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METTL2B

gene
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Also known as METLFLJ11350

Summary

METTL2B (methyltransferase 2B, tRNA N3-cytidine, HGNC:18272) is a protein-coding gene on chromosome 7q32.1, encoding tRNA N(3)-cytidine methyltransferase METTL2B (Q6P1Q9). S-adenosyl-L-methionine-dependent methyltransferase that mediates N(3)-methylcytidine modification of residue 32 of the tRNA anticodon loop of tRNA(Thr)(UGU) and tRNA(Arg)(CCU).

This gene is a member of a family of methyltransferases that share homology with, but are distinct from, the UbiE family of methyltransferases. Alternatively spliced variants which encode different protein isoforms have been described; however, not all variants have been fully characterized.

Source: NCBI Gene 55798 — RefSeq curated summary.

At a glance

  • GWAS associations: 2
  • Clinical variants (ClinVar): 64 total
  • MANE Select transcript: NM_018396

Identifiers

Gene identifiers

FieldValue
HGNC IDHGNC:18272
Approved symbolMETTL2B
Namemethyltransferase 2B, tRNA N3-cytidine
Location7q32.1
Locus typegene with protein product
StatusApproved
AliasesMETL, FLJ11350
Ensembl geneENSG00000165055
Ensembl biotypeprotein_coding
OMIM607846
Entrez55798

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 6 protein_coding, 1 protein_coding_CDS_not_defined, 1 retained_intron, 1 nonsense_mediated_decay

ENST00000262432, ENST00000419443, ENST00000473488, ENST00000480046, ENST00000481392, ENST00000482555, ENST00000497665, ENST00000880219, ENST00000930216

RefSeq mRNA: 1 — MANE Select: NM_018396 NM_018396

CCDS: CCDS5803

Canonical transcript exons

ENST00000262432 — 9 exons

ExonStartEnd
ENSE00001417519128476748128476875
ENSE00002522152128477082128477173
ENSE00003492625128500903128500968
ENSE00003500081128493804128493943
ENSE00003538792128498036128498142
ENSE00003702754128479158128479513
ENSE00003704286128488101128488161
ENSE00003711127128480647128480696
ENSE00003899208128501762128506602

Expression profiles

Bgee: expression breadth ubiquitous, 137 present calls, max score 88.86.

FANTOM5 (CAGE): breadth broad, TPM avg 1.0224 / max 20.8486, expressed in 576 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter IDTPM avgSamples expressed
809231.0224576

Top tissues by expression

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

TissueAnatomy IDExpression scoreQuality
colonic epitheliumUBERON:000039788.86gold quality
adrenal tissueUBERON:001830387.36gold quality
cerebellar vermisUBERON:000472085.93silver quality
cortical plateUBERON:000534384.85gold quality
islet of LangerhansUBERON:000000684.79gold quality
quadriceps femorisUBERON:000137784.69silver quality
skeletal muscle tissueUBERON:000113484.55gold quality
primordial germ cell in gonadCL:0000670 ∩ UBERON:000099183.87gold quality
muscle tissueUBERON:000238583.76gold quality
endometriumUBERON:000129583.39gold quality
tonsilUBERON:000237283.34gold quality
stromal cell of endometriumCL:000225583.29gold quality
hindlimb stylopod muscleUBERON:000425282.91gold quality
ganglionic eminenceUBERON:000402382.90gold quality
male germ line stem cell (sensu Vertebrata) in testisCL:0000089 ∩ UBERON:000047382.80gold quality
muscle of legUBERON:000138382.72gold quality
gastrocnemiusUBERON:000138882.72gold quality
ventricular zoneUBERON:000305382.38gold quality
rectumUBERON:000105282.27gold quality
lower esophagus mucosaUBERON:003583481.92gold quality
placentaUBERON:000198781.84gold quality
pancreasUBERON:000126481.80gold quality
esophagus mucosaUBERON:000246981.49gold quality
monocyteCL:000057681.07gold quality
liverUBERON:000210781.07gold quality
leukocyteCL:000073880.92gold quality
lymph nodeUBERON:000002980.89gold quality
mucosa of transverse colonUBERON:000499180.78gold quality
smooth muscle tissueUBERON:000113580.71gold quality
adrenal glandUBERON:000236980.57gold quality

Single-cell (SCXA)

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

ExperimentMarker?Max mean expression
E-ANND-3yes4.46

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): E2F6

miRNA regulators (miRDB)

35 targeting METTL2B, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNAMax scoreAvg scoremiRNA target_count
HSA-MIR-371B-5P99.9975.344759
HSA-MIR-373-5P99.9875.364753
HSA-MIR-616-5P99.9875.584775
HSA-MIR-520D-5P99.9873.344883
HSA-MIR-524-5P99.9873.434882
HSA-MIR-6778-3P99.9667.292693
HSA-MIR-430799.8270.453374
HSA-MIR-4639-5P99.8167.371028
HSA-MIR-187-5P99.7470.261404
HSA-MIR-471999.7372.103329
HSA-MIR-4524A-3P99.7266.852406
HSA-MIR-472999.6972.184233
HSA-MIR-3942-3P99.5769.032854
HSA-MIR-443799.5265.291266
HSA-MIR-57899.4668.361787
HSA-MIR-450599.2767.812678
HSA-MIR-578799.2267.862628
HSA-MIR-6504-3P99.1769.312891
HSA-MIR-4717-3P99.0666.341072
HSA-MIR-7151-3P99.0469.722370
HSA-MIR-6876-3P98.9765.69765
HSA-MIR-939-3P98.9765.072347
HSA-MIR-62698.8966.21762
HSA-MIR-876-3P98.7668.23945
HSA-MIR-38498.7167.341229
HSA-MIR-4680-3P98.6468.602093
HSA-MIR-619-5P98.5764.971988
HSA-MIR-5089-5P98.4566.061388
HSA-MIR-660-3P98.1466.041434
HSA-MIR-427597.9668.421549

Literature-anchored findings (GeneRIF, showing 1)

  • Mutually exclusive substrate selection strategy by human m3C RNA transferases METTL2A and METTL6. (PMID:34268557)

Cross-species orthologs

3 orthologs

OrganismSymbolGene ID
danio_reriomettl2aENSDARG00000008105
mus_musculusMettl2ENSMUSG00000020691
rattus_norvegicusMettl2ENSRNOG00000006131

Paralogs (3): METTL2A (ENSG00000087995), METTL8 (ENSG00000123600), METTL6 (ENSG00000206562)

Protein

Protein identifiers

tRNA N(3)-cytidine methyltransferase METTL2B — Q6P1Q9 (reviewed: Q6P1Q9)

Alternative names: Methyltransferase-like protein 2B

All UniProt accessions (4): Q6P1Q9, F8WAS9, H7C2C8, H7C552

UniProt curated annotations — full annotation on UniProt →

Function. S-adenosyl-L-methionine-dependent methyltransferase that mediates N(3)-methylcytidine modification of residue 32 of the tRNA anticodon loop of tRNA(Thr)(UGU) and tRNA(Arg)(CCU).

Subunit / interactions. Monomer. Interacts with DALRD3.

Subcellular location. Cytoplasm.

Similarity. Belongs to the methyltransferase superfamily. METL family.

Isoforms (2)

UniProt IDNamesCanonical?
Q6P1Q9-11yes
Q6P1Q9-22

RefSeq proteins (1): NP_060866* (*=MANE)

Domains & families (InterPro)

IDNameType
IPR013217Methyltransf_12Domain
IPR026113METTL2/6/8-likeFamily
IPR029063SAM-dependent_MTases_sfHomologous_superfamily

Pfam: PF08242

Enzyme classification (BRENDA):

  • EC 2.1.1.268 — tRNAThr (cytosine32-N3)-methyltransferase (BRENDA: 2 organisms, 31 substrates, 1 inhibitors, 0 Km, 0 kcat entries)
  • EC 2.1.1.B109 — (BRENDA: organisms, substrates, inhibitors, Km, kcat entries)

Catalyzed reactions (Rhea), 2 shown:

  • cytidine(32) in tRNA(Thr) + S-adenosyl-L-methionine = N(3)-methylcytidine(32) in tRNA(Thr) + S-adenosyl-L-homocysteine + H(+) (RHEA:50960)
  • cytidine(32) in tRNA(Arg)(CCU) + S-adenosyl-L-methionine = N(3)-methylcytidine(32) in tRNA(Arg)(CCU) + S-adenosyl-L-homocysteine + H(+) (RHEA:60912)

UniProt features (18 total): binding site 7, sequence variant 5, modified residue 3, initiator methionine 1, chain 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

ModelpLDDTFraction very-high
AF-Q6P1Q9-F182.020.67

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): 78; 82; 188; 213; 239; 240; 260

Post-translational modifications (3): 4, 154, 2

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 105 (showing top): GOBP_TRNA_METABOLIC_PROCESS, GOBP_RNA_METHYLATION, KEGG_HISTIDINE_METABOLISM, GOBP_RNA_MODIFICATION, chr7q32, GOBP_TRNA_METHYLATION, NRF2_Q4, RYTTCCTG_ETS2_B, FISCHER_DREAM_TARGETS, GOBP_METHYLATION, GOBP_TRNA_PROCESSING, GRADE_COLON_AND_RECTAL_CANCER_UP, KEGG_TYROSINE_METABOLISM, GOBP_TRNA_MODIFICATION, GAL_LEUKEMIC_STEM_CELL_UP

GO Biological Process (4): tRNA metabolic process (GO:0006399), tRNA methylation (GO:0030488), tRNA processing (GO:0008033), methylation (GO:0032259)

GO Molecular Function (7): tRNA (cytidine) methyltransferase activity (GO:0016427), tRNA (cytidine-N3)-methyltransferase activity (GO:0052735), protein binding (GO:0005515), methyltransferase activity (GO:0008168), RNA methyltransferase activity (GO:0008173), S-adenosylmethionine-dependent methyltransferase activity (GO:0008757), transferase activity (GO:0016740)

GO Cellular Component (2): cytoplasm (GO:0005737), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

CategoryTerms
methyltransferase activity2
cellular anatomical structure2
RNA metabolic process1
RNA methylation1
tRNA modification1
RNA processing1
tRNA metabolic process1
metabolic process1
tRNA methyltransferase activity1
S-adenosylmethionine-dependent methyltransferase activity1
tRNA (cytidine) methyltransferase activity1
binding1
transferase activity, transferring one-carbon groups1
catalytic activity, acting on RNA1
catalytic activity1
intracellular anatomical structure1

Protein interactions and networks

STRING

1266 interactions, top by confidence (×1000):

Protein AProtein BPartner UniProtScore
METTL2BPSEN2P49810766
METTL2BMETTL25Q8N6Q8756
METTL2BPSEN1P49768747
METTL2BMETTL21CQ5VZV1691
METTL2BMETTL24Q5JXM2654
METTL2BMETTL16Q86W50647
METTL2BMETTL13Q8N6R0647
METTL2BMETTL9Q9H1A3636
METTL2BTMT1BQ6UX53632
METTL2BDALRD3Q5D0E6600
METTL2BEFCAB3Q8N7B9584
METTL2BTRMT10AQ8TBZ6556
METTL2BEEF1AKMT2Q5JPI9529
METTL2BTRMT10BQ6PF06525
METTL2BSARS1P49591493

IntAct

18 interactions, top by confidence:

ABTypeScore
DALRD3METTL2Bpsi-mi:“MI:0915”(physical association)0.500
DALRD3METTL2Bpsi-mi:“MI:0914”(association)0.500
CENPUCENPXpsi-mi:“MI:0914”(association)0.350
LRRK2psi-mi:“MI:0914”(association)0.350
Mpsi-mi:“MI:0914”(association)0.350
BDH2CKS2psi-mi:“MI:0914”(association)0.350
NAT16HSPA8psi-mi:“MI:0914”(association)0.350
YJEFN3HSPA8psi-mi:“MI:0914”(association)0.350
MRPS6DBTpsi-mi:“MI:0914”(association)0.350
MTPNPLCG1psi-mi:“MI:0914”(association)0.350
INSRUBXN8psi-mi:“MI:0914”(association)0.350
METTL2AACACBpsi-mi:“MI:0914”(association)0.350
METTL2BEIF3Fpsi-mi:“MI:0914”(association)0.350
METTL6EIF3Fpsi-mi:“MI:0914”(association)0.350
DALRD3psi-mi:“MI:0914”(association)0.350
METTL2Bpsi-mi:“MI:0914”(association)0.350

BioGRID (37): METTL2B (Co-fractionation), METTL2B (Affinity Capture-MS), METTL2B (Affinity Capture-MS), METTL2B (Affinity Capture-MS), METTL2B (Affinity Capture-MS), METTL2B (Affinity Capture-MS), METTL2B (Affinity Capture-MS), METTL2B (Positive Genetic), METTL2B (Affinity Capture-MS), METTL2B (Affinity Capture-MS), METTL2B (Affinity Capture-MS), METTL2B (Affinity Capture-MS), METTL2B (Affinity Capture-MS), METTL2B (Affinity Capture-MS), METTL2B (Affinity Capture-MS)

ESM2 similar proteins: A0A0R4IB93, A0JMU5, A1A4L5, A2PYH4, A2RUV5, B3M1E1, B3P4N5, B4GZ20, B4HJC0, B4KA23, B4LVS8, B4NKI9, B4PVH6, B4QVW6, B6DMK2, D3Z4R1, O75417, O93530, O94830, Q07G10, Q0P5B2, Q15326, Q28ES8, Q29B63, Q4KLT3, Q4R6F3, Q5M8E6, Q5ZIJ9, Q5ZJM3, Q6GQ76, Q6NRS1, Q6NTR1, Q6P1Q9, Q6ZPR6, Q7ZU90, Q80Y20, Q84MA1, Q8BMK1, Q8BYH3, Q8MNT9

Diamond homologs: A2AUU0, A8KBL7, Q0P5B2, Q5M8E6, Q5ZHP8, Q6P1Q9, Q86BS6, Q8BMK1, Q96IZ6, Q9H825, G0REX6, O74386, Q08641, Q5ATG8, Q5RDV8, Q6AXU8, Q8BVH9, Q8T199, Q8TCB7, Q9P7L6, A0A0C6E0I7, A1JRM2, A4TJK8, A7FID3, A9QYY1, B1JLL8, B2K316, Q1C823, Q1CJH3, Q66AU7, Q7CIB7, A0A1D6NER6, C8YTM5

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

ClassificationCount (floor)
Pathogenic0
Likely pathogenic0
Uncertain significance50
Likely benign1
Benign1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1349 predictions. Top by Δscore:

VariantEffectΔscore
7:128479156:A:AGacceptor_gain1.0000
7:128479156:AGTT:Aacceptor_gain1.0000
7:128479157:G:GGacceptor_gain1.0000
7:128479157:GTT:Gacceptor_gain1.0000
7:128479157:GTTG:Gacceptor_gain1.0000
7:128479511:G:GTdonor_gain1.0000
7:128480547:T:Gdonor_gain1.0000
7:128480697:G:GGdonor_gain1.0000
7:128493889:G:Tdonor_gain1.0000
7:128493939:GACAA:Gdonor_gain1.0000
7:128498031:CACA:Cacceptor_loss1.0000
7:128498034:A:AGacceptor_gain1.0000
7:128498034:AG:Aacceptor_gain1.0000
7:128498035:G:GAacceptor_gain1.0000
7:128498035:G:GCacceptor_loss1.0000
7:128498035:GG:Gacceptor_gain1.0000
7:128498035:GGAT:Gacceptor_gain1.0000
7:128498138:AAAAG:Adonor_loss1.0000
7:128498139:AAAG:Adonor_loss1.0000
7:128498140:AAGG:Adonor_loss1.0000
7:128498141:AGG:Adonor_loss1.0000
7:128498142:GGTAT:Gdonor_loss1.0000
7:128498143:G:Tdonor_loss1.0000
7:128498144:T:Adonor_loss1.0000
7:128501755:A:AGacceptor_gain1.0000
7:128501756:C:Gacceptor_gain1.0000
7:128501757:A:AGacceptor_gain1.0000
7:128501758:C:Gacceptor_gain1.0000
7:128501760:A:AGacceptor_gain1.0000
7:128501761:G:GGacceptor_gain1.0000

AlphaMissense

2511 scored. Top likely-pathogenic:

VariantProtein changeam_pathogenicity
7:128479196:T:CF81L0.999
7:128479198:C:AF81L0.999
7:128479198:C:GF81L0.999
7:128479187:T:AW78R0.998
7:128479187:T:CW78R0.998
7:128479220:T:CF89L0.998
7:128479222:T:AF89L0.998
7:128479222:T:GF89L0.998
7:128479238:T:AW95R0.998
7:128479238:T:CW95R0.998
7:128493915:T:CF261L0.998
7:128493917:T:AF261L0.998
7:128493917:T:GF261L0.998
7:128498098:G:CR291P0.998
7:128501828:T:CL350P0.998
7:128501869:T:AW364R0.998
7:128501869:T:CW364R0.998
7:128479189:G:CW78C0.997
7:128479189:G:TW78C0.997
7:128479208:C:GH85D0.997
7:128479233:G:CR93T0.997
7:128479234:A:CR93S0.997
7:128479234:A:TR93S0.997
7:128498100:G:CD292H0.997
7:128498116:A:TD297V0.997
7:128501825:G:CR349P0.997
7:128476874:T:AW37R0.996
7:128476874:T:CW37R0.996
7:128479197:T:CF81S0.996
7:128479240:G:CW95C0.996

dbSNP variants (sampled 300 via entrez): RS1000068181 (7:128505887 A>G), RS1000170248 (7:128482568 C>A), RS1000179787 (7:128500410 C>G), RS1000220334 (7:128489613 G>A,C), RS1000235961 (7:128496495 G>C), RS1000266264 (7:128476591 G>A), RS1000352213 (7:128483208 C>T), RS1000663487 (7:128496174 A>G), RS1000719175 (7:128489354 T>C), RS1000781720 (7:128501601 A>G), RS1000857069 (7:128477657 A>T), RS1000963075 (7:128501347 C>A,G,T), RS1001322664 (7:128490811 A>G,T), RS1001382308 (7:128484868 A>G), RS1001394444 (7:128477379 T>A)

Disease associations

OMIM: gene MIM:607846 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

StudyTraitp-value
GCST007665_4Treatment resistant depression3.000000e-06
GCST008153_28Lean body mass6.000000e-06

EFO canonical traits (2, from GWAS)

EFO IDTrait name
EFO:0009854treatment resistant depression
EFO:0004995lean body mass

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

15 total (human), top 15 by PubMed support.

ChemicalActions (top 5)PubMed papers
triphenyl phosphateaffects expression1
beta-lapachoneincreases expression1
di-n-butylphosphoric acidaffects expression1
cylindrospermopsinincreases expression1
CGP 52608increases reaction, affects binding1
Air Pollutantsincreases abundance, affects expression1
Caffeinedecreases phosphorylation1
Diethylstilbestrolincreases expression1
Enzyme Inhibitorsdecreases activity, increases O-linked glycosylation1
Folic Aciddecreases expression1
Ozoneaffects expression, increases abundance1
Smokedecreases expression1
Tretinoindecreases expression1
Valproic Aciddecreases expression1
Lactic Acidincreases expression1

Clinical trials (associated diseases)

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

No linked Atlas pages yet — the cross-entity mesh grows as the corpus expands.

About this page

Generated deterministically by Sugi Atlas from primary biomedical databases via BioBTree. Every record on this page traces to a primary source.

Generated
Atlas version
v1.1.4
BioBTree
v2.0.2

Sources 74

This page pulls from 74 datasets indexed by BioBTree:

alphafoldalphamissenseantibodybgeebgee_evidencebindingdbbiogrid_interactionbrendabrenda_kineticsccdscellosauruschembl_activitychembl_targetciviccivic_evidenceclingen_dosageclingen_gene_validityclinical_trialsclinvarcollectrictd_gene_interactiondbsnpdepmapdiamond_similarityefoensemblentrezesm2_similarityexonfantom5_genefantom5_promotergenccgenerifgogoparentgtopdbgwasgwas_studyhgnchpointactinterprointogenjasparmeshmimmirdbmondomsigdborphanetorthologparalogpdbpfampharmgkb_clinicalpharmgkb_genepharmgkb_guidelinepharmgkb_variantpubchempubchem_activitypubchem_assaypubmedreactomerefseqrhearnacentralscxa_expressionscxa_gene_experimentsignorspliceaistring_interactiontranscriptufeatureuniprot