ADAT2

Summary

ADAT2 (adenosine deaminase tRNA specific 2, HGNC:21172) is a protein-coding gene on chromosome 6q24.2, encoding tRNA-specific adenosine-34 deaminase catalytic subunit ADAT2 (Q7Z6V5). Catalytic subunit of the tRNA-specific adenosine-34 deaminase complex, composed of the ADAT2 catalytic subunit and the ADAT3 regulatory subunit, which deaminates adenosine-34 (the first, also called wobble position of the anticodon) to inosine in many tRNAs. It is a selective cancer dependency (DepMap: 35.8% of cell lines).

Predicted to enable tRNA-specific adenosine-34 deaminase activity. Predicted to be involved in tRNA wobble adenosine to inosine editing. Predicted to be located in nucleoplasm.

Source: NCBI Gene 134637 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 42 total — 4 pathogenic
• Cancer dependency (DepMap): dependent in 35.8% of screened cell lines
• MANE Select transcript: NM_182503

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21172
Approved symbol	ADAT2
Name	adenosine deaminase tRNA specific 2
Location	6q24.2
Locus type	gene with protein product
Status	Approved
Aliases	dJ20N2.1, TAD2
Ensembl gene	ENSG00000189007
Ensembl biotype	protein_coding
OMIM	615388
Entrez	134637

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 4 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000237283, ENST00000367593, ENST00000606514, ENST00000933835, ENST00000933836

RefSeq mRNA: 2 — MANE Select: NM_182503 NM_001286259, NM_182503

CCDS: CCDS43511, CCDS69219

Canonical transcript exons

ENST00000237283 — 6 exons

Exon	Start	End
ENSE00000798996	143428612	143428684
ENSE00000798998	143432505	143432611
ENSE00000799002	143433831	143433981
ENSE00002506787	143438590	143438694
ENSE00003696468	143422832	143428506
ENSE00003700858	143450563	143450695

Expression profiles

Bgee: expression breadth ubiquitous, 201 present calls, max score 86.45.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 14.9638 / max 788.5808, expressed in 1773 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
76039	14.9638	1773

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
rectum	UBERON:0001052	86.45	gold quality
body of pancreas	UBERON:0001150	83.22	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	82.60	gold quality
vermiform appendix	UBERON:0001154	81.89	gold quality
tibial nerve	UBERON:0001323	81.02	gold quality
body of stomach	UBERON:0001161	80.70	gold quality
sural nerve	UBERON:0015488	80.64	gold quality
esophagus mucosa	UBERON:0002469	80.20	gold quality
right adrenal gland cortex	UBERON:0035827	79.85	gold quality
skin of abdomen	UBERON:0001416	79.77	gold quality
transverse colon	UBERON:0001157	79.69	gold quality
right adrenal gland	UBERON:0001233	79.60	gold quality
lymph node	UBERON:0000029	79.45	gold quality
small intestine Peyer’s patch	UBERON:0003454	79.44	gold quality
left lobe of thyroid gland	UBERON:0001120	79.27	gold quality
left adrenal gland cortex	UBERON:0035825	79.09	gold quality
esophagus	UBERON:0001043	79.04	gold quality
left adrenal gland	UBERON:0001234	78.87	gold quality
granulocyte	CL:0000094	78.75	gold quality
right lobe of thyroid gland	UBERON:0001119	78.65	gold quality
epithelial cell of pancreas	CL:0000083	78.58	gold quality
upper lobe of left lung	UBERON:0008952	78.58	gold quality
mucosa of stomach	UBERON:0001199	78.51	gold quality
right lobe of liver	UBERON:0001114	78.30	gold quality
stomach	UBERON:0000945	78.27	gold quality
smooth muscle tissue	UBERON:0001135	78.21	gold quality
thyroid gland	UBERON:0002046	78.21	gold quality
lower esophagus muscularis layer	UBERON:0035833	78.10	gold quality
skin of leg	UBERON:0001511	78.09	gold quality
lower esophagus	UBERON:0013473	78.06	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.08

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): WT1

miRNA regulators (miRDB)

205 targeting ADAT2, 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-6867-5P	100.00	82.21	3464
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4776-3P	100.00	68.73	1340
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-499A-5P	99.98	70.79	1323
HSA-MIR-607	99.97	73.62	5593

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 35.8% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 3)

• data indicate that ATAD2 overexpression in somatic cells, by acting on basic properties of chromatin, may contribute to malignant transformation (PMID:20581866)
• Transfer RNAs (tRNAs) are among the most heavily modified RNA species. Data confirm that ADAT2 exhibits substrate specificity that includes tRNA(Ala-AGC) and tRNA(Thr-AGU), deaminating adenosine-34 to inosine-34 as post-transcriptional modifications. (PMID:28703578)
• Identification and rescue of a tRNA wobble inosine deficiency causing intellectual disability disorder. (PMID:32763916)

Cross-species orthologs

9 orthologs

Organism	Symbol	Gene ID
danio_rerio	adat2	ENSDARG00000041944
mus_musculus	Adat2	ENSMUSG00000019808
rattus_norvegicus	Adat2	ENSRNOG00000046983
drosophila_melanogaster	CG5292	FBGN0038491
caenorhabditis_elegans		WBGENE00007440
caenorhabditis_elegans		WBGENE00010436
caenorhabditis_elegans		WBGENE00015574
caenorhabditis_elegans		WBGENE00016495
caenorhabditis_elegans		WBGENE00020747

Paralogs (1): ADAT3 (ENSG00000213638)

Protein

Protein identifiers

tRNA-specific adenosine-34 deaminase catalytic subunit ADAT2 — Q7Z6V5 (reviewed: Q7Z6V5)

Alternative names: Deaminase domain-containing protein 1

All UniProt accessions (1): Q7Z6V5

UniProt curated annotations — full annotation on UniProt →

Function. Catalytic subunit of the tRNA-specific adenosine-34 deaminase complex, composed of the ADAT2 catalytic subunit and the ADAT3 regulatory subunit, which deaminates adenosine-34 (the first, also called wobble position of the anticodon) to inosine in many tRNAs. Inosine-34 allows the decoding of 3 different nucleotides at the third position of mRNA codons, as inosine is able to pair with U, C, and A. Binding of the ADAT2-ADAT3 complex to tRNA is mediated by the N-terminus of ADAT3 which rotates with respect to the catalytic domain of the complex, formed by ADAT2 and the ADAT3 C-terminal domain, to position the tRNA anticodon stem-loop correctly in the ADAT2 active site. The ADAT2-ADAT3 complex is required for radial migration of projection neurons in the developing brain cortex, and the catalytic activity of the complex is necessary for this function.

Subunit / interactions. Heterodimer with regulatory subunit ADAT3 to form the tRNA-specific adenosine-34 deaminase complex.

Subcellular location. Nucleus. Cytoplasm.

Similarity. Belongs to the cytidine and deoxycytidylate deaminase family. ADAT2 subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
Q7Z6V5-1	1	yes
Q7Z6V5-2	2

RefSeq proteins (2): NP_001273188, NP_872309* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002125	CMP_dCMP_dom	Domain
IPR016192	APOBEC/CMP_deaminase_Zn-bd	Binding_site
IPR016193	Cytidine_deaminase-like	Homologous_superfamily
IPR028883	tRNA_aden_deaminase	Family

Pfam: PF00383

Catalyzed reactions (Rhea), 1 shown:

• adenosine(34) in tRNA + H2O + H(+) = inosine(34) in tRNA + NH4(+) (RHEA:43168)

UniProt features (19 total): helix 6, strand 5, binding site 3, chain 1, domain 1, turn 1, active site 1, splice variant 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
3DH1	X-RAY DIFFRACTION	2.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q7Z6V5-F1	90.25	0.83

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): 73 (proton donor)

Ligand- & substrate-binding residues (3): 71; 107; 110

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-6782315	tRNA modification in the nucleus and cytosol
R-HSA-72306	tRNA processing
R-HSA-8953854	Metabolism of RNA

MSigDB gene sets: 169 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_DN, GOBP_TRNA_METABOLIC_PROCESS, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, GOBP_RNA_MODIFICATION, ATTACAT_MIR3803P, JAATINEN_HEMATOPOIETIC_STEM_CELL_UP, BREDEMEYER_RAG_SIGNALING_NOT_VIA_ATM_UP, GOBP_TRNA_PROCESSING, REACTOME_METABOLISM_OF_RNA, GOBP_TRNA_MODIFICATION, GAVIN_FOXP3_TARGETS_CLUSTER_P2, JEPSEN_SMRT_TARGETS, GOMF_HYDROLASE_ACTIVITY_ACTING_ON_CARBON_NITROGEN_BUT_NOT_PEPTIDE_BONDS_IN_CYCLIC_AMIDINES, GOMF_ADENOSINE_DEAMINASE_ACTIVITY

GO Biological Process (2): tRNA wobble adenosine to inosine editing (GO:0002100), tRNA processing (GO:0008033)

GO Molecular Function (7): zinc ion binding (GO:0008270), tRNA-specific adenosine-34 deaminase activity (GO:0052717), catalytic activity (GO:0003824), protein binding (GO:0005515), tRNA-specific adenosine deaminase activity (GO:0008251), hydrolase activity (GO:0016787), metal ion binding (GO:0046872)

GO Cellular Component (1): nucleoplasm (GO:0005654)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
tRNA processing	1
Metabolism of RNA	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
tRNA wobble base modification	1
adenosine to inosine editing	1
RNA processing	1
tRNA metabolic process	1
transition metal ion binding	1
tRNA-specific adenosine deaminase activity	1
molecular_function	1
binding	1
adenosine deaminase activity	1
catalytic activity, acting on a tRNA	1
catalytic activity	1
cation binding	1
nuclear lumen	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1458 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ADAT2	ADAT3	Q96EY9	999
ADAT2	ADAT1	Q9BUB4	931
ADAT2	RPSA	P08865	779
ADAT2	GTF2H1	P32780	772
ADAT2	EP300	Q09472	720
ADAT2	GNRH2	O43555	712
ADAT2	RPA1	P27694	698
ADAT2	MDM2	Q00987	651
ADAT2	WDR4	P57081	617
ADAT2	TRMT6	Q9UJA5	614
ADAT2	TRMT61A	Q96FX7	614
ADAT2	METTL1	Q9UBP6	593
ADAT2	ADA	P00813	571
ADAT2	ADARB2	Q9NS39	557
ADAT2	TRMT112	Q9UI30	557

IntAct

17 interactions, top by confidence:

A	B	Type	Score
NAV2	ADAT2	psi-mi:“MI:0915”(physical association)	0.560
SMARCD1	ADAT2	psi-mi:“MI:0915”(physical association)	0.560
ADAT2	SGTB	psi-mi:“MI:0915”(physical association)	0.560
ADAT2	SMARCD1	psi-mi:“MI:0915”(physical association)	0.560
ADAT2	SPRED1	psi-mi:“MI:0915”(physical association)	0.560
ADAT2	ADAT3	psi-mi:“MI:0915”(physical association)	0.500
ADAT3	ABLIM1	psi-mi:“MI:0914”(association)	0.350
ADAT2	FGG	psi-mi:“MI:0914”(association)	0.350
ADAT2	SGTB	psi-mi:“MI:0915”(physical association)	0.000
rne	ADAT2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (23): ADAT2 (Two-hybrid), ADAT3 (Affinity Capture-MS), ADAT3 (Affinity Capture-MS), ADAT2 (Affinity Capture-RNA), ARL2 (Negative Genetic), ATP1A1 (Positive Genetic), BDP1 (Positive Genetic), UBA2 (Positive Genetic), USE1 (Negative Genetic), ADAT2 (Two-hybrid), SGTB (Two-hybrid), ADAT2 (Affinity Capture-MS), ADAT2 (Affinity Capture-RNA), ADAT3 (Affinity Capture-MS), ADAT2 (Affinity Capture-MS)

ESM2 similar proteins: A2VE14, A2VE52, A7MB28, A9X1D0, B0VX69, B1MTJ4, B2KI88, B5FW36, B7ZUF3, C1FXW2, D3Z7P3, E2RBS6, G3V6U9, O43502, O54804, O73884, O94925, O95544, P0DKC3, P0DKC4, P13264, P35790, P58058, Q01134, Q08DW9, Q3SZB3, Q3ZCQ8, Q4R4U1, Q4R766, Q5RA95, Q5RAJ8, Q5RKN4, Q5U1X1, Q5ZIN0, Q5ZML9, Q6AXQ0, Q6AYR2, Q6AYT7, Q7Z6V5, Q86TU7

Diamond homologs: A9CK16, C1D1Q9, F4KH86, O34598, O66534, O67050, O94642, P0DA20, P0DA21, P21335, P44931, P57343, P68397, P68398, P68999, Q1RGK7, Q4UJW9, Q561R2, Q5E9J7, Q5SI38, Q5XE14, Q68Y02, Q6IDB6, Q6P6J0, Q6PAT0, Q72IF6, Q7CQ08, Q7Z6V5, Q89AM8, Q8FF24, Q8JFW4, Q8K9R4, Q8P2R7, Q8XA44, Q8XGY4, Q92G39, Q94BU8, Q96EY9, Q99W51, Q9RV23

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	4
Likely pathogenic	0
Uncertain significance	30
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (4)

Variant ID	HGVS	Classification
1527299	GRCh37/hg19 6q24.2-24.3(chr6:143331663-145817051)	Pathogenic
2424710	NC_000006.11:g.(?142623467)(144508628_?)del	Pathogenic
442470	GRCh37/hg19 6q24.1-25.1(chr6:139513020-150389231)x1	Pathogenic
4682665	GRCh37/hg19 6q24.1-24.2(chr6:142220207-144502854)x3	Pathogenic

SpliceAI

1842 predictions. Top by Δscore:

Variant	Effect	Δscore
6:143428502:TGGTG:T	acceptor_gain	1.0000
6:143428505:TG:T	acceptor_gain	1.0000
6:143428507:C:CC	acceptor_gain	1.0000
6:143428683:CA:C	acceptor_gain	1.0000
6:143432602:A:T	acceptor_gain	1.0000
6:143433829:A:AC	donor_gain	1.0000
6:143433830:C:CC	donor_gain	1.0000
6:143433833:A:AC	donor_gain	1.0000
6:143433834:T:C	donor_gain	1.0000
6:143433905:T:TA	donor_gain	1.0000
6:143433978:TAGC:T	acceptor_gain	1.0000
6:143433982:C:CC	acceptor_gain	1.0000
6:143438585:CATA:C	donor_gain	1.0000
6:143428503:GGTG:G	acceptor_gain	0.9900
6:143428504:GTG:G	acceptor_gain	0.9900
6:143428505:TGC:T	acceptor_loss	0.9900
6:143428506:GC:G	acceptor_loss	0.9900
6:143428507:C:A	acceptor_loss	0.9900
6:143428508:T:A	acceptor_loss	0.9900
6:143428509:G:C	acceptor_gain	0.9900
6:143428509:G:GC	acceptor_gain	0.9900
6:143428518:A:AC	acceptor_gain	0.9900
6:143428518:A:C	acceptor_gain	0.9900
6:143428685:C:CC	acceptor_gain	0.9900
6:143432601:C:CT	acceptor_gain	0.9900
6:143432610:T:C	acceptor_gain	0.9900
6:143433810:A:C	donor_gain	0.9900
6:143433833:AT:A	donor_gain	0.9900
6:143433977:GTAGC:G	acceptor_gain	0.9900
6:143433979:AGC:A	acceptor_gain	0.9900

AlphaMissense

1256 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:143432571:A:C	F131L	1.000
6:143432571:A:T	F131L	1.000
6:143432573:A:G	F131L	1.000
6:143428634:G:C	F170L	0.999
6:143428634:G:T	F170L	0.999
6:143428636:A:G	F170L	0.999
6:143428644:A:G	L167S	0.999
6:143433862:G:C	C107W	0.999
6:143433864:A:G	C107R	0.999
6:143433974:C:G	R70P	0.999
6:143432569:C:T	G132D	0.998
6:143432580:A:C	N128K	0.998
6:143432580:A:T	N128K	0.998
6:143433853:A:C	C110W	0.998
6:143433855:A:G	C110R	0.998
6:143433863:C:T	C107Y	0.998
6:143433970:A:C	H71Q	0.998
6:143433970:A:T	H71Q	0.998
6:143438611:A:C	N60K	0.998
6:143438611:A:T	N60K	0.998
6:143438653:A:C	C46W	0.998
6:143432569:C:A	G132V	0.997
6:143432573:A:C	F131V	0.997
6:143432573:A:T	F131I	0.997
6:143433866:G:T	P106Q	0.997
6:143433971:T:C	H71R	0.997
6:143433972:G:C	H71D	0.997
6:143433972:G:T	H71N	0.997
6:143438655:A:G	C46R	0.997
6:143438660:A:T	V44D	0.997

dbSNP variants (sampled 300 via entrez): RS1000044745 (6:143426209 A>G,T), RS1000071114 (6:143440689 T>C), RS1000165893 (6:143438846 G>A), RS1000174634 (6:143448239 C>G,T), RS1000225130 (6:143447241 A>T), RS1000279571 (6:143433866 G>A), RS1000339562 (6:143445138 G>A,T), RS1000534587 (6:143447606 T>A,C), RS1000575058 (6:143452373 A>G), RS1000624206 (6:143451896 A>G), RS1000805909 (6:143427930 C>T), RS1000836144 (6:143445424 CTAGA>C,CTAGATAGA), RS1000961283 (6:143445532 C>G), RS1001033519 (6:143433854 C>T), RS1001094829 (6:143427250 A>T)

Disease associations

OMIM: gene MIM:615388 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST007576_157	Chronotype	3.000000e-08

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
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

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

Chemical	Actions (top 5)	PubMed papers
(+)-JQ1 compound	decreases expression	5
Valproic Acid	affects expression, decreases expression	4
Tetrachlorodibenzodioxin	decreases expression, affects expression	3
sodium arsenite	decreases expression, increases abundance, increases expression	2
Formaldehyde	decreases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Tobacco Smoke Pollution	decreases expression	2
Tretinoin	decreases expression	2
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
trichostatin A	affects expression	1
methylparaben	decreases expression	1
cobaltous chloride	decreases expression	1
butyraldehyde	decreases expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Arsenic	increases expression, increases abundance	1
Dichlorodiphenyl Dichloroethylene	increases expression	1
Dimethyl Sulfoxide	increases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Estradiol	increases expression	1
Ethyl Methanesulfonate	decreases expression	1
Methyl Methanesulfonate	decreases expression	1
Phenobarbital	affects expression	1
Plant Extracts	affects cotreatment, increases expression	1
Thiram	decreases expression	1
Urethane	decreases expression	1

Clinical trials (associated diseases)

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