DTWD1

Summary

DTWD1 (DTW motif tRNA-uridine aminocarboxypropyltransferase 1, HGNC:30926) is a protein-coding gene on chromosome 15q21.2, encoding tRNA-uridine aminocarboxypropyltransferase 1 (Q8N5C7). Catalyzes the formation of 3-(3-amino-3-carboxypropyl)uridine (acp3U) at position 20 in the D-loop of several cytoplasmic tRNAs (acp3U(20)).

Enables tRNA-uridine aminocarboxypropyltransferase activity. Involved in tRNA modification. Located in nucleus.

Source: NCBI Gene 56986 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 45 total
• MANE Select transcript: NM_001144955

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30926
Approved symbol	DTWD1
Name	DTW motif tRNA-uridine aminocarboxypropyltransferase 1
Location	15q21.2
Locus type	gene with protein product
Status	Approved
Aliases	MDS009, MGC111207
Ensembl gene	ENSG00000104047
Ensembl biotype	protein_coding
OMIM	621116
Entrez	56986

Gene structure

Transcript identifiers

Ensembl transcripts: 30 — 25 protein_coding, 2 nonsense_mediated_decay, 2 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000251250, ENST00000403028, ENST00000557968, ENST00000557988, ENST00000558653, ENST00000559164, ENST00000559223, ENST00000559405, ENST00000560632, ENST00000560735, ENST00000561188, ENST00000861606, ENST00000861607, ENST00000861608, ENST00000861609, ENST00000861610, ENST00000861611, ENST00000861612, ENST00000861613, ENST00000861614, ENST00000916087, ENST00000916088, ENST00000916089, ENST00000916090, ENST00000916091, ENST00000916092, ENST00000916093, ENST00000941441, ENST00000941442, ENST00000941443

RefSeq mRNA: 2 — MANE Select: NM_001144955 NM_001144955, NM_020234

CCDS: CCDS10132

Canonical transcript exons

ENST00000403028 — 5 exons

Exon	Start	End
ENSE00002539156	49621048	49621122
ENSE00002583991	49643331	49656232
ENSE00003486011	49625113	49625431
ENSE00003499126	49632159	49632302
ENSE00003592361	49634536	49634794

Expression profiles

Bgee: expression breadth ubiquitous, 253 present calls, max score 96.81.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 21.2921 / max 335.0840, expressed in 1770 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
146577	20.6227	1769
146575	0.5648	284
146576	0.1046	41

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	96.81	gold quality
body of pancreas	UBERON:0001150	95.81	gold quality
mucosa of stomach	UBERON:0001199	95.49	gold quality
gall bladder	UBERON:0002110	94.91	gold quality
endocervix	UBERON:0000458	94.46	gold quality
left ovary	UBERON:0002119	93.49	gold quality
body of uterus	UBERON:0009853	93.26	gold quality
left uterine tube	UBERON:0001303	93.20	gold quality
tibial nerve	UBERON:0001323	92.71	gold quality
stromal cell of endometrium	CL:0002255	92.64	gold quality
right ovary	UBERON:0002118	92.61	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	92.27	gold quality
descending thoracic aorta	UBERON:0002345	92.01	gold quality
ectocervix	UBERON:0012249	91.97	gold quality
muscle layer of sigmoid colon	UBERON:0035805	91.90	gold quality
lower esophagus muscularis layer	UBERON:0035833	91.72	gold quality
lower esophagus	UBERON:0013473	91.71	gold quality
rectum	UBERON:0001052	91.68	gold quality
pancreas	UBERON:0001264	91.67	gold quality
omental fat pad	UBERON:0010414	91.63	gold quality
peritoneum	UBERON:0002358	91.56	gold quality
tibial artery	UBERON:0007610	91.37	gold quality
popliteal artery	UBERON:0002250	91.35	gold quality
subcutaneous adipose tissue	UBERON:0002190	90.93	gold quality
aorta	UBERON:0000947	90.88	gold quality
adipose tissue of abdominal region	UBERON:0007808	90.85	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	90.64	gold quality
thoracic aorta	UBERON:0001515	90.63	gold quality
ascending aorta	UBERON:0001496	90.55	gold quality
left coronary artery	UBERON:0001626	90.53	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	8.22

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

73 targeting DTWD1, 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-190A-3P	100.00	80.35	5520
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-3682-5P	99.93	67.97	1163
HSA-MIR-6835-3P	99.93	70.49	2904
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-4698	99.84	71.41	4303
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-139-5P	99.80	69.50	1399
HSA-MIR-4517	99.76	69.19	1867
HSA-MIR-3617-5P	99.75	69.41	1968
HSA-MIR-641	99.75	69.35	1975
HSA-MIR-4719	99.73	72.10	3329
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-1296-3P	99.72	64.04	636
HSA-MIR-33A-3P	99.70	70.27	3362
HSA-MIR-379-3P	99.69	69.60	1524
HSA-MIR-411-3P	99.69	69.63	1524
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-4530	99.69	66.47	1509
HSA-MIR-3679-3P	99.64	69.88	1599
HSA-MIR-7150	99.62	66.80	1322
HSA-MIR-3616-5P	99.55	67.02	989
HSA-MIR-573	99.55	67.44	955
HSA-MIR-3120-3P	99.54	70.28	2669
HSA-MIR-6081	99.48	66.07	1446

Literature-anchored findings (GeneRIF, showing 1)

• Inactivating mutations of tumor suppressor genes KLOTHO and DTWD1 in colorectal cancers. (PMID:31924336)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	dtwd1	ENSDARG00000111509
mus_musculus	Dtwd1	ENSMUSG00000023330
rattus_norvegicus	Dtwd1	ENSRNOG00000009593
drosophila_melanogaster	CG2006	FBGN0039664
caenorhabditis_elegans		WBGENE00175030

Paralogs (1): YIPF3 (ENSG00000137207)

Protein

Protein identifiers

tRNA-uridine aminocarboxypropyltransferase 1 — Q8N5C7 (reviewed: Q8N5C7)

Alternative names: DTW domain-containing protein 1

All UniProt accessions (5): Q8N5C7, H0YK73, H0YL61, H0YML0, H0YMP4

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the formation of 3-(3-amino-3-carboxypropyl)uridine (acp3U) at position 20 in the D-loop of several cytoplasmic tRNAs (acp3U(20)).

Subcellular location. Nucleus.

Similarity. Belongs to the TDD superfamily. DTWD1 family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q8N5C7-1	1	yes
Q8N5C7-2	2
Q8N5C7-3	3

RefSeq proteins (2): NP_001138427, NP_064619 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR005636	DTW	Domain
IPR051521	DTWD1/YIPF3	Family

Pfam: PF03942

Catalyzed reactions (Rhea), 1 shown:

• a uridine in tRNA + S-adenosyl-L-methionine = a 3-[(3S)-3-amino-3-carboxypropyl]uridine in tRNA + S-methyl-5’-thioadenosine + H(+) (RHEA:62432)

UniProt features (9 total): sequence variant 3, splice variant 2, initiator methionine 1, chain 1, short sequence motif 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8N5C7-F1	80.50	0.62

Functional residue map

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

Post-translational modifications (1): 2

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 169 (showing top): GOBP_TRNA_METABOLIC_PROCESS, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, BEIER_GLIOMA_STEM_CELL_DN, AACWWCAANK_UNKNOWN, FERREIRA_EWINGS_SARCOMA_UNSTABLE_VS_STABLE_DN, GOBP_RNA_MODIFICATION, NAKAMURA_TUMOR_ZONE_PERIPHERAL_VS_CENTRAL_DN, ACEVEDO_LIVER_CANCER_UP, GOBP_TRNA_PROCESSING, ZHAN_MULTIPLE_MYELOMA_CD1_AND_CD2_DN, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_DN, GOBP_TRNA_MODIFICATION, ACEVEDO_LIVER_CANCER_WITH_H3K27ME3_DN, NUYTTEN_EZH2_TARGETS_DN, HAMAI_APOPTOSIS_VIA_TRAIL_UP

GO Biological Process (2): tRNA modification (GO:0006400), tRNA processing (GO:0008033)

GO Molecular Function (2): tRNA-uridine aminocarboxypropyltransferase activity (GO:0016432), transferase activity (GO:0016740)

GO Cellular Component (1): nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
tRNA processing	1
RNA modification	1
RNA processing	1
tRNA metabolic process	1
transferase activity, transferring alkyl or aryl (other than methyl) groups	1
catalytic activity, acting on a tRNA	1
catalytic activity	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

526 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DTWD1	DTWD2	Q8NBA8	757
DTWD1	TSR3	Q9UJK0	709
DTWD1	ZNF98	A6NK75	567
DTWD1	CCDC85C	A6NKD9	529
DTWD1	DUS4L	O95620	523
DTWD1	DUS2	Q9NX74	512
DTWD1	ZNF653	Q96CK0	480
DTWD1	ZBTB39	O15060	475
DTWD1	MPHOSPH10	O00566	474
DTWD1	NIFK	Q9BYG3	459
DTWD1	NKPD1	Q17RQ9	448
DTWD1	TYW2	Q53H54	446
DTWD1	EBNA1BP2	Q99848	445
DTWD1	ZNF827	Q17R98	430
DTWD1	SACK1F	Q8NEG4	413

IntAct

8 interactions, top by confidence:

A	B	Type	Score
SLC31A1	C2orf72	psi-mi:“MI:0914”(association)	0.530
SLC31A1	PRORP	psi-mi:“MI:0914”(association)	0.530
MAD2L2		psi-mi:“MI:0914”(association)	0.350
DTWD1	ACTA2	psi-mi:“MI:0914”(association)	0.350
LY86	TMEM131L	psi-mi:“MI:0914”(association)	0.350
NUBP2	TK2	psi-mi:“MI:0914”(association)	0.350
DTWD1	HP	psi-mi:“MI:0914”(association)	0.350

BioGRID (16): DTWD1 (Affinity Capture-MS), DTWD1 (Affinity Capture-MS), DTWD1 (Reconstituted Complex), DTWD1 (Affinity Capture-MS), DTWD1 (Positive Genetic), DTWD1 (Affinity Capture-MS), GALM (Affinity Capture-MS), ACTA2 (Affinity Capture-MS), SPATA33 (Affinity Capture-MS), HBA2 (Affinity Capture-MS), DTWD1 (Affinity Capture-MS), HBB (Affinity Capture-MS), APOA1 (Affinity Capture-MS), DTWD1 (Affinity Capture-MS), HP (Affinity Capture-MS)

ESM2 similar proteins: A1KXW8, A6QL50, E1BGQ2, H0Y354, O94955, P47224, Q08326, Q0IIH8, Q1JQA1, Q1RMS8, Q1RMZ1, Q2TBU5, Q3T1H6, Q4R372, Q4R528, Q4R9C4, Q5F480, Q5F4A1, Q5I0G3, Q5RCQ0, Q5RFG8, Q5TFE4, Q5TYM5, Q641X7, Q6L9T8, Q6PIP5, Q7L622, Q7Z6J8, Q7ZX59, Q86X60, Q8BFZ8, Q8BKW4, Q8BM85, Q8BX13, Q8CEL2, Q8N5C7, Q8N635, Q8NHU2, Q8TCF1, Q8TCJ0

Diamond homologs: Q28I29, Q5RCQ0, Q5XJ56, Q6AYF5, Q6DDV1, Q8N5C7, Q9D8U7

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	38
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1451 predictions. Top by Δscore:

Variant	Effect	Δscore
15:49621206:G:GT	donor_gain	1.0000
15:49632300:G:GT	donor_gain	1.0000
15:49632300:GAA:G	donor_gain	1.0000
15:49632303:G:GG	donor_gain	1.0000
15:49634530:TTTTA:T	acceptor_loss	1.0000
15:49634531:TTTA:T	acceptor_loss	1.0000
15:49634533:TA:T	acceptor_loss	1.0000
15:49634535:G:GT	acceptor_loss	1.0000
15:49643389:A:T	donor_gain	1.0000
15:49643478:GGCAA:G	donor_gain	1.0000
15:49621206:G:T	donor_gain	0.9900
15:49621237:G:GT	donor_gain	0.9900
15:49625111:A:AG	acceptor_gain	0.9900
15:49625112:G:GG	acceptor_gain	0.9900
15:49625112:GT:G	acceptor_gain	0.9900
15:49632157:A:AG	acceptor_gain	0.9900
15:49632158:G:GG	acceptor_gain	0.9900
15:49632294:GACCA:G	donor_gain	0.9900
15:49634534:A:AG	acceptor_gain	0.9900
15:49634535:G:GG	acceptor_gain	0.9900
15:49634535:GGTT:G	acceptor_gain	0.9900
15:49632307:GCAAC:G	donor_gain	0.9800
15:49634534:AGGTT:A	acceptor_gain	0.9800
15:49634535:GGT:G	acceptor_gain	0.9800
15:49634535:GGTTG:G	acceptor_gain	0.9800
15:49634790:TCAAG:T	donor_loss	0.9800
15:49634791:CAAG:C	donor_loss	0.9800
15:49634792:AAG:A	donor_loss	0.9800
15:49634793:AGG:A	donor_loss	0.9800
15:49634794:GGTA:G	donor_loss	0.9800

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000056121 (15:49625915 A>G), RS1000269723 (15:49653355 C>T), RS1000279160 (15:49620598 A>T), RS1000325724 (15:49653168 T>C), RS1000361883 (15:49647749 G>A,T), RS1000368003 (15:49632048 T>C), RS1000512225 (15:49621829 T>C), RS1000618882 (15:49635310 T>A,C), RS1000714034 (15:49649344 A>G), RS1000714148 (15:49620813 G>A), RS1000867316 (15:49640332 A>G), RS1000981067 (15:49642025 C>G,T), RS1001008678 (15:49621606 A>G), RS1001033908 (15:49641202 A>C,G), RS1001065139 (15:49641617 C>T)

Disease associations

OMIM: gene MIM:621116 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST001308_17	Response to anti-depressant treatment in major depressive disorder	5.000000e-07
GCST004744_1	Lung adenocarcinoma	9.000000e-09
GCST004748_35	Lung cancer	3.000000e-06
GCST007692_110	Chronic obstructive pulmonary disease	8.000000e-09

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0006321	antidepressant-induced dizziness

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases stability	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Valproic Acid	affects expression, decreases expression	2
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, decreases expression, increases abundance	1
pirinixic acid	affects binding, increases activity, increases expression	1
bisphenol A	affects cotreatment, increases methylation	1
lead acetate	decreases expression	1
quercitrin	decreases expression	1
trichostatin A	affects expression	1
arsenite	affects binding, increases reaction	1
mono-(2-ethylhexyl)phthalate	decreases expression	1
methacrylaldehyde	decreases expression, increases abundance, affects cotreatment	1
beta-methylcholine	affects expression	1
garcinol	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
pomalidomide	decreases expression, increases degradation	1
dorsomorphin	affects cotreatment, increases expression	1
jinfukang	decreases expression	1
Temozolomide	increases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Vorinostat	increases expression	1
Panobinostat	decreases expression	1
Acetaminophen	decreases expression	1
Acrolein	affects cotreatment, decreases expression, increases abundance	1
Air Pollutants	decreases expression, increases abundance, affects cotreatment	1
Vehicle Emissions	increases abundance, increases expression	1
Calcitriol	increases expression	1
Camptothecin	increases expression	1

Clinical trials (associated diseases)

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