DTWD2

Summary

DTWD2 (DTW motif tRNA-uridine aminocarboxypropyltransferase 2, HGNC:19334) is a protein-coding gene on chromosome 5q23.1, encoding tRNA-uridine aminocarboxypropyltransferase 2 (Q8NBA8). Catalyzes the formation of 3-(3-amino-3-carboxypropyl)uridine (acp3U) at position 20a in the D-loop of several cytoplasmic tRNAs (acp3U(20a)).

Enables tRNA-uridine aminocarboxypropyltransferase activity. Involved in RNA glycosylation and tRNA modification. Located in cytoplasm and nucleus.

Source: NCBI Gene 285605 — RefSeq curated summary.

At a glance

• GWAS associations: 13
• Clinical variants (ClinVar): 94 total
• MANE Select transcript: NM_173666

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19334
Approved symbol	DTWD2
Name	DTW motif tRNA-uridine aminocarboxypropyltransferase 2
Location	5q23.1
Locus type	gene with protein product
Status	Approved
Aliases	FLJ33977
Ensembl gene	ENSG00000169570
Ensembl biotype	protein_coding
OMIM	621117
Entrez	285605

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 6 protein_coding, 1 nonsense_mediated_decay

ENST00000304058, ENST00000506980, ENST00000510708, ENST00000515439, ENST00000884864, ENST00000944323, ENST00000944324

RefSeq mRNA: 2 — MANE Select: NM_173666 NM_001308081, NM_173666

CCDS: CCDS34216, CCDS78050

Canonical transcript exons

ENST00000510708 — 6 exons

Exon	Start	End
ENSE00001130442	118988294	118988547
ENSE00001131925	118928537	118928729
ENSE00002034231	118836074	118841087
ENSE00002223132	118939196	118939290
ENSE00002303012	118944559	118944649
ENSE00003558821	118848090	118848218

Expression profiles

Bgee: expression breadth ubiquitous, 223 present calls, max score 90.43.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 5.6473 / max 48.9428, expressed in 1586 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
63069	5.6473	1586

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
upper arm skin	UBERON:0004263	90.43	gold quality
epithelial cell of pancreas	CL:0000083	88.67	gold quality
secondary oocyte	CL:0000655	87.71	gold quality
kidney epithelium	UBERON:0004819	87.58	gold quality
oocyte	CL:0000023	86.62	gold quality
pancreatic ductal cell	CL:0002079	86.04	silver quality
vena cava	UBERON:0004087	85.56	silver quality
vastus lateralis	UBERON:0001379	85.43	silver quality
epithelium of nasopharynx	UBERON:0001951	85.18	silver quality
subthalamic nucleus	UBERON:0001906	85.15	silver quality
ventral tegmental area	UBERON:0002691	84.20	silver quality
dorsal plus ventral thalamus	UBERON:0001897	84.09	silver quality
quadriceps femoris	UBERON:0001377	83.99	silver quality
body of tongue	UBERON:0011876	83.92	silver quality
tongue	UBERON:0001723	83.89	silver quality
superior surface of tongue	UBERON:0007371	83.83	silver quality
inferior vagus X ganglion	UBERON:0005363	83.50	silver quality
trachea	UBERON:0003126	83.31	gold quality
pharyngeal mucosa	UBERON:0000355	83.06	silver quality
pericardium	UBERON:0002407	82.99	silver quality
pylorus	UBERON:0001166	82.98	silver quality
lateral globus pallidus	UBERON:0002476	82.94	silver quality
dorsal root ganglion	UBERON:0000044	82.93	silver quality
pons	UBERON:0000988	82.89	silver quality
deltoid	UBERON:0001476	82.89	silver quality
nipple	UBERON:0002030	82.83	silver quality
medulla oblongata	UBERON:0001896	82.82	silver quality
saphenous vein	UBERON:0007318	82.80	gold quality
lateral nuclear group of thalamus	UBERON:0002736	82.78	gold quality
substantia nigra pars compacta	UBERON:0001965	82.71	silver quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.83
E-GEOD-109979	no	107.17

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

206 targeting DTWD2, 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-3646	100.00	73.56	5283
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4682	100.00	68.89	1258
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-568	99.98	69.86	2084
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-3148	99.97	75.06	6478

Literature-anchored findings (GeneRIF, showing 1)

• The rs17144687 near DTWD2 associated with MaxDirnks. (PMID:23953852)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	dtwd2	ENSDARG00000101873
mus_musculus	Dtwd2	ENSMUSG00000024505
rattus_norvegicus	Dtwd2	ENSRNOG00000059142
drosophila_melanogaster	Dtwd2	FBGN0037492

Protein

Protein identifiers

tRNA-uridine aminocarboxypropyltransferase 2 — Q8NBA8 (reviewed: Q8NBA8)

Alternative names: DTW domain-containing protein 2

All UniProt accessions (3): D6RBD8, D6REE2, Q8NBA8

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the formation of 3-(3-amino-3-carboxypropyl)uridine (acp3U) at position 20a in the D-loop of several cytoplasmic tRNAs (acp3U(20a)). Also has a weak activity to form acp3U at position 20 in the D-loop of tRNAs (acp3U(20)). Involved in glycoRNA biosynthesis by mediating formation of acp3U, which acts as an attachment site for N-glycans on tRNAs. GlycoRNAs consist of RNAs modified with secretory N-glycans that are presented on the cell surface.

Subcellular location. Cytoplasm Nucleus. Cytoplasm.

Similarity. Belongs to the TDD superfamily. DTWD2 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8NBA8-1	1, DTWD2L, Long	yes
Q8NBA8-2	2, DTWD2S, Short

RefSeq proteins (2): NP_001295010, NP_775937* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR005636	DTW	Domain
IPR039262	DTWD2/TAPT	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 (7 total): modified residue 2, chain 1, region of interest 1, short sequence motif 1, compositionally biased region 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8NBA8-F1	83.75	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 (2): 1, 132

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 95 (showing top): GOBP_TRNA_METABOLIC_PROCESS, GOBP_RNA_MODIFICATION, AP2_Q6_01, GOBP_TRNA_PROCESSING, GOBP_TRNA_MODIFICATION, LU_EZH2_TARGETS_DN, GOMF_CATALYTIC_ACTIVITY_ACTING_ON_RNA, GOMF_CATALYTIC_ACTIVITY_ACTING_ON_A_TRNA, GSE13522_WT_VS_IFNAR_KO_SKING_T_CRUZI_Y_STRAIN_INF_DN, ARNT2_TARGET_GENES, CBX5_TARGET_GENES, TEAD2_TARGET_GENES, ZNF618_TARGET_GENES, ZNF711_TARGET_GENES, MIR12136

GO Biological Process (3): tRNA modification (GO:0006400), glycoRNA biosynthetic process (GO:0141217), tRNA processing (GO:0008033)

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

GO Cellular Component (2): nucleus (GO:0005634), cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
RNA processing	2
tRNA processing	1
RNA modification	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
intracellular anatomical structure	1
cellular anatomical structure	1

Protein interactions and networks

STRING

472 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DTWD2	DTWD1	Q8N5C7	757
DTWD2	TSR3	Q9UJK0	733
DTWD2	DUS2	Q9NX74	530
DTWD2	TRMT1	Q9NXH9	498
DTWD2	DUS4L	O95620	494
DTWD2	NUDT13	Q86X67	492
DTWD2	TTC23L	Q6PF05	484
DTWD2	EIPR1	Q53HC9	480
DTWD2	MSL1	Q68DK7	459
DTWD2	ZNF460	Q14592	447
DTWD2	C12orf56	Q8IXR9	447
DTWD2	OCRL	Q01968	422
DTWD2	BRIX1	Q8TDN6	416
DTWD2	SERINC1	Q9NRX5	411
DTWD2	ARSK	Q6UWY0	410

IntAct

17 interactions, top by confidence:

A	B	Type	Score
	TOMM70	psi-mi:“MI:0914”(association)	0.690
MAD2L2		psi-mi:“MI:0914”(association)	0.350
DTWD2	ERBB2	psi-mi:“MI:0914”(association)	0.350
M		psi-mi:“MI:0914”(association)	0.350
ATG16L1	ESYT2	psi-mi:“MI:0914”(association)	0.350
DTWD2	DNAJA2	psi-mi:“MI:0914”(association)	0.350
TUBB		psi-mi:“MI:0914”(association)	0.350
DTWD2	ATP1A3	psi-mi:“MI:0914”(association)	0.350
DCAF8	RFPL4A	psi-mi:“MI:0914”(association)	0.350
LYPD1	ADAM10	psi-mi:“MI:0914”(association)	0.350
MAGEA8	B4GALT5	psi-mi:“MI:0914”(association)	0.350
TUBB	VWA8	psi-mi:“MI:0914”(association)	0.350
TUBB2A	TXNDC9	psi-mi:“MI:0914”(association)	0.350
SLC1A3	DDX11L8	psi-mi:“MI:0914”(association)	0.350
SLC30A8	UPK3BL1	psi-mi:“MI:0914”(association)	0.350
SLC39A12	ESYT2	psi-mi:“MI:0914”(association)	0.350

BioGRID (46): MFAP3 (Affinity Capture-MS), POLE (Affinity Capture-MS), FREM2 (Affinity Capture-MS), PCDH7 (Affinity Capture-MS), PC (Affinity Capture-MS), TUBB8 (Affinity Capture-MS), CBWD1 (Affinity Capture-MS), ERBB2 (Affinity Capture-MS), PEX1 (Affinity Capture-MS), FAT3 (Affinity Capture-MS), CELSR2 (Affinity Capture-MS), MFAP3 (Affinity Capture-MS), CELSR2 (Affinity Capture-MS), ERBB2 (Affinity Capture-MS), CBWD1 (Affinity Capture-MS)

ESM2 similar proteins: A2AIG8, A6NFX1, O15315, O35083, O35719, O35790, O43502, O54783, O54804, O55229, O73884, P16442, P20417, P35790, P35821, P47802, Q01134, Q08DW9, Q27HK4, Q2TBS1, Q3T9M1, Q3U129, Q4R3I0, Q4R766, Q4R7M4, Q5E9H2, Q5E9T4, Q5SUV1, Q5SX19, Q5VYX0, Q6GV29, Q86XW9, Q8BVM4, Q8CIW5, Q8N2K0, Q8NBA8, Q8QGV6, Q8R2J9, Q8TCT0, Q924H5

Diamond homologs: Q4R7M4, Q8NBA8, Q9D0U1, Q9VI85

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	83
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2413 predictions. Top by Δscore:

Variant	Effect	Δscore
5:118848085:CGTA:C	donor_loss	1.0000
5:118848086:GTA:G	donor_loss	1.0000
5:118848087:TACCT:T	donor_loss	1.0000
5:118848088:A:C	donor_loss	1.0000
5:118848089:C:A	donor_loss	1.0000
5:118848089:CCT:C	donor_gain	1.0000
5:118848217:ACC:A	acceptor_loss	1.0000
5:118848218:CCTG:C	acceptor_loss	1.0000
5:118848219:CTGAA:C	acceptor_loss	1.0000
5:118928532:TTTA:T	donor_loss	1.0000
5:118928533:TTAC:T	donor_loss	1.0000
5:118928534:TAC:T	donor_loss	1.0000
5:118928535:ACCT:A	donor_loss	1.0000
5:118928536:C:T	donor_loss	1.0000
5:118928582:AG:A	donor_gain	1.0000
5:118939191:TTTAC:T	donor_loss	1.0000
5:118939192:TTA:T	donor_loss	1.0000
5:118939193:TACC:T	donor_loss	1.0000
5:118939194:A:AT	donor_loss	1.0000
5:118939293:T:TC	acceptor_gain	1.0000
5:118939297:T:TC	acceptor_gain	1.0000
5:118988311:AGG:A	donor_gain	1.0000
5:118848088:A:AC	donor_gain	0.9900
5:118848089:C:CC	donor_gain	0.9900
5:118848214:TGCAC:T	acceptor_gain	0.9900
5:118848216:CAC:C	acceptor_gain	0.9900
5:118848219:C:CC	acceptor_gain	0.9900
5:118848226:C:CT	acceptor_gain	0.9900
5:118852397:A:AC	donor_gain	0.9900
5:118928728:CT:C	acceptor_gain	0.9900

AlphaMissense

1937 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:118928593:A:G	W181R	1.000
5:118928593:A:T	W181R	1.000
5:118928584:C:G	A184P	0.999
5:118928591:C:A	W181C	0.999
5:118928591:C:G	W181C	0.999
5:118928598:C:T	G179D	0.999
5:118928601:T:A	D178V	0.999
5:118928680:A:C	Y152D	0.999
5:118944568:A:C	H100Q	0.999
5:118944568:A:T	H100Q	0.999
5:118944569:T:C	H100R	0.999
5:118944578:A:T	I97K	0.999
5:118841058:G:C	C252W	0.998
5:118928583:G:T	A184D	0.998
5:118928598:C:A	G179V	0.998
5:118928599:C:G	G179R	0.998
5:118928600:A:C	D178E	0.998
5:118928600:A:T	D178E	0.998
5:118939268:A:T	V111D	0.998
5:118988298:A:G	C72R	0.998
5:118841047:A:G	L256P	0.997
5:118848124:A:G	L231P	0.997
5:118848133:G:T	A228D	0.997
5:118848134:C:G	A228P	0.997
5:118848136:G:T	A227E	0.997
5:118848178:C:G	R213P	0.997
5:118848181:A:T	I212N	0.997
5:118848188:A:G	Y210H	0.997
5:118848192:A:C	S208R	0.997
5:118848192:A:T	S208R	0.997

dbSNP variants (sampled 300 via entrez): RS1000002862 (5:118840502 C>A,G,T), RS1000029029 (5:118870794 G>A), RS1000042596 (5:118914522 G>A), RS1000053137 (5:118950159 G>A), RS1000062637 (5:118836245 T>A,G), RS1000110073 (5:118907906 C>A,T), RS1000114922 (5:118866619 A>C), RS1000156083 (5:118948084 T>C), RS1000172837 (5:118981101 G>A,C,T), RS1000182641 (5:118964149 C>T), RS1000203166 (5:118907589 G>A,C), RS1000228708 (5:118861993 G>A), RS1000236746 (5:118883835 A>G), RS1000239487 (5:118837044 TA>T), RS1000286900 (5:118918392 T>A,G)

Disease associations

OMIM: gene MIM:621117 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

13 associations (top):

Study	Trait	p-value
GCST001521_11	Subcutaneous adipose tissue	5.000000e-07
GCST002875_61	Diisocyanate-induced asthma	3.000000e-06
GCST004070_9	Cerebrospinal P-tau181p levels	8.000000e-06
GCST004071_10	Cerebrospinal T-tau levels	2.000000e-06
GCST004570_19	Iron status biomarkers (iron levels)	1.000000e-07
GCST005183_1	Common carotid intima-media thickness	6.000000e-06
GCST005183_5	Common carotid intima-media thickness	3.000000e-06
GCST005184_7	Common carotid intima-media thickness in HIV infection	7.000000e-06
GCST005956_40	Waist-to-hip ratio adjusted for BMI	2.000000e-06
GCST005958_18	Waist-to-hip ratio adjusted for BMI (age >50)	9.000000e-07
GCST005962_27	Waist-to-hip ratio adjusted for BMI x sex x age interaction (4df test)	9.000000e-09
GCST007325_24	General risk tolerance (MTAG)	4.000000e-08
GCST009798_70	Asthma	3.000000e-11

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0006995	response to diisocyanate
EFO:0004763	p-tau measurement
EFO:0004760	t-tau measurement
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0008007	age at assessment
EFO:0008343	sex interaction measurement
EFO:0008579	risk-taking behaviour

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Particulate Matter	increases abundance, increases expression, affects cotreatment, decreases expression	2
aristolochic acid I	decreases expression	1
urushiol	increases expression	1
triphenyl phosphate	affects expression	1
sodium arsenite	increases expression	1
butyraldehyde	decreases expression	1
perfluorooctanoic acid	increases expression	1
potassium chromate(VI)	decreases expression, affects cotreatment	1
epigallocatechin gallate	decreases expression, affects cotreatment	1
pentanal	decreases expression	1
CGP 52608	affects binding, increases reaction	1
ICG 001	increases expression	1
abrine	decreases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Zoledronic Acid	decreases expression	1
Air Pollutants	increases expression, increases abundance	1
Doxorubicin	decreases expression	1
Endosulfan	decreases expression	1
Estradiol	affects cotreatment, decreases expression	1
Folic Acid	decreases expression	1
Gasoline	affects cotreatment, decreases expression, increases abundance	1
Hydrogen Peroxide	affects expression	1
Polycyclic Aromatic Hydrocarbons	affects cotreatment, decreases expression, increases abundance	1
Tobacco Smoke Pollution	decreases expression	1
Urethane	decreases expression	1
Cyclosporine	increases expression	1
Aflatoxin B1	decreases expression	1
Asbestos, Crocidolite	decreases expression	1
Copper Sulfate	decreases expression	1
1-Butanol	affects cotreatment, decreases expression, increases abundance	1

Clinical trials (associated diseases)

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