TRMT2B

Summary

TRMT2B (tRNA methyltransferase 2B, HGNC:25748) is a protein-coding gene on chromosome Xq22.1, encoding tRNA (uracil-5-)-methyltransferase homolog B (Q96GJ1). Mitochondrial S-adenosyl-L-methionine-dependent methyltransferase that catalyzes the formation of 5-methyl-uridine in tRNAs and 12S rRNA.

This gene encodes a homolog of the TRM2 gene in S. cerevisiae. The yeast gene encodes a tRNA methyltransferase that plays a role in tRNA maturation. The yeast protein also has endo-exonuclease activity and may be involved in DNA double strand break repair. Alternative splicing results in multiple transcripts encoding different isoforms.

Source: NCBI Gene 79979 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 177 total
• MANE Select transcript: NM_024917

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25748
Approved symbol	TRMT2B
Name	tRNA methyltransferase 2B
Location	Xq22.1
Locus type	gene with protein product
Status	Approved
Aliases	FLJ12687
Ensembl gene	ENSG00000188917
Ensembl biotype	protein_coding
OMIM	301128
Entrez	79979

Gene structure

Transcript identifiers

Ensembl transcripts: 22 — 20 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000372935, ENST00000372936, ENST00000372939, ENST00000478422, ENST00000488615, ENST00000545398, ENST00000862825, ENST00000862828, ENST00000862831, ENST00000862833, ENST00000862834, ENST00000928859, ENST00000928860, ENST00000928861, ENST00000928862, ENST00000928863, ENST00000943810, ENST00000943811, ENST00000943812, ENST00000943813, ENST00000943814, ENST00000943815

RefSeq mRNA: 4 — MANE Select: NM_024917 NM_001167970, NM_001167971, NM_001167972, NM_024917

CCDS: CCDS14477, CCDS55464

Canonical transcript exons

ENST00000372936 — 14 exons

Exon	Start	End
ENSE00001365176	101019284	101019403
ENSE00001370082	101018971	101019070
ENSE00001370719	101021968	101022062
ENSE00001373221	101021101	101021315
ENSE00001382193	101023470	101023616
ENSE00001383347	101020487	101020588
ENSE00001459089	101051251	101051733
ENSE00001459095	101009350	101010707
ENSE00001936923	101051817	101052111
ENSE00002183382	101042042	101042312
ENSE00003479181	101036974	101037073
ENSE00003484244	101037917	101038051
ENSE00003568618	101035613	101035683
ENSE00003576004	101041317	101041371

Expression profiles

Bgee: expression breadth ubiquitous, 218 present calls, max score 84.16.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 6.4333 / max 55.9687, expressed in 1728 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
199940	3.9396	1493
199938	1.8826	1182
199939	0.6110	327

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	84.16	gold quality
muscle of leg	UBERON:0001383	82.12	gold quality
gastrocnemius	UBERON:0001388	81.94	gold quality
monocyte	CL:0000576	81.34	gold quality
leukocyte	CL:0000738	81.31	gold quality
hindlimb stylopod muscle	UBERON:0004252	81.21	gold quality
mononuclear cell	CL:0000842	81.05	gold quality
rectum	UBERON:0001052	81.00	gold quality
mucosa of transverse colon	UBERON:0004991	79.92	gold quality
bone marrow cell	CL:0002092	79.41	gold quality
colonic epithelium	UBERON:0000397	79.36	gold quality
buccal mucosa cell	CL:0002336	79.26	silver quality
lymph node	UBERON:0000029	79.17	gold quality
spleen	UBERON:0002106	78.80	gold quality
small intestine Peyer’s patch	UBERON:0003454	78.60	gold quality
minor salivary gland	UBERON:0001830	78.37	gold quality
islet of Langerhans	UBERON:0000006	78.32	gold quality
tonsil	UBERON:0002372	78.23	gold quality
apex of heart	UBERON:0002098	78.17	gold quality
body of stomach	UBERON:0001161	78.12	gold quality
right adrenal gland cortex	UBERON:0035827	78.09	gold quality
right atrium auricular region	UBERON:0006631	78.08	gold quality
transverse colon	UBERON:0001157	78.05	gold quality
heart left ventricle	UBERON:0002084	77.92	gold quality
esophagus mucosa	UBERON:0002469	77.86	gold quality
stomach	UBERON:0000945	77.65	gold quality
right adrenal gland	UBERON:0001233	77.62	gold quality
small intestine	UBERON:0002108	77.55	gold quality
left adrenal gland	UBERON:0001234	77.43	gold quality
cardiac ventricle	UBERON:0002082	77.35	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-7008	yes	50.38
E-ANND-3	no	5.37

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

37 targeting TRMT2B, 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-3613-3P	100.00	76.36	7965
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-145-5P	99.92	71.13	1836
HSA-MIR-5195-3P	99.92	70.92	1877
HSA-MIR-6715A-3P	99.83	68.05	1473
HSA-MIR-6817-3P	99.79	68.35	2126
HSA-MIR-4766-5P	99.75	69.23	2662
HSA-MIR-4755-5P	99.71	70.34	2716
HSA-MIR-5006-3P	99.71	70.26	2728
HSA-MIR-4328	99.57	71.06	4094
HSA-MIR-216A-5P	99.50	68.02	1288
HSA-MIR-146A-3P	99.13	68.99	1881
HSA-MIR-548AS-3P	99.12	69.12	2294
HSA-MIR-10A-5P	98.89	69.85	712
HSA-MIR-10B-5P	98.89	69.86	711
HSA-MIR-500A-5P	98.76	69.13	1241
HSA-MIR-4726-3P	98.49	63.89	1385
HSA-MIR-6792-5P	98.39	68.16	1330
HSA-MIR-6509-3P	98.32	67.33	1343
HSA-MIR-891A-3P	98.05	67.99	970
HSA-MIR-5681A	97.99	67.17	1658
HSA-MIR-3921	97.81	67.45	1431
HSA-MIR-4433A-3P	97.75	62.82	1435
HSA-MIR-4253	97.48	65.11	692
HSA-MIR-6862-5P	97.48	64.84	713

Literature-anchored findings (GeneRIF, showing 2)

• TRMT2B is responsible for both tRNA and rRNA m(5)U-methylation in human mitochondria. (PMID:31948311)
• Association of TRMT2B gene variants with juvenile amyotrophic lateral sclerosis. (PMID:37874476)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
danio_rerio	trmt2b	ENSDARG00000033967
mus_musculus	Trmt2b	ENSMUSG00000067369

Paralogs (1): TRMT2A (ENSG00000099899)

Protein

Protein identifiers

tRNA (uracil-5-)-methyltransferase homolog B — Q96GJ1 (reviewed: Q96GJ1)

Alternative names: TRM2 homolog B, rRNA (uracil-5-)-methyltransferase TRMT2B

All UniProt accessions (1): Q96GJ1

UniProt curated annotations — full annotation on UniProt →

Function. Mitochondrial S-adenosyl-L-methionine-dependent methyltransferase that catalyzes the formation of 5-methyl-uridine in tRNAs and 12S rRNA. Catalyzes the methylation of uridine at position 54 (m5U54) in all tRNAs. Specifically methylates the uridine in position 429 of 12S rRNA (m5U429). Does not affect RNA stability or mitochondrial translation.

Subcellular location. Mitochondrion Mitochondrion matrix.

Similarity. Belongs to the class I-like SAM-binding methyltransferase superfamily. RNA M5U methyltransferase family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q96GJ1-1	1	yes
Q96GJ1-2	2
Q96GJ1-3	3

RefSeq proteins (4): NP_001161442, NP_001161443, NP_001161444, NP_079193* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR010280	U5_MeTrfase_fam	Family
IPR025714	Methyltranfer_dom	Domain
IPR025823	TRM2B_chor	Family
IPR029063	SAM-dependent_MTases_sf	Homologous_superfamily
IPR045850	TRM2_met	Family

Pfam: PF13847

Catalyzed reactions (Rhea), 2 shown:

• uridine(54) in tRNA + S-adenosyl-L-methionine = 5-methyluridine(54) in tRNA + S-adenosyl-L-homocysteine + H(+) (RHEA:42712)
• a uridine in 12S rRNA + S-adenosyl-L-methionine = a 5-methyluridine in 12S rRNA + S-adenosyl-L-homocysteine + H(+) (RHEA:69859)

UniProt features (12 total): binding site 3, sequence conflict 2, active site 2, splice variant 2, transit peptide 1, chain 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96GJ1-F1	82.76	0.72

Functional residue map

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

Catalytic / active sites (2): 451 (nucleophile); 497 (proton acceptor)

Ligand- & substrate-binding residues (3): 323; 373; 423

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 81 (showing top): GOBP_RIBOSOME_BIOGENESIS, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, GOBP_TRNA_METABOLIC_PROCESS, GOBP_RNA_METHYLATION, GOBP_RNA_MODIFICATION, RYTTCCTG_ETS2_B, GOBP_RRNA_MODIFICATION, GOBP_METHYLATION, GOBP_RIBONUCLEOPROTEIN_COMPLEX_BIOGENESIS, IVANOVA_HEMATOPOIESIS_EARLY_PROGENITOR, GOBP_TRNA_PROCESSING, GOBP_RRNA_METHYLATION, GOCC_MITOCHONDRIAL_MATRIX, MGGAAGTG_GABP_B, GOMF_RNA_METHYLTRANSFERASE_ACTIVITY

GO Biological Process (5): tRNA processing (GO:0008033), rRNA processing (GO:0006364), RNA processing (GO:0006396), rRNA methylation (GO:0031167), methylation (GO:0032259)

GO Molecular Function (6): tRNA (uracil(54)-C5)-methyltransferase activity, S-adenosyl methionine-dependent (GO:0030697), rRNA (uridine-C5-)-methyltransferase activity (GO:0070041), protein binding (GO:0005515), methyltransferase activity (GO:0008168), RNA methyltransferase activity (GO:0008173), transferase activity (GO:0016740)

GO Cellular Component (2): mitochondrion (GO:0005739), mitochondrial matrix (GO:0005759)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
RNA processing	2
tRNA metabolic process	1
rRNA metabolic process	1
ribosome biogenesis	1
gene expression	1
RNA biosynthetic process	1
primary metabolic process	1
rRNA modification	1
RNA methylation	1
metabolic process	1
S-adenosylmethionine-dependent methyltransferase activity	1
tRNA (uridine) methyltransferase activity	1
C-methyltransferase activity	1
rRNA (uridine) methyltransferase activity	1
binding	1
transferase activity, transferring one-carbon groups	1
methyltransferase activity	1
catalytic activity, acting on RNA	1
catalytic activity	1
cytoplasm	1
intracellular membrane-bounded organelle	1
mitochondrion	1
intracellular organelle lumen	1

Protein interactions and networks

STRING

1665 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TRMT2B	METTL15	A6NJ78	695
TRMT2B	TRMT61B	Q9BVS5	621
TRMT2B	RPUSD4	Q96CM3	610
TRMT2B	MRM3	Q9HC36	606
TRMT2B	MRM2	Q9UI43	590
TRMT2B	NSUN4	Q96CB9	583
TRMT2B	RBFA	Q8N0V3	571
TRMT2B	TFB1M	Q8WVM0	568
TRMT2B	MRM1	Q6IN84	525
TRMT2B	TRUB2	O95900	481
TRMT2B	TRMT1L	Q7Z2T5	441
TRMT2B	QTRT2	Q9H974	434
TRMT2B	THUMPD2	Q9BTF0	433
TRMT2B	QTRT1	Q9BXR0	430
TRMT2B	TFB2M	Q9H5Q4	423

IntAct

29 interactions, top by confidence:

A	B	Type	Score
HSPD1	NUDT19	psi-mi:“MI:0914”(association)	0.710
NDUFS7	NDUFS8	psi-mi:“MI:0914”(association)	0.640
ERCC1	TRMT2B	psi-mi:“MI:0915”(physical association)	0.560
RABGGTB	PIPSL	psi-mi:“MI:0914”(association)	0.530
PPTC7	UBB	psi-mi:“MI:0914”(association)	0.530
KCTD17	CBX4	psi-mi:“MI:0914”(association)	0.530
ABL1	TRMT2B	psi-mi:“MI:0915”(physical association)	0.370
TRMT2B	PTPN11	psi-mi:“MI:0915”(physical association)	0.370
Rmdn3	DERL1	psi-mi:“MI:0914”(association)	0.350
PPTC7	AKAP10	psi-mi:“MI:0914”(association)	0.350
LDLRAD1	GXYLT2	psi-mi:“MI:0914”(association)	0.350
FBLN5	ZNF320	psi-mi:“MI:0914”(association)	0.350
UQCRFS1	VWA8	psi-mi:“MI:0914”(association)	0.350
PFDN5	GTPBP10	psi-mi:“MI:0914”(association)	0.350
MRPL12		psi-mi:“MI:0914”(association)	0.350
NELL1	MATN2	psi-mi:“MI:0914”(association)	0.350
RNF181	CHEK1	psi-mi:“MI:0914”(association)	0.350
VWC2L	CHEK1	psi-mi:“MI:0914”(association)	0.350
SCYL3	AURKA	psi-mi:“MI:0914”(association)	0.350
OXLD1	PRORP	psi-mi:“MI:0914”(association)	0.350
LMNB2	SPOP	psi-mi:“MI:0914”(association)	0.350
PPTC7	MAOB	psi-mi:“MI:0914”(association)	0.350
KLHL22	TRAV18	psi-mi:“MI:0914”(association)	0.350
FECH	GTPBP10	psi-mi:“MI:0914”(association)	0.350
FHIP2B	VWA8	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (39): TRMT2B (Two-hybrid), TRMT2B (Affinity Capture-MS), TRMT2B (Affinity Capture-MS), TRMT2B (Affinity Capture-MS), TRMT2B (Affinity Capture-MS), TRMT2B (Affinity Capture-MS), TRMT2B (Affinity Capture-MS), TRMT2B (Affinity Capture-MS), TRMT2B (Affinity Capture-MS), TRMT2B (Affinity Capture-MS), TRMT2B (Affinity Capture-MS), TRMT2B (Affinity Capture-MS), TRMT2B (Two-hybrid), TRMT2B (Two-hybrid), TRMT2B (Affinity Capture-MS)

ESM2 similar proteins: A0JPF9, A4D126, A5PKL6, A6QP81, B2GUS6, D2H8V8, E1BCH6, E1BVR9, E9PYK3, F1ND48, G5E8F4, P79106, Q28CZ7, Q32PY6, Q3U269, Q3U3W5, Q3U5Q7, Q3UVV9, Q49MI3, Q4R3W5, Q5F3V0, Q5ND52, Q5R5X9, Q5RCP1, Q5RFM7, Q5RJG7, Q5RL51, Q5S6T3, Q5T8I9, Q5VZV1, Q6AYG3, Q8BIW1, Q8BK58, Q8BQJ6, Q8BTK5, Q8BZ20, Q8C5V5, Q8CAE2, Q8IXQ6, Q8IYR2

Diamond homologs: A4QP75, B5EPA4, B7J921, D0L1G3, O58864, O66617, P33753, Q13Z67, Q1LLI5, Q2SWE9, Q3IIC0, Q3JCY2, Q3JRP8, Q47F12, Q57836, Q5E6T2, Q5HN37, Q5RFM7, Q606W5, Q62JV9, Q63UT8, Q6GFG0, Q6MAY1, Q71YR7, Q72VP7, Q73EJ5, Q74D67, Q74I68, Q74IG2, Q74N58, Q7MVG9, Q7NGN4, Q814A6, Q81ZD6, Q8AA22, Q8BNV1, Q8BQJ6, Q8CRU6, Q8DNH6, Q8DSK3

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	33
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2133 predictions. Top by Δscore:

Variant	Effect	Δscore
X:101018964:GACTT:G	donor_loss	1.0000
X:101018965:ACTTA:A	donor_loss	1.0000
X:101018966:CTT:C	donor_loss	1.0000
X:101018967:TTA:T	donor_loss	1.0000
X:101018968:TA:T	donor_loss	1.0000
X:101018969:A:AC	donor_gain	1.0000
X:101018969:ACT:A	donor_gain	1.0000
X:101018970:C:CT	donor_gain	1.0000
X:101018970:CT:C	donor_gain	1.0000
X:101018970:CTC:C	donor_gain	1.0000
X:101018970:CTCA:C	donor_gain	1.0000
X:101018970:CTCAA:C	donor_gain	1.0000
X:101018972:CAATG:C	donor_gain	1.0000
X:101018973:A:AC	donor_gain	1.0000
X:101018973:AATGA:A	donor_gain	1.0000
X:101019069:ATC:A	acceptor_loss	1.0000
X:101019070:TC:T	acceptor_loss	1.0000
X:101019071:C:CC	acceptor_gain	1.0000
X:101019071:CTGA:C	acceptor_loss	1.0000
X:101019251:A:AC	donor_gain	1.0000
X:101019252:C:CC	donor_gain	1.0000
X:101019269:G:C	donor_gain	1.0000
X:101019277:T:TA	donor_gain	1.0000
X:101019283:CG:C	donor_gain	1.0000
X:101020453:C:A	donor_gain	1.0000
X:101020481:GTGTA:G	donor_loss	1.0000
X:101020484:TACCA:T	donor_loss	1.0000
X:101020485:ACC:A	donor_loss	1.0000
X:101021083:C:A	donor_gain	1.0000
X:101021092:T:TA	donor_gain	1.0000

AlphaMissense

3278 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:101037046:A:G	S156P	0.986
X:101023534:A:T	V231D	0.985
X:101023531:C:G	R232P	0.979
X:101036997:C:T	G172E	0.974
X:101023550:A:G	W226R	0.973
X:101023550:A:T	W226R	0.973
X:101023540:A:G	L229P	0.972
X:101010626:G:C	F490L	0.967
X:101010626:G:T	F490L	0.967
X:101010628:A:G	F490L	0.967
X:101035667:A:C	C185W	0.966
X:101019384:A:C	F396L	0.962
X:101019384:A:T	F396L	0.962
X:101019386:A:G	F396L	0.962
X:101021192:G:C	N325K	0.961
X:101021192:G:T	N325K	0.961
X:101037038:G:C	F158L	0.959
X:101037038:G:T	F158L	0.959
X:101037039:A:G	F158S	0.959
X:101037040:A:G	F158L	0.959
X:101036998:C:A	G172W	0.957
X:101023504:G:T	A241D	0.956
X:101041323:C:A	Q99H	0.956
X:101041323:C:G	Q99H	0.956
X:101022024:A:C	F265L	0.955
X:101022024:A:T	F265L	0.955
X:101022026:A:G	F265L	0.955
X:101023546:C:G	R227P	0.955
X:101035669:A:G	C185R	0.954
X:101036998:C:G	G172R	0.954

dbSNP variants (sampled 300 via entrez): RS1000007259 (X:101046265 G>T), RS1000212027 (X:101036538 C>T), RS1000276878 (X:100979953 GTCTC>G,GTCTCTC), RS1000353251 (X:101046500 C>T), RS1000368456 (X:101009216 G>A), RS1000439008 (X:101010127 C>T), RS1000567 (X:101006795 T>A,C), RS1000608013 (X:100976532 C>T), RS1000624719 (X:100994498 A>G), RS1000650147 (X:101028957 T>C), RS1000777211 (X:101005523 G>A,T), RS1000779812 (X:101033699 T>C), RS1000883093 (X:101020684 G>A,C,T), RS1000936398 (X:101010083 C>T), RS1000953132 (X:101038614 T>C)

Disease associations

OMIM: gene MIM:301128 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

22 total (human), top 22 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases methylation, affects expression	2
butyraldehyde	decreases expression	1
benzo(e)pyrene	increases methylation	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
abrine	decreases expression	1
Sunitinib	decreases expression	1
Leflunomide	decreases expression	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Cisplatin	increases expression	1
Diazinon	increases methylation	1
Doxorubicin	decreases expression	1
Methapyrilene	increases methylation	1
Smoke	decreases expression	1
Tetrachlorodibenzodioxin	affects expression	1
Tobacco Smoke Pollution	decreases expression	1
Tretinoin	decreases expression	1
Urethane	decreases expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	1
Lactic Acid	decreases expression	1
Acrylamide	decreases expression	1

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_TU80	HAP1 TRMT2B (-) 1	Cancer cell line	Male
CVCL_TU81	HAP1 TRMT2B (-) 2	Cancer cell line	Male
CVCL_TU82	HAP1 TRMT2B (-) 3	Cancer cell line	Male

Clinical trials (associated diseases)

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