MAT1A

Summary

MAT1A (methionine adenosyltransferase 1A, HGNC:6903) is a protein-coding gene on chromosome 10q22.3, encoding S-adenosylmethionine synthase isoform type-1 (Q00266). Catalyzes the formation of S-adenosylmethionine from methionine and ATP.

This gene catalyzes a two-step reaction that involves the transfer of the adenosyl moiety of ATP to methionine to form S-adenosylmethionine and tripolyphosphate, which is subsequently cleaved to PPi and Pi. S-adenosylmethionine is the source of methyl groups for most biological methylations. The encoded protein is found as a homotetramer (MAT I) or a homodimer (MAT III) whereas a third form, MAT II (gamma), is encoded by the MAT2A gene. Mutations in this gene are associated with methionine adenosyltransferase deficiency.

Source: NCBI Gene 4143 — RefSeq curated summary.

At a glance

• Gene–disease (curated): methionine adenosyltransferase deficiency (Definitive, ClinGen)
• GWAS associations: 1
• Clinical variants (ClinVar): 378 total — 26 pathogenic, 8 likely-pathogenic
• Phenotypes (HPO): 9
• Druggable target: yes
• MANE Select transcript: NM_000429

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6903
Approved symbol	MAT1A
Name	methionine adenosyltransferase 1A
Location	10q22.3
Locus type	gene with protein product
Status	Approved
Aliases	MAT, SAMS, MATA1, SAMS1, MAT-I/III
Ensembl gene	ENSG00000151224
Ensembl biotype	protein_coding
OMIM	610550
Entrez	4143

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 12 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000372213, ENST00000455001, ENST00000480845, ENST00000485270, ENST00000871619, ENST00000871620, ENST00000871621, ENST00000871622, ENST00000871623, ENST00000871624, ENST00000871625, ENST00000871626, ENST00000871627, ENST00000871628

RefSeq mRNA: 1 — MANE Select: NM_000429 NM_000429

CCDS: CCDS7365

Canonical transcript exons

ENST00000372213 — 9 exons

Exon	Start	End
ENSE00000998389	80285512	80285589
ENSE00000998391	80280173	80280316
ENSE00000998396	80280680	80280792
ENSE00000998397	80283916	80284038
ENSE00001910847	80289333	80289658
ENSE00002287840	80276376	80276594
ENSE00003482452	80275017	80275199
ENSE00003593735	80274520	80274653
ENSE00003656676	80271820	80273883

Expression profiles

Bgee: expression breadth ubiquitous, 146 present calls, max score 99.66.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 2.4734 / max 898.2675, expressed in 104 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
110349	1.5986	50
110346	0.4071	43
110345	0.2754	27
110347	0.0537	15
110352	0.0523	11
110350	0.0381	19
110351	0.0321	9
110348	0.0162	8

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right lobe of liver	UBERON:0001114	99.66	gold quality
liver	UBERON:0002107	99.11	gold quality
corpus epididymis	UBERON:0004359	93.54	gold quality
body of pancreas	UBERON:0001150	89.22	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	87.05	gold quality
cauda epididymis	UBERON:0004360	85.19	gold quality
pancreas	UBERON:0001264	83.90	gold quality
type B pancreatic cell	CL:0000169	81.44	gold quality
diaphragm	UBERON:0001103	80.42	gold quality
olfactory bulb	UBERON:0002264	80.26	gold quality
right uterine tube	UBERON:0001302	79.02	gold quality
oocyte	CL:0000023	78.80	silver quality
secondary oocyte	CL:0000655	78.61	silver quality
mucosa of urinary bladder	UBERON:0001259	77.85	gold quality
endometrium epithelium	UBERON:0004811	77.24	gold quality
islet of Langerhans	UBERON:0000006	76.19	gold quality
adrenal tissue	UBERON:0018303	75.00	gold quality
hair follicle	UBERON:0002073	73.58	gold quality
skin of leg	UBERON:0001511	73.42	gold quality
caput epididymis	UBERON:0004358	73.27	gold quality
right testis	UBERON:0004534	73.05	gold quality
thymus	UBERON:0002370	72.92	silver quality
left testis	UBERON:0004533	72.66	gold quality
skin of abdomen	UBERON:0001416	71.95	gold quality
epithelial cell of pancreas	CL:0000083	71.65	gold quality
testis	UBERON:0000473	71.48	gold quality
tongue squamous epithelium	UBERON:0006919	71.36	gold quality
cervix squamous epithelium	UBERON:0006922	71.31	gold quality
zone of skin	UBERON:0000014	71.26	gold quality
epithelium of bronchus	UBERON:0002031	70.86	silver quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-130473	yes	446.63
E-HCAD-9	yes	57.15
E-ANND-3	yes	7.60

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CEBPA, CEBPB, THRA

miRNA regulators (miRDB)

95 targeting MAT1A, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-520G-5P	99.99	66.76	658
HSA-MIR-4650-5P	99.98	64.69	999
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-6739-5P	99.80	67.87	2806
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-6733-5P	99.74	67.94	2759
HSA-MIR-10393-3P	99.72	66.56	961
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-3175	99.65	66.30	2031
HSA-MIR-4690-5P	99.65	66.24	813
HSA-MIR-3679-3P	99.64	69.88	1599
HSA-MIR-1251-3P	99.64	67.21	1408
HSA-MIR-4649-3P	99.56	66.90	1783

Literature-anchored findings (GeneRIF, showing 32)

• Mutations in the MAT1A gene are the most prevalent cause of isolated hypermethioninemia in Taiwanese. (PMID:15935930)
• Results show a rather high frequency of hypermethioninaemia due to MAT I/III deficiency (MAT1A dominant mutation) in the Galician neonatal population. (PMID:18500573)
• expression of the MAT1A gene is mediated by C/EBP and is indirectly upregulated by T(3) in hepatoma cell lines (PMID:20146079)
• MAT1A variants were strongly associated with hypertension and stroke; improving folate and vitamin B-6 status may decrease cardiovascular disease risk of only a subset of the population, depending on genotype. (PMID:20335551)
• MAT and tripolyphosphatase (PPPase) activities of 18 MAT1A variants, six of them novel, and none of them previously assayed for activity. With the exception of G69S and Y92H, all recombinant proteins showed impairment (usually severe) of MAT activity. (PMID:20675163)
• genetic variant MAT1A 3U1510 displayed a significant interaction with dietary n-3:n-6 polyunsaturated fatty acids ratio in determining plasma homocysteine (PMID:21185701)
• Methylation of the MAT1A coding region can inhibit gene transcription. This represents a key mechanism for decreased MAT1A expression in hepatocellular carcinoma. (PMID:21678410)
• Coexpression of MAT2A and MAT2B in COS-1 cells resulted in significantly increased MAT enzyme activity. (PMID:21813468)
• Human Dead-box protein 3 (DDX3X), a RNA helicase regulating RNA splicing, export, transcription and translation was down-regulated upon MAT1A expression. (PMID:22270009)
• we found for the first time a post-transcriptional regulation of MAT1A and MAT2A by AUF1 and HuR in hepatocellular carcinoma. (PMID:22318685)
• Report SNPs that are highly associated with hepatic GNMT protein expression and the coordinate regulation of MAT1A levels. (PMID:22807109)
• Methionine adenosyltransferase I/III deficiency is caused by mutations in the MAT1A gene. (Review) (PMID:22951388)
• upregulation of miR-664, miR-485-3p, and miR-495 contributes to lower MAT1A expression in HCC, and enhanced tumorigenesis may provide potential targets for HCC therapy. (PMID:23241961)
• 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)
• The mutations in the other 10 patients showed autosomal recessive inheritance and included eight novel MAT1A mutations. (PMID:24231718)
• 5-Aza-CdR showed no effects on MAT2A methylation. (PMID:24377546)
• interplay between MATalpha1, c-Myc, and Maf proteins, and their deregulation during chronic cholestasis may facilitate cholangiocarcinoma oncogenesis (PMID:26969892)
• S-adenosyl-L-methionine diminishes hepatitis C virus expression by altering MAT1A/2A signaling in hepatocytes. (PMID:27076759)
• Of the 22 single nucleotide polymorphisms studied, the rs8193 polymorphism lying in the micro-RNA binding site of 3’-UTR of CD44 was significantly (P=.0270) associated with RT-induced adverse skin reactions. Generalized multifactor dimensionality reduction analysis showed significant (P=.0107) gene-gene interactions between MAT1A and CD44. (PMID:27816361)
• A compound mutation of the methionine adenosyltransferase 1A (MAT1A) gene, c.345delA and c.529C>T, was identified in the patient, and His father and mother were found to be heterozygous for the c.345delA mutation and c.529C>T mutation, respectively. (PMID:28186605)
• Increased MAT1A 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)
• Overexpression of MAT1A in 5637 bladder cancer cells increased tolerance to gemcitabine and stalled cell proliferation rates, suggesting MAT1A upregulation as a potential mechanism by which bladder cancer cells persist in a quiescent state to evade chemotherapy. (PMID:31600961)
• Reciprocal Regulation Between Forkhead Box M1/NF-kappaB and Methionine Adenosyltransferase 1A Drives Liver Cancer. (PMID:32080887)
• Three newborns were identified with MAT I/III deficiency by newborn screening were found to carry MAT1A gene variants including two missense variants [c.776C>T (p.Ala259Val) and c.791G>A (p.Arg264His)] and a synonymous variant [c.360C>T (p.Cys120Cys)] (PMID:32335878)
• Structural basis of the dominant inheritance of hypermethioninemia associated with the Arg264His mutation in the MAT1A gene. (PMID:32496220)
• Methionine adenosyltransferase I/III deficiency: Long-term follow-up and treatment of 3 adult siblings. (PMID:32980525)
• Deregulated 14-3-3zeta and methionine adenosyltransferase alpha1 interplay promotes liver cancer tumorigenesis in mice and humans. (PMID:34349244)
• Downregulation of Methionine Cycle Genes MAT1A and GNMT Enriches Protein-Associated Translation Process and Worsens Hepatocellular Carcinoma Prognosis. (PMID:35008908)
• Depletion of mitochondrial methionine adenosyltransferase alpha1 triggers mitochondrial dysfunction in alcohol-associated liver disease. (PMID:35091576)
• Hepatic prohibitin 1 and methionine adenosyltransferase alpha1 defend against primary and secondary liver cancer metastasis. (PMID:38086446)
• MAT1A activation of glycolysis to promote NSCLC progression depends on stabilizing CCND1. (PMID:39438468)

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
danio_rerio	mat1a	ENSDARG00000039605
mus_musculus	Mat1a	ENSMUSG00000037798
rattus_norvegicus	Mat1a	ENSRNOG00000011351
drosophila_melanogaster	Sam-S	FBGN0005278
caenorhabditis_elegans		WBGENE00006416
caenorhabditis_elegans		WBGENE00008205
caenorhabditis_elegans		WBGENE00015538
caenorhabditis_elegans		WBGENE00015540

Paralogs (1): MAT2A (ENSG00000168906)

Protein

Protein identifiers

S-adenosylmethionine synthase isoform type-1 — Q00266 (reviewed: Q00266)

Alternative names: Methionine adenosyltransferase 1, Methionine adenosyltransferase I/III

All UniProt accessions (2): Q00266, B1ANE6

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. Homotetramer (MAT-I); dimer of dimers. Homodimer (MAT-III).

Tissue specificity. Expressed in liver.

Post-translational modifications. S-nitrosylation of Cys-120 inactivates the enzyme. An intrachain disulfide bond can be formed. The protein structure shows that the relevant Cys residues are in a position that would permit formation of a disulfide bond.

Disease relevance. Methionine adenosyltransferase deficiency (MATD) [MIM:250850] An inborn error of metabolism resulting in isolated hypermethioninemia. Most patients have no clinical abnormalities, although some neurologic symptoms may be present in rare cases with severe loss of methionine adenosyltransferase activity. The disease is caused by variants affecting the gene represented in this entry.

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.

Similarity. Belongs to the AdoMet synthase family.

RefSeq proteins (1): NP_000420* (*=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 (66 total): strand 15, helix 15, binding site 14, sequence variant 13, turn 4, chain 1, region of interest 1, modified residue 1, disulfide bond 1, sequence conflict 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
8SWA	X-RAY DIFFRACTION	2
2OBV	X-RAY DIFFRACTION	2.05
6SW5	X-RAY DIFFRACTION	2.35
6SW6	X-RAY DIFFRACTION	2.85

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q00266-F1	96.77	0.96

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; 289 (in other chain); 23; 29 (in other chain); 57; 70 (in other chain); 113 (in other chain); 179–181 (in other chain) …

Post-translational modifications (1): 120

Disulfide bonds (1): 34–60

Function

Pathways and Gene Ontology

Reactome pathways

12 pathways

ID	Pathway
R-HSA-156581	Methylation
R-HSA-1614635	Sulfur amino acid metabolism
R-HSA-2408508	Metabolism of ingested SeMet, Sec, MeSec into H2Se
R-HSA-5579024	Defective MAT1A causes MATD
R-HSA-1430728	Metabolism
R-HSA-156580	Phase II - Conjugation of compounds
R-HSA-1643685	Disease
R-HSA-211859	Biological oxidations
R-HSA-2408522	Selenoamino acid metabolism
R-HSA-5579029	Metabolic disorders of biological oxidation enzymes
R-HSA-5668914	Diseases of metabolism
R-HSA-71291	Metabolism of amino acids and derivatives

MSigDB gene sets: 195 (showing top): TGGTGCT_MIR29A_MIR29B_MIR29C, MODULE_52, REACTOME_BIOLOGICAL_OXIDATIONS, GRUETZMANN_PANCREATIC_CANCER_DN, GOBP_PROTEIN_HOMOTETRAMERIZATION, GNF2_GSTM1, GOBP_ALPHA_AMINO_ACID_METABOLIC_PROCESS, MODULE_45, KEGG_CYSTEINE_AND_METHIONINE_METABOLISM, GNF2_HPN, ACEVEDO_NORMAL_TISSUE_ADJACENT_TO_LIVER_TUMOR_DN, MODULE_66, MODULE_118, GOBP_SULFUR_COMPOUND_BIOSYNTHETIC_PROCESS, GOBP_SULFUR_COMPOUND_CATABOLIC_PROCESS

GO Biological Process (5): S-adenosylmethionine biosynthetic process (GO:0006556), one-carbon metabolic process (GO:0006730), L-methionine catabolic process (GO:0009087), protein homotetramerization (GO:0051289), protein complex oligomerization (GO:0051259)

GO Molecular Function (7): methionine adenosyltransferase activity (GO:0004478), ATP binding (GO:0005524), 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-8 pathways:

Category	Pathways
Metabolism of amino acids and derivatives	2
Metabolism	2
Phase II - Conjugation of compounds	1
Selenoamino acid metabolism	1
Metabolic disorders of biological oxidation enzymes	1
Biological oxidations	1
Diseases of metabolism	1
Disease	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
sulfur compound biosynthetic process	1
S-adenosylmethionine metabolic process	1
small molecule metabolic process	1
sulfur amino acid catabolic process	1
L-methionine metabolic process	1
L-amino acid catabolic process	1
proteinogenic amino acid catabolic process	1
protein homooligomerization	1
protein tetramerization	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
protein binding	1
cation binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
catalytic activity	1
cytoplasm	1
cellular anatomical structure	1
intracellular protein-containing complex	1
transferase complex	1

Protein interactions and networks

STRING

3049 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MAT1A	H7C2H4	H7C2H4	800
MAT1A	P0DN79	P0DN79	797
MAT1A	SMPD1	P17405	785
MAT1A	AHCY	P23526	778
MAT1A	BHMT	Q93088	778
MAT1A	MAT2B	Q9NZL9	746
MAT1A	GNMT	Q14749	742
MAT1A	MTR	Q99707	731
MAT1A	MTHFR	P42898	730
MAT1A	CTH	P32929	681
MAT1A	BHMT2	Q9H2M3	636
MAT1A	MYB	P10242	624
MAT1A	HNRNPD	P07029	623
MAT1A	SHMT1	P34896	583
MAT1A	GAMT	Q14353	578

IntAct

23 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
MAT1A	MAT1A	psi-mi:“MI:0915”(physical association)	0.670
APP	MAT1A	psi-mi:“MI:0915”(physical association)	0.560
HTT	MAT1A	psi-mi:“MI:0915”(physical association)	0.560
TECTB	MAT1A	psi-mi:“MI:0915”(physical association)	0.400
PPP1R21	STX10	psi-mi:“MI:0914”(association)	0.350
MAT1A	MAT2A	psi-mi:“MI:0915”(physical association)	0.000
MAT2A	MAT1A	psi-mi:“MI:0915”(physical association)	0.000
MAT1A	MAT1A	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (46): MAT1A (Two-hybrid), MAT2A (Affinity Capture-MS), MAT2B (Affinity Capture-MS), ASPSCR1 (Affinity Capture-MS), DSCR3 (Co-fractionation), EEF1A1 (Co-fractionation), MAT1A (Co-fractionation), MAT1A (Co-fractionation), MVK (Co-fractionation), RABIF (Co-fractionation), RPE (Co-fractionation), MAT2A (Affinity Capture-MS), MAT2B (Affinity Capture-MS), ASPSCR1 (Affinity Capture-MS), MAT1A (Affinity Capture-MS)

ESM2 similar proteins: A2Y053, A3N186, A4WE78, A5GA66, A5UCT6, A5UIU0, A6XMY9, A7MJQ6, A9PHC5, A9PHE9, B0BQ17, B0LXM0, B0UWT3, B3H1W3, B4THH4, B4TV58, B5F5L4, B5RE50, B8F4B2, O43938, P13444, P18298, P31153, P40320, P50305, P50306, P57897, P61946, P66764, P66765, P93254, Q00266, Q0DKY4, Q0I559, Q27522, Q2KJC6, Q3THS6, Q4LB23, Q4QLC5, Q4R924

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.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	26
Likely pathogenic	8
Uncertain significance	187
Likely benign	85
Benign	36

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1202	NM_000429.3(MAT1A):c.966T>G (p.Ile322Met)	Pathogenic
1204	NM_000429.3(MAT1A):c.1070C>T (p.Pro357Leu)	Pathogenic
1205	NM_000429.3(MAT1A):c.914T>C (p.Leu305Pro)	Pathogenic
1206	NM_000429.3(MAT1A):c.826dup (p.Ala276fs)	Pathogenic
1207	NM_000429.3(MAT1A):c.1043_1044del (p.Val348fs)	Pathogenic
1208	NM_000429.3(MAT1A):c.791G>A (p.Arg264His)	Pathogenic
1210	NM_000429.3(MAT1A):c.790C>T (p.Arg264Cys)	Pathogenic
1969591	NM_000429.3(MAT1A):c.1042del (p.Val348fs)	Pathogenic
2005287	NM_000429.3(MAT1A):c.705C>A (p.Tyr235Ter)	Pathogenic
2082436	NM_000429.3(MAT1A):c.110T>C (p.Ile37Thr)	Pathogenic
2103029	NM_000429.3(MAT1A):c.125_131del (p.Leu42fs)	Pathogenic
2735423	NM_000429.3(MAT1A):c.964A>G (p.Ile322Val)	Pathogenic
2742248	NC_000010.11:g.80275200del	Pathogenic
279845	NM_000429.3(MAT1A):c.776C>T (p.Ala259Val)	Pathogenic
2836833	NM_000429.3(MAT1A):c.355C>T (p.Gln119Ter)	Pathogenic
2839010	NM_000429.3(MAT1A):c.260T>A (p.Ile87Asn)	Pathogenic
2841978	NM_000429.3(MAT1A):c.768+2T>A	Pathogenic
285974	NM_000429.3(MAT1A):c.596G>A (p.Arg199His)	Pathogenic
3656125	NM_000429.3(MAT1A):c.456del (p.Thr153fs)	Pathogenic
3692299	NM_000429.3(MAT1A):c.875G>T (p.Arg292Leu)	Pathogenic
4767583	NM_000429.3(MAT1A):c.821G>A (p.Trp274Ter)	Pathogenic
503624	NM_000429.3(MAT1A):c.524G>A (p.Trp175Ter)	Pathogenic
578314	NM_000429.3(MAT1A):c.773A>T (p.Asp258Val)	Pathogenic
834512	NM_000429.3(MAT1A):c.1066C>T (p.Arg356Trp)	Pathogenic
871406	NM_000429.3(MAT1A):c.1132G>A (p.Gly378Ser)	Pathogenic
977208	NM_000429.3(MAT1A):c.538_539insTG (p.Ser180fs)	Pathogenic
2047221	NM_000429.3(MAT1A):c.293-2A>G	Likely pathogenic
2201097	NM_000429.3(MAT1A):c.769G>A (p.Gly257Arg)	Likely pathogenic
2430231	NM_000429.3(MAT1A):c.623A>C (p.Gln208Pro)	Likely pathogenic
3255557	NC_000010.11:g.80274654del	Likely pathogenic

SpliceAI

1532 predictions. Top by Δscore:

Variant	Effect	Δscore
10:80273795:T:TA	donor_gain	1.0000
10:80273807:C:A	donor_gain	1.0000
10:80273894:A:T	acceptor_gain	1.0000
10:80275011:GCTTA:G	donor_loss	1.0000
10:80275012:CTTA:C	donor_loss	1.0000
10:80275013:TTAC:T	donor_loss	1.0000
10:80275014:TA:T	donor_loss	1.0000
10:80275015:ACCT:A	donor_loss	1.0000
10:80275016:C:A	donor_loss	1.0000
10:80275196:CCCC:C	acceptor_gain	1.0000
10:80275197:CCCC:C	acceptor_gain	1.0000
10:80276385:T:TA	donor_gain	1.0000
10:80280167:GCTCA:G	donor_loss	1.0000
10:80280168:CTCAC:C	donor_loss	1.0000
10:80280169:TCACC:T	donor_loss	1.0000
10:80280170:CACCT:C	donor_loss	1.0000
10:80280171:ACCT:A	donor_loss	1.0000
10:80280172:C:G	donor_loss	1.0000
10:80280314:ACCC:A	acceptor_loss	1.0000
10:80280315:CC:C	acceptor_gain	1.0000
10:80280316:CC:C	acceptor_gain	1.0000
10:80280317:C:CA	acceptor_loss	1.0000
10:80280318:T:A	acceptor_loss	1.0000
10:80280392:C:CA	donor_gain	1.0000
10:80283914:AC:A	donor_gain	1.0000
10:80283915:CC:C	donor_gain	1.0000
10:80284034:TGTCT:T	acceptor_gain	1.0000
10:80284035:GTCT:G	acceptor_gain	1.0000
10:80284037:CT:C	acceptor_gain	1.0000
10:80284039:C:CC	acceptor_gain	1.0000

AlphaMissense

2589 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:80285579:A:C	C34W	1.000
10:80273810:A:G	W387R	0.999
10:80273810:A:T	W387R	0.999
10:80275117:C:A	G284V	0.999
10:80275117:C:T	G284E	0.999
10:80275118:C:A	G284W	0.999
10:80275162:T:A	D269V	0.999
10:80275177:C:G	R264P	0.999
10:80275178:G:T	R264S	0.999
10:80275180:C:A	G263V	0.999
10:80275180:C:T	G263D	0.999
10:80275189:C:T	G260D	0.999
10:80275194:A:C	D258E	0.999
10:80275194:A:T	D258E	0.999
10:80275195:T:A	D258V	0.999
10:80276394:A:C	F250L	0.999
10:80276394:A:T	F250L	0.999
10:80276396:A:G	F250L	0.999
10:80280179:C:A	K181N	0.999
10:80280179:C:G	K181N	0.999
10:80285577:T:A	D35V	0.999
10:80285578:C:G	D35H	0.999
10:80285580:C:T	C34Y	0.999
10:80275096:T:A	D291V	0.998
10:80275135:C:T	G278D	0.998
10:80275163:C:G	D269H	0.998
10:80275173:C:A	K265N	0.998
10:80275173:C:G	K265N	0.998
10:80275175:T:C	K265E	0.998
10:80275181:C:G	G263R	0.998

dbSNP variants (sampled 300 via entrez): RS1000135320 (10:80284260 T>A,G), RS1000173503 (10:80275285 T>C), RS1000228196 (10:80275699 C>T), RS1000288065 (10:80274997 G>A,T), RS1000497729 (10:80274167 C>T), RS1001079239 (10:80279973 A>G), RS1001094727 (10:80282963 A>C), RS1001161328 (10:80276920 G>A), RS1001185428 (10:80273945 C>G,T), RS1001424347 (10:80286121 G>A,T), RS1001480534 (10:80288947 C>G), RS1001530283 (10:80279710 A>G), RS1001824098 (10:80287558 G>A), RS1001847380 (10:80287904 C>T), RS1002129904 (10:80280992 T>C)

Disease associations

OMIM: gene MIM:610550 | disease phenotypes: MIM:250850

GenCC curated gene-disease

Disease	Classification	Inheritance
methionine adenosyltransferase deficiency	Definitive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
methionine adenosyltransferase deficiency	Definitive	AR

Mondo (1): methionine adenosyltransferase deficiency (MONDO:0009607)

Orphanet (1): Methionine adenosyltransferase I/III deficiency (Orphanet:168598)

HPO phenotypes

9 total (9 of 9 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0001249	Intellectual disability
HP:0001332	Dystonia
HP:0001347	Hyperreflexia
HP:0003235	Hypermethioninemia
HP:0007305	CNS demyelination
HP:0011096	Peripheral demyelination
HP:0100812	Halitosis

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST003098_8	Diabetic kidney disease	9.000000e-07

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5169142 (SINGLE PROTEIN)

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

ChEMBL bioactivities

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

pChembl	Type	Value	Unit	Molecule
6.09	IC50	813	nM	CHEMBL5427280

PubChem BioAssay actives

1 with measured affinity, of 9 total; 1 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
7-chloro-4-[(3R)-3-fluoropyrrolidin-1-yl]-1-phenylquinazolin-2-one	2012575: Inhibition of human MAT1A	ic50	0.8130	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Aflatoxin B1	affects expression, decreases expression	5
Tetrachlorodibenzodioxin	increases expression	3
Cyclosporine	decreases expression, increases expression	3
bisphenol A	decreases expression, increases methylation	2
Benzo(a)pyrene	affects methylation, decreases expression, decreases methylation	2
Estradiol	decreases expression, increases expression	2
Methyl Methanesulfonate	decreases expression, increases expression	2
2,4,6-tribromophenol	decreases expression	1
methyleugenol	decreases expression	1
propionaldehyde	decreases expression	1
decabromobiphenyl ether	decreases expression	1
ethyl-p-hydroxybenzoate	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	decreases expression	1
butyraldehyde	decreases expression	1
tetrabromobisphenol A	decreases expression	1
periodate-oxidized adenosine	affects expression	1
perfluoro-n-nonanoic acid	increases expression	1
K 7174	decreases expression	1
perfluorohexanesulfonic acid	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
Panobinostat	affects cotreatment, affects expression	1
Acetaminophen	decreases expression	1
Arsenic	affects methylation	1
Carmustine	decreases expression	1
Cisplatin	affects cotreatment, affects expression	1
Ethyl Methanesulfonate	increases expression	1
Isoniazid	decreases expression	1

ChEMBL screening assays

4 unique, capped per target: 4 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5141065	Binding	Inhibition of N-terminal TEV cleavable 6His-tagged human MAT1A (1 to 334 residues) expressed in Escherichia coli BL21 (DE3) cells assessed as S-adenosyl methionine production using L-methionine as substrate incubated for 30 mins followed by	Overview of Methionine Adenosyltransferase 2A (MAT2A) as an Anticancer Target: Structure, Function, and Inhibitors. — J Med Chem

Cellosaurus cell lines

4 cell lines: 3 cancer cell line, 1 finite cell line

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

Cellosaurus	Name	Category	Sex
CVCL_4T28	GM00911	Finite cell line	Male
CVCL_D1NR	Abcam K-562 MAT1A KO	Cancer cell line	Female
CVCL_D2KC	Abcam Raji MAT1A KO	Cancer cell line	Male
CVCL_UQ93	Abcam Jurkat MAT1A KO	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00006061	Not specified	COMPLETED	Study of Phosphatidylcholine in a Patient With Methionine Adenosyltransferase Deficiency