ADARB2

Summary

ADARB2 (adenosine deaminase RNA specific B2 (inactive), HGNC:227) is a protein-coding gene on chromosome 10p15.3, encoding Inactive double-stranded RNA-specific editase B2 (Q9NS39). Single- and double-stranded RNA-binding protein that interferes with the RNA editing activities of ADAR/ADAR1 and ADARB1/ADAR2.

This gene encodes a member of the double-stranded RNA adenosine deaminase family of RNA-editing enzymes and may play a regulatory role in RNA editing.

Source: NCBI Gene 105 — RefSeq curated summary.

At a glance

• GWAS associations: 14
• Clinical variants (ClinVar): 196 total — 9 pathogenic, 2 likely-pathogenic
• GTEx eGene: eQTL in 42 tissues, sQTL in 3 (q < 0.05)
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 0.68 (unconstrained)
• MANE Select transcript: NM_018702
• Notable: 196 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:227
Approved symbol	ADARB2
Name	adenosine deaminase RNA specific B2 (inactive)
Location	10p15.3
Locus type	gene with protein product
Status	Approved
Aliases	RED2, hRED2, ADAR3
Ensembl gene	ENSG00000185736
Ensembl biotype	protein_coding
OMIM	602065
Entrez	105

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 4 protein_coding, 4 protein_coding_CDS_not_defined

MANE Select: ENST00000381312

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 3, TSL 2: 4

ENST00000381312, ENST00000381305, ENST00000381310, ENST00000469464, ENST00000474762, ENST00000477140, ENST00000490172, ENST00001137237

RefSeq mRNA: 1 — MANE Select: NM_018702 NM_018702

CCDS: CCDS7058

Canonical transcript exons

ENST00000381312 — 10 exons

Exon	Start	End
ENSE00001303776	1379074	1379160
ENSE00001488147	1177313	1183369
ENSE00001488160	1737051	1737525
ENSE00001601056	1363028	1363917
ENSE00001672126	1242131	1242299
ENSE00001751553	1216951	1217119
ENSE00001780142	1270955	1271069
ENSE00003629183	1199966	1200147
ENSE00003644419	1184861	1185039
ENSE00003656306	1233694	1233845

Expression profiles

Bgee: expression breadth ubiquitous, 184 present calls, max score 92.62.

FANTOM5 (CAGE): breadth broad, TPM avg 5.1843 / max 457.5963, expressed in 447 samples.

Highest expression (Bgee): C1 segment of cervical spinal cord, spinal cord, substantia nigra, amygdala, midbrain.

Genetic regulation across tissues (GTEx eQTL / sQTL)

ADARB2 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 42 tissues and its splicing (sQTL) in 3 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 45 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Whole Blood	eqtl	8.7e-147	+1.11	10:1240467:C:A
Artery Aorta	eqtl	1.2e-67	+1.05	10:1240467:C:A
Artery Tibial	eqtl	1.2e-53	+0.83	10:1240467:C:A
Spleen	eqtl	1.1e-42	+1.12	10:1240467:C:A
Thyroid	eqtl	1.5e-40	+0.66	10:1240467:C:A
Adipose Visceral Omentum	eqtl	5.9e-30	+0.62	10:1240467:C:A
Esophagus Muscularis	eqtl	1.3e-21	+0.37	10:1240467:C:A
Esophagus Gastroesophageal Junction	eqtl	7.5e-18	+0.36	10:1240467:C:A
Brain Caudate basal ganglia	eqtl	1.6e-15	+0.45	10:1242775:AGGACAGGAGCT:A
Heart Atrial Appendage	eqtl	2.0e-14	+0.43	10:1240467:C:A
Testis	sqtl	2.1e-14	-0.81	10:1240467:C:A
Colon Transverse	eqtl	3.8e-14	+0.31	10:1240765:T:C
Stomach	eqtl	1.9e-13	+0.38	10:1240765:T:C
Prostate	eqtl	3.3e-13	+0.42	10:1240467:C:A
Brain Putamen basal ganglia	eqtl	3.5e-12	+0.55	10:1242775:AGGACAGGAGCT:A
Brain Hippocampus	eqtl	4.5e-12	+0.44	10:1242775:AGGACAGGAGCT:A
Brain Nucleus accumbens basal ganglia	eqtl	8.8e-12	-0.51	10:1233561:T:G
Skin Not Sun Exposed Suprapubic	eqtl	4.5e-11	+0.28	10:1240467:C:A
Nerve Tibial	eqtl	6.1e-11	+0.17	10:1240467:C:A
Small Intestine Terminal Ileum	eqtl	1.5e-10	+0.59	10:1240467:C:A

FANTOM5 promoters

showing 10 of 21 alternative TSS:

Promoter ID	TPM avg	Samples expressed
107899	1.0878	160
107911	0.8501	197
107897	0.5797	175
107908	0.4790	174
107882	0.4073	72
107888	0.3974	64
107886	0.2471	60
107910	0.1882	101
107900	0.1878	38
107909	0.1850	103

Top tissues by expression

showing 100 of 279 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
C1 segment of cervical spinal cord	UBERON:0006469	92.62	gold quality
spinal cord	UBERON:0002240	89.84	gold quality
substantia nigra	UBERON:0002038	85.41	gold quality
amygdala	UBERON:0001876	83.84	gold quality
midbrain	UBERON:0001891	83.69	gold quality
Ammon’s horn	UBERON:0001954	83.02	gold quality
corpus callosum	UBERON:0002336	82.85	gold quality
putamen	UBERON:0001874	81.82	gold quality
prefrontal cortex	UBERON:0000451	81.76	gold quality
Brodmann (1909) area 9	UBERON:0013540	81.75	gold quality
anterior cingulate cortex	UBERON:0009835	81.28	gold quality
cingulate cortex	UBERON:0003027	81.18	gold quality
pons	UBERON:0000988	81.17	gold quality
inferior olivary complex	UBERON:0002127	80.89	gold quality
right frontal lobe	UBERON:0002810	80.57	gold quality
caudate nucleus	UBERON:0001873	80.43	gold quality
nucleus accumbens	UBERON:0001882	79.79	gold quality
hypothalamus	UBERON:0001898	79.74	gold quality
temporal lobe	UBERON:0001871	79.64	gold quality
telencephalon	UBERON:0001893	78.84	gold quality
frontal cortex	UBERON:0001870	78.79	gold quality
parotid gland	UBERON:0001831	78.74	silver quality
medial globus pallidus	UBERON:0002477	78.74	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	78.68	gold quality
cranial nerve II	UBERON:0000941	78.53	gold quality
neocortex	UBERON:0001950	78.33	gold quality
cerebral cortex	UBERON:0000956	78.05	gold quality
postcentral gyrus	UBERON:0002581	77.77	gold quality
globus pallidus	UBERON:0001875	77.67	gold quality
forebrain	UBERON:0001890	76.53	gold quality
tibial nerve	UBERON:0001323	76.44	gold quality
brain	UBERON:0000955	75.90	gold quality
parietal lobe	UBERON:0001872	75.66	gold quality
entorhinal cortex	UBERON:0002728	75.40	gold quality
subthalamic nucleus	UBERON:0001906	74.50	gold quality
body of pancreas	UBERON:0001150	73.83	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	73.49	gold quality
substantia nigra pars reticulata	UBERON:0001966	73.39	gold quality
superior frontal gyrus	UBERON:0002661	73.36	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	73.03	gold quality
right uterine tube	UBERON:0001302	72.74	gold quality
right hemisphere of cerebellum	UBERON:0014890	72.69	gold quality
primary visual cortex	UBERON:0002436	72.52	gold quality
inferior vagus X ganglion	UBERON:0005363	71.37	gold quality
muscle layer of sigmoid colon	UBERON:0035805	71.35	gold quality
cerebellar cortex	UBERON:0002129	71.29	gold quality
cerebellar hemisphere	UBERON:0002245	71.29	gold quality
dorsal plus ventral thalamus	UBERON:0001897	70.68	gold quality
saliva-secreting gland	UBERON:0001044	70.51	gold quality
cerebellum	UBERON:0002037	70.43	gold quality
medulla oblongata	UBERON:0001896	70.34	gold quality
lateral nuclear group of thalamus	UBERON:0002736	70.09	silver quality
substantia nigra pars compacta	UBERON:0001965	70.00	gold quality
right testis	UBERON:0004534	69.96	gold quality
occipital lobe	UBERON:0002021	69.79	gold quality
left testis	UBERON:0004533	69.09	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	68.96	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	68.95	gold quality
minor salivary gland	UBERON:0001830	68.42	gold quality
ventral tegmental area	UBERON:0002691	68.41	silver quality
lower esophagus muscularis layer	UBERON:0035833	67.92	gold quality
lower esophagus	UBERON:0013473	67.81	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	67.31	gold quality
testis	UBERON:0000473	67.24	gold quality
mouth mucosa	UBERON:0003729	67.07	gold quality
pancreas	UBERON:0001264	65.92	gold quality
superior vestibular nucleus	UBERON:0007227	65.92	silver quality
right lung	UBERON:0002167	64.64	gold quality
cerebellar vermis	UBERON:0004720	64.61	gold quality
endocervix	UBERON:0000458	64.41	gold quality
sural nerve	UBERON:0015488	64.25	gold quality
Brodmann (1909) area 46	UBERON:0006483	64.13	silver quality
amniotic fluid	UBERON:0000173	64.07	gold quality
tonsil	UBERON:0002372	64.02	gold quality
seminal vesicle	UBERON:0000998	63.77	gold quality
mucosa of stomach	UBERON:0001199	63.22	gold quality
superficial temporal artery	UBERON:0001614	63.17	gold quality
nasal cavity mucosa	UBERON:0001826	63.08	gold quality
left uterine tube	UBERON:0001303	62.79	gold quality
small intestine Peyer’s patch	UBERON:0003454	62.59	gold quality
ganglionic eminence	UBERON:0004023	62.54	gold quality
pharyngeal mucosa	UBERON:0000355	62.34	gold quality
colon	UBERON:0001155	61.71	gold quality
transverse colon	UBERON:0001157	61.64	gold quality
nasal cavity epithelium	UBERON:0005384	61.62	gold quality
body of stomach	UBERON:0001161	61.31	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	61.21	gold quality
large intestine	UBERON:0000059	61.17	gold quality
cortical plate	UBERON:0005343	60.90	gold quality
esophagus	UBERON:0001043	60.83	gold quality
Brodmann (1909) area 23	UBERON:0013554	60.73	silver quality
nipple	UBERON:0002030	60.64	gold quality
intestine	UBERON:0000160	60.61	gold quality
small intestine	UBERON:0002108	60.47	gold quality
body of tongue	UBERON:0011876	60.44	gold quality
pericardium	UBERON:0002407	60.38	gold quality
saphenous vein	UBERON:0007318	60.36	gold quality
superior surface of tongue	UBERON:0007371	60.35	gold quality
trigeminal ganglion	UBERON:0001675	60.33	gold quality
cardia of stomach	UBERON:0001162	60.30	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 6.

Experiment	Marker?	Max mean expression
E-HCAD-35	yes	4817.63
E-GEOD-180759	yes	4766.21
E-HCAD-25	yes	4613.63
E-HCAD-30	yes	4143.73
E-GEOD-84465	yes	6.65
E-ANND-3	yes	4.00

HPA expression

RNA tissue specificity: Tissue enriched

showing 60 of 63 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM
Nucleus accumbens	tissue	30.2
Hippocampus	tissue	26.0
Locus coeruleus	tissue	23.1
Olfactory bulb	tissue	20.1
Postcentral gyrus	tissue	17.5
Superior colliculi	tissue	16.8
Thalamus	tissue	12.8
Midbrain	tissue	10.6
Substantia nigra	tissue	10.2
Pons	tissue	9.5
Hippocampal formation	tissue	8.2
Cerebral cortex	tissue	7.7
Entorhinal cortex	tissue	7.7
Ventral forebrain	tissue	7.7
Temporal cortex	tissue	7.7
Prefrontal cortex	tissue	7.5
Insular cortex	tissue	7.4
Amygdala	tissue	7.0
Somatosensory cortex	tissue	7.0
Motor cortex	tissue	6.4
Occipital cortex	tissue	6.2
Retrosplenial and cingulate cortex	tissue	5.8
Choroid plexus	tissue	5.7
Septum	tissue	5.5
Basal ganglia	tissue	5.3
Putamen	tissue	4.8
Retrosplenial cortex	tissue	4.8
Salivary gland	tissue	4.0
Pancreas	tissue	3.3
Hypothalamus	tissue	3.3
Cerebellum	tissue	3.0
Periaqueductal gray	tissue	2.9
Retina	tissue	2.7
Medulla oblongata	tissue	2.4
Frontal cortex	tissue	2.1
Spinal cord	tissue	2.0
Caudate putamen	tissue	1.8
Corpus callosum	tissue	1.6
Fallopian tube	tissue	1.1
Testis	tissue	1.0
Thymus	tissue	0.9
Breast	tissue	0.8
Seminal vesicle	tissue	0.8
Vagina	tissue	0.5
Pituitary gland	tissue	0.4
Lung	tissue	0.3
Tonsil	tissue	0.3
Stomach 1	tissue	0.2
Adrenal gland	tissue	0.2
Bone marrow	tissue	0.2
Cervix	tissue	0.1
Lymph node	tissue	0.1
Heart muscle	tissue	0.1
Ovary	tissue	0.1
Adipose tissue	tissue	0.1
Esophagus	tissue	0.1
Colon	tissue	0.1
Tongue	tissue	0.1
Placenta	tissue	0.1
Spleen	tissue	0.1

Brain sub-regions (HPA Brain Atlas): detected in 189; highest nTPM — Parieto-temporal junction (white matter) (102.7), Corpus callosum, genu (white matter) (96.0), Corpus callosum, splenium (white matter) (81.5), Temporal white matter (78.6), Cerebellar white matter (72.7).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): SFPQ

miRNA regulators (miRDB)

Targeting ADARB2 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 275 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-4776-3P	100.00	68.73	1340
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-4425	100.00	67.59	1049
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-3689D	100.00	66.14	1181
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
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-5696	99.98	72.36	4487
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-4645-5P	99.98	65.81	1284

Functional genomics

gnomAD constraint: pLI 0.00447, LOEUF 0.681, missense Z -1.55 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000381312 — one region, missense o/e 0.99.

Literature-anchored findings (GeneRIF, showing 8)

• The SNP in ADARB2 related to longevity is associated with metabolic disorders. This finding suggests that genetic factors modulate human longevity via the regulation of metabolic factors such as abdominal obesity and lipid profiles. (PMID:22210125)
• High ADAR3 expression is associated with Glioblastoma. (PMID:28167531)
• Results found that DNA methylation mark in ADARB2 gene is not predictive for Alzheimer’s disease and becomes differentially methylated after disease onset. (PMID:31477183)
• Novel ADAR3 binding sites discovered include the 3’-UTRs of the mRNAs encoding early growth response 1 (EGR1) and dual specificity phosphatase 1. (PMID:31552420)
• RNA binding by ADAR3 inhibits adenosine-to-inosine editing and promotes expression of immune response protein MAVS. (PMID:35850307)
• ADAR3 activates NF-kappaB signaling and promotes glioblastoma cell resistance to temozolomide. (PMID:35922651)
• The allelic regulation of tumor suppressor ADARB2 in papillary thyroid carcinoma. (PMID:36305508)
• Genome-wide association study reveals a locus in ADARB2 for complete freedom from headache in Danish Blood Donors. (PMID:38802570)

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
danio_rerio	adarb2	ENSDARG00000071823
mus_musculus	Adarb2	ENSMUSG00000052551
rattus_norvegicus	Adarb2	ENSRNOG00000030775
drosophila_melanogaster	loqs	FBGN0032515
drosophila_melanogaster	CG12493	FBGN0035571
drosophila_melanogaster	blanks	FBGN0035608
drosophila_melanogaster	Zn72D	FBGN0263603
caenorhabditis_elegans	zfr-1	WBGENE00022388

Paralogs (14): STAU2 (ENSG00000040341), ZFR (ENSG00000056097), ADAT1 (ENSG00000065457), ZFR2 (ENSG00000105278), STAU1 (ENSG00000124214), ILF3 (ENSG00000129351), TARBP2 (ENSG00000139546), ADAD2 (ENSG00000140955), ILF2 (ENSG00000143621), ADAR (ENSG00000160710), ADAD1 (ENSG00000164113), STRBP (ENSG00000165209), PRKRA (ENSG00000180228), ADARB1 (ENSG00000197381)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:2151118) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 8 distinct phenotype terms.

Mouse phenotype (MP)	Records
decreased bone mineral density	1
abnormal coat/ hair morphology	1
abnormal spleen morphology	1
small testis	1
increased anxiety-related response	1
limb grasping	1
small kidney	1
impaired contextual conditioning behavior	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Pongo abelii	Q5R6Y5	99.9%	Diamond
Bos taurus	Q08E27	98.2%	Diamond
Macaca fascicularis	Q95JV3	95.2%	Diamond
Gallus gallus	Q5ZIL4	92.0%	Diamond
Xenopus tropicalis	Q6GL57	89.8%	Diamond
Xenopus laevis	Q91550	89.8%	Diamond
Dictyostelium discoideum	Q54XP3	63.2%	Diamond
Schizosaccharomyces pombe 972h-	O42912	34.8%	Diamond
Arabidopsis thaliana	F4HU58	31.5%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
LINC00200	ncRNA	399706
ADARB2-AS1	ncRNA	642394
WDR37	protein-coding	22884
IDI1	protein-coding	3422
IDI2-AS1	ncRNA	55853
IDI2	protein-coding	91734
LINC00700	ncRNA	282980
MIR6072	ncRNA	102465944

Protein

Protein identifiers

Inactive double-stranded RNA-specific editase B2 — Q9NS39 (reviewed: Q9NS39)

Alternative names: RNA-dependent adenosine deaminase 3, RNA-editing deaminase 2, RNA-editing enzyme 2, dsRNA adenosine deaminase B2

All UniProt accessions (2): Q5VW43, Q9NS39

UniProt curated annotations — full annotation on UniProt →

Function. Single- and double-stranded RNA-binding protein that interferes with the RNA editing activities of ADAR/ADAR1 and ADARB1/ADAR2. Likely competes with these proteins for target binding, repressing RNA editing across the transcriptome. Additionally, it binds and stabilizes specific mRNAs and regulates the expression of proteins such as MAVS, DUSP1, and EGR1, independently of RNA editing mechanisms.

Subunit / interactions. Probable homodimer in vivo. Interacts with KPNA2; could mediate ADARB2 localization to the nucleus.

Subcellular location. Nucleus.

Tissue specificity. Brain specific. Expressed at higher levels in astrocytomas as compared to the normal brain tissue.

Domain organisation. The R-domain could function as a nuclear localization signal, mediating interaction with the importin KPNA2. It could also mediate ssRNA-binding. The DRBM domains involved in RNA-binding are crucial for the negative regulation of RNA editing.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9NS39-1	1	yes
Q9NS39-2	2

RefSeq proteins (1): NP_061172* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002466	A_deamin	Domain
IPR014720	dsRBD_dom	Domain
IPR044460	ADAR3_DSRM_1	Domain

Pfam: PF00035, PF02137

UniProt features (23 total): mutagenesis site 6, sequence variant 4, domain 3, binding site 3, region of interest 3, splice variant 2, chain 1, compositionally biased region 1

Structure

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NS39-F1	71.69	0.36

Human Protein Atlas

Protein class: Predicted intracellular proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): nucleoplasm; cytosol; mitochondria

Antibody reliability (HPA): IF approved

Functional residue map

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

Ligand- & substrate-binding residues (3)

Position	Role
555	Zn(2+)
432	Zn(2+)
490	Zn(2+)

Mutagenesis-validated functional residues (6)

Position	Phenotype
389	novel double-stranded rna adenosine deaminase activity; when associated with i-485, q-527, r-549 and d-733.
432–434	no effect on negative regulation of rna editing.
485	novel double-stranded rna adenosine deaminase activity; when associated with v-389, q-527, r-549 and d-733.
527	novel double-stranded rna adenosine deaminase activity; when associated with v-389, i-485, r-549 and d-733.
549	novel double-stranded rna adenosine deaminase activity; when associated with v-389, i-485, q-527 and d-733.
733	novel double-stranded rna adenosine deaminase activity; when associated with v-389, i-485, q-527 and r-549.

Function

Pathways and Gene Ontology

Reactome pathways

0 curated (TAS) of 0; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

MSigDB gene sets: 158 (showing top): BENPORATH_ES_WITH_H3K27ME3, GOBP_REGULATION_OF_MRNA_CATABOLIC_PROCESS, GOBP_3_UTR_MEDIATED_MRNA_STABILIZATION, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_MRNA_MODIFICATION, GOBP_POST_TRANSCRIPTIONAL_REGULATION_OF_GENE_EXPRESSION, GOBP_RNA_MODIFICATION, GOBP_REGULATION_OF_CATABOLIC_PROCESS, ATF1_Q6, BLALOCK_ALZHEIMERS_DISEASE_UP, TGCTGAY_UNKNOWN, SCHAEFFER_PROSTATE_DEVELOPMENT_48HR_UP, TGACATY_UNKNOWN, ATF3_Q6, TANAKA_METHYLATED_IN_ESOPHAGEAL_CARCINOMA

GO Biological Process (5): adenosine to inosine editing (GO:0006382), RNA processing (GO:0006396), mRNA processing (GO:0006397), 3’-UTR-mediated mRNA stabilization (GO:0070935), negative regulation of mRNA modification (GO:0090367)

GO Molecular Function (8): RNA binding (GO:0003723), double-stranded RNA binding (GO:0003725), mRNA binding (GO:0003729), tRNA-specific adenosine deaminase activity (GO:0008251), metal ion binding (GO:0046872), RNA sequestering activity (GO:0140610), adenosine deaminase activity (GO:0004000), deaminase activity (GO:0019239)

GO Cellular Component (4): nucleus (GO:0005634), nucleoplasm (GO:0005654), nucleolus (GO:0005730), cytoplasm (GO:0005737)

GO top-level categories

24 GO namespaces:

Category	Terms
RNA binding	3
nuclear lumen	2
cellular anatomical structure	2
base conversion or substitution editing	1
gene expression	1
RNA biosynthetic process	1
primary metabolic process	1
RNA processing	1
mRNA metabolic process	1
mRNA stabilization	1
mRNA modification	1
regulation of mRNA modification	1
negative regulation of mRNA metabolic process	1
nucleic acid binding	1
adenosine deaminase activity	1
catalytic activity, acting on a tRNA	1
cation binding	1
molecular sequestering activity	1
hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in cyclic amidines	1
deaminase activity	1
hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds	1
intracellular membrane-bounded organelle	1
intracellular membraneless organelle	1
intracellular anatomical structure	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 7 of 17 annotations. The rest are phylogenetic / computational / electronic (IEA).

7 experimentally-supported GO terms:

GO term	NS	Evidence
3’-UTR-mediated mRNA stabilization	BP	direct assay
negative regulation of mRNA modification	BP	direct assay
nucleoplasm	CC	direct assay
nucleus	CC	direct assay
RNA binding	MF	high-throughput assay
RNA sequestering activity	MF	direct assay
mRNA binding	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 892 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ADARB2	EARS2	Q5JPH6	864
ADARB2	ADA	P00813	860
ADARB2	EPRS1	P07814	739
ADARB2	GRIA2	P42262	713
ADARB2	GSR	P00390	614
ADARB2	ALYREF	Q86V81	586
ADARB2	LAMP5	Q9UJQ1	568
ADARB2	PURA	Q00577	543
ADARB2	AZIN1	O14977	499
ADARB2	C9orf72	Q96LT7	493
ADARB2	PTPRN2	Q92932	491
ADARB2	ADAT2	Q7Z6V5	489
ADARB2	TRMT6	Q9UJA5	482
ADARB2	ADAT3	Q96EY9	481
ADARB2	TRMT61A	Q96FX7	476

IntAct

BioGRID (22 interactions; top human partners by supporting records): ADARB1 (Proximity Label-MS), ANKHD1 (Affinity Capture-MS), CENPE (Affinity Capture-MS), DDX58 (Affinity Capture-RNA), EEF1A1 (Cross-Linking-MS (XL-MS)), EEF1A1P5 (Cross-Linking-MS (XL-MS)), EEF1A2 (Cross-Linking-MS (XL-MS)), EMC2 (Affinity Capture-MS), GPATCH4 (Affinity Capture-MS), KIAA1429 (Affinity Capture-RNA), KIF11 (Affinity Capture-MS), NOP16 (Affinity Capture-MS), NUDT21 (Affinity Capture-RNA), PARP16 (Proximity Label-MS), PARP2 (Proximity Label-MS)

Disease & clinical

Genetic variants

Variant evidence for ADARB2: 196 ClinVar records (11 pathogenic / likely pathogenic); 14 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	9
Likely pathogenic	2
Uncertain significance	158
Likely benign	12
Benign	6

Top pathogenic / likely-pathogenic (11)

Showing all 11 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
58711	GRCh38/hg38 10p15.3(chr10:87458-2482736)x1	Pathogenic	criteria provided, single submitter	1
3148908	GRCh37/hg19 10p15.3(chr10:100048-1247374)x1	Pathogenic	criteria provided, single submitter	1
146014	GRCh38/hg38 10p15.3-13(chr10:73856-12815915)x3	Pathogenic	no assertion criteria provided	1
146220	GRCh38/hg38 10p15.3-14(chr10:90421-11713049)x3	Pathogenic	no assertion criteria provided	1
154088	GRCh38/hg38 10p15.3(chr10:54086-1600803)x1	Pathogenic	no assertion criteria provided	1
154187	GRCh38/hg38 10p15.3-13(chr10:54086-13205916)x3	Pathogenic	no assertion criteria provided	1
395536	GRCh37/hg19 10p15.3-14(chr10:136361-8850609)x1	Pathogenic	no assertion criteria provided	1
441537	GRCh37/hg19 10p15.3-15.1(chr10:100026-4761588)x1	Pathogenic	no assertion criteria provided	1
442589	GRCh37/hg19 10p15.3-13(chr10:100026-12842179)x1	Pathogenic	no assertion criteria provided	1
146280	GRCh38/hg38 10p15.3-15.2(chr10:90421-3058742)x1	Likely pathogenic	no assertion criteria provided	1
154099	GRCh38/hg38 10p15.3-14(chr10:1601172-9203729)x3	Likely pathogenic	no assertion criteria provided	1

Per-variant reference — Sugi Variant

Explore ADARB2’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 41 predictions of 3,040):

Position(s)	Effect	Δscore	Sites
10:1185040–1185041	acceptor_loss	1.0000	5
10:1199964–1199965	donor_loss	1.0000	5
10:1242129–1242130	donor_loss	1.0000	5
10:1363918–1363919	acceptor_loss	1.0000	6
10:1183168	donor_gain	0.9900
10:1183370–1183371	acceptor_loss	0.9900	6
10:1185040	acceptor_loss	0.9900
10:1199964	donor_loss	0.9900
10:1200148–1200149	acceptor_loss	0.9900	6
10:1216949–1216950	donor_loss	0.9900	5

AlphaMissense

1,304 missense substitutions predicted likely pathogenic (of 4,753 scored), across 349 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
D557	8	0.975	0.995
F156	8	0.966	0.999
D430	8	0.962	0.990
H152	8	0.949	0.987
F167	8	0.945	0.998
H432	8	0.944	0.970
F212	8	0.938	0.993
F189	8	0.925	0.986
F317	8	0.918	0.996
D215	8	0.917	0.964
F306	8	0.917	0.996
D211	8	0.908	0.968
F224	8	0.903	0.958
H482	8	0.898	0.978
D492	8	0.890	0.951
N72	8	0.876	0.955
N128	8	0.870	0.984
F465	8	0.851	0.978
M553	8	0.827	0.950
M308	8	0.814	0.970

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Disease associations

OMIM: gene MIM:602065 | disease phenotypes:

GWAS associations

14 associations:

Study	Trait	p-value
GCST002541_79	Menarche (age at onset)	2e-12
GCST006186_1	Systolic blood pressure x smoking status (current vs non-current) interaction (1df test)	7e-9
GCST006195_3	Systolic blood pressure x smoking status (current vs non-current) interaction (2df test)	2e-8
GCST009028_8	Adverse response to drug	5e-8
GCST007013_4	Hippocampal volume in mild cognitive impairment	7e-7
GCST002587_28	Blood pressure (smoking interaction)	8e-7
GCST000337_1	Quantitative traits	2e-6
GCST004253_7	Accelerated cognitive decline after conversion of mild cognitive impairment to Alzheimer’s disease (Alzhiemer’s diagnosis trajectory interaction)	3e-6
GCST009391_1694	Metabolite levels	3e-6
GCST006086_11	Familial lung cancer	4e-6
GCST008162_79	Hip circumference	5e-6
GCST000770_7	Emphysema-related traits	6e-6
GCST000823_2	Radiation response	6e-6
GCST000337_18	Quantitative traits	8e-6

EFO canonical traits (from GWAS)

11 canonical traits:

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0004341	body fat distribution
EFO:0004703	age at menarche
EFO:0006335	systolic blood pressure
EFO:0006526	pack-years measurement
EFO:0007710	cognitive decline measurement
EFO:0006953	family history of lung cancer
EFO:0006527	smoking status measurement
EFO:0005035	hippocampal volume
EFO:0009658	adverse effect
EFO:0010542	ureidopropionic acid measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (CPIC guideline: no)

CTD chemical–gene interactions

29 total (human), top 29 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases methylation, increases expression	3
Benzo(a)pyrene	affects methylation, decreases expression, increases methylation	3
Aflatoxin B1	affects methylation, decreases expression, decreases methylation	3
bisphenol F	affects cotreatment, increases methylation	1
TAK-243	increases sumoylation	1
methyleugenol	decreases expression	1
11-nor-delta(9)-tetrahydrocannabinol-9-carboxylic acid	affects methylation, increases abundance	1
sodium arsenite	decreases expression	1
benzo(e)pyrene	affects methylation	1
N-acetyl-4-benzoquinoneimine	affects response to substance	1
ferrous chloride	increases expression	1
aflatoxin B2	affects methylation	1
coumarin	decreases phosphorylation	1
hydroquinone	decreases reaction, increases expression	1
bisphenol S	affects methylation	1
Sunitinib	decreases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Acetaminophen	decreases expression	1
Cannabinoids	affects methylation, increases abundance	1
Endosulfan	increases expression	1
Estradiol	increases expression, decreases reaction	1
Methapyrilene	affects methylation	1
Oxygen	increases expression	1
Phthalic Acids	decreases methylation	1
Ribonucleotides	affects binding	1
Tobacco Smoke Pollution	decreases expression	1
Toluene	decreases expression, increases methylation	1
Valproic Acid	increases methylation	1
Asbestos, Serpentine	increases methylation	1

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

1 trials:

NCT	Phase	Status	Title
NCT07164248	Not specified	COMPLETED	Evaluation of Bone Mineral Density Indications and Outcomes in Female Adolescents: Implications for Early Detection of Osteopenia/Osteoporosis and Gynecologic Practice