ADARB1

Summary

ADARB1 (adenosine deaminase RNA specific B1, HGNC:226) is a protein-coding gene on chromosome 21q22.3, encoding Double-stranded RNA-specific editase 1 (P78563). Catalyzes the hydrolytic deamination of adenosine to inosine in double-stranded RNA (dsRNA) referred to as A-to-I RNA editing.

This gene encodes the enzyme responsible for pre-mRNA editing of the glutamate receptor subunit B by site-specific deamination of adenosines. Studies in rat found that this enzyme acted on its own pre-mRNA molecules to convert an AA dinucleotide to an AI dinucleotide which resulted in a new splice site. Alternative splicing of this gene results in several transcript variants, some of which have been characterized by the presence or absence of an ALU cassette insert and a short or long C-terminal region.

Source: NCBI Gene 104 — RefSeq curated summary.

At a glance

• Gene–disease (curated): neurodevelopmental disorder with hypotonia, microcephaly, and seizures (Strong, GenCC)
• GWAS associations: 13
• Clinical variants (ClinVar): 146 total — 18 pathogenic
• Phenotypes (HPO): 33
• Druggable target: yes
• MANE Select transcript: NM_001112

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:226
Approved symbol	ADARB1
Name	adenosine deaminase RNA specific B1
Location	21q22.3
Locus type	gene with protein product
Status	Approved
Aliases	ADAR2, DRADA2, ADAR2g, DRABA2, RED1, hRED1, ADAR2a-L1, ADAR2a-L2, ADAR2a-L3, ADAR2a, ADAR2b, ADAR2c, ADAR2d
Ensembl gene	ENSG00000197381
Ensembl biotype	protein_coding
OMIM	601218
Entrez	104

Gene structure

Transcript identifiers

Ensembl transcripts: 18 — 10 protein_coding, 5 protein_coding_CDS_not_defined, 3 nonsense_mediated_decay

ENST00000348831, ENST00000360697, ENST00000389861, ENST00000389863, ENST00000449478, ENST00000460734, ENST00000462214, ENST00000464215, ENST00000481022, ENST00000492414, ENST00000496664, ENST00000631642, ENST00000705392, ENST00000705393, ENST00000874894, ENST00000913573, ENST00000962803, ENST00000962804

RefSeq mRNA: 7 — MANE Select: NM_001112 NM_001112, NM_001160230, NM_001346687, NM_001346688, NM_001410722, NM_015833, NM_015834

CCDS: CCDS33589, CCDS33590, CCDS42970, CCDS93105, CCDS93106

Canonical transcript exons

ENST00000348831 — 11 exons

Exon	Start	End
ENSE00001050989	45175730	45176664
ENSE00001210927	45128402	45128573
ENSE00001530203	45222018	45226560
ENSE00003625084	45171610	45171684
ENSE00003718967	45220836	45221014
ENSE00003721505	45180330	45180444
ENSE00003721925	45182585	45182753
ENSE00003732074	45183362	45183510
ENSE00003736672	45184923	45185091
ENSE00003745511	45204555	45204736
ENSE00003842491	45074580	45074793

Expression profiles

Bgee: expression breadth ubiquitous, 273 present calls, max score 98.14.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 15.1633 / max 195.5707, expressed in 1753 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
189531	8.8441	1682
189530	5.7743	749
189535	0.3858	165
189536	0.1437	82
189534	0.0154	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
blood vessel layer	UBERON:0004797	98.14	gold quality
popliteal artery	UBERON:0002250	97.98	gold quality
tibial artery	UBERON:0007610	97.98	gold quality
mucosa of stomach	UBERON:0001199	97.78	gold quality
aorta	UBERON:0000947	96.83	gold quality
lower esophagus muscularis layer	UBERON:0035833	96.54	gold quality
lower esophagus	UBERON:0013473	96.47	gold quality
right coronary artery	UBERON:0001625	96.41	gold quality
cerebellar vermis	UBERON:0004720	96.38	gold quality
saphenous vein	UBERON:0007318	96.37	gold quality
lateral nuclear group of thalamus	UBERON:0002736	95.67	gold quality
descending thoracic aorta	UBERON:0002345	95.40	gold quality
thoracic aorta	UBERON:0001515	95.38	gold quality
ascending aorta	UBERON:0001496	95.31	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	95.30	gold quality
calcaneal tendon	UBERON:0003701	95.21	gold quality
coronary artery	UBERON:0001621	93.95	gold quality
left coronary artery	UBERON:0001626	93.73	gold quality
pons	UBERON:0000988	93.69	gold quality
vena cava	UBERON:0004087	93.50	silver quality
right lung	UBERON:0002167	93.13	gold quality
cerebellum	UBERON:0002037	93.00	gold quality
cerebellar cortex	UBERON:0002129	93.00	gold quality
cerebellar hemisphere	UBERON:0002245	92.95	gold quality
middle temporal gyrus	UBERON:0002771	92.91	gold quality
tibia	UBERON:0000979	92.89	gold quality
tendon	UBERON:0000043	92.70	gold quality
right hemisphere of cerebellum	UBERON:0014890	92.34	gold quality
type B pancreatic cell	CL:0000169	92.18	gold quality
upper lobe of left lung	UBERON:0008952	91.99	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.18

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CREB1, E2F4, JUN, TP53

miRNA regulators (miRDB)

176 targeting ADARB1, 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-4262	100.00	73.26	3931
HSA-MIR-518D-5P	100.00	67.51	979
HSA-MIR-518E-5P	100.00	67.66	954
HSA-MIR-518F-5P	100.00	67.51	979
HSA-MIR-519A-5P	100.00	67.66	954
HSA-MIR-519B-5P	100.00	67.66	954
HSA-MIR-519C-5P	100.00	67.66	954
HSA-MIR-520C-5P	100.00	67.51	979
HSA-MIR-522-5P	100.00	67.66	954
HSA-MIR-523-5P	100.00	67.66	954
HSA-MIR-526A-5P	100.00	67.51	979
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-8485	100.00	77.57	4731
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-520G-5P	99.99	66.76	658
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-7153-5P	99.94	68.89	1006
HSA-MIR-552-5P	99.93	68.56	1583
HSA-MIR-450B-5P	99.92	71.48	3175

Literature-anchored findings (GeneRIF, showing 40)

• overexpression inhibits HDV RNA replication and compromises virus viability (PMID:11907222)
• Adenosine to inosine RNA editing requires formation of a ternary complex on the GluR-B R/G site (PMID:12163487)
• short inhibitory RNA-mediated knockdown of host ADAR1 expression but not that of ADAR2 led to decreased HDV amber/W editing and virus production (PMID:12414985)
• the Q/R site of GluRs editing is regulated in a regional manner and the GluR2 Q/R site editing is critically regulated by ADAR2 in human brain (PMID:12859334)
• assayed enzymatic activity of N-terminal deletion constructs of hADAR2 to determine the role of the double-stranded RNA binding motifs and the intervening linker peptide (PMID:15383678)
• Inositol hexakisphosphate is buried within the catalytic domain of ADAR2 and is required for editing of transfer RNA. (PMID:16141067)
• results show that bipolar affective disorder may not be caused by mutations in ADARB1. (PMID:16733555)
• Serum adenosine deaminase (ADA) activity of active Behcet’s disease (BD) was higher than that of inactive BD (P < 0.01), but erythrocyte ADA activity was found to be lower in active BD than inactive BD (P < 0.01). (PMID:16961545)
• CD26 and cell surface adenosine deaminase are selectively expressed on ALK-positive, but not on ALK-negative, anaplastic large cell lymphoma and Hodgkin’s lymphoma (PMID:17071493)
• The CTD of POLR2A and ADAR2 function together to enforce the order of events that allows editing to precede splicing, and they furthermore suggest a new role for the CTD as a coordinator of two interdependent pre-mRNA processing events. (PMID:17525170)
• Reference values of serum adenosine deaminase (ADA) in normal pregnancy may provide important database for making clinical decisions in pregnancies complicated by conditions where cellular immunity has been altered. (PMID:17728516)
• elevated levels of ADAR1, as found in astrocytomas, do indeed interfere with ADAR2 specific editing activity, and the endogenous ADAR1 can form heterodimers with ADAR2 in astrocytes (PMID:18178553)
• analysis of a splice variant that extends the open reading frame of ADAR2 by 49 amino acids through the utilization of an exon located 18 kilobases upstream of the previously annotated first coding exon and driven by a candidate alternative promoter (PMID:19156214)
• our understanding of the importance of functional groups found in the edited nucleotide and the role of specific active site residues of ADAR2 (PMID:19642681)
• Results imply that ADAR1 and ADAR2 have biological functions as RNA-binding proteins that extend beyond editing per se and that even genomically encoded ADARs that are catalytically inactive may have such functions. (PMID:19713932)
• The high conservation of the novel ADAR2 alternative exon in mammals indicates a physiological importance for this exon. (PMID:20215858)
• Elucidation of the molecular mechanism underlying the co-occurrence of reduced ADAR2 activity and abnormal TDP-43 pathology in the same motor neurons may provide a clue to the neurodegenerative process of sporadic amyotrophic lateral sclerosis. (PMID:20372915)
• The authors found that, analogously to ADAR1, ADAR2 enhances the release of progeny virions by an editing-dependent mechanism. (PMID:21289159)
• The strong functional similarity of human ADAR2 and Drosophila Adar suggests rather that these are true orthologs. (PMID:21622951)
• These results indicated that ADAR2 downregulation is a profound pathological change relevant to death of motor neurons in ALS. (PMID:22226999)
• ADAR2 activity at the GluA2 pre-mRNA Q/R site correlates with the ADAR2 mRNA level relative to the GluA2 pre-mRNA in different cultured cell lines. (PMID:22366356)
• ADAR2 activity does not consistently change due to the overexpression or knockdown of TDP-43 or the expression of abnormal TDP-43 in amyotrophic lateral sclerosis (ALS) motor neurons. (PMID:22414730)
• Findings demonstrate that post-transcriptional A-to-I RNA editing might be crucial for glioblastoma pathogenesis, identify ADAR2-editing enzyme as a candidate tumor suppressor gene and provide proof that ADAR2 may represent a suitable target. (PMID:22525274)
• The results represent the first evidence that the ADAR1 p150 isoform is the determinant of DSH and may give insight into the currently unknown mechanisms involved in the development of DSH. (PMID:23621630)
• ADAR2-mediated editing of the complementary antisense transcripts is a novel mechanism for regulating the biogenesis of specific miRNAs during hepatocarcinogenesis. (PMID:24386085)
• altered RNA editing efficiency of AMPA receptors due to down-regulation of ADAR2 has a possible role in the pathophysiology of mental disorders. (PMID:24443933)
• The ADAR2 alternative splicing variants may be correlated with the invasiveness of gliomas. (PMID:24509948)
• Characterization of the ADAR2 catalytic domain-RNA interaction. (PMID:25564529)
• ADAR2 is a key factor for maintaining edited-miRNA population and balancing the expression of several essential miRNAs involved in cancer. (PMID:25582055)
• Therefore, the expression of ADAR1 and ADAR2 was analyzed in chordoma tissues. It was found that ADAR1 was significantly overexpressed, which was accompanied by enhanced pre-miR-10a and pri-miR-125a A-to-I editing (PMID:25673044)
• Data show that a large fraction of the edited genes are positively correlated ADAR (ADAR1) and ADARB1 (ADAR2). (PMID:25692240)
• ADARB1 rs9983925 and rs4819035 and HTR2C rs6318 were associated with suicide attempt risk. (PMID:25732952)
• we conclude that this aberrant alternative splicing pattern of ADAR2 downregulates A-to-I editing in glioma (PMID:25873329)
• Detailed structural analysis indicates that the minor groove width of dsRNA and global shape of RNA may play an important role in the specific reading mechanism of ADAR2. (PMID:26252972)
• These findings suggest that adenosine deaminase acting on RNA 2 is subject to different regulations by DNA methyltransferase and histone deacetylase enzymes in neuronal SH-SY5Y cells. (PMID:26485095)
• A-to-I RNA editing levels catalyzed by ADAR1 and ADARB1 decreased in Alzheimer’s disease patients’ brain tissues, mainly in the hippocampus and to a lesser degree in the temporal and frontal lobes. (PMID:26655226)
• These data suggest that, like ADAR2, underlying sequences in dsRNA may influence how NF90 recognizes its target RNAs (PMID:26712564)
• Four crystal structures of the human ADAR2 deaminase domain bound to RNA duplexes bearing a mimic of the deamination reaction intermediate. (PMID:27065196)
• we determined the importance of specific amino acids at 19 different positions in the ADAR2 5’ binding loop and revealed six residues that provide essential structural elements supporting the fold of the loop and key RNA-binding functional groups. This work provided new insight into RNA recognition by ADAR2 and established a new tool for defining structure-function relationships in ADAR reactions. (PMID:27614075)
• Data indicate that ADAR2 suppresses tumor growth and induces apoptosis by editing and stabilizing IGFBP7 in esophageal squamous cell carcinoma. (PMID:28035363)

Cross-species orthologs

9 orthologs

Organism	Symbol	Gene ID
danio_rerio	adarb1b	ENSDARG00000003544
danio_rerio	adarb1a	ENSDARG00000041609
mus_musculus	Adarb1	ENSMUSG00000020262
rattus_norvegicus	Adarb1	ENSRNOG00000001227
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), ADARB2 (ENSG00000185736)

Protein

Protein identifiers

Double-stranded RNA-specific editase 1 — P78563 (reviewed: P78563)

Alternative names: RNA-editing deaminase 1, RNA-editing enzyme 1, dsRNA adenosine deaminase

All UniProt accessions (4): A0A0A0MSG8, A0A994J4V7, A0A994J7T5, P78563

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the hydrolytic deamination of adenosine to inosine in double-stranded RNA (dsRNA) referred to as A-to-I RNA editing. This may affect gene expression and function in a number of ways that include mRNA translation by changing codons and hence the amino acid sequence of proteins; pre-mRNA splicing by altering splice site recognition sequences; RNA stability by changing sequences involved in nuclease recognition; genetic stability in the case of RNA virus genomes by changing sequences during viral RNA replication; and RNA structure-dependent activities such as microRNA production or targeting or protein-RNA interactions. Can edit both viral and cellular RNAs and can edit RNAs at multiple sites (hyper-editing) or at specific sites (site-specific editing). Its cellular RNA substrates include: bladder cancer-associated protein (BLCAP), neurotransmitter receptors for glutamate (GRIA2 and GRIK2) and serotonin (HTR2C), GABA receptor (GABRA3) and potassium voltage-gated channel (KCNA1). Site-specific RNA editing of transcripts encoding these proteins results in amino acid substitutions which consequently alter their functional activities. Edits GRIA2 at both the Q/R and R/G sites efficiently but converts the adenosine in hotspot1 much less efficiently. Can exert a proviral effect towards human immunodeficiency virus type 1 (HIV-1) and enhances its replication via both an editing-dependent and editing-independent mechanism. The former involves editing of adenosines in the 5’UTR while the latter occurs via suppression of EIF2AK2/PKR activation and function. Can inhibit cell proliferation and migration and can stimulate exocytosis. Has a lower catalytic activity than isoform 2. Has a higher catalytic activity than isoform 1.

Subunit / interactions. Homodimer. Homodimerization is essential for its catalytic activity. Can form heterodimers with isoform 5 of ADAR/ADAR1.

Subcellular location. Nucleus. Nucleolus Nucleus. Nucleolus.

Tissue specificity. Highly expressed in brain and heart and at lower levels in placenta. Fair expression in lung, liver and kidney. Detected in brain, heart, kidney, lung and liver (at protein level). Highly expressed in hippocampus and colon. Expressed in pediatric astrocytomas and the protein has a decreased RNA-editing activity. The decrease in RNA editing correlates with the grade of malignancy of the tumors, with the high grade tumors showing lower editing is seen.

Disease relevance. Neurodevelopmental disorder with hypotonia, microcephaly, and seizures (NEDHYMS) [MIM:618862] An autosomal recessive neurodevelopmental disorder characterized by global developmental delay with axial hypotonia, inability to sit or walk, impaired intellectual development with absent language, and early-onset intractable seizures in most patients. Additional features include poor overall growth, microcephaly, dysmorphic features, poor eye contact due to cortical blindness, and non-specific brain abnormalities. The disease is caused by variants affecting the gene represented in this entry.

Cofactor. Binds 1 myo-inositol hexakisphosphate (IP6) per subunit.

Miscellaneous. Alu insert from position 465 to 505. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay. Likely expressed from an alternative promoter. Contains a region highly similar to the so-called ssRNA-binding R-domain of ADARB2.

Isoforms (6)

UniProt ID	Names	Canonical?
P78563-1	1, ADAR2b, ADAR2L, DRADA2B, RED1-L	yes
P78563-2	2, ADAR2a, ADAR2S, DRADA2A, RED1-S
P78563-3	3, DRADA2C
P78563-4	4
P78563-5	5, ADAR2R
P78563-6	6, ADAR2d

RefSeq proteins (7): NP_001103, NP_001153702, NP_001333616, NP_001333617, NP_001397651, NP_056648, NP_056649 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002466	A_deamin	Domain
IPR008996	IL1/FGF	Homologous_superfamily
IPR014720	dsRBD_dom	Domain
IPR044458	ADAR2_DSRM_1	Domain
IPR044459	ADAR2_DSRM_2	Domain

Pfam: PF00035, PF02137

Enzyme classification (BRENDA):

• EC 3.5.4.37 — double-stranded RNA adenine deaminase (BRENDA: 11 organisms, 31 substrates, 15 inhibitors, 0 Km, 2 kcat entries)

Substrate kinetics (BRENDA)

2 substrates with measured Km, best-characterized 2. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
8-AZAADENINE IN DOUBLE-STRANDED RNA	—	0
ADENINE IN DOUBLE-STRANDED RNA	—	0

Catalyzed reactions (Rhea), 1 shown:

• adenosine in double-stranded RNA + H2O + H(+) = inosine in double-stranded RNA + NH4(+) (RHEA:10120)

UniProt features (83 total): helix 20, strand 19, binding site 11, sequence variant 6, region of interest 6, splice variant 4, turn 4, domain 3, compositionally biased region 3, sequence conflict 3, modified residue 2, chain 1, active site 1

Structure

Experimental structures (PDB)

13 structures.

PDB	Method	Resolution (Å)
1ZY7	X-RAY DIFFRACTION	1.7
7KFN	X-RAY DIFFRACTION	2.5
6D06	X-RAY DIFFRACTION	2.55
9OP3	X-RAY DIFFRACTION	2.59
9D5K	X-RAY DIFFRACTION	2.7
8E0F	X-RAY DIFFRACTION	2.7
5ED1	X-RAY DIFFRACTION	2.77
6VFF	X-RAY DIFFRACTION	2.8
8E4X	X-RAY DIFFRACTION	2.8
9D5J	X-RAY DIFFRACTION	2.8
5ED2	X-RAY DIFFRACTION	2.95
5HP2	X-RAY DIFFRACTION	2.98
5HP3	X-RAY DIFFRACTION	3.09

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P78563-F1	77.12	0.54

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 (11): 394; 400; 401; 451; 556; 559; 562; 669; 702; 712; 730

Post-translational modifications (2): 26, 149

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-75102	C6 deamination of adenosine
R-HSA-77042	Formation of editosomes by ADAR proteins

MSigDB gene sets: 405 (showing top): GSE37336_LY6C_POS_VS_NEG_NAIVE_CD4_TCELL_UP, GOBP_SPINAL_CORD_DEVELOPMENT, GOBP_BEHAVIOR, GOBP_REGULATION_OF_PHOSPHORYLATION, GOBP_NEGATIVE_REGULATION_OF_KINASE_ACTIVITY, GOBP_GROWTH, GOBP_POSITIVE_REGULATION_OF_VIRAL_GENOME_REPLICATION, GOBP_REGULATION_OF_TRANSFERASE_ACTIVITY, GOBP_NEUROGENESIS, GOBP_CRANIAL_NERVE_MORPHOGENESIS, GOBP_CRANIAL_NERVE_DEVELOPMENT, GOBP_MRNA_MODIFICATION, GOBP_CELL_CELL_SIGNALING, BROWNE_HCMV_INFECTION_24HR_UP, GOBP_ANIMAL_ORGAN_MORPHOGENESIS

GO Biological Process (23): adenosine to inosine editing (GO:0006382), RNA processing (GO:0006396), mRNA processing (GO:0006397), neuromuscular synaptic transmission (GO:0007274), negative regulation of cell population proliferation (GO:0008285), base conversion or substitution editing (GO:0016553), mRNA modification (GO:0016556), facial nerve morphogenesis (GO:0021610), hypoglossal nerve morphogenesis (GO:0021618), spinal cord ventral commissure morphogenesis (GO:0021965), negative regulation of cell migration (GO:0030336), multicellular organism growth (GO:0035264), negative regulation of protein kinase activity by regulation of protein phosphorylation (GO:0044387), positive regulation of viral genome replication (GO:0045070), innate immune response (GO:0045087), neuromuscular process controlling posture (GO:0050884), defense response to virus (GO:0051607), regulation of cell cycle (GO:0051726), innervation (GO:0060384), muscle tissue morphogenesis (GO:0060415), motor behavior (GO:0061744), motor neuron apoptotic process (GO:0097049), immune system process (GO:0002376)

GO Molecular Function (11): RNA binding (GO:0003723), double-stranded RNA binding (GO:0003725), double-stranded RNA adenosine deaminase activity (GO:0003726), mRNA binding (GO:0003729), tRNA-specific adenosine deaminase activity (GO:0008251), identical protein binding (GO:0042802), metal ion binding (GO:0046872), adenosine deaminase activity (GO:0004000), protein binding (GO:0005515), hydrolase activity (GO:0016787), deaminase activity (GO:0019239)

GO Cellular Component (6): nucleus (GO:0005634), nucleoplasm (GO:0005654), nucleolus (GO:0005730), cytoplasm (GO:0005737), cytosol (GO:0005829), synapse (GO:0045202)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
mRNA Editing: A to I Conversion	2

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
mRNA metabolic process	2
RNA modification	2
cranial nerve morphogenesis	2
multicellular organismal process	2
RNA binding	2
deaminase activity	2
nuclear lumen	2
base conversion or substitution editing	1
gene expression	1
RNA biosynthetic process	1
primary metabolic process	1
RNA processing	1
chemical synaptic transmission	1
cell population proliferation	1
regulation of cell population proliferation	1
negative regulation of cellular process	1
facial nerve development	1
hypoglossal nerve development	1
spinal cord development	1
central nervous system projection neuron axonogenesis	1
cell migration	1
regulation of cell migration	1
negative regulation of cell motility	1
developmental growth	1
negative regulation of protein kinase activity	1
viral genome replication	1
regulation of viral genome replication	1
positive regulation of viral process	1
immune response	1
defense response to symbiont	1
musculoskeletal movement	1
neuromuscular process	1
defense response	1
response to virus	1
cell cycle	1
regulation of cellular process	1
nerve development	1
muscle organ morphogenesis	1
tissue morphogenesis	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

51 interactions, top by confidence:

A	B	Type	Score
N	ADARB1	psi-mi:“MI:0915”(physical association)	0.600
PIN1	ADARB1	psi-mi:“MI:0915”(physical association)	0.570
ADARB1	PIN1	psi-mi:“MI:0915”(physical association)	0.570
ADARB1	PIN1	psi-mi:“MI:0407”(direct interaction)	0.570
PIN1	ADARB1	psi-mi:“MI:0407”(direct interaction)	0.570
PIN1	ADARB1	psi-mi:“MI:0403”(colocalization)	0.570
ADARB1	PIN1	psi-mi:“MI:0403”(colocalization)	0.570
ADARB1	CSNK2A1	psi-mi:“MI:0915”(physical association)	0.560
ADARB1	JUN	psi-mi:“MI:0915”(physical association)	0.560
ADARB1	SPTY2D1	psi-mi:“MI:0914”(association)	0.530
TNFAIP3	LRRIQ3	psi-mi:“MI:2364”(proximity)	0.420
WWP2	ADARB1	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (547): ADARB1 (Affinity Capture-MS), ADARB1 (Co-fractionation), LRPPRC (Co-fractionation), ADARB1 (Reconstituted Complex), ADARB1 (Affinity Capture-MS), ADARB1 (Affinity Capture-MS), ADARB1 (Affinity Capture-MS), ADARB1 (Affinity Capture-MS), ADARB1 (Affinity Capture-MS), ADARB1 (Affinity Capture-RNA), ADARB1 (Affinity Capture-RNA), ADARB1 (Affinity Capture-MS), ADARB1 (Two-hybrid), ADARB1 (Two-hybrid), ADARB1 (Two-hybrid)

ESM2 similar proteins: A2A2Y4, A2VDD2, A7MBL8, B2RQE8, B9EJ86, D4A1F2, E9Q4Z2, E9Q5G3, F1MF74, F1ND48, F1QDI9, G9CGD6, O00763, O08874, O94851, O95630, P0C928, P78563, Q0P4Q4, Q0VGY8, Q16513, Q2TBH6, Q3B8D7, Q498D5, Q4U2V3, Q5R803, Q62698, Q66IC8, Q6F6B3, Q6P9H4, Q6ZMV9, Q76N33, Q7ZU92, Q7ZYZ7, Q8BHD4, Q8BML1, Q8BPM2, Q8IVH8, Q8IZC4, Q8K394

Diamond homologs: A2RFW8, A8AWC2, B5XKB7, B8GAM6, C0MCR4, P0DF14, P0DF15, P51400, P55265, P55266, P66670, P66672, P78563, P97473, P97616, Q08E27, Q0IIG6, Q12906, Q15633, Q1J7V3, Q1JCZ9, Q1JI19, Q1JMX4, Q22618, Q3KR54, Q3SWU0, Q48UR6, Q5BJ52, Q5R6Y5, Q5SUE7, Q5XDA6, Q5ZIL4, Q6DCD0, Q6DD04, Q6GL57, Q6NXA4, Q8NCV1, Q91550, Q91WM1, Q91ZS8

SIGNOR signaling

8 interactions.

A	Effect	B	Mechanism
ADARB1	“up-regulates activity”	EIF2AK2	binding
PRKCZ	“up-regulates activity”	ADARB1	phosphorylation
FUS	“down-regulates quantity by repression”	ADARB1	“post transcriptional regulation”
AKT	“down-regulates activity”	ADARB1	phosphorylation
AKT1	“down-regulates activity”	ADARB1	phosphorylation
AKT3	“down-regulates activity”	ADARB1	phosphorylation
AKT2	“down-regulates activity”	ADARB1	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	18
Likely pathogenic	0
Uncertain significance	90
Likely benign	17
Benign	6

Top pathogenic / likely-pathogenic (18)

Variant ID	HGVS	Classification
1526724	GRCh37/hg19 21q22.3(chr21:45265857-47057233)	Pathogenic
1526725	GRCh37/hg19 21q22.3(chr21:45773272-48097372)	Pathogenic
1710511	GRCh37/hg19 21q22.3(chr21:45808650-47529568)x1	Pathogenic
2443914	NM_001112.4(ADARB1):c.1769G>A (p.Arg590Gln)	Pathogenic
2443915	NM_001112.4(ADARB1):c.1245_1247+1del	Pathogenic
253527	GRCh37/hg19 21q22.3(chr21:46363553-48080926)x1	Pathogenic
3062427	GRCh37/hg19 21q22.3(chr21:45102309-48097372)x1	Pathogenic
3062430	GRCh37/hg19 21q22.3(chr21:44577746-48097372)x1	Pathogenic
3248207	NC_000021.8:g.(?44296792)(47865240_?)del	Pathogenic
4279154	GRCh37/hg19 21q22.3(chr21:46569369-46621106)x1	Pathogenic
4682975	GRCh37/hg19 21q22.3(chr21:44762021-48097372)x1	Pathogenic
59046	GRCh38/hg38 21q22.3(chr21:45110477-46648012)x1	Pathogenic
59068	GRCh38/hg38 21q22.3(chr21:45138321-46670405)x1	Pathogenic
686963	GRCh37/hg19 21q22.3(chr21:44310057-47503155)x1	Pathogenic
870450	NM_001112.4(ADARB1):c.1492A>G (p.Ser498Gly)	Pathogenic
870451	NM_001112.4(ADARB1):c.379A>G (p.Lys127Glu)	Pathogenic
870452	NM_001112.4(ADARB1):c.1688G>A (p.Arg563Gln)	Pathogenic
870453	NM_001112.4(ADARB1):c.2045C>T (p.Ala682Val)	Pathogenic

SpliceAI

5333 predictions. Top by Δscore:

Variant	Effect	Δscore
21:45134710:A:AG	acceptor_gain	1.0000
21:45134711:C:G	acceptor_gain	1.0000
21:45171683:GA:G	donor_gain	1.0000
21:45171685:G:GG	donor_gain	1.0000
21:45171706:T:TG	donor_gain	1.0000
21:45171707:A:AA	donor_gain	1.0000
21:45180325:CACA:C	acceptor_loss	1.0000
21:45180327:CAGGT:C	acceptor_loss	1.0000
21:45180328:A:AC	acceptor_loss	1.0000
21:45180329:G:GT	acceptor_loss	1.0000
21:45182754:G:GG	donor_gain	1.0000
21:45183358:TCA:T	acceptor_loss	1.0000
21:45183359:CA:C	acceptor_loss	1.0000
21:45183360:A:AG	acceptor_gain	1.0000
21:45183360:A:AT	acceptor_loss	1.0000
21:45183361:G:GT	acceptor_gain	1.0000
21:45183361:GT:G	acceptor_gain	1.0000
21:45183361:GTA:G	acceptor_gain	1.0000
21:45183361:GTAA:G	acceptor_gain	1.0000
21:45183361:GTAAC:G	acceptor_gain	1.0000
21:45183508:AAGGT:A	donor_loss	1.0000
21:45183512:T:G	donor_loss	1.0000
21:45184921:A:AG	acceptor_gain	1.0000
21:45184922:G:GG	acceptor_gain	1.0000
21:45185088:CACGG:C	donor_loss	1.0000
21:45185090:CGG:C	donor_loss	1.0000
21:45185092:GTA:G	donor_loss	1.0000
21:45185093:TAAGG:T	donor_loss	1.0000
21:45204735:TGGC:T	donor_gain	1.0000
21:45204736:GGCA:G	donor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000008252 (21:45101368 C>T), RS1000009578 (21:45163843 C>A,T), RS1000015194 (21:45095667 C>T), RS1000020823 (21:45211177 G>A,T), RS1000023078 (21:45176994 T>G), RS1000091138 (21:45226146 T>C), RS1000096880 (21:45104035 A>T), RS1000117707 (21:45162573 A>T), RS1000169397 (21:45213972 T>A), RS1000176583 (21:45132941 A>G,T), RS1000176718 (21:45208553 T>A), RS1000198780 (21:45124887 A>G), RS1000296762 (21:45207632 A>G), RS1000308882 (21:45190286 G>A,T), RS1000313100 (21:45171231 C>T)

Disease associations

OMIM: gene MIM:601218 | disease phenotypes: MIM:618862

GenCC curated gene-disease

Disease	Classification	Inheritance
neurodevelopmental disorder with hypotonia, microcephaly, and seizures	Strong	Autosomal recessive

Mondo (5): neurodevelopmental disorder with hypotonia, microcephaly, and seizures (MONDO:0030025), breast ductal adenocarcinoma (MONDO:0005590), neurodevelopmental disorder (MONDO:0700092), syndromic intellectual disability (MONDO:0000508), microcephaly (MONDO:0001149)

Orphanet (1): Rare genetic syndromic intellectual disability (Orphanet:183763)

HPO phenotypes

33 total (30 of 33 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000218	High palate
HP:0000219	Thin upper lip vermilion
HP:0000248	Brachycephaly
HP:0000252	Microcephaly
HP:0000300	Oval face
HP:0000311	Round face
HP:0000577	Exotropia
HP:0000582	Upslanted palpebral fissure
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001257	Spasticity
HP:0001263	Global developmental delay
HP:0001270	Motor delay
HP:0001290	Generalized hypotonia
HP:0001344	Absent speech
HP:0001357	Plagiocephaly
HP:0001561	Polyhydramnios
HP:0001601	Laryngomalacia
HP:0002079	Hypoplasia of the corpus callosum
HP:0002188	Delayed CNS myelination
HP:0003202	Skeletal muscle atrophy
HP:0004322	Short stature
HP:0005487	Prominent metopic ridge
HP:0007112	Temporal cortical atrophy
HP:0008936	Axial hypotonia
HP:0009890	High anterior hairline
HP:0010880	Increased nuchal translucency
HP:0011182	Interictal epileptiform activity
HP:0011968	Feeding difficulties

GWAS associations

13 associations (top):

Study	Trait	p-value
GCST000106_10	Pulmonary function	3.000000e-06
GCST002783_129	Body mass index	4.000000e-07
GCST002783_310	Body mass index	2.000000e-07
GCST002783_598	Body mass index	2.000000e-07
GCST004904_242	Body mass index	9.000000e-10
GCST006484_4	Type 2 diabetes	6.000000e-07
GCST006999_5	Logical memory (immediate recall) in mild cognitive impairment	4.000000e-07
GCST010242_190	HDL cholesterol levels	5.000000e-08
GCST010244_175	Triglyceride levels	2.000000e-08
GCST010988_511	Adult body size	1.000000e-18
GCST90000050_83	Age at first birth	5.000000e-08
GCST90000514_32	Gastroesophageal reflux disease	3.000000e-08
GCST90026415_12	Mild obesity-related type 2 diabetes	2.000000e-06

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0003892	pulmonary function measurement
EFO:0004340	body mass index
EFO:0004874	memory performance
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004530	triglyceride measurement
EFO:0009101	age at first birth measurement

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D018270	Carcinoma, Ductal, Breast	C04.557.470.200.025.232.500; C04.557.470.615.132.500; C04.588.180.390; C17.800.090.500.390
D008831	Microcephaly	C05.660.207.620; C10.500.507.400.500; C16.131.621.207.620; C16.131.666.507.400.500
D065886	Neurodevelopmental Disorders	F03.625

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5725136 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, increases expression, increases methylation	4
Valproic Acid	increases methylation, affects expression, increases expression	4
(+)-JQ1 compound	increases expression	3
Benzo(a)pyrene	affects methylation, decreases expression, increases methylation	3
trichostatin A	affects expression, decreases expression	2
sodium arsenite	affects cotreatment, decreases expression, increases abundance, increases expression	2
potassium chromate(VI)	increases expression, affects cotreatment, decreases expression	2
Acetaminophen	increases expression	2
Aflatoxin B1	decreases expression, increases methylation	2
aristolochic acid I	decreases expression	1
FR900359	increases phosphorylation	1
triphenyl phosphate	affects expression	1
arsenite	increases methylation	1
mono-(2-ethylhexyl)phthalate	decreases expression	1
cobaltous chloride	decreases expression	1
manganese chloride	decreases expression, increases abundance, affects cotreatment	1
benzo(e)pyrene	increases methylation	1
aflatoxin B2	affects methylation	1
triacsin C	decreases expression	1
beta-methylcholine	affects expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
chromium hexavalent ion	affects expression	1
CGP 52608	affects binding, increases reaction	1
abrine	increases expression	1
Sunitinib	increases expression	1
Troglitazone	decreases expression	1
Arsenic	increases abundance, affects cotreatment, decreases expression	1
Copper	affects binding, increases expression	1
Disulfiram	affects binding, increases expression	1
Manganese	decreases expression, increases abundance, affects cotreatment	1

ChEMBL screening assays

5 unique, capped per target: 5 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5714629	Binding	Inhibition of ADARB1 in human S68 cells assessed as K-score by measuring ALDHbr cells by LSR2 cytometer	A genome-wide RNAi screen reveals essential therapeutic targets of breast cancer stem cells. — EMBO Mol Med

Cellosaurus cell lines

4 cell lines: 3 cancer cell line, 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B1J1	Abcam HeLa ADARB1 KO	Cancer cell line	Female
CVCL_B2R6	Abcam HEK293T ADARB1 KO	Transformed cell line	Female
CVCL_DX22	HAP1 ADAR (-) ADARB1 (-)	Cancer cell line	Male
CVCL_SB55	HAP1 ADARB1 (-)	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT03414970	PHASE3	ACTIVE_NOT_RECRUITING	Hypofractionated Radiation Therapy After Mastectomy in Preventing Recurrence in Patients With Stage IIa-IIIa Breast Cancer
NCT02559102	PHASE3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	PHASE3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	PHASE3	RECRUITING	Reducing Missed Appointments
NCT07377032	PHASE3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT00461344	PHASE2	TERMINATED	Docetaxel + Doxorubicin as Neoadjuvant Chemotherapy in Patients With Breast Cancer
NCT07499999	PHASE2	NOT_YET_RECRUITING	Randomized Double-Blind Phase II Trial of Baby Exemestane Versus Baby Tamoxifen in Post-Menopausal Women at High Risk for Breast Cancer
NCT02909959	PHASE2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	PHASE2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	PHASE2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT00503191	PHASE1	COMPLETED	NeuroModulation Technique Treatment of Autism
NCT04475848	PHASE1	COMPLETED	A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants
NCT06300398	PHASE1	COMPLETED	IAMA-6 Oral Dose Study in Healthy Adults
NCT00637364	PHASE1/PHASE2	SUSPENDED	High Intensity Focused Ultrasound Tumor Treatment for Pancreatic Cancer Pain
NCT02779855	PHASE1/PHASE2	COMPLETED	Talimogene Laherparepvec in Combination With Neoadjuvant Chemotherapy in Triple Negative Breast Cancer
NCT01753908	EARLY_PHASE1	COMPLETED	Broccoli Sprout Extract in Treating Patients With Breast Cancer
NCT01796041	EARLY_PHASE1	COMPLETED	Intraoperative Imaging of Breast Cancer With Indocyanine Green
NCT01208974	Not specified	ACTIVE_NOT_RECRUITING	Nipple-Areola Complex (NAC) Irradiation After Nipple-Sparing Mastectomy and Reconstruction
NCT01875198	Not specified	TERMINATED	Oncologic Impact of Splenectomy-omitting Radical Pancreatectomy in Well-selected Left-sided Pancreatic Cancer
NCT03543397	Not specified	UNKNOWN	MRI in Ductal Carcinoma in Situ (DCIS)
NCT03834532	Not specified	COMPLETED	Living Well After Breast Surgery
NCT01783041	PHASE2/PHASE3	COMPLETED	Effect of Early L-Carnitine Supplementation on Neurodevelopmental Outcomes in Very Preterm Infants
NCT05767385	PHASE2/PHASE3	RECRUITING	Fetal Cerebrovascular Autoregulation in Congenital Heart Disease and Association With Neonatal Neurobehavior
NCT05675098	EARLY_PHASE1	NOT_YET_RECRUITING	Central Nervous System Stimulants and Physical Function in Children With Cerebral Palsy
NCT00783783	Not specified	COMPLETED	CYP2D6 Pharmacogenetics in Risperidone-Treated Children
NCT01778504	Not specified	RECRUITING	Studying Childhood-onset Behavioral, Psychiatric, and Developmental Disorders
NCT01850784	Not specified	UNKNOWN	High Energy Formula Feeding in Infants With Congenital Heart Disease
NCT01922791	Not specified	COMPLETED	Nutrition and Pregnancy Intervention Study
NCT01942525	Not specified	UNKNOWN	Influence of Intrauterine Growth Restriction on Amplitude-integrated EEG in Preterm Infants
NCT02003170	Not specified	COMPLETED	Etiology and Early Diagnosis of Neurodevelopmental Disorders
NCT02118649	Not specified	ACTIVE_NOT_RECRUITING	Enhancing Behavior and Brain Response to Visual Targets Using a Computer Game
NCT02557191	Not specified	TERMINATED	Biomarkers, Neurodevelopment and Preterm Infants
NCT02690675	Not specified	COMPLETED	Iron Supplement Effect on Child Development
NCT02694003	Not specified	COMPLETED	Better Nights, Better Days for Children With Neurodevelopment Disorders
NCT02792894	Not specified	COMPLETED	Family Networks (FaNs) for Children With Developmental Disorders and Delays
NCT02871674	Not specified	UNKNOWN	Good Night Project: Behavioural Sleep Interventions for Children With ADHD: A Randomised Controlled Trial
NCT02887157	Not specified	COMPLETED	Analyzing Retinal Microanatomy in ROP
NCT02898298	Not specified	COMPLETED	Positive Emotion Regulation Training in Children, Adolescents and Young Adults With and Without Developmental Disorder