MAT2B

Summary

MAT2B (methionine adenosyltransferase 2 non-catalytic beta subunit, HGNC:6905) is a protein-coding gene on chromosome 5q34, encoding Methionine adenosyltransferase 2 subunit beta (Q9NZL9). Regulatory subunit of S-adenosylmethionine synthetase 2, an enzyme that catalyzes the formation of S-adenosylmethionine from methionine and ATP.

The protein encoded by this gene belongs to the methionine adenosyltransferase (MAT) family. MAT catalyzes the biosynthesis of S-adenosylmethionine from methionine and ATP. This protein is the regulatory beta subunit of MAT. Alternative splicing results in multiple transcript variants encoding different isoforms.

Source: NCBI Gene 27430 — RefSeq curated summary.

At a glance

• GWAS associations: 16
• Clinical variants (ClinVar): 54 total
• Druggable target: yes
• MANE Select transcript: NM_013283

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6905
Approved symbol	MAT2B
Name	methionine adenosyltransferase 2 non-catalytic beta subunit
Location	5q34
Locus type	gene with protein product
Status	Approved
Aliases	MATIIbeta, SDR23E1
Ensembl gene	ENSG00000038274
Ensembl biotype	protein_coding
OMIM	605527
Entrez	27430

Gene structure

Transcript identifiers

Ensembl transcripts: 35 — 19 protein_coding, 11 retained_intron, 4 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000280969, ENST00000321757, ENST00000421814, ENST00000518095, ENST00000519719, ENST00000520449, ENST00000523606, ENST00000694938, ENST00000694939, ENST00000694940, ENST00000694941, ENST00000694942, ENST00000694943, ENST00000694944, ENST00000694945, ENST00000694946, ENST00000694947, ENST00000694952, ENST00000694953, ENST00000694954, ENST00000694955, ENST00000695023, ENST00000695024, ENST00000695025, ENST00000695026, ENST00000695027, ENST00000695028, ENST00000695029, ENST00000695030, ENST00000695031, ENST00000695032, ENST00000695033, ENST00000695034, ENST00000891311, ENST00000911813

RefSeq mRNA: 2 — MANE Select: NM_013283 NM_013283, NM_182796

CCDS: CCDS4364, CCDS4365

Canonical transcript exons

ENST00000321757 — 7 exons

Exon	Start	End
ENSE00001132174	163513555	163513669
ENSE00001223544	163512002	163512196
ENSE00001923790	163505619	163505749
ENSE00002137078	163517561	163517674
ENSE00003570632	163518193	163519354
ENSE00003585966	163516518	163516711
ENSE00003690485	163513842	163513994

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 99.34.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 53.1985 / max 435.9345, expressed in 1817 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
59978	41.8960	1815
59976	6.7811	1426
59975	2.7719	1036
59974	1.1975	685
59980	0.2363	82
59979	0.2048	78
59973	0.1109	43

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	99.34	gold quality
germinal epithelium of ovary	UBERON:0001304	98.44	gold quality
ventricular zone	UBERON:0003053	98.29	gold quality
mucosa of sigmoid colon	UBERON:0004993	98.20	gold quality
corpus epididymis	UBERON:0004359	98.16	gold quality
palpebral conjunctiva	UBERON:0001812	98.12	gold quality
oocyte	CL:0000023	98.04	gold quality
caput epididymis	UBERON:0004358	98.02	gold quality
colonic mucosa	UBERON:0000317	97.89	gold quality
trabecular bone tissue	UBERON:0002483	97.70	gold quality
leukocyte	CL:0000738	97.55	gold quality
mononuclear cell	CL:0000842	97.53	gold quality
heart right ventricle	UBERON:0002080	97.50	gold quality
monocyte	CL:0000576	97.49	gold quality
ileal mucosa	UBERON:0000331	97.47	gold quality
cartilage tissue	UBERON:0002418	97.42	gold quality
adult organism	UBERON:0007023	97.42	gold quality
upper leg skin	UBERON:0004262	97.39	gold quality
lymph node	UBERON:0000029	97.37	gold quality
eye	UBERON:0000970	97.36	gold quality
nephron tubule	UBERON:0001231	97.36	gold quality
skin of hip	UBERON:0001554	97.31	gold quality
jejunal mucosa	UBERON:0000399	97.28	gold quality
cardiac muscle of right atrium	UBERON:0003379	97.24	gold quality
myocardium	UBERON:0002349	97.09	gold quality
duodenum	UBERON:0002114	96.99	gold quality
rectum	UBERON:0001052	96.97	gold quality
esophagus squamous epithelium	UBERON:0006920	96.97	gold quality
left ventricle myocardium	UBERON:0006566	96.94	gold quality
cauda epididymis	UBERON:0004360	96.86	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-7606	no	568.03
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): SP1, SP3

miRNA regulators (miRDB)

104 targeting MAT2B, 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-4795-3P	100.00	74.62	4024
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-3064-3P	100.00	70.09	1254
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-454-3P	99.91	74.01	1925
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-130A-3P	99.90	73.31	1861
HSA-MIR-130B-3P	99.90	73.27	1850
HSA-MIR-301A-3P	99.90	73.15	1839
HSA-MIR-301B-3P	99.90	73.19	1836

Literature-anchored findings (GeneRIF, showing 19)

• Lower expression of both MAT2A and MAT2beta and interfere with leptin signaling in liver cancer cells. (PMID:18041713)
• Splicing variants of MAT2beta are up-regulated in hepatocellular carcinoma and regulated tumor cell growth and death. (PMID:18045590)
• a switch in MAT expression in liver cancer was accompanied by increasing expression of MAT2B (PMID:18698677)
• differences in malignant cell survival, effected by MAT-IIbeta ablation, suggest that it may be possible to use this approach to disadvantage leukemic cell survival in vivo with little to no harm to normal cells. (PMID:18753136)
• Data show MAT2beta variants reside mostly in the nucleus and regulate HuR subcellular content to affect cell proliferation. (PMID:20421296)
• Coexpression of MAT2A and MAT2B in COS-1 cells resulted in significantly increased MAT enzyme activity. (PMID:21813468)
• MAT2B and GIT1 form a scaffold, which recruits and activates MEK and ERK to promote growth and tumorigenesis. (PMID:23325601)
• The structure of MAT2B reveals a short-chain dehydrogenase/reductase (SDR) core with specificity for the NADP/H cofactor, and harbors the SDR catalytic triad. (PMID:23425511)
• resveratrol induces HuR, SIRT1, and MAT2B expression; the last may represent a compensatory response against apoptosis and growth inhibition. (PMID:23814050)
• Mutagenesis of MATalpha2 and MATbeta phospho-sites destabilized them and prevented hepatic stellate cell trans-differentiation. (PMID:25294683)
• Interaction between MAT2B and GIT1 serves as a scaffold and facilitates signaling in multiple steps of the Ras/Raf/MEK/ERK pathway (PMID:25794709)
• Results show that MAT2B expression is frequently upregulated in malignant melanoma tissues. MAT2B downregulation delays tumor growth in vivo, and suppressed cell growth, colony formation ability and induced apoptosis in vitro indicating that MAT2B is critical for melanoma cell proliferation and tumorigenicity. (PMID:27573889)
• This study showed that variant upstream of MAT2B whose association is prominent in back, hip, knee, and neck pain-provides preliminary evidence of shared contributing mechanisms at the genetic-molecular level. (PMID:29240606)
• 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)
• MAT2B was markedly increased in osteosarcoma (OS) specimens compared with the normal bone tissues, and it was additionally abundantly expressed in OS cell lines. Inhibition of MAT2B expression caused a marked decrease in proliferation and significant increase in apoptosis. Results demonstrated that MAT2B functions as a tumor oncogene in OS in vivo and in vitro via regulation of EGFR and PCNA. (PMID:30942439)
• Results found that MAT2B was overexpressed in hepatocellular carcinoma (HCC) tissues and correlated with poor prognosis for HCC patients. Its silencing could suppress liver cancer cell migration and invasion through the inhibition of EGFR signaling, which suggested that MAT2B might serve as a new prognostic marker for HCC. (PMID:31493275)
• lncMat2B regulated by severe hypoxia induces cisplatin resistance by increasing DNA damage repair and tumor-initiating population in breast cancer cells. (PMID:32710610)
• Human Mat2A Uses an Ordered Kinetic Mechanism and Is Stabilized but Not Regulated by Mat2B. (PMID:34780697)
• CircMAT2B facilitates the progression of head and neck squamous cell carcinoma via sponging miR-491-5p to trigger ASCT2-mediated glutaminolysis. (PMID:36219356)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	mat2b	ENSDARG00000012932
mus_musculus	Mat2b	ENSMUSG00000042032
rattus_norvegicus	Mat2b	ENSRNOG00000003177

Protein

Protein identifiers

Methionine adenosyltransferase 2 subunit beta — Q9NZL9 (reviewed: Q9NZL9)

Alternative names: Methionine adenosyltransferase II beta, Putative dTDP-4-keto-6-deoxy-D-glucose 4-reductase

All UniProt accessions (12): A0A140VJP2, A0A8Q3SIE5, A0A8Q3WK74, A0A8Q3WK80, A0A8Q3WK84, A0A8Q3WK93, A0A8Q3WKR9, A0A8Q3WLC0, A0A8Q3WLP1, E5RJR3, H7C0X7, Q9NZL9

UniProt curated annotations — full annotation on UniProt →

Function. Regulatory subunit of S-adenosylmethionine synthetase 2, an enzyme that catalyzes the formation of S-adenosylmethionine from methionine and ATP. Regulates MAT2A catalytic activity by changing its kinetic properties, increasing its affinity for L-methionine. Can bind NADP (in vitro).

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. NADP binding increases the affinity for MAT2A.

Tissue specificity. Widely expressed.

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

Miscellaneous. Its expression in hepatoma cell lines may lead to increase DNA synthesis and thereby participate in cell proliferation.

Similarity. Belongs to the dTDP-4-dehydrorhamnose reductase family. MAT2B subfamily.

Isoforms (5)

UniProt ID	Names	Canonical?
Q9NZL9-1	1	yes
Q9NZL9-2	2
Q9NZL9-3	3
Q9NZL9-4	4
Q9NZL9-5	5

RefSeq proteins (2): NP_037415, NP_877725 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR005913	RmlD	Family
IPR029903	RmlD-like-bd	Domain
IPR036291	NAD(P)-bd_dom_sf	Homologous_superfamily

Pfam: PF04321

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

UniProt features (56 total): helix 16, strand 14, splice variant 7, binding site 7, turn 5, sequence conflict 2, initiator methionine 1, chain 1, modified residue 1, sequence variant 1, region of interest 1

Structure

Experimental structures (PDB)

9 structures.

PDB	Method	Resolution (Å)
2YDY	X-RAY DIFFRACTION	2.25
4NDN	X-RAY DIFFRACTION	2.34
4KTT	X-RAY DIFFRACTION	2.59
9QPO	ELECTRON MICROSCOPY	2.6
9QPP	ELECTRON MICROSCOPY	2.6
2YDX	X-RAY DIFFRACTION	2.8
30GD	ELECTRON MICROSCOPY	2.9
30GH	ELECTRON MICROSCOPY	3.1
4KTV	X-RAY DIFFRACTION	3.3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NZL9-F1	93.82	0.83

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 (7): 37–40; 60–62; 71–72; 93; 97; 159; 185

Post-translational modifications (1): 309

Function

Pathways and Gene Ontology

Reactome pathways

8 pathways

ID	Pathway
R-HSA-156581	Methylation
R-HSA-5689880	Ub-specific processing proteases
R-HSA-1430728	Metabolism
R-HSA-156580	Phase II - Conjugation of compounds
R-HSA-211859	Biological oxidations
R-HSA-392499	Metabolism of proteins
R-HSA-5688426	Deubiquitination
R-HSA-597592	Post-translational protein modification

MSigDB gene sets: 182 (showing top): LIANG_HEMATOPOIESIS_STEM_CELL_NUMBER_SMALL_VS_HUGE_UP, TAATAAT_MIR126, REACTOME_BIOLOGICAL_OXIDATIONS, KEGG_CYSTEINE_AND_METHIONINE_METABOLISM, JOHANSSON_GLIOMAGENESIS_BY_PDGFB_DN, KOKKINAKIS_METHIONINE_DEPRIVATION_96HR_UP, JOHANSSON_BRAIN_CANCER_EARLY_VS_LATE_DN, GOBP_SULFUR_COMPOUND_BIOSYNTHETIC_PROCESS, GOBP_S_ADENOSYLMETHIONINE_METABOLIC_PROCESS, GOBP_ONE_CARBON_METABOLIC_PROCESS, KOKKINAKIS_METHIONINE_DEPRIVATION_48HR_UP, ACTTTAT_MIR1425P, DANG_BOUND_BY_MYC, GOCC_TRANSFERASE_COMPLEX, MARSON_BOUND_BY_FOXP3_STIMULATED

GO Biological Process (2): S-adenosylmethionine biosynthetic process (GO:0006556), one-carbon metabolic process (GO:0006730)

GO Molecular Function (5): enzyme binding (GO:0019899), enzyme regulator activity (GO:0030234), methionine adenosyltransferase regulator activity (GO:0048270), protein binding (GO:0005515), transferase activity (GO:0016740)

GO Cellular Component (4): nucleus (GO:0005634), cytosol (GO:0005829), methionine adenosyltransferase complex (GO:0048269), extracellular exosome (GO:0070062)

Reactome top-level categories

Rollup of top-6 pathways:

Category	Pathways
Phase II - Conjugation of compounds	1
Deubiquitination	1
Biological oxidations	1
Metabolism	1
Post-translational protein modification	1
Metabolism of proteins	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
catalytic activity	2
sulfur compound biosynthetic process	1
S-adenosylmethionine metabolic process	1
small molecule metabolic process	1
protein binding	1
molecular function regulator activity	1
methionine adenosyltransferase activity	1
enzyme regulator activity	1
binding	1
intracellular membrane-bounded organelle	1
cytoplasm	1
cellular anatomical structure	1
intracellular protein-containing complex	1
transferase complex	1
extracellular vesicle	1

Protein interactions and networks

STRING

3076 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MAT2B	MAT2A	P31153	992
MAT2B	MAT1A	Q00266	746
MAT2B	BHMT	Q93088	638
MAT2B	GNMT	Q14749	635
MAT2B	AHCY	P23526	545
MAT2B	ACTL6A	O96019	530
MAT2B	MTR	Q99707	515
MAT2B	CHD4	Q14839	495
MAT2B	SHMT1	P34896	476
MAT2B	BHMT2	Q9H2M3	475
MAT2B	MTRR	Q9UBK8	468
MAT2B	AHCYL1	O43865	463
MAT2B	MTHFR	P42898	458
MAT2B	GIT1	Q9Y2X7	446
MAT2B	SHMT2	P34897	443

IntAct

46 interactions, top by confidence:

A	B	Type	Score
MAT1A	MAT2A	psi-mi:“MI:0914”(association)	0.800
rep	GTF2F2	psi-mi:“MI:0914”(association)	0.730
MAT2B	KPNA3	psi-mi:“MI:0915”(physical association)	0.720
KPNA3	MAT2B	psi-mi:“MI:0915”(physical association)	0.720
MAT2A	MAT2B	psi-mi:“MI:0915”(physical association)	0.680
MAT2B	MAT2A	psi-mi:“MI:0915”(physical association)	0.680
MAT2B	rep	psi-mi:“MI:0915”(physical association)	0.660
KPNA4	MAT2B	psi-mi:“MI:0915”(physical association)	0.560
MAT2B	TRIM27	psi-mi:“MI:0915”(physical association)	0.560
TRIM27	MAT2B	psi-mi:“MI:0915”(physical association)	0.560
RABEP1	MAT2B	psi-mi:“MI:0915”(physical association)	0.560
PLA2G6	MAT2B	psi-mi:“MI:0915”(physical association)	0.560
TEPSIN	MAT2B	psi-mi:“MI:0915”(physical association)	0.560
HSCB	NDUFS8	psi-mi:“MI:0914”(association)	0.460
MAT2B	HRH1	psi-mi:“MI:0915”(physical association)	0.370
ORF69	PEPD	psi-mi:“MI:0914”(association)	0.350
PRNP	WDR91	psi-mi:“MI:0914”(association)	0.350
SH3GL3	HMGB1P1	psi-mi:“MI:0914”(association)	0.350
PRKD1	MYO1C	psi-mi:“MI:0914”(association)	0.350

BioGRID (137): MAT2B (Two-hybrid), MAT2B (Two-hybrid), MAT2B (Two-hybrid), MAT2B (Two-hybrid), MAT2A (Affinity Capture-MS), MAT2B (Affinity Capture-MS), GALE (Co-fractionation), GMDS (Co-fractionation), MAT2A (Co-fractionation), SEPHS1 (Co-fractionation), TSTA3 (Co-fractionation), XPO1 (Co-fractionation), MAT2A (Two-hybrid), MAT2B (Affinity Capture-MS), MAT2B (Reconstituted Complex)

ESM2 similar proteins: A2Z7B3, A3C4S4, A8Y0L5, B0M3E8, H9BFW7, O14172, O45583, O60547, O65780, O65781, P87228, P93031, Q0E671, Q0P8I7, Q18801, Q29RI9, Q2R1V8, Q3SZM5, Q43070, Q4QQZ4, Q553X7, Q566L8, Q5BJJ6, Q5R4E0, Q5R6R5, Q5U2R0, Q6DIQ1, Q6K2E1, Q6ZDJ7, Q84MD8, Q8K0C9, Q8K3X3, Q8LDN8, Q8LNZ3, Q8NFW8, Q8VDR7, Q91WT9, Q93VR3, Q99KK2, Q99LB6

Diamond homologs: A0QSK6, A0QTF8, D4GP33, D4GU71, E5F146, O66251, P26392, P29781, P37760, P37778, P39631, P55463, P9WH08, P9WH09, P9WN64, P9WN65, Q29RI9, Q2SYI1, Q46769, Q5R4E0, Q5U2R0, Q8PDW5, Q99LB6, Q9L9E9, Q9NZL9, Q9RR27, A3N308, A5UIN9, B0BSD7, B3GYT6, B4F132, P45048, Q4QLI0, Q4QQZ4, Q566L8, Q5BJJ6, Q9L9E8, A0R5C5

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
MAT2B	up-regulates	Proliferation
MAT2B	down-regulates	Apoptosis
MAT2B	“up-regulates activity”	GIT1	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	37
Likely benign	0
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

897 predictions. Top by Δscore:

Variant	Effect	Δscore
5:163505755:G:GT	donor_gain	1.0000
5:163513837:T:TA	acceptor_gain	1.0000
5:163513840:A:AG	acceptor_gain	1.0000
5:163513840:AGCT:A	acceptor_gain	1.0000
5:163513841:G:GA	acceptor_gain	1.0000
5:163513841:GC:G	acceptor_gain	1.0000
5:163513841:GCT:G	acceptor_gain	1.0000
5:163513841:GCTG:G	acceptor_gain	1.0000
5:163513841:GCTGC:G	acceptor_gain	1.0000
5:163513990:TCTAG:T	donor_gain	1.0000
5:163513992:TAG:T	donor_gain	1.0000
5:163513992:TAGGT:T	donor_loss	1.0000
5:163513993:AG:A	donor_gain	1.0000
5:163513993:AGGT:A	donor_loss	1.0000
5:163513994:GG:G	donor_gain	1.0000
5:163513994:GGTAA:G	donor_loss	1.0000
5:163513995:G:C	donor_loss	1.0000
5:163513995:G:GG	donor_gain	1.0000
5:163513996:T:A	donor_loss	1.0000
5:163516506:A:AG	acceptor_gain	1.0000
5:163516507:T:G	acceptor_gain	1.0000
5:163516513:TCTAG:T	acceptor_loss	1.0000
5:163516515:TA:T	acceptor_loss	1.0000
5:163516516:A:AG	acceptor_gain	1.0000
5:163516516:A:G	acceptor_loss	1.0000
5:163516516:AG:A	acceptor_gain	1.0000
5:163516517:G:GT	acceptor_gain	1.0000
5:163516517:GG:G	acceptor_gain	1.0000
5:163516517:GGA:G	acceptor_gain	1.0000
5:163516517:GGAGC:G	acceptor_gain	1.0000

AlphaMissense

2205 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:163512060:G:A	G41D	0.999
5:163513575:T:G	C93W	0.999
5:163513871:A:C	S135R	0.999
5:163513873:C:A	S135R	0.999
5:163513873:C:G	S135R	0.999
5:163513886:T:C	F140L	0.999
5:163513888:T:A	F140L	0.999
5:163513888:T:G	F140L	0.999
5:163513947:G:A	G160D	0.999
5:163513957:A:C	K163N	0.999
5:163513957:A:T	K163N	0.999
5:163516533:G:T	R181M	0.999
5:163512042:G:A	G35D	0.998
5:163512051:G:A	G38E	0.998
5:163513565:T:A	I90K	0.998
5:163513574:G:A	C93Y	0.998
5:163513893:G:A	G142E	0.998
5:163513893:G:T	G142V	0.998
5:163513947:G:T	G160V	0.998
5:163513956:A:T	K163I	0.998
5:163516533:G:C	R181T	0.998
5:163516574:A:C	S195R	0.998
5:163516576:T:A	S195R	0.998
5:163516576:T:G	S195R	0.998
5:163516682:T:C	C231R	0.998
5:163516692:T:C	L234P	0.998
5:163517588:T:A	W250R	0.998
5:163517588:T:C	W250R	0.998
5:163517667:T:C	L276S	0.998
5:163512036:T:A	V33D	0.997

dbSNP variants (sampled 300 via entrez): RS1000078228 (5:163509954 C>G), RS1000091216 (5:163501838 T>C), RS1000183993 (5:163501092 T>A), RS1000314529 (5:163519175 T>A), RS1000324252 (5:163507773 A>G), RS1000612568 (5:163519715 A>C), RS1000623687 (5:163519834 C>T), RS1000667501 (5:163510982 C>T), RS1000914662 (5:163512971 G>A), RS1001236313 (5:163511605 A>C,G), RS1001349065 (5:163506437 GC>G,GCC), RS1001643302 (5:163506814 G>A), RS1001739309 (5:163519400 G>A,C,T), RS1001855508 (5:163519028 G>C), RS1002494763 (5:163502046 T>A)

Disease associations

OMIM: gene MIM:605527 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

16 associations (top):

Study	Trait	p-value
GCST001178_16	Plasma omega-3 polyunsaturated fatty acid level (eicosapentaenoic acid)	8.000000e-08
GCST001599_1	Aging	1.000000e-06
GCST002337_35	Amyotrophic lateral sclerosis (sporadic)	2.000000e-06
GCST002396_23	Smoking initiation	2.000000e-06
GCST002688_1	Very long-chain saturated fatty acid levels (fatty acid 22:0)	6.000000e-06
GCST002689_1	Very long-chain saturated fatty acid levels (fatty acid 24:0)	9.000000e-07
GCST003963_2	Possible neuropathic pain in post total joint replacement surgery for osteoarthritis	5.000000e-06
GCST004136_20	Methadone dose in opioid dependence	4.000000e-06
GCST005183_6	Common carotid intima-media thickness	5.000000e-06
GCST006618_1	Uterine fibroid size (maximum dimension)	2.000000e-09
GCST007254_2	Broad depression or major depressive disorder (self-reported)	8.000000e-16
GCST007325_178	General risk tolerance (MTAG)	1.000000e-08
GCST007326_48	Number of sexual partners	2.000000e-09
GCST007576_176	Chronotype	6.000000e-10
GCST008829_8	Neuritic plaque	6.000000e-06
GCST90000047_110	Age at first sexual intercourse	7.000000e-09

EFO canonical traits (11, from GWAS)

EFO ID	Trait name
EFO:0007760	eicosapentaenoic acid measurement
EFO:0022597	aging
EFO:0005670	smoking initiation
EFO:0006796	very long-chain saturated fatty acid measurement
EFO:0005762	neuropathic pain
EFO:0007907	methadone dose measurement
EFO:0009410	uterine fibroid measurement
EFO:0008579	risk-taking behaviour
EFO:0008328	chronotype measurement
EFO:0006798	neuritic plaque measurement
EFO:0009749	age at first sexual intercourse measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067225 (SINGLE PROTEIN)

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

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.28	Kd	52.64	nM	CHEMBL5653589
7.04	ED50	90.29	nM	CHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 2 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
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148723: Binding affinity to human MAT2B incubated for 45 mins by Kinobead based pull down assay	kd	0.0526	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Resveratrol	decreases reaction, increases expression, affects binding, affects cotreatment, increases reaction (+1 more)	2
Air Pollutants	affects cotreatment, increases abundance, increases oxidation, affects expression	2
Ozone	increases abundance, affects expression, affects cotreatment, increases oxidation	2
Valproic Acid	affects expression, decreases expression	2
Cadmium Chloride	decreases reaction, increases abundance, increases palmitoylation, decreases expression	2
Particulate Matter	decreases expression, increases abundance, affects cotreatment	2
dicrotophos	decreases expression	1
bismuth tripotassium dicitrate	increases expression	1
alpha-pinene	increases abundance, affects cotreatment, increases oxidation	1
uranyl acetate	affects expression	1
bisphenol A	decreases expression	1
decabromobiphenyl ether	increases expression	1
sodium arsenite	decreases expression	1
butyraldehyde	decreases expression	1
tetrabromobisphenol A	decreases expression	1
2-bromopalmitate	decreases reaction, increases abundance, increases palmitoylation	1
manganese chloride	increases abundance, increases expression	1
4-aminophenylarsenoxide	affects binding, decreases reaction	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
isobutyl alcohol	affects cotreatment, decreases expression, increases abundance	1
beta-methylcholine	affects expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression, affects cotreatment	1
nutlin 3	affects cotreatment, increases secretion	1
ICG 001	increases expression	1
pentabrominated diphenyl ether 100	increases expression	1
LDN 193189	affects cotreatment, increases expression	1
bisphenol AF	increases expression	1
Arsenic Trioxide	affects binding, decreases reaction	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5651765	Binding	Binding affinity to human MAT2B incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Cellosaurus cell lines

5 cell lines: 4 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B3AU	Abcam HEK293T MAT2B KO	Transformed cell line	Female
CVCL_SX30	HAP1 MAT2B (-) 1	Cancer cell line	Male
CVCL_SX31	HAP1 MAT2B (-) 2	Cancer cell line	Male
CVCL_SX32	HAP1 MAT2B (-) 3	Cancer cell line	Male
CVCL_SX33	HAP1 MAT2B (-) 4	Cancer cell line	Male

Clinical trials (associated diseases)

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