thyroid gland.

Genetic regulation across tissues (GTEx eQTL / sQTL)

MAT2A is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 12 tissues and its splicing (sQTL) in 1 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

13 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Brain Cerebellum	eqtl	1.3e-22	-0.53	2:85431870:T:C
Whole Blood	eqtl	2.2e-18	-0.26	2:85501572:A:T
Brain Cerebellar Hemisphere	eqtl	5.1e-17	-0.36	2:85431739:G:A
Artery Tibial	eqtl	1.2e-06	+0.21	2:85393065:T:C
Artery Aorta	eqtl	2.6e-06	+0.19	2:85533272:C:T
Artery Coronary	eqtl	1.2e-04	+0.27	2:85534925:A:T
Skin Not Sun Exposed Suprapubic	eqtl	1.9e-03	-0.13	2:85472627:C:T
Skin Sun Exposed Lower leg	eqtl	2.1e-03	+0.13	2:85487970:C:T
Prostate	eqtl	3.0e-03	-0.61	2:85496421:C:G
Colon Transverse	sqtl	4.3e-03	-1.32	2:86114133:CA:C
Esophagus Mucosa	eqtl	8.1e-03	+0.13	2:85468335:C:T
Nerve Tibial	eqtl	1.3e-02	-0.27	2:85539159:C:G
Brain Nucleus accumbens basal ganglia	eqtl	3.9e-02	+0.46	2:85685839:C:T

FANTOM5 promoters

1 alternative TSS:

Promoter ID	TPM avg	Samples expressed
21215	193.1528	1828

Top tissues by expression

showing 100 of 295 tissues 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
upper lobe of left lung	UBERON:0008952	98.82	gold quality
right hemisphere of cerebellum	UBERON:0014890	98.82	gold quality
left adrenal gland cortex	UBERON:0035825	98.82	gold quality
endocervix	UBERON:0000458	98.81	gold quality
rectum	UBERON:0001052	98.81	gold quality
tibial nerve	UBERON:0001323	98.81	gold quality
peritoneum	UBERON:0002358	98.81	gold quality
omental fat pad	UBERON:0010414	98.81	gold quality
right testis	UBERON:0004534	98.78	gold quality
fundus of stomach	UBERON:0001160	98.75	gold quality
upper leg skin	UBERON:0004262	98.75	gold quality
right uterine tube	UBERON:0001302	98.72	gold quality
cervix squamous epithelium	UBERON:0006922	98.72	gold quality
metanephros cortex	UBERON:0010533	98.71	gold quality
vermiform appendix	UBERON:0001154	98.70	gold quality
left adrenal gland	UBERON:0001234	98.70	gold quality
upper lobe of lung	UBERON:0008948	98.70	gold quality
adrenal cortex	UBERON:0001235	98.68	gold quality
minor salivary gland	UBERON:0001830	98.68	gold quality
mucosa of urinary bladder	UBERON:0001259	98.67	gold quality
cerebellar hemisphere	UBERON:0002245	98.65	gold quality
left testis	UBERON:0004533	98.65	gold quality
sigmoid colon	UBERON:0001159	98.64	gold quality
skin of abdomen	UBERON:0001416	98.63	gold quality
medial globus pallidus	UBERON:0002477	98.62	gold quality
pancreatic ductal cell	CL:0002079	98.60	gold quality
esophagus	UBERON:0001043	98.60	gold quality
inferior olivary complex	UBERON:0002127	98.60	gold quality
descending thoracic aorta	UBERON:0002345	98.60	gold quality
fallopian tube	UBERON:0003889	98.60	gold quality
right adrenal gland	UBERON:0001233	98.59	gold quality
cerebellar cortex	UBERON:0002129	98.59	gold quality
stomach	UBERON:0000945	98.56	gold quality
ovary	UBERON:0000992	98.56	gold quality
blood vessel layer	UBERON:0004797	98.56	gold quality
adrenal gland	UBERON:0002369	98.54	gold quality
lower esophagus mucosa	UBERON:0035834	98.54	gold quality
seminal vesicle	UBERON:0000998	98.53	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	98.52	gold quality
smooth muscle tissue	UBERON:0001135	98.51	gold quality
adipose tissue of abdominal region	UBERON:0007808	98.50	gold quality
right adrenal gland cortex	UBERON:0035827	98.50	gold quality
right atrium auricular region	UBERON:0006631	98.48	gold quality
globus pallidus	UBERON:0001875	98.47	gold quality
oviduct epithelium	UBERON:0004804	98.45	gold quality
mouth mucosa	UBERON:0003729	98.44	gold quality
prostate gland	UBERON:0002367	98.43	gold quality
esophagus mucosa	UBERON:0002469	98.42	gold quality
pancreas	UBERON:0001264	98.41	gold quality
hindlimb stylopod muscle	UBERON:0004252	98.41	gold quality
colon	UBERON:0001155	98.37	gold quality
gastrocnemius	UBERON:0001388	98.37	gold quality
mucosa of paranasal sinus	UBERON:0005030	98.37	gold quality
small intestine	UBERON:0002108	98.35	gold quality
caecum	UBERON:0001153	98.34	gold quality
urinary bladder	UBERON:0001255	98.33	gold quality
large intestine	UBERON:0000059	98.32	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	98.32	gold quality
intestine	UBERON:0000160	98.31	gold quality
right frontal lobe	UBERON:0002810	98.31	gold quality
nucleus accumbens	UBERON:0001882	98.28	gold quality
apex of heart	UBERON:0002098	98.26	gold quality
olfactory bulb	UBERON:0002264	98.23	gold quality
skin of leg	UBERON:0001511	98.22	gold quality
caudate nucleus	UBERON:0001873	98.21	gold quality
muscle of leg	UBERON:0001383	98.19	gold quality
uterine cervix	UBERON:0000002	98.18	gold quality
lymph node	UBERON:0000029	98.18	gold quality
spinal cord	UBERON:0002240	98.17	gold quality
mucosa of transverse colon	UBERON:0004991	98.17	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

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 78 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Pancreas	tissue	825.0	low
Thyroid gland	tissue	363.3	medium
Pituitary gland	tissue	273.5
Adrenal gland	tissue	262.0	low
Urinary bladder	tissue	245.1	medium
Retina	tissue	230.6
Corpus callosum	tissue	224.1
Epididymis	tissue	222.9	medium
Adipose tissue	tissue	210.5	not detected
Gallbladder	tissue	196.3	medium
Locus coeruleus	tissue	194.4
Nucleus accumbens	tissue	192.9
Kidney	tissue	190.2	medium
Spinal cord	tissue	189.9
Skeletal muscle	tissue	183.2	not detected
Substantia nigra	tissue	175.2
Medulla oblongata	tissue	172.3
Midbrain	tissue	171.9
Putamen	tissue	162.6
Superior colliculi	tissue	162.3
Vagina	tissue	161.5	medium
Hippocampus	tissue	158.5	not detected
Septum	tissue	157.5
Ventral forebrain	tissue	157.3
Stomach 1	tissue	157.1	not detected
Thalamus	tissue	156.6
Parathyroid gland	tissue	156.0	low
Pons	tissue	152.0
Hypothalamus	tissue	151.7
Postcentral gyrus	tissue	150.3
Periaqueductal gray	tissue	148.5
Olfactory bulb	tissue	146.7
Appendix	tissue	144.7	not detected
Hippocampal formation	tissue	141.0
Prostate	tissue	139.7	not detected
Cerebral cortex	tissue	138.5	low
Retrosplenial cortex	tissue	138.5
Somatosensory cortex	tissue	138.3
Occipital cortex	tissue	138.0
Rectum	tissue	137.7	low
Motor cortex	tissue	136.9
Insular cortex	tissue	135.5
Amygdala	tissue	134.5
Basal ganglia	tissue	134.0	not detected
Skin 1	tissue	133.4	medium
Prefrontal cortex	tissue	133.3
Duodenum	tissue	133.3	not detected
Retrosplenial and cingulate cortex	tissue	132.4
Entorhinal cortex	tissue	128.7
Temporal cortex	tissue	125.0
Esophagus	tissue	124.6	medium
Small intestine	tissue	121.9	not detected
Tonsil	tissue	119.7	medium
Smooth muscle	tissue	118.8	not detected
Placenta	tissue	114.9	not detected
Lymph node	tissue	113.9	low
Breast	tissue	113.6	medium
Seminal vesicle	tissue	113.1	medium
Endometrium 1	tissue	110.9	low
Colon	tissue	109.7	low

Brain sub-regions (HPA Brain Atlas): detected in 190; highest nTPM — Parieto-temporal junction (white matter) (379.0), Corpus callosum, genu (white matter) (353.0), Temporal white matter (335.7), Corpus callosum, splenium (white matter) (333.7), Angular gyrus (white matter) (324.9).

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)

Targeting MAT2A by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 122 miRNAs:

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

gnomAD constraint: pLI 1, LOEUF 0.158, missense Z 4.68 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000306434 splits into 6 regions with different missense tolerance; 3 are missense-constrained (≈27% of the expected missense variation). Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
2:85,539,288–85,539,342	36 / 24.2	1.49	no
2:85,539,343–85,541,151	12 / 42.4	0.28	yes (p 3.0e-06)
2:85,541,152–85,541,287	0 / 16.2	0.00	yes (p 5.6e-05)
2:85,541,288–85,542,360	103 / 226.4	0.45	no
2:85,542,361–85,542,715	8 / 73.1	0.11	yes (p 2.7e-14)
2:85,542,716–85,543,769	45 / 106.8	0.42	no
DepMap (CRISPR cell-line fitness): dependent in 95.0% of screened cell lines, common-essential.

Most-dependent cell lines (DepMap gene-effect, lower = stronger; ≤ −0.5 shown): UACC-893 (-3.638), HUP-T4 (-3.34), AsPC-1 (-3.152), Capan-1 (-2.744), Caov-4 (-2.653), SW 1990 (-2.566), KMS-20 (-2.5), NOMO-1 (-2.472), COV362 (-2.445), TUHR10TKB (-2.439), HPAF-II (-2.43), JHOS-2 (-2.355), PK-45H (-2.299), RCM-1 (-2.287), KP-N-YN (-2.235).

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)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:2443731) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 2 distinct phenotype terms.

Mouse phenotype (MP)	Records
decreased prepulse inhibition	1
preweaning lethality, complete penetrance	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Oryza sativa Indica Group	A2Y053	100.0%	Diamond
Oryza sativa Japonica Group	Q0DKY4	100.0%	Diamond
Macaca fascicularis	Q4R924	100.0%	Diamond
Brassica rapa subsp. pekinensis	Q5DNB1	100.0%	Diamond
Pongo abelii	Q5R5H1	100.0%	Diamond
Brassica juncea	Q94FA4	100.0%	Diamond
Atriplex nummularia	Q6F3F1	99.7%	Diamond
Populus trichocarpa	A9PEK8	99.5%	Diamond
Populus deltoides	P47916	99.2%	Diamond
Hordeum vulgare	P50299	99.2%	Diamond
Arabidopsis thaliana	P17562	99.0%	Diamond
Petunia x hybrida	P48498	99.0%	Diamond
Triticum aestivum	B0LXM0	98.7%	Diamond
Solanum lycopersicum	P43282	98.7%	Diamond
Solanum tuberosum	Q38JH8	98.7%	Diamond
Petroselinum crispum	P31155	98.6%	Diamond
Solanum palustre	Q6GV10	98.2%	Diamond
Nicotiana tabacum	Q9M7K8	98.2%	Diamond
Picea sitchensis	A9NYY0	97.7%	Diamond
Pinus contorta	Q9FVG7	97.7%	Diamond
Triticum monococcum	A6XMY9	97.2%	Diamond
Beta vulgaris	Q4H1G4	97.2%	Diamond
Vitis vinifera	A7NVX9	96.9%	Diamond
Carica papaya	Q8GTL5	96.9%	Diamond
Catharanthus roseus	Q96551	96.9%	Diamond
Elaeagnus umbellata	Q9AT55	96.9%	Diamond
Acacia koa	A0A9E8G339	96.6%	Diamond
Medicago sativa subsp. falcata	A4ULF8	96.6%	Diamond
Phaseolus lunatus	Q8W3Y4	96.4%	Diamond
Mesembryanthemum crystallinum	P93254	96.2%	Diamond
Camellia sinensis	Q9LDQ7	96.1%	Diamond
Actinidia chinensis var. chinensis	P50301	95.9%	Diamond
Bos taurus	Q2KJC6	95.5%	Diamond
Medicago truncatula	A4PU48	95.3%	Diamond
Gossypium hirsutum	A7L2Z6	95.2%	Diamond
Litchi chinensis	Q84MM2	95.2%	Diamond
Pinus banksiana	P50300	94.9%	Diamond
Daucus carota	Q56TU3	94.9%	Diamond
Dendrobium crumenatum	Q944U4	94.9%	Diamond
Suaeda salsa	Q9FPL6	94.4%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
PARTICL	ncRNA	100630918
GGCX	protein-coding	2677
VAMP5	protein-coding	10791
VAMP8	protein-coding	8673
RNF181	protein-coding	51255

Protein

Protein identifiers

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

Alternative names: Methionine adenosyltransferase 2, Methionine adenosyltransferase II

All UniProt accessions (3): P31153, A0A140VJP5, B4DEX8

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)

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

UniProt features (64 total): helix 18, strand 18, binding site 14, turn 5, modified residue 3, cross-link 2, splice variant 2, chain 1, region of interest 1

Structure

Experimental structures (PDB)

showing 30 of 59 structures by resolution:

PDB	Title	Method	Resolution (Å)
7RWG	“Crystal structure of human methionine adenosyltransferase 2A (MAT2A) in complex with SAM …	X-RAY DIFFRACTION	0.97
7BHS	Crystal structure of MAT2a with quinazoline fragment 2 bound in the allosteric site	X-RAY DIFFRACTION	1.05
7BHT	Crystal structure of MAT2a with quinazolinone fragment 5 bound in the allosteric site	X-RAY DIFFRACTION	1.05
7RXV	Human Methionine Adenosyltransferase 2A bound to Methylthioadenosine, Malonate (MLA) and …	X-RAY DIFFRACTION	1.07
7RXW	Human Methionine Adenosyltransferase 2A bound to Methylthioadenosine and inhibitor …	X-RAY DIFFRACTION	1.07
7BHR	Crystal structure of MAT2a with triazinone fragment 1 bound in the allosteric site	X-RAY DIFFRACTION	1.08
7BHX	Crystal structure of MAT2a bound to allosteric inhibitor (compound 31)	X-RAY DIFFRACTION	1.08
8QE3	Crystal structure of human MAT2a bound to S-Adenosylmethionine and Compound 31	X-RAY DIFFRACTION	1.09
5A1I	The structure of Human MAT2A in complex with SAM, Adenosine, Methionine and PPNP.	X-RAY DIFFRACTION	1.09
8QE1	Crystal structure of human MAT2a bound to S-Adenosylmethionine and Compound 15	X-RAY DIFFRACTION	1.09
7KCF	Crystal structure of human methionine adenosyltransferase 2A (MAT2A) in complex with SAM …	X-RAY DIFFRACTION	1.1
8QE2	Crystal structure of human MAT2a bound to S-Adenosylmethionine and Compound 21	X-RAY DIFFRACTION	1.11
8QE0	Crystal structure of human MAT2a bound to S-Adenosylmethionine and Compound 12	X-RAY DIFFRACTION	1.12
8XB0	Structure-Based Design and Optimization of Methionine Adenosyltransferase 2A (MAT2A) …	X-RAY DIFFRACTION	1.12
7KCE	Crystal structure of human methionine adenosyltransferase 2A (MAT2A) in complex with SAM …	X-RAY DIFFRACTION	1.14
7BHU	Crystal structure of MAT2a with elaborated fragment 26 bound in the allosteric site	X-RAY DIFFRACTION	1.15
7BHW	Crystal structure of MAT2a bound to allosteric inhibitor (compound 29)	X-RAY DIFFRACTION	1.15
8P1W	Crystal structure of human methionine adenosyltransferase 2A (MAT2A) in complex with …	X-RAY DIFFRACTION	1.15
8AXZ	Crystal structure of human methionine adenosyltransferase 2A (MAT2A) in complex with …	X-RAY DIFFRACTION	1.15
7BHV	Crystal structure of MAT2a bound to allosteric inhibitor and in vivo tool compound 28	X-RAY DIFFRACTION	1.16
8QDZ	Crystal structure of human MAT2a bound to S-Adenosylmethionine and Compound 11	X-RAY DIFFRACTION	1.16
7RWH	Crystal structure of human methionine adenosyltransferase 2A (MAT2A) in complex with SAM …	X-RAY DIFFRACTION	1.17
7RW7	Crystal structure of human methionine adenosyltransferase 2A (MAT2A) in complex with SAM …	X-RAY DIFFRACTION	1.19
8QDY	Crystal structure of human MAT2a bound to S-Adenosylmethionine and Compound 8	X-RAY DIFFRACTION	1.19
8XAR	Structure-Based Design and Optimization of Methionine Adenosyltransferase 2A (MAT2A) …	X-RAY DIFFRACTION	1.19
2P02	Crystal structure of the alpha subunit of human S-adenosylmethionine synthetase 2	X-RAY DIFFRACTION	1.21
7KDA	Crystal structure of human methionine adenosyltransferase 2A (MAT2A) in complex with SAM …	X-RAY DIFFRACTION	1.24
7KDB	Crystal structure of human methionine adenosyltransferase 2A (MAT2A) in complex with SAM …	X-RAY DIFFRACTION	1.24
7L1A	Human Methionine Adenosyltransferase 2A bound to Methylthioadenosine and inhibitor …	X-RAY DIFFRACTION	1.25
7RXX	Human Methionine Adenosyltransferase 2A bound to Methylthioadenosine and two sulfate in …	X-RAY DIFFRACTION	1.25

Predicted structure (AlphaFold)

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

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Transferases, Metabolic proteins, Predicted intracellular proteins, Plasma proteins, Essential proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): nucleoplasm; cytosol

Antibody reliability (HPA): IH approved · IF approved

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)

Position	Role
258	L-methionine
264–265	ATP
281	ATP
285	ATP
289	L-methionine
291	ATP
29	ATP
31	Mg(2+)
57	K(+)
70	L-methionine
113	L-methionine
179–181	ATP
247–250	ATP
258	ATP

Post-translational modifications (5)

Type	Positions
N6-acetyllysine	81
Phosphoserine	114, 384
Glycyl lysine isopeptide (lys-gly) (interchain with g-cter in sumo2)	228, 234

Function

Pathways and Gene Ontology

Reactome pathways

1 curated (TAS) of 4; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

4 pathways:

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

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 (7): 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), protein complex oligomerization (GO:0051259)

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

3 top-level categories:

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

GO top-level categories

27 GO namespaces:

Category	Terms
protein complex oligomerization	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
TORC1 signaling	1
regulation of TORC1 signaling	1
protein-containing complex assembly	1
transferase activity, transferring alkyl or aryl (other than methyl) groups	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
anion 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

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 9 of 17 annotations. The rest are phylogenetic / computational / electronic (IEA).

9 experimentally-supported GO terms:

GO term	NS	Evidence
S-adenosylmethionine biosynthetic process	BP	direct assay
cellular response to methionine	BP	direct assay
positive regulation of TORC1 signaling	BP	direct assay
protein heterooligomerization	BP	direct assay
protein hexamerization	BP	direct assay
methionine adenosyltransferase complex	CC	direct assay
identical protein binding	MF	physical interaction
methionine adenosyltransferase activity	MF	direct assay
small molecule binding	MF	experiment

Protein interactions and networks

STRING

showing 15 of 2,411 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MAT2A	MAT2B	Q9NZL9	984
MAT2A	EMG1	Q92979	837
MAT2A	NOP14	P78316	830
MAT2A	METTL16	Q86W50	785
MAT2A	AHCY	P23526	709
MAT2A	MTAP	Q13126	687
MAT2A	BHMT	Q93088	641
MAT2A	MTR	Q99707	641
MAT2A	ADRA1D	P25100	630
MAT2A	GNMT	Q14749	595
MAT2A	MYB	P10242	593
MAT2A	ZCCHC4	Q9H5U6	575
MAT2A	METTL14	Q9HCE5	575
MAT2A	METTL3	Q86U44	571
MAT2A	PRMT5	O14744	558

IntAct

Human interaction partners of MAT2A in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

showing 30 of 32 partners by confidence:

Partner	Interaction type	MIscore	Records
MAT1A	association	0.800	10
MAT2B	physical association	0.680	6
BOD1	physical association	0.560	3
CAMK1G	physical association	0.560	3
CCDC141	physical association	0.560	3
CRLF3	physical association	0.560	3
FAM117B	physical association	0.560	3
GATA1	physical association	0.560	3
IFI35	physical association	0.560	3
KCTD13	physical association	0.560	3
KLF15	physical association	0.560	3
MT2A	physical association	0.560	3
PELO	physical association	0.560	3
PRC1	physical association	0.560	3
PRKAB2	physical association	0.560	3
RBM11	physical association	0.560	3
RYBP	physical association	0.560	3
SAM1	physical association	0.560	3
SAM2	physical association	0.560	3
SLC3A2	physical association	0.560	3
SNW1	physical association	0.560	3
SPATA24	physical association	0.560	3
ZMYM6	physical association	0.560	3
HSPA4	physical association	0.400	1
ARHGAP25	association	0.350	1
ACTR6	physical association	0.000	1
ARF6	physical association	0.000	1
DSCAM	physical association	0.000	1
IKBKE	physical association	0.000	1
PRKAB1	physical association	0.000	1

BioGRID (299 interactions; top human partners by supporting records): MAT2B (Two-hybrid; 12 records), MAT1A (Affinity Capture-MS; 6 records), PARK2 (Affinity Capture-MS; 5 records), CUL3 (Affinity Capture-Western; 3 records), AIMP2 (Affinity Capture-MS; 2 records), BRD4 (Affinity Capture-MS; 2 records), COPS5 (Affinity Capture-MS; 2 records), DNM1L (Affinity Capture-MS; 2 records), DUSP6 (Affinity Capture-MS; 2 records), HSD17B10 (Affinity Capture-MS; 2 records), HSPA1A (Co-fractionation; 2 records), IFI16 (Affinity Capture-MS; 2 records), NUDC (Co-fractionation; 2 records), OGT (Reconstituted Complex; 2 records), PRNP (Affinity Capture-MS; 2 records)

Protein complexes (CORUM) (2)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

2 complexes by size:

Complex	Subunits	Members
Methionine adenosyltransferase alpha2 beta-v1	2	MAT2A, MAT2B
Methionine adenosyltransferase alpha2 beta-v2	2	MAT2A, MAT2B

Disease & clinical

Genetic variants

Variant evidence for MAT2A: 341 ClinVar records (2 pathogenic / likely pathogenic); 5 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	0
Uncertain significance	106
Likely benign	192
Benign	12

Top pathogenic / likely-pathogenic (2)

Showing all 2 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
265866	NM_005911.6(MAT2A):c.1031A>C (p.Glu344Ala)	Pathogenic	criteria provided, single submitter	2
1180533	GRCh37/hg19 2p12-11.2(chr2:81209244-86688030)x1	Pathogenic	criteria provided, single submitter	1

Per-variant reference — Sugi Variant

Explore MAT2A’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 30 predictions of 791):

Position(s)	Effect	Δscore	Sites
2:85539379–85539380	donor_loss	1.0000	3
2:85541253–85541254	acceptor_loss	1.0000	5
2:85541289	acceptor_gain	1.0000
2:85541378–85541379	donor_loss	1.0000	5
2:85541624	acceptor_gain	1.0000
2:85541632	acceptor_loss	1.0000	2
2:85541746–85541747	donor_loss	1.0000	4
2:85541827	acceptor_loss	1.0000	3
2:85541828	acceptor_gain	1.0000
2:85541973–85541974	donor_loss	1.0000	5

AlphaMissense

1,433 missense substitutions predicted likely pathogenic (of 2,581 scored), across 309 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M138	9	0.919	0.992
D291	8	0.997	0.999
D134	8	0.995	0.999
D269	8	0.995	0.999
D31	8	0.994	0.998
D35	8	0.994	0.998
D39	8	0.994	0.998
D179	8	0.994	0.997
D258	8	0.993	0.998
D286	8	0.993	0.998
H29	8	0.989	0.998
F250	8	0.986	0.999
H277	8	0.984	0.998
H379	8	0.982	0.996
D43	8	0.976	0.992
F282	8	0.975	0.995
F139	8	0.971	0.999
F20	8	0.967	0.997
H209	8	0.966	0.984
F380	8	0.959	0.992

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

4 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	8.19e-06
Skin Cutaneous Melanoma (TCGA)	unfavorable	1.07e-05
Liver Hepatocellular Carcinoma (TCGA)	unfavorable	0.00067
Breast Invasive Carcinoma (TCGA)	unfavorable	0.00098

Disease associations

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

GenCC curated gene-disease

1 curated gene-disease records:

Disease	Classification	Inheritance	Records
thoracic aortic aneurysm	Moderate	Autosomal dominant

ClinGen Gene-Disease Validity

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

1 validity classifications:

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

Mondo (2): familial thoracic aortic aneurysm and aortic dissection (MONDO:0019625), thoracic aortic aneurysm (MONDO:0005396)

Orphanet (1): Familial thoracic aortic aneurysm and aortic dissection (Orphanet:91387)

HPO phenotypes

42 phenotypes (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
HP:0004944	Dilatation of the cerebral artery
HP:0004950	Peripheral arterial stenosis
HP:0004959	Descending thoracic aorta aneurysm
HP:0005112	Abdominal aortic aneurysm
HP:0005162	Abnormal left ventricular function
HP:0011106	Hypovolemia
HP:0012163	Carotid artery dilatation
HP:0012499	Descending aortic dissection
HP:0012763	Paroxysmal dyspnea
HP:0100749	Chest pain
HP:0100775	Dural ectasia
HP:0200146	Mucoid extracellular matrix accumulation

GWAS associations

5 associations:

Study	Trait	p-value
GCST005195_68	Coronary artery disease	2e-23
GCST011365_98	Myocardial infarction	9e-18
GCST006586_21	Urinary albumin excretion	4e-10
GCST011364_4	Myocardial infarction	1e-9
GCST003927_6	Dysmenorrheic pain	8e-7

EFO canonical traits (from GWAS)

2 canonical traits:

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

MeSH disease descriptors

1 disease descriptors:

Descriptor	Name	Tree numbers
D017545	Aortic Aneurysm, Thoracic	C14.907.055.239.125; C14.907.109.139.125

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3313835 (SINGLE PROTEIN)

PharmGKB: 1 entry (CPIC guideline: no)

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
tuvutromstat	Inhibition	6.7	pIC50

Binding affinities (BindingDB)

957 measured of 1825 human assays (1829 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
CHEMBL6174106	IC50	1 nM
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

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

380 with measured affinity, of 784 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
(5R)-1’-(trideuteriomethylimino)-6’-(trifluoromethyl)spiro[6,7-dihydrocyclopenta[b]pyridine-5,4’-isoquinoline]-3’-one	2251503: Inhibition of MAT2A in MTAP-knock out human HCT-116 cells assessed as inhibition of PRMT5-mediated symmetric demethyl-arginine (SDMA) level	ic50	0.0010	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
(5R)-6’-(1,1-difluoroethyl)-1’-(trideuteriomethylimino)spiro[6,7-dihydrocyclopenta[b]pyridine-5,4’-isoquinoline]-3’-one	2251503: Inhibition of MAT2A in MTAP-knock out human HCT-116 cells assessed as inhibition of PRMT5-mediated symmetric demethyl-arginine (SDMA) level	ic50	0.0020	uM
1-(2-chlorophenyl)-4-(methylamino)-7-(trifluoromethyl)pyrido[2,3-d]pyrimidin-2-one	2251492: Inhibition of MAT2A (unknown origin) assessed as release of inorganic phosphate using ATP/L-methionine pre-incubated for 30 mins followed by substrate addition measured after 2.5 hrs by colorimetric assay	ic50	0.0030	uM
4-amino-1-(2-chlorophenyl)-7-(trifluoromethyl)pyrido[2,3-d]pyrimidin-2-one	2251492: Inhibition of MAT2A (unknown origin) assessed as release of inorganic phosphate using ATP/L-methionine pre-incubated for 30 mins followed by substrate addition measured after 2.5 hrs by colorimetric assay	ic50	0.0030	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
6’-cyclopropyl-7’-fluoro-1’-methyliminospiro[6,7-dihydrocyclopenta[b]pyridine-5,4’-isoquinoline]-3’-one	2251492: Inhibition of MAT2A (unknown origin) assessed as release of inorganic phosphate using ATP/L-methionine pre-incubated for 30 mins followed by substrate addition measured after 2.5 hrs by colorimetric assay	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
(5R)-6’-(1,1-difluoroethyl)-7’-fluoro-1’-(trideuteriomethylimino)spiro[6,7-dihydrocyclopenta[b]pyridine-5,4’-isoquinoline]-3’-one	2251492: Inhibition of MAT2A (unknown origin) assessed as release of inorganic phosphate using ATP/L-methionine pre-incubated for 30 mins followed by substrate addition measured after 2.5 hrs by colorimetric assay	ic50	0.0040	uM
1’-cyclopropylimino-6’-(trifluoromethyl)spiro[6,7-dihydrocyclopenta[b]pyridine-5,4’-isoquinoline]-3’-one	2251492: Inhibition of MAT2A (unknown origin) assessed as release of inorganic phosphate using ATP/L-methionine pre-incubated for 30 mins followed by substrate addition measured after 2.5 hrs by colorimetric assay	ic50	0.0040	uM
(5R)-6’-cyclopropyl-7’-fluoro-1’-(trideuteriomethylimino)spiro[6,7-dihydrocyclopenta[b]pyridine-5,4’-isoquinoline]-3’-one	2251492: Inhibition of MAT2A (unknown origin) assessed as release of inorganic phosphate using ATP/L-methionine pre-incubated for 30 mins followed by substrate addition measured after 2.5 hrs by colorimetric assay	ic50	0.0040	uM
1’-imino-6’-(trifluoromethyl)spiro[6,7-dihydrocyclopenta[b]pyridine-5,4’-isoquinoline]-3’-one	2251492: Inhibition of MAT2A (unknown origin) assessed as release of inorganic phosphate using ATP/L-methionine pre-incubated for 30 mins followed by substrate addition measured after 2.5 hrs by colorimetric assay	ic50	0.0040	uM
(5R)-6’-cyclopropyl-1’-(trideuteriomethylimino)spiro[6,7-dihydrocyclopenta[b]pyridine-5,4’-isoquinoline]-3’-one	2251492: Inhibition of MAT2A (unknown origin) assessed as release of inorganic phosphate using ATP/L-methionine pre-incubated for 30 mins followed by substrate addition measured after 2.5 hrs by colorimetric assay	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
1’-(3,3-difluorocyclobutyl)imino-6’-(trifluoromethyl)spiro[6,7-dihydrocyclopenta[b]pyridine-5,4’-isoquinoline]-3’-one	2251492: Inhibition of MAT2A (unknown origin) assessed as release of inorganic phosphate using ATP/L-methionine pre-incubated for 30 mins followed by substrate addition measured after 2.5 hrs by colorimetric assay	ic50	0.0050	uM
1’-methylimino-6’-(1,1,2,2,2-pentafluoroethyl)spiro[6,7-dihydrocyclopenta[b]pyridine-5,4’-isoquinoline]-3’-one	2251492: Inhibition of MAT2A (unknown origin) assessed as release of inorganic phosphate using ATP/L-methionine pre-incubated for 30 mins followed by substrate addition measured after 2.5 hrs by colorimetric assay	ic50	0.0060	uM
6’-cyclopropyl-1’-methyliminospiro[6,7-dihydrocyclopenta[b]pyridine-5,4’-isoquinoline]-3’-one	2251492: Inhibition of MAT2A (unknown origin) assessed as release of inorganic phosphate using ATP/L-methionine pre-incubated for 30 mins followed by substrate addition measured after 2.5 hrs by colorimetric assay	ic50	0.0060	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
5’-methylimino-2’-(trifluoromethyl)spiro[1,2-dihydroindene-3,8’-1,6-naphthyridine]-7’-one	2251492: Inhibition of MAT2A (unknown origin) assessed as release of inorganic phosphate using ATP/L-methionine pre-incubated for 30 mins followed by substrate addition measured after 2.5 hrs by colorimetric assay	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
6’-(difluoromethoxy)-1’-methyliminospiro[6,7-dihydrocyclopenta[b]pyridine-5,4’-isoquinoline]-3’-one	2251492: Inhibition of MAT2A (unknown origin) assessed as release of inorganic phosphate using ATP/L-methionine pre-incubated for 30 mins followed by substrate addition measured after 2.5 hrs by colorimetric assay	ic50	0.0080	uM
1’-(trideuteriomethylimino)-6’-(trifluoromethyl)spiro[6,7-dihydrocyclopenta[b]pyridine-5,4’-isoquinoline]-3’-one	2251492: Inhibition of MAT2A (unknown origin) assessed as release of inorganic phosphate using ATP/L-methionine pre-incubated for 30 mins followed by substrate addition measured after 2.5 hrs by colorimetric assay	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
5-methylimino-2-(trifluoromethyl)spiro[1,6-naphthyridine-8,5’-6,7-dihydrocyclopenta[b]pyridine]-7-one	2251492: Inhibition of MAT2A (unknown origin) assessed as release of inorganic phosphate using ATP/L-methionine pre-incubated for 30 mins followed by substrate addition measured after 2.5 hrs by colorimetric assay	ic50	0.0090	uM
6’-(1,1-difluoroethyl)-1’-methyliminospiro[6,7-dihydrocyclopenta[b]pyridine-5,4’-isoquinoline]-3’-one	2251492: Inhibition of MAT2A (unknown origin) assessed as release of inorganic phosphate using ATP/L-methionine pre-incubated for 30 mins followed by substrate addition measured after 2.5 hrs by colorimetric assay	ic50	0.0090	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
1’-(2,2,2-trifluoroethylimino)-6’-(trifluoromethyl)spiro[6,7-dihydrocyclopenta[b]pyridine-5,4’-isoquinoline]-3’-one	2251492: Inhibition of MAT2A (unknown origin) assessed as release of inorganic phosphate using ATP/L-methionine pre-incubated for 30 mins followed by substrate addition measured after 2.5 hrs by colorimetric assay	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
1’-methylimino-6’-(trifluoromethyl)spiro[6,7-dihydrocyclopenta[b]pyridine-5,4’-isoquinoline]-3’-one	2251492: Inhibition of MAT2A (unknown origin) assessed as release of inorganic phosphate using ATP/L-methionine pre-incubated for 30 mins followed by substrate addition measured after 2.5 hrs by colorimetric assay	ic50	0.0110	uM
7-fluoro-5’-methylimino-2’-(trifluoromethyl)spiro[1,2-dihydroindene-3,8’-1,6-naphthyridine]-7’-one	2251492: Inhibition of MAT2A (unknown origin) assessed as release of inorganic phosphate using ATP/L-methionine pre-incubated for 30 mins followed by substrate addition measured after 2.5 hrs by colorimetric assay	ic50	0.0110	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	decreases expression, affects cotreatment, increases abundance, increases 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	decreases expression, affects cotreatment, increases expression	2
Formaldehyde	decreases expression	2
Rotenone	increases expression, decreases 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	affects binding, decreases expression, increases activity	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)

Via MONDO — disease-level, not drug-specific.

58 trials:

NCT	Phase	Status	Title
NCT00339053	Phase 4	UNKNOWN	Immunonutrition and Thoracoabdominal Aorta Aneurysm Repair
NCT02291718	Phase 4	COMPLETED	Thoracoabdominal Arortic CTA Study
NCT01033214	Phase 1	UNKNOWN	ENTRUST - TAArget® Thoracic Stent Graft Clinical Trial
NCT03998631	Phase 1	UNKNOWN	Comparison of Carbon Dioxide and Saline Flush to Saline Flush in TEVAR and TAVI Procedures to Reduce Cerebral Ischemia
NCT00604799	Phase 2/3	COMPLETED	VALOR: The Talent Thoracic Stent Graft System Clinical Study
NCT07483177	Phase 1/2	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	UNKNOWN	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
NCT05414318	Not specified	COMPLETED	CTAG Dissection/Trauma Post Marketing Surveillance Japan
NCT05639400	Not specified	ACTIVE_NOT_RECRUITING	Thoraflex Hybrid and Relay Extension Post-Approval Study
NCT05650892	Not specified	COMPLETED	Male-female Differences in Immunohistological and Biomechanical Properties of the Thoracic Aorta
NCT05777460	Not specified	RECRUITING	Mid- and Long-term Outcomes of Custom-made Aortic Devices
NCT06028789	Not specified	UNKNOWN	AOrtic Surgery: Systemic Inflammatory Response Versus Sepsis
NCT06094127	Not specified	ACTIVE_NOT_RECRUITING	Zenith Thoracic Alpha (ZTA) Post-Market Data Collection
NCT06336213	Not specified	RECRUITING	Antibacterial Tactics Based on Presepsin Level in Thoracic Aorta Surgery Patients
NCT06353607	Not specified	RECRUITING	Genetic Architecture of Acute Aortic Syndromes and Aortic Aneurysm.
NCT06377033	Not specified	RECRUITING	Using the EHR to Advance Genomic Medicine Across a Diverse Health System
NCT06507865	Not specified	ACTIVE_NOT_RECRUITING	Post Market Registry for GORE® TAG® Thoracic Branch Endoprosthesis
NCT06639243	Not specified	ACTIVE_NOT_RECRUITING	Quick Yielding Modified Short-Distance Fenestration Technique for the Treatment of Complex Aortic Arch Diseases: a Multicenter Single-Arm Objective Performance Criteria Trial(QYM-Tech Study)
NCT06786351	Not specified	NOT_YET_RECRUITING	Impact of Right Atrial Occlusion on TEVAR Outcomes
NCT06786754	Not specified	ENROLLING_BY_INVITATION	Fibroblasts and Thoracic Aortic Aneurysms: in Vitro Characterization in With Marfan Syndrome and Genetic Aortic Diseases
NCT06854588	Not specified	NOT_YET_RECRUITING	POCUS Screening for TAA in Hypertensive Patients in the ED
NCT06882967	Not specified	RECRUITING	Active Thoracic Compromised Distal LANding in TEvar
NCT07391293	Not specified	RECRUITING	Genetic Aortic Diseases and Cardiovascular Complications. An Observational Survey of Risk Factors.
NCT07564375	Not specified	RECRUITING	MBA Early Feasibility Study
NCT06783803	Not specified	ACTIVE_NOT_RECRUITING	Application of Linkage Analysis in the Identification of Novel Hereditary Factors in Familial Aneurysms

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for MAT2A across ~30M SureChEMBL compounds — explore on Sugi Predict.