THUMPD3

Summary

THUMPD3 (THUMP domain 3 tRNA guanosine methyltransferase, HGNC:24493) is a protein-coding gene on chromosome 3p25.3, encoding tRNA (guanine(6)-N(2))-methyltransferase THUMP3 (Q9BV44). Catalytic subunit of the THUMPD3-TRM112 methyltransferase complex, that specifically mediates the S-adenosyl-L-methionine-dependent N(2)-methylation of guanosine nucleotide at position 6 (m2G6) in tRNAs.

Enables tRNA (guanine(6)-N2)-methyltransferase activity and tRNA (guanine(7)-N2)-methyltransferase activity. Involved in tRNA methylation. Located in cytosol and nucleolus. Part of tRNA methyltransferase complex.

Source: NCBI Gene 25917 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 95 total — 1 pathogenic
• MANE Select transcript: NM_001114092

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24493
Approved symbol	THUMPD3
Name	THUMP domain 3 tRNA guanosine methyltransferase
Location	3p25.3
Locus type	gene with protein product
Status	Approved
Aliases	DKFZP434F091
Ensembl gene	ENSG00000134077
Ensembl biotype	protein_coding
Entrez	25917

Gene structure

Transcript identifiers

Ensembl transcripts: 40 — 37 protein_coding, 3 retained_intron

ENST00000345094, ENST00000416603, ENST00000417036, ENST00000419437, ENST00000441127, ENST00000452837, ENST00000461636, ENST00000464045, ENST00000484006, ENST00000515662, ENST00000874843, ENST00000874844, ENST00000874845, ENST00000874846, ENST00000874847, ENST00000874848, ENST00000874849, ENST00000874850, ENST00000874851, ENST00000912094, ENST00000912095, ENST00000912096, ENST00000912097, ENST00000912098, ENST00000912099, ENST00000912100, ENST00000951554, ENST00000951555, ENST00000951556, ENST00000951557, ENST00000951558, ENST00000951559, ENST00000951560, ENST00000951561, ENST00000951562, ENST00000951563, ENST00000951564, ENST00000951565, ENST00000951566, ENST00000951567

RefSeq mRNA: 2 — MANE Select: NM_001114092 NM_001114092, NM_015453

CCDS: CCDS2573

Canonical transcript exons

ENST00000452837 — 10 exons

Exon	Start	End
ENSE00001029278	9380503	9380618
ENSE00001029280	9383199	9383309
ENSE00001029281	9371060	9371536
ENSE00001121021	9366908	9366985
ENSE00001301866	9365016	9365320
ENSE00001391623	9384524	9386791
ENSE00001794513	9363054	9363127
ENSE00003517014	9377819	9377888
ENSE00003569800	9374516	9374646
ENSE00003628052	9384212	9384335

Expression profiles

Bgee: expression breadth ubiquitous, 253 present calls, max score 96.90.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 27.2542 / max 328.5775, expressed in 1816 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
35201	26.3752	1813
35202	0.5774	305
35203	0.3016	136

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	96.90	gold quality
left testis	UBERON:0004533	96.78	gold quality
right testis	UBERON:0004534	96.75	gold quality
testis	UBERON:0000473	95.59	gold quality
islet of Langerhans	UBERON:0000006	94.17	gold quality
stromal cell of endometrium	CL:0002255	93.50	gold quality
calcaneal tendon	UBERON:0003701	93.26	gold quality
tibialis anterior	UBERON:0001385	93.08	gold quality
adrenal tissue	UBERON:0018303	93.03	gold quality
gastrocnemius	UBERON:0001388	92.80	gold quality
muscle of leg	UBERON:0001383	92.70	gold quality
ganglionic eminence	UBERON:0004023	92.34	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	92.29	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	92.22	gold quality
left ventricle myocardium	UBERON:0006566	92.15	silver quality
cortical plate	UBERON:0005343	92.01	gold quality
rectum	UBERON:0001052	91.98	gold quality
hindlimb stylopod muscle	UBERON:0004252	91.69	gold quality
deltoid	UBERON:0001476	91.63	silver quality
tendon	UBERON:0000043	91.48	gold quality
heart left ventricle	UBERON:0002084	91.48	gold quality
pancreas	UBERON:0001264	91.37	gold quality
adenohypophysis	UBERON:0002196	91.37	gold quality
cardiac ventricle	UBERON:0002082	91.25	gold quality
right lobe of thyroid gland	UBERON:0001119	91.04	gold quality
ventricular zone	UBERON:0003053	90.98	gold quality
body of pancreas	UBERON:0001150	90.78	gold quality
apex of heart	UBERON:0002098	90.72	gold quality
right atrium auricular region	UBERON:0006631	90.71	gold quality
heart	UBERON:0000948	90.54	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.37
E-CURD-10	no	679.09
E-GEOD-99795	no	147.25

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

85 targeting THUMPD3, 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-3134	100.00	66.43	777
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-9-3P	99.96	70.88	2068
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-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-374B-5P	99.90	69.98	2734
HSA-MIR-380-3P	99.89	70.18	1978
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-629-3P	99.85	67.99	1875
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-369-3P	99.85	70.52	2264
HSA-MIR-5010-3P	99.83	70.60	2357
HSA-MIR-205-5P	99.81	70.05	1557
HSA-MIR-3133	99.81	70.92	3506
HSA-MIR-26A-5P	99.78	73.52	2303
HSA-MIR-26B-5P	99.78	73.51	2305
HSA-MIR-4713-5P	99.78	67.80	1794
HSA-MIR-370-5P	99.78	66.81	706
HSA-MIR-92A-2-5P	99.75	67.01	2164

Literature-anchored findings (GeneRIF, showing 1)

• THUMPD3-TRMT112 is a m2G methyltransferase working on a broad range of tRNA substrates. (PMID:34669960)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	thumpd3	ENSDARG00000059634
mus_musculus	Thumpd3	ENSMUSG00000030264
rattus_norvegicus	Thumpd3	ENSRNOG00000006941
caenorhabditis_elegans		WBGENE00010846

Paralogs (1): THUMPD2 (ENSG00000138050)

Protein

Protein identifiers

tRNA (guanine(6)-N(2))-methyltransferase THUMP3 — Q9BV44 (reviewed: Q9BV44)

Alternative names: THUMP domain-containing protein 3, tRNA(Trp) (guanine(7)-N(2))-methyltransferase THUMP3

All UniProt accessions (5): C9J9V2, Q9BV44, C9JP31, H7C0R6, H7C3J3

UniProt curated annotations — full annotation on UniProt →

Function. Catalytic subunit of the THUMPD3-TRM112 methyltransferase complex, that specifically mediates the S-adenosyl-L-methionine-dependent N(2)-methylation of guanosine nucleotide at position 6 (m2G6) in tRNAs. This is one of the major tRNA (guanine-N(2))-methyltransferases. Also catalyzes the S-adenosyl-L-methionine-dependent N(2)-methylation of guanosine nucleotide at position 7 of tRNA(Trp).

Subunit / interactions. Part of the heterodimeric THUMPD3-TRM112 methyltransferase complex; this complex forms an active tRNA methyltransferase, where TRMT112 acts as an activator of the catalytic subunit THUMPD3.

Subcellular location. Cytoplasm.

Similarity. Belongs to the methyltransferase superfamily.

RefSeq proteins (2): NP_001107564, NP_056268 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000241	RlmKL-like_Mtase	Domain
IPR004114	THUMP_dom	Domain
IPR029063	SAM-dependent_MTases_sf	Homologous_superfamily
IPR053943	RlmKL-like_Mtase_CS	Conserved_site

Pfam: PF01170, PF02926

Catalyzed reactions (Rhea), 2 shown:

• guanosine(6) in tRNA + S-adenosyl-L-methionine = N(2)-methylguanosine(6) in tRNA + S-adenosyl-L-homocysteine + H(+) (RHEA:51116)
• guanosine(7) in tRNA + S-adenosyl-L-methionine = N(2)-methylguanosine(7) in tRNA + S-adenosyl-L-homocysteine + H(+) (RHEA:83419)

UniProt features (4 total): chain 1, domain 1, sequence variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BV44-F1	78.46	0.61

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 126 (showing top): GOBP_TRNA_METABOLIC_PROCESS, GOBP_RNA_METHYLATION, MODULE_205, GARGALOVIC_RESPONSE_TO_OXIDIZED_PHOSPHOLIPIDS_BLUE_DN, GOBP_RNA_MODIFICATION, WANG_LMO4_TARGETS_DN, MILI_PSEUDOPODIA_HAPTOTAXIS_UP, GGAANCGGAANY_UNKNOWN, GOBP_TRNA_METHYLATION, ZHOU_INFLAMMATORY_RESPONSE_LIVE_DN, LASTOWSKA_NEUROBLASTOMA_COPY_NUMBER_DN, NOUZOVA_TRETINOIN_AND_H4_ACETYLATION, GOBP_METHYLATION, GOBP_TRNA_PROCESSING, GOBP_TRNA_MODIFICATION

GO Biological Process (4): tRNA methylation (GO:0030488), RNA processing (GO:0006396), tRNA processing (GO:0008033), methylation (GO:0032259)

GO Molecular Function (8): tRNA binding (GO:0000049), tRNA (guanine) methyltransferase activity (GO:0016423), tRNA (guanine(6)-N2)-methyltransferase activity (GO:0160117), tRNA (guanine(7)-N2)-methyltransferase activity (GO:0160118), RNA binding (GO:0003723), protein binding (GO:0005515), methyltransferase activity (GO:0008168), transferase activity (GO:0016740)

GO Cellular Component (4): nucleolus (GO:0005730), cytoplasm (GO:0005737), cytosol (GO:0005829), tRNA methyltransferase complex (GO:0043527)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
N-methyltransferase activity	2
tRNA (guanine) methyltransferase activity	2
cellular anatomical structure	2
RNA methylation	1
tRNA modification	1
gene expression	1
RNA biosynthetic process	1
primary metabolic process	1
RNA processing	1
tRNA metabolic process	1
metabolic process	1
RNA binding	1
tRNA methyltransferase activity	1
S-adenosylmethionine-dependent methyltransferase activity	1
nucleic acid binding	1
binding	1
transferase activity, transferring one-carbon groups	1
catalytic activity	1
nuclear lumen	1
intracellular membraneless organelle	1
intracellular anatomical structure	1
cytoplasm	1
methyltransferase complex	1

Protein interactions and networks

STRING

1422 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
THUMPD3	SETD5	Q9C0A6	717
THUMPD3	LHFPL4	Q7Z7J7	585
THUMPD3	TRMT11	Q7Z4G4	501
THUMPD3	LHFPL3	Q86UP9	487
THUMPD3	ZNF213	O14771	431
THUMPD3	FANCD2OS	Q96PS1	419
THUMPD3	BUD23	O43709	414
THUMPD3	RPUSD3	Q6P087	414
THUMPD3	DHX57	Q6P158	399
THUMPD3	TRMT112	Q9UI30	398
THUMPD3	METTL5	Q9NRN9	394
THUMPD3	PUS10	Q3MIT2	389
THUMPD3	PRRT3	Q5FWE3	380
THUMPD3	RPUSD1	Q9UJJ7	374
THUMPD3	ZNF486	Q96H40	370

IntAct

72 interactions, top by confidence:

A	B	Type	Score
TRMT112	BUD23	psi-mi:“MI:0914”(association)	0.910
THUMPD3	TRMT112	psi-mi:“MI:0915”(physical association)	0.870
THUMPD3	TRMT112	psi-mi:“MI:0403”(colocalization)	0.870
TSEN2	TSEN54	psi-mi:“MI:0914”(association)	0.830
EFNB3	DENND11	psi-mi:“MI:0914”(association)	0.640
FXR2	CSNK2A2	psi-mi:“MI:0914”(association)	0.640
LIN28A	IGF2BP3	psi-mi:“MI:0914”(association)	0.640
RPL10A	RRP8	psi-mi:“MI:0914”(association)	0.640
GATC	NME4	psi-mi:“MI:0914”(association)	0.530
RBM3	PRMT5	psi-mi:“MI:0914”(association)	0.530
ZNF501	THUMPD3	psi-mi:“MI:0914”(association)	0.530
GRK7	HSP90AA1	psi-mi:“MI:0914”(association)	0.530
LIN28B	ELAVL2	psi-mi:“MI:0914”(association)	0.530
SRSF5	CBX6	psi-mi:“MI:0914”(association)	0.530
ACOT11	THUMPD3	psi-mi:“MI:0915”(physical association)	0.400
LRRK2		psi-mi:“MI:0914”(association)	0.350
ESRP1	RGPD3	psi-mi:“MI:0914”(association)	0.350
AVIL	DDX11L8	psi-mi:“MI:0914”(association)	0.350
SLAMF1	RTCA	psi-mi:“MI:0914”(association)	0.350
CAMK2D	SETD1A	psi-mi:“MI:0914”(association)	0.350
THUMPD3	TRMU	psi-mi:“MI:0914”(association)	0.350
PPM1B	BPGM	psi-mi:“MI:0914”(association)	0.350
APOBEC3C	GTPBP10	psi-mi:“MI:0914”(association)	0.350
DNAJA2	DENND11	psi-mi:“MI:0914”(association)	0.350
PRR3	ZNF316	psi-mi:“MI:0914”(association)	0.350

BioGRID (133): THUMPD3 (Affinity Capture-MS), THUMPD3 (Affinity Capture-MS), THUMPD3 (Affinity Capture-MS), THUMPD3 (Affinity Capture-MS), THUMPD3 (Affinity Capture-MS), METTL5 (Co-fractionation), THUMPD3 (Co-fractionation), THUMPD3 (Affinity Capture-MS), MICU3 (Affinity Capture-MS), TRMU (Affinity Capture-MS), PUS1 (Affinity Capture-MS), EDRF1 (Affinity Capture-MS), USP46 (Affinity Capture-MS), THUMPD3 (Affinity Capture-MS), TRMT112 (Affinity Capture-MS)

ESM2 similar proteins: A1L3L1, A2RT67, A2RUS2, A3KPW7, B0CM32, B0KW86, D3ZV31, E1B8U2, E1BGQ2, O95456, P50747, P97770, Q05CL8, Q0IHB3, Q0P5F2, Q1RMZ1, Q2T9W2, Q2TBA3, Q496Y0, Q587J7, Q58DC7, Q5E9Y6, Q5RAH6, Q69ZK0, Q6GQ33, Q6GR37, Q7TPQ3, Q7Z2E3, Q80WC9, Q86TP1, Q8BKW4, Q8BNV1, Q8BXK4, Q8IYL2, Q8K2I9, Q8NFZ0, Q8NHU6, Q8TCU6, Q96CB9, Q96QE5

Diamond homologs: A0L8B5, P97770, Q2T9W2, Q9BTF0, Q9BV44, A7N0M8, Q6AQA5, Q72IH5, A0KIY0, A3QIE1, A4XZX0, A5UKU4, A6VDN5, B0U5Z5, B2FJ58, B2IA87, B2S3F1, B2UFG8, B7V3L1, B8D4I6, C1DHW2, C3MR91, C3MXI0, C3MZC6, C3N7E8, C3NG28, C4KIK6, E1B8U2, O83570, Q02EP8, Q1LRG9, Q1QXV9, Q3A2U5, Q3KJG6, Q475X0, Q4ZLX9, Q6LU02, Q6N3Y0, Q87A16, Q88AM9

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
THUMPD3	“form complex”	“THUMPD3-TRM112 methyltransferase complex”	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	73
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
818229	NC_000003.11:g.9387774_9503839del116066	Pathogenic

SpliceAI

1234 predictions. Top by Δscore:

Variant	Effect	Δscore
3:9365160:G:GT	donor_gain	1.0000
3:9371055:TACA:T	acceptor_loss	1.0000
3:9371057:CA:C	acceptor_loss	1.0000
3:9371058:A:AG	acceptor_gain	1.0000
3:9371058:A:G	acceptor_loss	1.0000
3:9371059:G:GA	acceptor_loss	1.0000
3:9371059:G:GG	acceptor_gain	1.0000
3:9371059:GGAA:G	acceptor_gain	1.0000
3:9374504:A:AG	acceptor_gain	1.0000
3:9374504:ACTTT:A	acceptor_gain	1.0000
3:9374505:C:G	acceptor_gain	1.0000
3:9374508:T:A	acceptor_gain	1.0000
3:9374511:TATA:T	acceptor_loss	1.0000
3:9374512:A:AG	acceptor_gain	1.0000
3:9374512:ATAG:A	acceptor_gain	1.0000
3:9374513:T:G	acceptor_gain	1.0000
3:9374513:TA:T	acceptor_loss	1.0000
3:9374514:A:AG	acceptor_gain	1.0000
3:9374514:AG:A	acceptor_gain	1.0000
3:9374515:G:GG	acceptor_gain	1.0000
3:9374515:GG:G	acceptor_gain	1.0000
3:9374515:GGT:G	acceptor_gain	1.0000
3:9374515:GGTT:G	acceptor_gain	1.0000
3:9374515:GGTTC:G	acceptor_gain	1.0000
3:9374647:G:GA	donor_loss	1.0000
3:9374647:G:GG	donor_gain	1.0000
3:9380614:GAAGG:G	donor_gain	1.0000
3:9380617:GG:G	donor_gain	1.0000
3:9380618:GG:G	donor_gain	1.0000
3:9383197:A:AC	acceptor_loss	1.0000

AlphaMissense

3345 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:9374586:G:C	R293T	1.000
3:9374587:A:C	R293S	1.000
3:9374587:A:T	R293S	1.000
3:9383299:T:C	F409L	1.000
3:9383301:T:A	F409L	1.000
3:9383301:T:G	F409L	1.000
3:9365223:C:A	A52D	0.999
3:9371408:T:C	F227L	0.999
3:9371409:T:C	F227S	0.999
3:9371410:T:A	F227L	0.999
3:9371410:T:G	F227L	0.999
3:9371412:G:C	R228T	0.999
3:9371413:A:C	R228S	0.999
3:9371413:A:T	R228S	0.999
3:9371422:C:G	C231W	0.999
3:9371428:G:C	R233S	0.999
3:9371428:G:T	R233S	0.999
3:9371478:G:A	G250E	0.999
3:9371487:T:A	V253D	0.999
3:9371504:T:A	W259R	0.999
3:9371504:T:C	W259R	0.999
3:9374586:G:T	R293I	0.999
3:9374600:T:C	F298L	0.999
3:9374602:T:A	F298L	0.999
3:9374602:T:G	F298L	0.999
3:9374603:G:A	G299R	0.999
3:9374603:G:C	G299R	0.999
3:9374604:G:A	G299E	0.999
3:9374616:T:A	L303H	0.999
3:9374619:G:C	R304T	0.999

dbSNP variants (sampled 300 via entrez): RS1000024181 (3:9363348 T>A), RS1000049842 (3:9362763 A>C,T), RS1000469328 (3:9370661 G>T), RS1000479284 (3:9375842 T>C), RS1000636378 (3:9364644 G>A,T), RS1000785466 (3:9386531 C>A,T), RS1000968347 (3:9381466 G>C), RS1000985847 (3:9364427 A>G), RS1001351164 (3:9369487 A>G), RS1001610466 (3:9376203 T>C,G), RS1001650188 (3:9378629 T>C), RS1001668851 (3:9382514 T>G), RS1001762311 (3:9383048 G>A,T), RS1001872001 (3:9363777 C>G,T), RS1001876070 (3:9379913 C>T)

Disease associations

OMIM: gene `` | disease phenotypes: MIM:613792

GenCC curated gene-disease

Mondo (1): 3p- syndrome (MONDO:0013424)

Orphanet (1): Distal deletion 3p syndrome (Orphanet:1620)

HPO phenotypes

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

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C536804	Chromosome 3, monosomy 3p (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
mercuric bromide	increases expression, affects cotreatment	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	2
Phenylmercuric Acetate	increases expression, affects cotreatment	2
Cadmium Chloride	decreases expression, increases expression	2
p-Chloromercuribenzoic Acid	increases expression, affects cotreatment	2
aristolochic acid I	decreases expression	1
FR900359	increases phosphorylation	1
triphenyl phosphate	affects expression	1
propionaldehyde	increases methylation	1
lead acetate	affects cotreatment, decreases expression	1
nonanal	increases methylation	1
sodium arsenate	decreases expression	1
salinomycin	decreases expression	1
n-hexanal	increases methylation	1
beta-lapachone	increases expression	1
sodium arsenite	decreases expression, affects cotreatment	1
butyraldehyde	increases methylation	1
coumarin	increases phosphorylation	1
caprylic aldehyde	increases methylation	1
pentanal	increases methylation	1
heptanal	increases methylation	1
di-n-butylphosphoric acid	affects expression	1
torcetrapib	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
jinfukang	decreases expression	1
LDN 193189	affects cotreatment, increases expression	1
(+)-JQ1 compound	decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Sunitinib	decreases expression	1
Air Pollutants	affects expression, increases abundance	1

Clinical trials (associated diseases)

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