TRMO

Summary

TRMO (tRNA methyltransferase O, HGNC:30967) is a protein-coding gene on chromosome 9q22.33, encoding tRNA (adenine(37)-N6)-methyltransferase (Q9BU70). S-adenosyl-L-methionine-dependent methyltransferase responsible for the addition of the methyl group in the formation of N6-methyl-N6-threonylcarbamoyladenosine at position 37 (m(6)t(6)A37) of the tRNA anticodon loop of tRNA(Ser)(GCU).

Enables tRNA (L-threonylcarbamoyladenosine(37)-C2) methyltransferase activity. Involved in tRNA methylation.

Source: NCBI Gene 51531 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 72 total
• MANE Select transcript: NM_016481

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30967
Approved symbol	TRMO
Name	tRNA methyltransferase O
Location	9q22.33
Locus type	gene with protein product
Status	Approved
Aliases	HSPC219
Ensembl gene	ENSG00000136932
Ensembl biotype	protein_coding
Entrez	51531

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 6 protein_coding, 2 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000375117, ENST00000375118, ENST00000375119, ENST00000455506, ENST00000471580, ENST00000478126, ENST00000718443, ENST00000864009, ENST00000864011

RefSeq mRNA: 7 — MANE Select: NM_016481 NM_001330725, NM_001371657, NM_001371658, NM_001371659, NM_001371660, NM_001371661, NM_016481

CCDS: CCDS6730, CCDS83387

Canonical transcript exons

ENST00000375119 — 5 exons

Exon	Start	End
ENSE00001465813	97904489	97904992
ENSE00001632054	97909960	97910616
ENSE00001754677	97916164	97916338
ENSE00002237452	97922418	97922500
ENSE00003555853	97913401	97913558

Expression profiles

Bgee: expression breadth ubiquitous, 263 present calls, max score 93.85.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 18.6300 / max 246.7396, expressed in 1801 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
101641	14.3796	1795
101639	3.5009	696
101640	0.3899	174
101642	0.3596	163

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
epithelium of nasopharynx	UBERON:0001951	93.85	gold quality
calcaneal tendon	UBERON:0003701	91.47	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	90.22	gold quality
amniotic fluid	UBERON:0000173	87.55	gold quality
bone marrow cell	CL:0002092	86.48	gold quality
tongue squamous epithelium	UBERON:0006919	85.74	silver quality
blood	UBERON:0000178	85.61	gold quality
bone marrow	UBERON:0002371	85.43	gold quality
sperm	CL:0000019	84.76	gold quality
germinal epithelium of ovary	UBERON:0001304	84.53	gold quality
corpus callosum	UBERON:0002336	84.35	gold quality
mucosa of urinary bladder	UBERON:0001259	84.32	gold quality
leukocyte	CL:0000738	84.30	gold quality
monocyte	CL:0000576	84.15	gold quality
mononuclear cell	CL:0000842	84.10	gold quality
left lobe of thyroid gland	UBERON:0001120	84.04	gold quality
granulocyte	CL:0000094	83.93	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.81	gold quality
palpebral conjunctiva	UBERON:0001812	83.75	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	83.62	gold quality
thyroid gland	UBERON:0002046	83.61	gold quality
islet of Langerhans	UBERON:0000006	83.55	gold quality
right lobe of thyroid gland	UBERON:0001119	83.48	gold quality
cervix squamous epithelium	UBERON:0006922	83.26	silver quality
male germ cell	CL:0000015	83.02	gold quality
hair follicle	UBERON:0002073	82.93	silver quality
lymph node	UBERON:0000029	82.87	gold quality
rectum	UBERON:0001052	82.78	gold quality
tendon	UBERON:0000043	82.73	gold quality
tonsil	UBERON:0002372	82.73	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	3.38

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

14 targeting TRMO, 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-6833-3P	100.00	70.63	3197
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-4422	99.72	72.07	2908
HSA-MIR-7161-5P	99.68	68.92	1592
HSA-MIR-6083	99.47	68.73	2393
HSA-MIR-889-3P	99.40	69.76	2103
HSA-MIR-421	98.90	67.04	1883
HSA-MIR-1288-5P	98.85	67.01	734
HSA-MIR-4742-3P	98.73	69.82	1803
HSA-MIR-4690-3P	97.02	64.72	981
HSA-MIR-5685	97.02	64.34	1004
HSA-MIR-6856-3P	96.47	66.27	781

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	trmo	ENSDARG00000037245
mus_musculus	Trmo	ENSMUSG00000028331
rattus_norvegicus	Trmo	ENSRNOG00000009492
drosophila_melanogaster	CG12822	FBGN0033229

Protein

Protein identifiers

tRNA (adenine(37)-N6)-methyltransferase — Q9BU70 (reviewed: Q9BU70)

Alternative names: tRNA methyltransferase O

All UniProt accessions (4): Q9BU70, Q5T111, Q5T112, Q5T114

UniProt curated annotations — full annotation on UniProt →

Function. S-adenosyl-L-methionine-dependent methyltransferase responsible for the addition of the methyl group in the formation of N6-methyl-N6-threonylcarbamoyladenosine at position 37 (m(6)t(6)A37) of the tRNA anticodon loop of tRNA(Ser)(GCU). The methyl group of m(6)t(6)A37 may improve the efficiency of the tRNA decoding ability.

Similarity. Belongs to the tRNA methyltransferase O family.

RefSeq proteins (7): NP_001317654, NP_001358586, NP_001358587, NP_001358588, NP_001358589, NP_001358590, NP_057565* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR023368	UPF0066_cons_site	Conserved_site
IPR023370	TrmO-like_N	Domain
IPR036413	YaeB-like_sf	Homologous_superfamily
IPR036414	YaeB_N_sf	Homologous_superfamily
IPR040372	YaeB-like	Family

Pfam: PF01980

Catalyzed reactions (Rhea), 1 shown:

• N(6)-L-threonylcarbamoyladenosine(37) in tRNA + S-adenosyl-L-methionine = N(6)-methyl,N(6)-L-threonylcarbamoyladenosine(37) in tRNA + S-adenosyl-L-homocysteine + H(+) (RHEA:70027)

UniProt features (15 total): binding site 5, sequence variant 3, sequence conflict 2, region of interest 2, chain 1, domain 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BU70-F1	67.98	0.42

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 (5): 47–49; 90–91; 117; 127; 148–151

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 102 (showing top): TGCGCANK_UNKNOWN, GOBP_TRNA_METABOLIC_PROCESS, USF_C, GOBP_RNA_METHYLATION, GOBP_RNA_MODIFICATION, USF_01, GOBP_TRNA_METHYLATION, chr9q22, GOBP_METHYLATION, GOBP_TRNA_PROCESSING, GOBP_TRNA_MODIFICATION, SCGGAAGY_ELK1_02, GOMF_RNA_METHYLTRANSFERASE_ACTIVITY, MYCMAX_03, ARNT_01

GO Biological Process (3): tRNA methylation (GO:0030488), tRNA processing (GO:0008033), methylation (GO:0032259)

GO Molecular Function (4): tRNA (L-threonylcarbamoyladenosine(37)-C2) methyltransferase activity (GO:0089715), protein binding (GO:0005515), methyltransferase activity (GO:0008168), transferase activity (GO:0016740)

GO Cellular Component (0):

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
RNA methylation	1
tRNA modification	1
RNA processing	1
tRNA metabolic process	1
metabolic process	1
tRNA (adenine) methyltransferase activity	1
binding	1
transferase activity, transferring one-carbon groups	1
catalytic activity	1

Protein interactions and networks

STRING

684 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TRMO	HEMGN	Q9BXL5	802
TRMO	FOXE1	O00358	753
TRMO	TMEM253	P0C7T8	506
TRMO	STK32B	Q9NY57	496
TRMO	ADTRP	Q96IZ2	495
TRMO	ZNF202	O95125	495
TRMO	STX18	Q9P2W9	491
TRMO	TBX10	O75333	491
TRMO	EVC2	Q86UK5	491
TRMO	CRMP1	Q14194	490
TRMO	SEC22A	Q96IW7	484
TRMO	COX18	Q8N8Q8	469
TRMO	WNT11	O96014	468
TRMO	VPS37C	A5D8V6	460
TRMO	TIMM21	Q9BVV7	445

IntAct

36 interactions, top by confidence:

A	B	Type	Score
PSMC3	PSMD12	psi-mi:“MI:0914”(association)	0.640
TRMO	SPATC1L	psi-mi:“MI:0915”(physical association)	0.560
TRMO	SRC	psi-mi:“MI:0915”(physical association)	0.550
TRMO	STAT5B	psi-mi:“MI:0914”(association)	0.530
CD244	MTX2	psi-mi:“MI:0914”(association)	0.530
AURKA	TRMO	psi-mi:“MI:0915”(physical association)	0.370
TRMO	BCL10	psi-mi:“MI:0915”(physical association)	0.370
BMPR1A	TRMO	psi-mi:“MI:0915”(physical association)	0.370
TRMO	BUB1	psi-mi:“MI:0915”(physical association)	0.370
CCND1	TRMO	psi-mi:“MI:0915”(physical association)	0.370
TRMO	DCC	psi-mi:“MI:0915”(physical association)	0.370
DLC1	TRMO	psi-mi:“MI:0915”(physical association)	0.370
TRMO	EGFR	psi-mi:“MI:0915”(physical association)	0.370
ERBB2	TRMO	psi-mi:“MI:0915”(physical association)	0.370
TRMO	MCC	psi-mi:“MI:0915”(physical association)	0.370
TRMO	MLH1	psi-mi:“MI:0915”(physical association)	0.370
TRMO	NRAS	psi-mi:“MI:0915”(physical association)	0.370
PMS2	TRMO	psi-mi:“MI:0915”(physical association)	0.370
TRMO	PTEN	psi-mi:“MI:0915”(physical association)	0.370
TRMO	PTPRJ	psi-mi:“MI:0915”(physical association)	0.370
RAD54B	TRMO	psi-mi:“MI:0915”(physical association)	0.370
TRMO	RB1	psi-mi:“MI:0915”(physical association)	0.370
TRMO	SMAD2	psi-mi:“MI:0915”(physical association)	0.370
TRMO	STK11	psi-mi:“MI:0915”(physical association)	0.370
TRMO	TGFBR2	psi-mi:“MI:0915”(physical association)	0.370
PSMC3		psi-mi:“MI:0914”(association)	0.350
MYH9	MACROH2A1	psi-mi:“MI:0914”(association)	0.350
TRMT9B	RUFY3	psi-mi:“MI:0914”(association)	0.350
TRMO	NDUFA2	psi-mi:“MI:0914”(association)	0.350

BioGRID (41): RHPN2 (Affinity Capture-MS), C9orf156 (Affinity Capture-MS), STAT5B (Affinity Capture-MS), RHPN2 (Affinity Capture-MS), C9orf156 (Affinity Capture-MS), C9orf156 (Affinity Capture-MS), VPS26B (Affinity Capture-MS), SPATC1L (Two-hybrid), C9orf156 (Two-hybrid), C9orf156 (Two-hybrid), C9orf156 (Two-hybrid), C9orf156 (Two-hybrid), C9orf156 (Two-hybrid), C9orf156 (Two-hybrid), C9orf156 (Two-hybrid)

ESM2 similar proteins: A2AGX3, B2RX14, B8A5Y1, D2CLZ9, D3ZF42, E1BP74, O02776, O88622, O88850, O88974, O96028, P38432, Q071E0, Q08AY6, Q0V9E9, Q15047, Q2YDJ8, Q2YDW7, Q3UWM4, Q498E6, Q5NVM3, Q5QJC2, Q5RET9, Q5TAX3, Q5VT97, Q642B6, Q6IQ49, Q6P3Z3, Q6P7W0, Q6ZMT4, Q7TP65, Q86VV4, Q86W56, Q86XL3, Q8BUH8, Q8C267, Q8IW35, Q93075, Q96T68, Q9BU70

Diamond homologs: O27825, O29816, O29998, O52278, O58783, O68638, P28634, P37752, P44740, Q4V7E0, Q562D6, Q58978, Q6NDF6, Q9BU70, Q9HQK7, Q9RPT0, Q9V0X6

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 33 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Diseases of signal transduction by growth factor receptors and second messengers	5	10.5×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	57
Likely benign	5
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

951 predictions. Top by Δscore:

Variant	Effect	Δscore
9:97904990:CAT:C	acceptor_gain	1.0000
9:97913554:AAATC:A	acceptor_gain	1.0000
9:97913557:TC:T	acceptor_gain	1.0000
9:97913558:CC:C	acceptor_gain	1.0000
9:97913559:C:CA	acceptor_loss	1.0000
9:97913559:C:CC	acceptor_gain	1.0000
9:97913560:T:A	acceptor_loss	1.0000
9:97916163:CCAAA:C	donor_gain	1.0000
9:97916335:TTCC:T	acceptor_gain	1.0000
9:97916337:CC:C	acceptor_gain	1.0000
9:97916338:CC:C	acceptor_gain	1.0000
9:97904989:ACAT:A	acceptor_gain	0.9900
9:97904990:CATC:C	acceptor_gain	0.9900
9:97904993:C:CC	acceptor_gain	0.9900
9:97904993:CTGCA:C	acceptor_loss	0.9900
9:97904994:T:G	acceptor_loss	0.9900
9:97910615:ACC:A	acceptor_loss	0.9900
9:97910617:CT:C	acceptor_loss	0.9900
9:97910618:T:A	acceptor_loss	0.9900
9:97913395:GGTTA:G	donor_loss	0.9900
9:97913396:GTTA:G	donor_loss	0.9900
9:97913398:TA:T	donor_loss	0.9900
9:97913399:A:T	donor_loss	0.9900
9:97913555:AATC:A	acceptor_gain	0.9900
9:97913556:ATC:A	acceptor_gain	0.9900
9:97913561:A:C	acceptor_gain	0.9900
9:97916156:CAACT:C	donor_loss	0.9900
9:97916157:AACTT:A	donor_loss	0.9900
9:97916158:ACTT:A	donor_loss	0.9900
9:97916159:CTTAC:C	donor_loss	0.9900

AlphaMissense

2881 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:97910555:C:A	K157N	0.999
9:97910555:C:G	K157N	0.999
9:97913430:A:G	L127P	0.998
9:97913456:G:C	S118R	0.998
9:97913456:G:T	S118R	0.998
9:97913458:T:G	S118R	0.998
9:97913543:A:C	F89L	0.998
9:97913543:A:T	F89L	0.998
9:97913545:A:G	F89L	0.998
9:97913549:A:C	F87L	0.998
9:97913549:A:T	F87L	0.998
9:97913551:A:G	F87L	0.998
9:97916165:A:G	W84R	0.998
9:97916165:A:T	W84R	0.998
9:97913433:C:T	G126E	0.997
9:97913449:G:T	R121S	0.997
9:97913460:C:A	R117M	0.997
9:97916175:A:C	F80L	0.997
9:97916175:A:T	F80L	0.997
9:97916177:A:G	F80L	0.997
9:97910557:T:C	K157E	0.996
9:97910562:T:A	D155V	0.996
9:97910568:A:T	V153E	0.996
9:97913421:G:T	A130D	0.996
9:97913436:A:T	I125K	0.996
9:97904829:A:C	F410L	0.995
9:97904829:A:T	F410L	0.995
9:97904831:A:G	F410L	0.995
9:97910559:A:T	I156N	0.995
9:97910563:C:G	D155H	0.995

dbSNP variants (sampled 300 via entrez): RS1000018684 (9:97908030 T>A,C), RS1000275920 (9:97904506 A>G), RS1000279633 (9:97913496 C>T), RS1000385039 (9:97920202 C>T), RS1000407953 (9:97909553 G>C), RS1000452454 (9:97913143 T>G), RS1000579982 (9:97922305 A>G,T), RS1000710364 (9:97918406 A>G,T), RS1000806888 (9:97918798 C>T), RS1000854938 (9:97900115 C>T), RS1000896570 (9:97916671 G>C), RS1000922917 (9:97924477 C>G), RS1001046606 (9:97906098 C>A,G,T), RS1001242418 (9:97920035 A>G), RS1001388832 (9:97921631 A>G)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST000337_27	Quantitative traits	1.000000e-06
GCST000640_1	Thyroid cancer (Papillary, radiation-related)	5.000000e-12
GCST001474_18	Hypothyroidism	2.000000e-19
GCST004866_3	Alopecia areata	9.000000e-07
GCST011088_10	Orofacial clefts	5.000000e-06
GCST90002401_489	Platelet distribution width	5.000000e-41

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007984	platelet component distribution width

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
sodium arsenite	increases abundance, increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Cadmium Chloride	increases expression	2
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
beta-lapachone	decreases expression	1
ferrous chloride	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
cylindrospermopsin	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
abrine	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
Arsenic	increases abundance, increases expression	1
Atrazine	decreases expression	1
Carbamazepine	affects expression	1
Doxorubicin	decreases expression	1
Methyl Methanesulfonate	increases expression	1
Valproic Acid	decreases expression	1
Cyclosporine	increases expression	1
Copper Sulfate	increases expression	1
Lactic Acid	decreases expression	1

Clinical trials (associated diseases)

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