DALRD3

Summary

DALRD3 (DALR anticodon binding domain containing 3, HGNC:25536) is a protein-coding gene on chromosome 3p21.31, encoding DALR anticodon-binding domain-containing protein 3 (Q5D0E6). Involved in tRNA methylation.

The exact function of this gene is not known. It encodes a protein with a DALR anticodon binding domain similar to that of class Ia aminoacyl tRNA synthetases. This gene is located in a cluster of genes (with a complex sense-anti-sense genome architecture) on chromosome 3, and contains two micro RNA (miRNA) precursors (mir-425 and mir-191) in one of its introns. Preferential expression of this gene (the miRNAs and other genes in the cluster) in testis suggests a role of this gene in spermatogenesis (PMID:19906709).

Source: NCBI Gene 55152 — RefSeq curated summary.

At a glance

• Gene–disease (curated): developmental and epileptic encephalopathy, 86 (Moderate, GenCC) — +1 more curated relationship
• GWAS associations: 15
• Clinical variants (ClinVar): 114 total
• Phenotypes (HPO): 58
• MANE Select transcript: NM_001009996

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25536
Approved symbol	DALRD3
Name	DALR anticodon binding domain containing 3
Location	3p21.31
Locus type	gene with protein product
Status	Approved
Aliases	FLJ10496
Ensembl gene	ENSG00000178149
Ensembl biotype	protein_coding
OMIM	618904
Entrez	55152

Gene structure

Transcript identifiers

Ensembl transcripts: 23 — 15 protein_coding, 7 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000313778, ENST00000341949, ENST00000420952, ENST00000438585, ENST00000440857, ENST00000441576, ENST00000460505, ENST00000467457, ENST00000472331, ENST00000481001, ENST00000484831, ENST00000492585, ENST00000496568, ENST00000498498, ENST00000498794, ENST00000873681, ENST00000873682, ENST00000916245, ENST00000916246, ENST00000969752, ENST00000969753, ENST00000969754, ENST00000969755

RefSeq mRNA: 3 — MANE Select: NM_001009996 NM_001009996, NM_001276405, NM_018114

CCDS: CCDS2783, CCDS33754, CCDS63632

Canonical transcript exons

ENST00000341949 — 12 exons

Exon	Start	End
ENSE00003467635	49016612	49016673
ENSE00003484044	49017434	49017513
ENSE00003517189	49015973	49016086
ENSE00003539118	49016774	49016847
ENSE00003553901	49015804	49015872
ENSE00003600472	49018400	49018580
ENSE00003635880	49016429	49016511
ENSE00003639569	49016158	49016340
ENSE00003644049	49017613	49017869
ENSE00003660460	49017228	49017356
ENSE00003662275	49018023	49018318
ENSE00003669531	49015488	49015707

Expression profiles

Bgee: expression breadth ubiquitous, 266 present calls, max score 98.19.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 14.9971 / max 100.5685, expressed in 1794 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
42186	12.5051	1777
42182	1.0334	734
42184	0.6833	417
42183	0.2957	130
42185	0.2880	119
42188	0.1176	26
42187	0.0611	27
42189	0.0130	6

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left testis	UBERON:0004533	98.19	gold quality
right testis	UBERON:0004534	98.05	gold quality
right uterine tube	UBERON:0001302	97.96	gold quality
testis	UBERON:0000473	95.86	gold quality
cortical plate	UBERON:0005343	95.25	gold quality
epithelium of bronchus	UBERON:0002031	95.03	gold quality
bronchial epithelial cell	CL:0002328	94.78	gold quality
body of pancreas	UBERON:0001150	94.72	gold quality
bronchus	UBERON:0002185	94.47	gold quality
right lobe of thyroid gland	UBERON:0001119	94.09	gold quality
metanephros cortex	UBERON:0010533	93.57	gold quality
left lobe of thyroid gland	UBERON:0001120	93.44	gold quality
tendon of biceps brachii	UBERON:0008188	93.42	gold quality
ventricular zone	UBERON:0003053	93.17	gold quality
thyroid gland	UBERON:0002046	92.88	gold quality
adenohypophysis	UBERON:0002196	92.88	gold quality
right adrenal gland cortex	UBERON:0035827	92.64	gold quality
right adrenal gland	UBERON:0001233	92.52	gold quality
right frontal lobe	UBERON:0002810	92.35	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	92.27	gold quality
mucosa of transverse colon	UBERON:0004991	92.26	gold quality
lower esophagus mucosa	UBERON:0035834	92.17	gold quality
left adrenal gland cortex	UBERON:0035825	91.77	gold quality
left adrenal gland	UBERON:0001234	91.61	gold quality
granulocyte	CL:0000094	91.58	gold quality
stromal cell of endometrium	CL:0002255	91.58	gold quality
anterior cingulate cortex	UBERON:0009835	91.55	gold quality
cingulate cortex	UBERON:0003027	91.54	gold quality
pituitary gland	UBERON:0000007	91.24	gold quality
endocervix	UBERON:0000458	91.16	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-CURD-112	yes	7.32
E-ANND-3	yes	5.84

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): NR1I2

miRNA regulators (miRDB)

8 targeting DALRD3, 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-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-101-3P	99.94	75.03	2230
HSA-MIR-145-5P	99.92	71.13	1836
HSA-MIR-5195-3P	99.92	70.92	1877
HSA-MIR-6885-3P	99.75	70.36	3187
HSA-MIR-4726-3P	98.49	63.89	1385
HSA-MIR-624-5P	96.00	68.88	728

Literature-anchored findings (GeneRIF, showing 1)

• DALRD3 encodes a protein mutated in epileptic encephalopathy that targets arginine tRNAs for 3-methylcytosine modification. (PMID:32427860)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	dalrd3	ENSDARG00000068602
mus_musculus	Dalrd3	ENSMUSG00000019039
rattus_norvegicus	Dalrd3	ENSRNOG00000020159
drosophila_melanogaster	CG8097	FBGN0030660

Protein

Protein identifiers

DALR anticodon-binding domain-containing protein 3 — Q5D0E6 (reviewed: Q5D0E6)

All UniProt accessions (5): A0A096LNZ3, C9JA38, C9JJG6, Q5D0E6, H7C0T8

UniProt curated annotations — full annotation on UniProt →

Function. Involved in tRNA methylation. Facilitates the recognition and targeting of tRNA(Arg)(CCU) and tRNA(Arg)(UCU) substrates for N(3)-methylcytidine modification by METTL2A and METTL2B.

Subunit / interactions. Part of a complex containing tRNA(Arg), METTL2A or METTL2B. Interacts with tRNA(Arg)(CCU) and tRNA(Arg)(UCU). Interacts with METTL2A and METTL2B.

Disease relevance. Developmental and epileptic encephalopathy 86 (DEE86) [MIM:618910] A form of epileptic encephalopathy, a heterogeneous group of severe early-onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. DEE86 inheritance is autosomal recessive. The disease may be caused by variants affecting the gene represented in this entry.

Isoforms (4)

UniProt ID	Names	Canonical?
Q5D0E6-1	1	yes
Q5D0E6-2	2
Q5D0E6-3	3
Q5D0E6-4	4

RefSeq proteins (3): NP_001009996, NP_001263334, NP_060584 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR008909	DALR_anticod-bd	Domain
IPR009080	tRNAsynth_Ia_anticodon-bd	Homologous_superfamily
IPR037380	DALRD3	Family

Pfam: PF05746

UniProt features (9 total): splice variant 4, sequence variant 3, chain 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5D0E6-F1	88.57	0.66

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 266 (showing top): RNGTGGGC_UNKNOWN, GOBP_AMINO_ACID_ACTIVATION, YANG_BREAST_CANCER_ESR1_BULK_UP, GCANCTGNY_MYOD_Q6, CMYB_01, GOBP_TRNA_METABOLIC_PROCESS, CAGCTG_AP4_Q5, GOBP_RNA_METHYLATION, GOBP_TRANSLATION, GOBP_RNA_MODIFICATION, GATA1_01, GOBP_TRNA_METHYLATION, MYOD_Q6, PU1_Q6, LASTOWSKA_NEUROBLASTOMA_COPY_NUMBER_DN

GO Biological Process (5): arginyl-tRNA aminoacylation (GO:0006420), tRNA C3-cytosine methylation (GO:0106217), tRNA metabolic process (GO:0006399), tRNA aminoacylation for protein translation (GO:0006418), gene expression (GO:0010467)

GO Molecular Function (6): tRNA binding (GO:0000049), arginine-tRNA ligase activity (GO:0004814), ATP binding (GO:0005524), nucleotide binding (GO:0000166), aminoacyl-tRNA ligase activity (GO:0004812), protein binding (GO:0005515)

GO Cellular Component (0):

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
tRNA aminoacylation for protein translation	1
tRNA methylation	1
RNA metabolic process	1
translation	1
tRNA aminoacylation	1
macromolecule biosynthetic process	1
RNA binding	1
aminoacyl-tRNA ligase activity	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
ligase activity, forming carbon-oxygen bonds	1
catalytic activity, acting on a tRNA	1
binding	1

Protein interactions and networks

STRING

2224 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DALRD3	WDR6	Q9NNW5	795
DALRD3	METTL2A	Q96IZ6	602
DALRD3	METTL2B	Q6P1Q9	600
DALRD3	METTL6	Q8TCB7	600
DALRD3	NDUFAF3	Q9BU61	548
DALRD3	Q6NXN5	Q6NXN5	507
DALRD3	METTL8	Q9H825	503
DALRD3	CCDC9	Q9Y3X0	479
DALRD3	CCDC71	Q8IV32	476
DALRD3	RARS2	Q5T160	461
DALRD3	SMC4	Q9NTJ3	448
DALRD3	ZNF593	O00488	431
DALRD3	RARS1	P54136	413
DALRD3	DAZAP1	Q96EP5	409
DALRD3	C10orf71	Q711Q0	399

IntAct

22 interactions, top by confidence:

A	B	Type	Score
DALRD3	HNRNPK	psi-mi:“MI:0915”(physical association)	0.560
HNRNPK	DALRD3	psi-mi:“MI:0915”(physical association)	0.560
DALRD3	METTL2A	psi-mi:“MI:0915”(physical association)	0.500
DALRD3	METTL2B	psi-mi:“MI:0915”(physical association)	0.500
DALRD3	METTL2B	psi-mi:“MI:0914”(association)	0.500
DALRD3	LONP1	psi-mi:“MI:0915”(physical association)	0.400
CSNK2B	DALRD3	psi-mi:“MI:0915”(physical association)	0.370
TK1	DALRD3	psi-mi:“MI:0915”(physical association)	0.370
M		psi-mi:“MI:0914”(association)	0.350
RNF7	SOCS2	psi-mi:“MI:0914”(association)	0.350
INSR	UBXN8	psi-mi:“MI:0914”(association)	0.350
METTL2A	ACACB	psi-mi:“MI:0914”(association)	0.350
METTL2B	EIF3F	psi-mi:“MI:0914”(association)	0.350
DALRD3		psi-mi:“MI:0914”(association)	0.350
METTL2A		psi-mi:“MI:0914”(association)	0.350
METTL2B		psi-mi:“MI:0914”(association)	0.350
DALRD3		psi-mi:“MI:0915”(physical association)	0.000
RBM11	DALRD3	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (22): DALRD3 (Two-hybrid), DALRD3 (Two-hybrid), DALRD3 (Affinity Capture-MS), DALRD3 (Affinity Capture-RNA), DALRD3 (Affinity Capture-RNA), DALRD3 (Two-hybrid), DALRD3 (Two-hybrid), DALRD3 (Two-hybrid), CYSRT1 (Two-hybrid), KRTAP12-3 (Two-hybrid), KRTAP6-3 (Two-hybrid), NOTCH2NL (Two-hybrid), NBPF19 (Two-hybrid), DALRD3 (Affinity Capture-MS), DALRD3 (Affinity Capture-RNA)

ESM2 similar proteins: A1IGU3, A1IGU4, A1IGU5, A2VDW6, A6QP75, A7E3N7, B2RUP2, C3VPR6, D3ZI76, Q0VCR8, Q14DK4, Q1LZ97, Q3MIN7, Q3TAA7, Q3UR97, Q4FZD7, Q53B87, Q53B88, Q5D0E6, Q60I26, Q60I27, Q61085, Q641Y9, Q69Z89, Q6NUI2, Q6P5Z2, Q6PFY1, Q6PJN8, Q70J99, Q86UR1, Q86VI1, Q86WN1, Q8BI71, Q8BTM9, Q8C0R7, Q8C190, Q8K045, Q8N1F8, Q8N9H8, Q8R5I4

Diamond homologs: A0JML8, Q5D0E6, Q641Y9, Q6PJN8

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	82
Likely benign	10
Benign	4

Top pathogenic / likely-pathogenic (0)

SpliceAI

2218 predictions. Top by Δscore:

Variant	Effect	Δscore
3:49016423:GCTCA:G	donor_loss	1.0000
3:49016424:CTCAC:C	donor_loss	1.0000
3:49016425:TCACC:T	donor_loss	1.0000
3:49016426:CACCT:C	donor_loss	1.0000
3:49016427:A:T	donor_loss	1.0000
3:49016428:CCT:C	donor_loss	1.0000
3:49016428:CCTGA:C	donor_gain	1.0000
3:49016511:TCTGA:T	acceptor_loss	1.0000
3:49016512:C:CC	acceptor_gain	1.0000
3:49016512:CTGAG:C	acceptor_loss	1.0000
3:49016513:T:G	acceptor_loss	1.0000
3:49016772:A:AC	donor_gain	1.0000
3:49016773:C:CC	donor_gain	1.0000
3:49017514:C:CC	acceptor_gain	1.0000
3:49017607:TCCTA:T	donor_loss	1.0000
3:49017608:CCTA:C	donor_loss	1.0000
3:49017609:CTACC:C	donor_loss	1.0000
3:49017610:TACCC:T	donor_loss	1.0000
3:49017611:A:AC	donor_gain	1.0000
3:49017611:AC:A	donor_gain	1.0000
3:49017611:ACCC:A	donor_loss	1.0000
3:49017612:C:CC	donor_gain	1.0000
3:49017612:CC:C	donor_gain	1.0000
3:49017663:TCC:T	donor_gain	1.0000
3:49017868:CC:C	acceptor_gain	1.0000
3:49017869:CC:C	acceptor_gain	1.0000
3:49015703:GGCTC:G	acceptor_gain	0.9900
3:49015705:CTC:C	acceptor_gain	0.9900
3:49015706:TC:T	acceptor_gain	0.9900
3:49015707:CC:C	acceptor_gain	0.9900

AlphaMissense

3486 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:49015846:G:C	S490R	0.995
3:49015846:G:T	S490R	0.995
3:49015848:T:G	S490R	0.995
3:49015834:G:C	S494R	0.993
3:49015834:G:T	S494R	0.993
3:49015836:T:G	S494R	0.993
3:49016281:A:C	F402L	0.993
3:49016281:A:T	F402L	0.993
3:49016283:A:G	F402L	0.993
3:49016080:A:G	W446R	0.990
3:49016080:A:T	W446R	0.990
3:49016279:A:T	V403D	0.988
3:49018446:A:G	F40S	0.988
3:49016078:C:A	W446C	0.986
3:49016078:C:G	W446C	0.986
3:49016459:A:C	F372L	0.985
3:49016459:A:T	F372L	0.985
3:49016461:A:G	F372L	0.985
3:49016269:A:C	N406K	0.984
3:49016269:A:T	N406K	0.984
3:49018489:A:G	W26R	0.981
3:49018489:A:T	W26R	0.981
3:49016262:G:T	R409S	0.980
3:49018072:G:T	R138S	0.979
3:49018445:A:C	F40L	0.976
3:49018445:A:T	F40L	0.976
3:49018447:A:G	F40L	0.976
3:49016261:C:G	R409P	0.975
3:49015671:G:T	R517S	0.974
3:49015820:C:G	R499P	0.974

dbSNP variants (sampled 300 via entrez): RS1000550060 (3:49015348 G>C), RS1000722810 (3:49021477 C>G), RS1001071680 (3:49021160 C>G,T), RS1001154759 (3:49020937 T>A,G), RS1001770694 (3:49015972 C>A), RS1002058728 (3:49018004 G>A), RS1002163618 (3:49020470 T>C), RS1002462876 (3:49015701 G>A,C), RS1002658274 (3:49019006 C>A,T), RS1002663376 (3:49018780 C>A), RS1002672401 (3:49018868 A>G), RS1002833397 (3:49019086 T>C), RS1003158995 (3:49018817 G>A), RS1004592788 (3:49021516 A>C,G), RS1004638333 (3:49015389 G>A)

Disease associations

OMIM: gene MIM:618904 | disease phenotypes: MIM:618910

GenCC curated gene-disease

Disease	Classification	Inheritance
developmental and epileptic encephalopathy, 86	Moderate	Autosomal recessive
undetermined early-onset epileptic encephalopathy	Supportive	Autosomal dominant

Mondo (2): developmental and epileptic encephalopathy, 86 (MONDO:0030054), undetermined early-onset epileptic encephalopathy (MONDO:0018614)

Orphanet (0):

HPO phenotypes

58 total (30 of 58 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000252	Microcephaly
HP:0000348	High forehead
HP:0000494	Downslanted palpebral fissures
HP:0000504	Abnormality of vision
HP:0000508	Ptosis
HP:0000546	Retinal degeneration
HP:0000639	Nystagmus
HP:0000648	Optic atrophy
HP:0000668	Hypodontia
HP:0000708	Atypical behavior
HP:0000717	Autism
HP:0000750	Delayed speech and language development
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001251	Ataxia
HP:0001257	Spasticity
HP:0001263	Global developmental delay
HP:0001265	Hyporeflexia
HP:0001268	Mental deterioration
HP:0001273	Abnormal corpus callosum morphology
HP:0001288	Gait disturbance
HP:0001290	Generalized hypotonia
HP:0001298	Encephalopathy
HP:0001315	Reduced tendon reflexes
HP:0001332	Dystonia
HP:0001336	Myoclonus
HP:0001337	Tremor
HP:0001344	Absent speech
HP:0001508	Failure to thrive

GWAS associations

15 associations (top):

Study	Trait	p-value
GCST004131_23	Inflammatory bowel disease	1.000000e-33
GCST004132_17	Crohn’s disease	3.000000e-23
GCST004133_11	Ulcerative colitis	8.000000e-20
GCST007294_107	Body fat distribution (trunk fat ratio)	9.000000e-06
GCST007294_72	Body fat distribution (trunk fat ratio)	1.000000e-18
GCST007294_98	Body fat distribution (trunk fat ratio)	3.000000e-15
GCST007295_21	Body fat distribution (leg fat ratio)	8.000000e-06
GCST007295_45	Body fat distribution (leg fat ratio)	1.000000e-10
GCST007295_80	Body fat distribution (leg fat ratio)	1.000000e-14
GCST010050_2	Adiponectin levels	5.000000e-07
GCST010698_80	Subcortical volume (min-P)	3.000000e-24
GCST010699_110	Brain morphology (min-P)	4.000000e-08
GCST010701_52	Cortical surface area (MOSTest)	1.000000e-16
GCST010702_36	Subcortical volume (MOSTest)	1.000000e-10
GCST010703_262	Brain morphology (MOSTest)	2.000000e-13

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004341	body fat distribution
EFO:0004502	adiponectin measurement
EFO:0004346	neuroimaging measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs11706052	DALRD3, IMPDH2, MIR191, MIR425	4	-3.00	2	cyclosporine;mycophenolate mofetil;mycophenolate mofetil;mycophenolic acid

CTD chemical–gene interactions

28 total (human), top 28 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
aristolochic acid I	decreases expression	1
triphenyl phosphate	affects expression	1
pirinixic acid	affects binding, decreases expression, increases activity	1
bisphenol A	affects cotreatment, increases methylation	1
sodium arsenite	decreases expression	1
cobaltous chloride	decreases expression	1
N-benzyloxycarbonylprolylprolinal	increases expression	1
perfluorooctane sulfonic acid	increases expression	1
jinfukang	affects cotreatment, increases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Leflunomide	decreases expression	1
Air Pollutants	affects expression, increases abundance	1
Benzo(a)pyrene	increases methylation	1
Caffeine	decreases phosphorylation	1
Cisplatin	increases expression, affects cotreatment	1
Cytarabine	decreases expression	1
Diazinon	increases methylation	1
Ozone	affects expression, increases abundance	1
Smoke	decreases expression	1
Thiram	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Tretinoin	decreases expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	increases expression	1
Sodium Selenite	increases expression	1
Antirheumatic Agents	increases expression	1
Cadmium Chloride	decreases expression	1
Copper Sulfate	decreases expression	1
Acrylamide	decreases 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_E1V7	HAP1 DALRD3 (-) 2	Cancer cell line	Male
CVCL_E1V8	HAP1 DALRD3 (-) 3	Cancer cell line	Male
CVCL_XN09	HAP1 DALRD3 (-) 1	Cancer cell line	Male

Clinical trials (associated diseases)

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