DUS3L

Summary

DUS3L (dihydrouridine synthase 3 like, HGNC:26920) is a protein-coding gene on chromosome 19p13.3, encoding tRNA-dihydrouridine(47) synthase [NAD(P)(+)]-like (Q96G46). Catalyzes the synthesis of dihydrouridine, a modified base, in various RNAs, such as tRNAs, mRNAs and some long non-coding RNAs (lncRNAs).

Enables mRNA dihydrouridine synthase activity and tRNA-dihydrouridine47 synthase activity. Involved in regulation of translation and tRNA dihydrouridine synthesis.

Source: NCBI Gene 56931 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 145 total
• MANE Select transcript: NM_020175

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26920
Approved symbol	DUS3L
Name	dihydrouridine synthase 3 like
Location	19p13.3
Locus type	gene with protein product
Status	Approved
Aliases	DUS3, FLJ13896
Ensembl gene	ENSG00000141994
Ensembl biotype	protein_coding
OMIM	621104
Entrez	56931

Gene structure

Transcript identifiers

Ensembl transcripts: 20 — 9 protein_coding, 6 retained_intron, 4 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000309061, ENST00000320699, ENST00000585587, ENST00000589085, ENST00000589841, ENST00000589854, ENST00000590087, ENST00000590110, ENST00000590343, ENST00000590681, ENST00000591560, ENST00000592468, ENST00000592491, ENST00000592673, ENST00000593229, ENST00000880234, ENST00000880235, ENST00000931382, ENST00000931383, ENST00000958714

RefSeq mRNA: 2 — MANE Select: NM_020175 NM_001161619, NM_020175

CCDS: CCDS32880, CCDS54202

Canonical transcript exons

ENST00000309061 — 13 exons

Exon	Start	End
ENSE00001159131	5787061	5787171
ENSE00001261412	5786749	5786845
ENSE00001504864	5789207	5789719
ENSE00001504865	5790047	5790335
ENSE00002735666	5791044	5791163
ENSE00003464551	5787296	5787361
ENSE00003464703	5785383	5785511
ENSE00003482156	5788357	5788398
ENSE00003495680	5785140	5785275
ENSE00003518035	5787589	5787705
ENSE00003535904	5786467	5786542
ENSE00003572520	5788024	5788176
ENSE00003586434	5785603	5785791

Expression profiles

Bgee: expression breadth ubiquitous, 208 present calls, max score 95.08.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 16.9598 / max 217.6313, expressed in 1794 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
178562	15.1617	1787
178563	1.7981	918

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right testis	UBERON:0004534	95.08	gold quality
left testis	UBERON:0004533	94.98	gold quality
granulocyte	CL:0000094	94.92	gold quality
right uterine tube	UBERON:0001302	94.91	gold quality
lower esophagus mucosa	UBERON:0035834	94.51	gold quality
skin of abdomen	UBERON:0001416	93.64	gold quality
right lobe of thyroid gland	UBERON:0001119	93.51	gold quality
left uterine tube	UBERON:0001303	93.29	gold quality
skin of leg	UBERON:0001511	92.98	gold quality
minor salivary gland	UBERON:0001830	92.83	gold quality
left ovary	UBERON:0002119	92.55	gold quality
left lobe of thyroid gland	UBERON:0001120	92.54	gold quality
sural nerve	UBERON:0015488	92.30	gold quality
metanephros cortex	UBERON:0010533	92.25	gold quality
right ovary	UBERON:0002118	92.21	gold quality
right lobe of liver	UBERON:0001114	92.04	gold quality
small intestine Peyer’s patch	UBERON:0003454	92.00	gold quality
testis	UBERON:0000473	91.80	gold quality
body of pancreas	UBERON:0001150	91.65	gold quality
esophagus mucosa	UBERON:0002469	91.61	gold quality
body of stomach	UBERON:0001161	91.49	gold quality
apex of heart	UBERON:0002098	91.35	gold quality
body of uterus	UBERON:0009853	91.07	gold quality
endocervix	UBERON:0000458	90.99	gold quality
adenohypophysis	UBERON:0002196	90.99	gold quality
ectocervix	UBERON:0012249	90.98	gold quality
thyroid gland	UBERON:0002046	90.76	gold quality
transverse colon	UBERON:0001157	90.73	gold quality
zone of skin	UBERON:0000014	90.58	gold quality
spleen	UBERON:0002106	90.56	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.36

Regulation

Is transcription factor: no

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	dus3l	ENSDARG00000099528
mus_musculus	Dus3l	ENSMUSG00000007603
rattus_norvegicus	Dus3l	ENSRNOG00000050381
drosophila_melanogaster	Dus3	FBGN0032819
caenorhabditis_elegans		WBGENE00021377

Paralogs (3): DUS4L (ENSG00000105865), DUS2 (ENSG00000167264), DUS1L (ENSG00000169718)

Protein

Protein identifiers

tRNA-dihydrouridine(47) synthase [NAD(P)(+)]-like — Q96G46 (reviewed: Q96G46)

Alternative names: mRNA-dihydrouridine synthase DUS3L, tRNA-dihydrouridine synthase 3-like

All UniProt accessions (7): Q96G46, K7EJX8, K7EM42, K7EPA4, K7EQU9, K7ER20, K7ERF2

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the synthesis of dihydrouridine, a modified base, in various RNAs, such as tRNAs, mRNAs and some long non-coding RNAs (lncRNAs). Mainly modifies the uridine in position 47 (U47) in the D-loop of most cytoplasmic tRNAs. Also able to mediate the formation of dihydrouridine in some mRNAs, thereby regulating their translation.

Miscellaneous. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

Similarity. Belongs to the Dus family. Dus3 subfamily.

Isoforms (3)

UniProt ID	Names	Canonical?
Q96G46-1	1	yes
Q96G46-2	2
Q96G46-3	3

RefSeq proteins (2): NP_001155091, NP_064560* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000571	Znf_CCCH	Domain
IPR013785	Aldolase_TIM	Homologous_superfamily
IPR018517	tRNA_hU_synthase_CS	Conserved_site
IPR035587	DUS-like_FMN-bd	Domain

Pfam: PF01207, PF25585

Catalyzed reactions (Rhea), 4 shown:

• 5,6-dihydrouridine(47) in tRNA + NADP(+) = uridine(47) in tRNA + NADPH + H(+) (RHEA:53360)
• 5,6-dihydrouridine(47) in tRNA + NAD(+) = uridine(47) in tRNA + NADH + H(+) (RHEA:53364)
• a 5,6-dihydrouridine in mRNA + NAD(+) = a uridine in mRNA + NADH + H(+) (RHEA:69851)
• a 5,6-dihydrouridine in mRNA + NADP(+) = a uridine in mRNA + NADPH + H(+) (RHEA:69855)

UniProt features (30 total): binding site 6, modified residue 5, splice variant 3, region of interest 3, compositionally biased region 3, zinc finger region 2, sequence variant 2, initiator methionine 1, chain 1, active site 1, cross-link 1, mutagenesis site 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96G46-F1	81.22	0.63

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 (1): 396 (proton donor)

Ligand- & substrate-binding residues (6): 311–313; 365; 435; 465; 497–499; 520–521

Post-translational modifications (6): 2, 236, 273, 276, 277, 416

Mutagenesis-validated functional residues (1):

Position	Phenotype
396	abolished synthesis of dihydrouridine.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 90 (showing top): SHEPARD_BMYB_MORPHOLINO_UP, GOMF_OXIDOREDUCTASE_ACTIVITY_ACTING_ON_THE_CH_CH_GROUP_OF_DONORS, GOBP_TRNA_METABOLIC_PROCESS, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, MONNIER_POSTRADIATION_TUMOR_ESCAPE_UP, GOBP_TRANSLATION, WEI_MYCN_TARGETS_WITH_E_BOX, GOBP_POST_TRANSCRIPTIONAL_REGULATION_OF_GENE_EXPRESSION, GOBP_RNA_MODIFICATION, SENESE_HDAC1_TARGETS_UP, DOUGLAS_BMI1_TARGETS_UP, GOBP_TRNA_PROCESSING, GOBP_TRNA_MODIFICATION, GOBP_REGULATION_OF_TRANSLATION, SANSOM_APC_TARGETS_REQUIRE_MYC

GO Biological Process (4): tRNA dihydrouridine synthesis (GO:0002943), mRNA processing (GO:0006397), regulation of translation (GO:0006417), tRNA processing (GO:0008033)

GO Molecular Function (9): RNA binding (GO:0003723), zinc ion binding (GO:0008270), tRNA dihydrouridine synthase activity (GO:0017150), flavin adenine dinucleotide binding (GO:0050660), tRNA-dihydrouridine47 synthase activity (GO:0102265), mRNA dihydrouridine synthase activity (GO:0106414), protein binding (GO:0005515), oxidoreductase activity (GO:0016491), metal ion binding (GO:0046872)

GO Cellular Component (0):

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
RNA processing	2
RNA dihydrouridine synthase activity	2
tRNA modification	1
mRNA metabolic process	1
translation	1
post-transcriptional regulation of gene expression	1
regulation of protein metabolic process	1
tRNA metabolic process	1
nucleic acid binding	1
transition metal ion binding	1
tRNA dihydrouridine synthesis	1
catalytic activity, acting on a tRNA	1
nucleotide binding	1
anion binding	1
tRNA dihydrouridine synthase activity	1
binding	1
catalytic activity	1
cation binding	1

Protein interactions and networks

STRING

1846 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DUS3L	WDR4	P57081	562
DUS3L	TRMT10A	Q8TBZ6	526
DUS3L	METTL1	Q9UBP6	522
DUS3L	PRR22	Q8IZ63	456
DUS3L	PUS7	Q96PZ0	421
DUS3L	TMEM247	A6NEH6	419
DUS3L	ZBED8L	Q8TCP9	419
DUS3L	TRMT1	Q9NXH9	419
DUS3L	TRIT1	Q9H3H1	412
DUS3L	PUS1	Q9Y606	410
DUS3L	Q3KRG4	Q3KRG4	409
DUS3L	SCAMP4	Q969E2	408
DUS3L	TRMT5	Q32P41	404
DUS3L	CCDC140	Q96MF4	399
DUS3L	NUTM2F	A1L443	396

IntAct

53 interactions, top by confidence:

A	B	Type	Score
OPTN	DUS3L	psi-mi:“MI:0915”(physical association)	0.560
CDC37	DUS3L	psi-mi:“MI:0915”(physical association)	0.400
TRADD	HNRNPCL2	psi-mi:“MI:0914”(association)	0.350
CDC16	KRBA1	psi-mi:“MI:0914”(association)	0.350
AVIL	DDX11L8	psi-mi:“MI:0914”(association)	0.350
NCAPH2	MYO9A	psi-mi:“MI:0914”(association)	0.350
C1QL4	SMC2	psi-mi:“MI:0914”(association)	0.350
SARS1	R3HCC1L	psi-mi:“MI:0914”(association)	0.350
PLEKHG4B	ARHGEF11	psi-mi:“MI:0914”(association)	0.350
ARHGEF40	ARHGEF11	psi-mi:“MI:0914”(association)	0.350
IGF1R	HAX1	psi-mi:“MI:0914”(association)	0.350
SSB	RPS3A	psi-mi:“MI:0914”(association)	0.350
CDC16	IFT56	psi-mi:“MI:0914”(association)	0.350
PPP4R1L	IFT56	psi-mi:“MI:0914”(association)	0.350
PTGES3	SBNO1	psi-mi:“MI:0914”(association)	0.350
ARSG	YDJC	psi-mi:“MI:0914”(association)	0.350
GPIHBP1	SAC3D1	psi-mi:“MI:0914”(association)	0.350
	POLRMT	psi-mi:“MI:0914”(association)	0.350
	PES1	psi-mi:“MI:0914”(association)	0.350
	POLR3A	psi-mi:“MI:0914”(association)	0.350
AVIL	DCTN6	psi-mi:“MI:0914”(association)	0.350
HNRNPCL2	SMCHD1	psi-mi:“MI:0914”(association)	0.350
	SUPT5H	psi-mi:“MI:0914”(association)	0.350

BioGRID (64): DUS3L (Affinity Capture-MS), DUS3L (Co-fractionation), DUS3L (Co-fractionation), DUS3L (Co-fractionation), EIF2A (Co-fractionation), TRMT6 (Co-fractionation), DUS3L (Synthetic Growth Defect), DUS3L (Affinity Capture-MS), DUS3L (Affinity Capture-MS), DUS3L (Affinity Capture-MS), DUS3L (Affinity Capture-MS), DUS3L (Affinity Capture-MS), DUS3L (Two-hybrid), DUS3L (Affinity Capture-MS), DUS3L (Affinity Capture-MS)

ESM2 similar proteins: A1A4I4, A4K436, A6QLH6, D3ZVM4, F1M5F3, F1N2W9, O00459, O08908, O43272, O60336, O95294, P0C928, P23726, P70268, Q0VGM9, Q16512, Q1JQD7, Q1PSW8, Q3KRC5, Q496Y0, Q5M9F8, Q5R812, Q5RE34, Q5RJZ1, Q5RKZ7, Q5XIS9, Q5ZIW1, Q63433, Q63788, Q6H1L8, Q6NS57, Q6NYU2, Q6PFQ7, Q8BZ03, Q8R1T1, Q91XI1, Q920N2, Q92889, Q92994, Q96G46

Diamond homologs: A1CNY3, A1D1U0, A2QAU6, A3LUK5, A4RLF4, A5DBS1, A5DTS1, A6QYC6, A6RMI1, A7A1S5, A7EKL8, A7TQ73, A8NZY7, A8PTG4, P0CN28, P0CN29, Q06053, Q0CZL3, Q0U9D6, Q1E2F4, Q28BT8, Q2HDP2, Q2UL89, Q3KRC5, Q4P1U2, Q4UNJ4, Q4WRX4, Q50049, Q54CU9, Q5ALL3, Q5BF62, Q6BS64, Q6C4K3, Q6CWM0, Q6FJ14, Q757E3, Q7SG01, Q7XT07, Q7ZWS1, Q91XI1

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 60 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.

GO biological processes:

GO term	Partners	Fold	FDR
cytoplasmic translation	5	17.5×	4e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	121
Likely benign	7
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1783 predictions. Top by Δscore:

Variant	Effect	Δscore
19:5785507:CGTAC:C	acceptor_gain	1.0000
19:5785508:GTAC:G	acceptor_gain	1.0000
19:5785509:TAC:T	acceptor_gain	1.0000
19:5785510:AC:A	acceptor_gain	1.0000
19:5785511:CC:C	acceptor_gain	1.0000
19:5785516:G:T	acceptor_gain	1.0000
19:5785518:C:CT	acceptor_gain	1.0000
19:5785519:G:T	acceptor_gain	1.0000
19:5785521:G:C	acceptor_gain	1.0000
19:5785521:G:GC	acceptor_gain	1.0000
19:5785599:CCA:C	donor_loss	1.0000
19:5785600:CAC:C	donor_loss	1.0000
19:5785601:A:AC	donor_gain	1.0000
19:5785602:C:CC	donor_gain	1.0000
19:5785602:C:CT	donor_loss	1.0000
19:5785622:A:AC	donor_gain	1.0000
19:5785623:C:CC	donor_gain	1.0000
19:5785654:C:CA	donor_gain	1.0000
19:5785761:C:CT	acceptor_gain	1.0000
19:5785787:CGCCA:C	acceptor_gain	1.0000
19:5785788:GCCA:G	acceptor_gain	1.0000
19:5785789:CCA:C	acceptor_gain	1.0000
19:5785789:CCAC:C	acceptor_gain	1.0000
19:5785790:CA:C	acceptor_gain	1.0000
19:5785790:CAC:C	acceptor_gain	1.0000
19:5785792:C:CC	acceptor_gain	1.0000
19:5786462:CTTA:C	donor_loss	1.0000
19:5786463:TTA:T	donor_loss	1.0000
19:5786464:TACCG:T	donor_loss	1.0000
19:5786465:A:AC	donor_gain	1.0000

AlphaMissense

4192 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:5785772:A:G	W528R	0.999
19:5785772:A:T	W528R	0.999
19:5785611:G:C	F581L	0.998
19:5785611:G:T	F581L	0.998
19:5785613:A:G	F581L	0.998
19:5787615:A:G	C396R	0.998
19:5787622:G:C	N393K	0.998
19:5787622:G:T	N393K	0.998
19:5788115:T:A	E335V	0.998
19:5788172:C:T	G316E	0.998
19:5788173:C:A	G316W	0.998
19:5785226:G:C	H644D	0.997
19:5785227:C:A	K643N	0.997
19:5785227:C:G	K643N	0.997
19:5785275:G:C	S627R	0.997
19:5785275:G:T	S627R	0.997
19:5785384:T:G	S627R	0.997
19:5785632:A:C	F574L	0.997
19:5785632:A:T	F574L	0.997
19:5785634:A:G	F574L	0.997
19:5786467:C:G	R521P	0.997
19:5786468:G:T	R521S	0.997
19:5786534:C:G	D499H	0.997
19:5786836:G:T	R467S	0.997
19:5788111:C:A	M336I	0.997
19:5788111:C:G	M336I	0.997
19:5788111:C:T	M336I	0.997
19:5788147:G:C	C324W	0.997
19:5788168:G:C	N317K	0.997
19:5788168:G:T	N317K	0.997

dbSNP variants (sampled 300 via entrez): RS1000497507 (19:5789957 G>A), RS1000665292 (19:5790805 G>A,C), RS1001076536 (19:5790960 C>T), RS1001565377 (19:5786289 C>G), RS1001804489 (19:5785683 G>A), RS1002594016 (19:5788855 C>G,T), RS1002624895 (19:5788560 G>A), RS1002789519 (19:5788889 T>G), RS1003084488 (19:5788662 G>A), RS1003477091 (19:5784919 C>A), RS1003477307 (19:5791953 T>A), RS1003526643 (19:5784774 G>A,C), RS1003811798 (19:5792313 A>AG), RS1004180304 (19:5792437 C>G,T), RS1004516896 (19:5791263 C>T)

Disease associations

OMIM: gene MIM:621104 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST007325_166	General risk tolerance (MTAG)	9.000000e-09
GCST007576_30	Chronotype	7.000000e-12

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0008579	risk-taking behaviour
EFO:0008328	chronotype measurement

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
Cyclosporine	increases expression	3
sodium arsenite	increases expression	2
Valproic Acid	affects expression, increases methylation	2
FR900359	increases phosphorylation	1
TAK-243	increases sumoylation	1
bisphenol A	increases expression	1
trichostatin A	affects expression	1
coumarin	increases phosphorylation	1
beta-methylcholine	affects expression	1
perfluoro-n-nonanoic acid	increases expression	1
2-palmitoylglycerol	increases expression	1
clothianidin	increases expression	1
abrine	increases expression	1
Caffeine	increases phosphorylation	1
Dichlorodiphenyl Dichloroethylene	increases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Progesterone	decreases expression	1
Ribonucleotides	affects binding	1
Rotenone	decreases expression	1
Smoke	decreases expression	1
Antirheumatic Agents	decreases expression	1
beta-Naphthoflavone	increases 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_D7IX	Ubigene 786-O DUS3L KO	Cancer cell line	Male
CVCL_E0BZ	Ubigene HeLa DUS3L KO	Cancer cell line	Female
CVCL_E0U1	Ubigene Hep G2 DUS3L KO	Cancer cell line	Male

Clinical trials (associated diseases)

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