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): 148 total — 17 pathogenic
• GTEx eGene: eQTL in 25 tissues, sQTL in 19 (q < 0.05)
• Phenotypes (HPO): 33
• Constraint (gnomAD): pLI 1.00 (loss-of-function intolerant), LOEUF 0.32 (highly constrained)
• 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: 29 — 17 protein_coding, 7 nonsense_mediated_decay, 5 protein_coding_CDS_not_defined

MANE Select: ENST00000348831

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 7, TSL 3: 3, TSL 5: 2

ENST00000348831, ENST00000360697, ENST00000389861, ENST00000389863, ENST00000449478, ENST00000460734, ENST00000462214, ENST00000464215, ENST00000481022, ENST00000492414, ENST00000496664, ENST00000631642, ENST00000705392, ENST00000705393, ENST00000874894, ENST00000913573, ENST00000962803, ENST00000962804, ENST00001046123, ENST00001046124, ENST00001046125, ENST00001046126, ENST00001046127, ENST00001046128, ENST00001046129, ENST00001046130, ENST00001110468, ENST00001110469, ENST00001115759

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.

Highest expression (Bgee): blood vessel layer, popliteal artery, tibial artery, mucosa of stomach, aorta.

Genetic regulation across tissues (GTEx eQTL / sQTL)

ADARB1 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 25 tissues and its splicing (sQTL) in 19 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 44 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Cells Cultured fibroblasts	eqtl	1.1e-60	+0.50	21:45050598:T:C
Artery Tibial	sqtl	9.7e-28	+1.13	21:45223528:C:T
Esophagus Muscularis	sqtl	4.2e-24	-0.66	21:45197672:A:G
Cells Cultured fibroblasts	sqtl	1.8e-17	+0.42	21:45168189:A:T
Muscle Skeletal	sqtl	6.7e-17	+0.47	21:45179799:C:T
Skin Sun Exposed Lower leg	sqtl	3.4e-15	-0.48	21:45160455:C:T
Brain Cerebellum	eqtl	5.2e-13	+0.55	21:45111237:T:G
Esophagus Gastroesophageal Junction	sqtl	9.3e-13	-0.63	21:45196526:A:G
Skin Not Sun Exposed Suprapubic	sqtl	7.4e-10	+0.45	21:45143099:G:A
Artery Aorta	sqtl	9.2e-09	-0.47	21:45158144:G:T
Adipose Subcutaneous	sqtl	1.4e-08	-0.42	21:45217498:T:C
Heart Left Ventricle	eqtl	4.1e-08	+0.25	21:45215051:C:T
Lung	eqtl	3.3e-07	+0.21	21:45050598:T:C
Lung	sqtl	9.6e-07	+0.78	21:45223528:C:T
Brain Nucleus accumbens basal ganglia	eqtl	1.1e-06	+0.17	21:45250130:C:A
Colon Sigmoid	sqtl	1.5e-06	-0.51	21:45196526:A:G
Skin Sun Exposed Lower leg	eqtl	2.4e-06	+0.22	21:45043955:G:A
Brain Cerebellar Hemisphere	eqtl	3.4e-06	+0.39	21:45097296:G:A
Skin Not Sun Exposed Suprapubic	eqtl	7.9e-05	+0.17	21:45050598:T:C
Esophagus Muscularis	eqtl	9.0e-05	+0.16	21:45053014:T:C

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

showing 100 of 289 tissues 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
olfactory bulb	UBERON:0002264	91.70	gold quality
upper lobe of lung	UBERON:0008948	91.68	gold quality
sural nerve	UBERON:0015488	91.35	gold quality
tendon of biceps brachii	UBERON:0008188	91.06	gold quality
muscle layer of sigmoid colon	UBERON:0035805	91.03	gold quality
cardia of stomach	UBERON:0001162	90.61	gold quality
Brodmann (1909) area 23	UBERON:0013554	90.39	gold quality
lung	UBERON:0002048	90.32	gold quality
triceps brachii	UBERON:0001509	90.06	silver quality
visceral pleura	UBERON:0002401	89.92	gold quality
lower lobe of lung	UBERON:0008949	89.56	gold quality
cervix squamous epithelium	UBERON:0006922	89.27	gold quality
gluteal muscle	UBERON:0002000	89.14	silver quality
primary visual cortex	UBERON:0002436	89.09	gold quality
body of tongue	UBERON:0011876	88.54	silver quality
dorsal plus ventral thalamus	UBERON:0001897	88.42	gold quality
occipital lobe	UBERON:0002021	88.39	gold quality
tongue squamous epithelium	UBERON:0006919	88.22	gold quality
fundus of stomach	UBERON:0001160	88.18	gold quality
substantia nigra pars compacta	UBERON:0001965	88.18	gold quality
body of uterus	UBERON:0009853	88.08	gold quality
caecum	UBERON:0001153	87.70	gold quality
stromal cell of endometrium	CL:0002255	87.55	gold quality
lateral globus pallidus	UBERON:0002476	87.39	gold quality
vermiform appendix	UBERON:0001154	87.38	gold quality
paraflocculus	UBERON:0005351	87.37	gold quality
superficial temporal artery	UBERON:0001614	87.21	gold quality
smooth muscle tissue	UBERON:0001135	87.20	gold quality
sigmoid colon	UBERON:0001159	87.03	gold quality
lymph node	UBERON:0000029	86.93	gold quality
myometrium	UBERON:0001296	86.85	gold quality
pericardium	UBERON:0002407	86.74	gold quality
esophagus	UBERON:0001043	86.63	gold quality
prefrontal cortex	UBERON:0000451	86.61	gold quality
subthalamic nucleus	UBERON:0001906	86.51	silver quality
ventral tegmental area	UBERON:0002691	86.47	gold quality
tongue	UBERON:0001723	86.41	silver quality
muscle of leg	UBERON:0001383	86.40	gold quality
gastrocnemius	UBERON:0001388	86.28	gold quality
pleura	UBERON:0000977	86.20	gold quality
medulla oblongata	UBERON:0001896	85.97	gold quality
pylorus	UBERON:0001166	85.83	gold quality
substantia nigra pars reticulata	UBERON:0001966	85.75	gold quality
frontal cortex	UBERON:0001870	85.72	gold quality
urinary bladder	UBERON:0001255	85.70	gold quality
skin of leg	UBERON:0001511	85.66	gold quality
inferior vagus X ganglion	UBERON:0005363	85.55	gold quality
buccal mucosa cell	CL:0002336	85.54	gold quality
pharyngeal mucosa	UBERON:0000355	85.52	silver quality
neocortex	UBERON:0001950	85.45	gold quality
prostate gland	UBERON:0002367	85.33	gold quality
apex of heart	UBERON:0002098	85.32	gold quality
subcutaneous adipose tissue	UBERON:0002190	85.28	gold quality
cortical plate	UBERON:0005343	85.22	gold quality
superior vestibular nucleus	UBERON:0007227	85.19	gold quality
right frontal lobe	UBERON:0002810	85.15	gold quality
hindlimb stylopod muscle	UBERON:0004252	85.14	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	84.97	gold quality
cingulate cortex	UBERON:0003027	84.76	gold quality
parietal pleura	UBERON:0002400	84.73	gold quality
Brodmann (1909) area 10	UBERON:0013541	84.73	gold quality
muscle organ	UBERON:0001630	84.70	gold quality
skin of hip	UBERON:0001554	84.66	gold quality
Brodmann (1909) area 9	UBERON:0013540	84.64	gold quality
anterior cingulate cortex	UBERON:0009835	84.58	gold quality
stomach	UBERON:0000945	84.55	gold quality
peritoneum	UBERON:0002358	84.49	gold quality
omental fat pad	UBERON:0010414	84.48	gold quality
cerebral cortex	UBERON:0000956	84.46	gold quality
superior frontal gyrus	UBERON:0002661	84.45	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

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 76 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM
Choroid plexus	tissue	60.7
Postcentral gyrus	tissue	45.1
Hippocampus	tissue	34.9
Superior colliculi	tissue	34.7
Thalamus	tissue	34.2
Cerebral cortex	tissue	34.0
Locus coeruleus	tissue	34.0
Somatosensory cortex	tissue	34.0
Putamen	tissue	32.3
Cerebellum	tissue	31.3
Motor cortex	tissue	30.0
Midbrain	tissue	29.5
Basal ganglia	tissue	29.1
Pons	tissue	27.2
Occipital cortex	tissue	27.0
Temporal cortex	tissue	25.9
Prefrontal cortex	tissue	25.5
Retina	tissue	25.0
Insular cortex	tissue	24.5
Retrosplenial and cingulate cortex	tissue	23.2
Nucleus accumbens	tissue	22.9
Hippocampal formation	tissue	22.9
Entorhinal cortex	tissue	22.9
Ventral forebrain	tissue	22.6
Olfactory bulb	tissue	21.1
Retrosplenial cortex	tissue	20.3
Frontal cortex	tissue	20.0
Lung	tissue	18.1
Amygdala	tissue	17.3
Septum	tissue	16.3
Medulla oblongata	tissue	15.5
Caudate putamen	tissue	15.2
Urinary bladder	tissue	13.9
Substantia nigra	tissue	12.6
Spinal cord	tissue	12.2
Hypothalamus	tissue	12.1
Lymph node	tissue	12.0
Placenta	tissue	11.4
Smooth muscle	tissue	10.8
Adipose tissue	tissue	10.7
Periaqueductal gray	tissue	10.7
Skin 1	tissue	10.3
Tongue	tissue	10.3
Vagina	tissue	10.0
Spleen	tissue	10.0
Endometrium 1	tissue	9.2
Prostate	tissue	9.2
Appendix	tissue	9.0
Parathyroid gland	tissue	8.5
Skeletal muscle	tissue	8.3
Tonsil	tissue	8.0
Gallbladder	tissue	7.5
Seminal vesicle	tissue	7.4
Fallopian tube	tissue	7.2
Esophagus	tissue	7.1
Heart muscle	tissue	6.2
Cervix	tissue	6.0
Epididymis	tissue	5.6
Pituitary gland	tissue	5.4
Thymus	tissue	5.3

Brain sub-regions (HPA Brain Atlas): detected in 189; highest nTPM — Blood vessel (110.4), Vermis (77.5), Flocculonodular lobe (71.4), Cerebellar cortex (67.9), Nucleus raphe magnus (60.9).

Regulation

Is transcription factor: no

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

miRNA regulators (miRDB)

Targeting ADARB1 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 176 miRNAs:

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

Functional genomics

gnomAD constraint: pLI 1, LOEUF 0.323, missense Z 3.74 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000348831 splits into 2 regions with different missense tolerance; 0 are missense-constrained. Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
21:45,171,657–45,180,400	380 / 446.5	0.85	no
21:45,180,401–45,222,194	263 / 475.8	0.55	no

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)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:891999) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 21 distinct phenotype terms.

Mouse phenotype (MP)	Records
motor neuron degeneration	1
abnormal neuromuscular synapse morphology	1
abnormal cranial nerve morphology	1
abnormal facial nerve morphology	1
abnormal hypoglossal nerve morphology	1
decreased body weight	1
decreased locomotor activity	1
impaired coordination	1
abnormal posture	1
seizures	1
premature death	1
abnormal innervation	1
abnormal AMPA-mediated synaptic currents	1
abnormal skeletal muscle fiber morphology	1
abnormal ventral spinal root morphology	1
abnormal limb posture	1
decreased spinal cord ventral horn cell number	1
centrally nucleated skeletal muscle fibers	1
skeletal muscle fiber atrophy	1
decreased grip strength	1
postnatal lethality, complete penetrance	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
Gallus gallus	Q5ZIL4	92.0%	Diamond
Xenopus tropicalis	Q6GL57	89.8%	Diamond
Xenopus laevis	Q91550	89.8%	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
LINC00334	ncRNA	114042
PICSAR	ncRNA	378825
LINC00165	ncRNA	727701
POFUT2	protein-coding	23275
LINC00205	ncRNA	642852
LINC00163	ncRNA	727699
LINC00316	ncRNA	388830

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)

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

UniProt features (93 total): helix 29, strand 20, 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 by resolution:

PDB	Title	Method	Resolution (Å)
1ZY7	Crystal structure of the catalytic domain of an adenosine deaminase that acts on RNA …	X-RAY DIFFRACTION	1.7
7KFN	Structure of Human Adenosine Deaminase Acting on dsRNA (ADAR2) bound to dsRNA containing …	X-RAY DIFFRACTION	2.5
6D06	Human ADAR2d E488Y mutant complexed with dsRNA containing an abasic site opposite the …	X-RAY DIFFRACTION	2.55
9OP3	Structure of Human ADAR2-R2D complexed with dsRNA containing 8-azaN and …	X-RAY DIFFRACTION	2.59
9D5K	Human Adenosine Deaminase Acting on dsRNA (ADAR2-RD) bound to dsRNA containing an …	X-RAY DIFFRACTION	2.7
8E0F	Human Adenosine Deaminase Acting on dsRNA (ADAR2-RD) bound to dsRNA containing a G-G pair …	X-RAY DIFFRACTION	2.7
5ED1	Human Adenosine Deaminase Acting on dsRNA (ADAR2) mutant E488Q bound to dsRNA sequence …	X-RAY DIFFRACTION	2.77
6VFF	Dimer of Human Adenosine Deaminase Acting on dsRNA (ADAR2) mutant E488Q bound to dsRNA …	X-RAY DIFFRACTION	2.8
8E4X	Human Adenosine Deaminase Acting on dsRNA (ADAR2-R2D) bound to dsRNA containing a …	X-RAY DIFFRACTION	2.8
9D5J	Human Adenosine Deaminase Acting on dsRNA (ADAR2-RD) bound to dsRNA containing …	X-RAY DIFFRACTION	2.8
5ED2	Human Adenosine Deaminase Acting on dsRNA (ADAR2) mutant E488Q bound to dsRNA sequence …	X-RAY DIFFRACTION	2.95
5HP2	Human Adenosine Deaminase Acting on dsRNA (ADAR2) bound to dsRNA sequence derived from S …	X-RAY DIFFRACTION	2.98
5HP3	Human Adenosine Deaminase Acting on dsRNA (ADAR2) bound to dsRNA sequence derived from S …	X-RAY DIFFRACTION	3.09

Predicted structure (AlphaFold)

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

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Hydrolases, Predicted intracellular proteins, Plasma proteins, Disease related genes, Potential drug targets, Human disease related genes, Congenital malformations, Congenital malformations of the nervous system

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): nucleoplasm; cytosol

Antibody reliability (HPA): IF supported

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)

Position	Role
396	proton donor

Ligand- & substrate-binding residues (11)

Position	Role
394	Zn(2+)
400	1D-myo-inositol hexakisphosphate
401	1D-myo-inositol hexakisphosphate
451	Zn(2+)
556	Zn(2+)
559	1D-myo-inositol hexakisphosphate
562	1D-myo-inositol hexakisphosphate
669	1D-myo-inositol hexakisphosphate
702	1D-myo-inositol hexakisphosphate
712	1D-myo-inositol hexakisphosphate
730	1D-myo-inositol hexakisphosphate

Post-translational modifications (2)

Type	Positions
Phosphoserine	26, 149

Function

Pathways and Gene Ontology

Reactome pathways

2 curated (TAS) of 5; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

5 pathways:

ID	Pathway	Evidence
R-HSA-75102	C6 deamination of adenosine	curated
R-HSA-77042	Formation of editosomes by ADAR proteins	curated
R-HSA-8953854	Metabolism of RNA	—
R-HSA-75072	mRNA Editing	—
R-HSA-75064	mRNA Editing: A to I Conversion	—

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 (13): adenosine to inosine editing (GO:0006382), RNA processing (GO:0006396), mRNA processing (GO:0006397), negative regulation of cell population proliferation (GO:0008285), base conversion or substitution editing (GO:0016553), mRNA modification (GO:0016556), negative regulation of cell migration (GO:0030336), 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), defense response to virus (GO:0051607), regulation of cell cycle (GO:0051726), 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 (4): nucleus (GO:0005634), nucleoplasm (GO:0005654), nucleolus (GO:0005730), cytoplasm (GO:0005737)

Reactome top-level categories

3 top-level categories:

Category	Pathways
mRNA Editing: A to I Conversion	2
mRNA Editing	1
Metabolism of RNA	1

GO top-level categories

40 GO namespaces:

Category	Terms
mRNA metabolic process	2
RNA modification	2
RNA binding	2
deaminase activity	2
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
cell population proliferation	1
regulation of cell population proliferation	1
negative regulation of cellular process	1
cell migration	1
regulation of cell migration	1
negative regulation of cell motility	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
defense response	1
response to virus	1
cell cycle	1
regulation of cellular process	1
biological_process	1
nucleic acid binding	1
adenosine deaminase activity	1
catalytic activity, acting on a tRNA	1
protein binding	1
cation binding	1
hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in cyclic amidines	1
binding	1
catalytic 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) — 16 of 28 annotations. The rest are phylogenetic / computational / electronic (IEA).

16 experimentally-supported GO terms:

GO term	NS	Evidence
RNA processing	BP	direct assay
adenosine to inosine editing	BP	direct assay
base conversion or substitution editing	BP	direct assay
mRNA modification	BP	direct assay
negative regulation of cell migration	BP	direct assay
negative regulation of cell population proliferation	BP	direct assay
negative regulation of protein kinase activity by regulation of protein phosphorylation	BP	direct assay
positive regulation of viral genome replication	BP	mutant phenotype
regulation of cell cycle	BP	direct assay
nucleolus	CC	direct assay
nucleoplasm	CC	direct assay
nucleus	CC	direct assay
RNA binding	MF	direct assay
double-stranded RNA adenosine deaminase activity	MF	direct assay
double-stranded RNA binding	MF	direct assay
identical protein binding	MF	physical interaction

Protein interactions and networks

IntAct

Human interaction partners of ADARB1 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

15 partners by confidence:

Partner	Interaction type	MIscore	Records
N	physical association	0.600	4
PIN1	physical association	0.570	12
CSNK2A1	physical association	0.560	3
JUN	physical association	0.560	3
SPTY2D1	association	0.530	1
WWP2	physical association	0.400	5
GTPBP10	association	0.350	1
DCN	physical association	0.000	1
EDIL3	physical association	0.000	1
LARP6	physical association	0.000	1
PRKRA	physical association	0.000	1
RSL1D1	physical association	0.000	1
SNRNP70	physical association	0.000	1
SURF6	physical association	0.000	1
UBE2I	physical association	0.000	1

BioGRID (547 interactions; top human partners by supporting records): STRBP (Two-hybrid; 4 records), BRIX1 (Affinity Capture-MS; 3 records), EBNA1BP2 (Affinity Capture-MS; 3 records), PRKRA (Two-hybrid; 3 records), ZFR (Affinity Capture-MS; 3 records), ADAR (Proximity Label-MS; 2 records), APP (Reconstituted Complex; 2 records), C7orf50 (Affinity Capture-MS; 2 records), CCDC124 (Affinity Capture-MS; 2 records), CD97 (Affinity Capture-MS; 2 records), CEBPZ (Affinity Capture-MS; 2 records), CHD3 (Affinity Capture-MS; 2 records), DDX10 (Affinity Capture-MS; 2 records), DDX21 (Affinity Capture-MS; 2 records), FTSJ3 (Affinity Capture-MS; 2 records)

SIGNOR signaling

showing 7 of 8 signaling 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

Genetic variants

Variant evidence for ADARB1: 148 ClinVar records (17 pathogenic / likely pathogenic); 13 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	17
Likely pathogenic	0
Uncertain significance	92
Likely benign	18
Benign	6

Top pathogenic / likely-pathogenic (15)

Showing the 15 best-reviewed of 17 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
59068	GRCh38/hg38 21q22.3(chr21:45138321-46670405)x1	Pathogenic	criteria provided, multiple submitters, no conflicts	2
59046	GRCh38/hg38 21q22.3(chr21:45110477-46648012)x1	Pathogenic	criteria provided, single submitter	1
253527	GRCh37/hg19 21q22.3(chr21:46363553-48080926)x1	Pathogenic	criteria provided, single submitter	1
1526724	GRCh37/hg19 21q22.3(chr21:45265857-47057233)x1	Pathogenic	criteria provided, single submitter	1
1710511	GRCh37/hg19 21q22.3(chr21:45808650-47529568)x1	Pathogenic	criteria provided, single submitter	1
3062427	GRCh37/hg19 21q22.3(chr21:45102309-48097372)x1	Pathogenic	criteria provided, single submitter	1
3062430	GRCh37/hg19 21q22.3(chr21:44577746-48097372)x1	Pathogenic	criteria provided, single submitter	1
3248207	NC_000021.8:g.(?44296792)(47865240_?)del	Pathogenic	criteria provided, single submitter	1
4279154	GRCh37/hg19 21q22.3(chr21:46569369-46621106)x1	Pathogenic	criteria provided, single submitter	1
4682975	GRCh37/hg19 21q22.3(chr21:44762021-48097372)x1	Pathogenic	criteria provided, single submitter	1
870450	NM_001112.4(ADARB1):c.1492A>G (p.Ser498Gly)	Pathogenic	no assertion criteria provided	1
870451	NM_001112.4(ADARB1):c.379A>G (p.Lys127Glu)	Pathogenic	no assertion criteria provided	1
870452	NM_001112.4(ADARB1):c.1688G>A (p.Arg563Gln)	Pathogenic	no assertion criteria provided	1
870453	NM_001112.4(ADARB1):c.2045C>T (p.Ala682Val)	Pathogenic	no assertion criteria provided	1
2443914	NM_001112.4(ADARB1):c.1769G>A (p.Arg590Gln)	Pathogenic	no assertion criteria provided	1

Per-variant reference — Sugi Variant

Explore ADARB1’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; 30 predictions of 2,649):

Position(s)	Effect	Δscore	Sites
21:45134711	acceptor_gain	1.0000
21:45180328–45180329	acceptor_loss	1.0000	6
21:45183360–45183361	acceptor_loss	1.0000	6
21:45183511–45183512	donor_loss	1.0000	2
21:45185092–45185093	donor_loss	1.0000	5
21:45220828	acceptor_gain	1.0000
21:45220834–45220835	acceptor_loss	1.0000	6
21:45081105	donor_gain	0.9900
21:45134709	acceptor_gain	0.9900
21:45134713	acceptor_gain	0.9900

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

3 prognostic cancer types:

Cancer	Prognostic	p-value
Liver Hepatocellular Carcinoma (validation)	favorable	3.47e-05
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	0.000341
Kidney Renal Clear Cell Carcinoma (validation)	favorable	0.00036

Disease associations

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

GenCC curated gene-disease

1 curated gene-disease records:

Disease	Classification	Inheritance	Records
neurodevelopmental disorder with hypotonia, microcephaly, and seizures	Strong	Autosomal recessive	4

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (7 panels, 7 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

7 panels:

Panel	Rating
Early onset or syndromic epilepsy	green
Hypotonic infant	green
Intellectual disability	green
Leukodystrophy, childhood onset	green
Paediatric disorders	green
Severe microcephaly	green
Unexplained death in infancy and sudden unexplained death in childhood	green

Mondo (1): neurodevelopmental disorder with hypotonia, microcephaly, and seizures (MONDO:0030025)

HPO phenotypes

33 phenotypes (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
HP:0012741	Unilateral cryptorchidism
HP:0031936	Delayed ability to walk
HP:0100704	Cerebral visual impairment

GWAS associations

13 associations:

Study	Trait	p-value
GCST010988_206	Adult body size	1e-18
GCST004904_34	Body mass index	9e-10
GCST010244_29	Triglyceride levels	2e-8
GCST90000514_20	Gastroesophageal reflux disease	3e-8
GCST010242_114	HDL cholesterol levels	5e-8
GCST90000050_83	Age at first birth	5e-8
GCST002783_339	Body mass index	2e-7
GCST002783_551	Body mass index	2e-7
GCST002783_179	Body mass index	4e-7
GCST006999_5	Logical memory (immediate recall) in mild cognitive impairment	4e-7
GCST006484_4	Type 2 diabetes	6e-7
GCST90026415_4	Mild obesity-related type 2 diabetes	2e-6
GCST000106_10	Pulmonary function	3e-6

EFO canonical traits (from GWAS)

6 canonical traits:

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

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5725136 (SINGLE PROTEIN)

PharmGKB: 1 entry (CPIC guideline: no)

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	affects expression, increases expression, increases methylation	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)	affects cotreatment, decreases expression, increases 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	affects cotreatment, decreases expression, increases abundance	1
Copper	affects binding, increases expression	1
Disulfiram	affects binding, increases expression	1
Manganese	affects cotreatment, decreases expression, increases abundance	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)

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

showing 60 of 223 trials:

NCT	Phase	Status	Title
NCT04586348	Phase 4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	Phase 4	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	Phase 3	ACTIVE_NOT_RECRUITING	Hypofractionated Radiation Therapy After Mastectomy in Preventing Recurrence in Patients With Stage IIa-IIIa Breast Cancer
NCT02559102	Phase 3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	Phase 3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	Phase 3	RECRUITING	Reducing Missed Appointments
NCT07377032	Phase 3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT00461344	Phase 2	TERMINATED	Docetaxel + Doxorubicin as Neoadjuvant Chemotherapy in Patients With Breast Cancer
NCT07499999	Phase 2	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	Phase 2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	Phase 2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	Phase 2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT00503191	Phase 1	COMPLETED	NeuroModulation Technique Treatment of Autism
NCT04475848	Phase 1	COMPLETED	A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants
NCT06300398	Phase 1	COMPLETED	IAMA-6 Oral Dose Study in Healthy Adults
NCT00637364	Phase 1/2	SUSPENDED	High Intensity Focused Ultrasound Tumor Treatment for Pancreatic Cancer Pain
NCT02779855	Phase 1/2	COMPLETED	Talimogene Laherparepvec in Combination With Neoadjuvant Chemotherapy in Triple Negative Breast Cancer
NCT01753908	Early Phase 1	COMPLETED	Broccoli Sprout Extract in Treating Patients With Breast Cancer
NCT01796041	Early Phase 1	COMPLETED	Intraoperative Imaging of Breast Cancer With Indocyanine Green
NCT07628634	Early Phase 1	RECRUITING	Feasibility Study on the Effect of a Methionine-Reduced Diet on Serum Levels in Pts w/ Solid Tumors
NCT01208974	Not specified	COMPLETED	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	Phase 2/3	COMPLETED	Effect of Early L-Carnitine Supplementation on Neurodevelopmental Outcomes in Very Preterm Infants
NCT05767385	Phase 2/3	COMPLETED	Fetal Cerebrovascular Autoregulation in Congenital Heart Disease and Association With Neonatal Neurobehavior
NCT05675098	Early Phase 1	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	COMPLETED	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
NCT02912780	Not specified	UNKNOWN	Introduction of Microsystems in a Level 3 Neonatal Intensive Care Unit
NCT03023293	Not specified	COMPLETED	n-3 PUFAs, Irisin and Maternal Glucose Metabolism From Pregnancy to Postpartum
NCT03023644	Not specified	COMPLETED	Improving Neurodevelopmental Outcomes in Children With Congenital Heart Disease: An Intervention Study
NCT03032991	Not specified	UNKNOWN	Early Biomarkers of Neurodevelopment in Offspring of Diabetic Mothers
NCT03088189	Not specified	TERMINATED	Effect of Parental Peri-conceptional Vitamin B12 Supplementation on Infant Neurocognitive Development in Offspring
NCT03096028	Not specified	COMPLETED	Developmental Origins of Mental Health Disorders
NCT03148782	Not specified	COMPLETED	Brain Plasticity Underlying Acquisition of New Organizational Skills in Children-R61 Phase
NCT03172104	Not specified	COMPLETED	Neurobehavioural Development of Infants Born <30 Weeks Gestational Age Between Birth and Five Years of Age
NCT03222375	Not specified	RECRUITING	SQUED™ Series 28.1 Home-use and Treatment of Autowave Reverberator of Autism
NCT03229928	Not specified	COMPLETED	Clinical Testing of a Real-Time Behavior Measurement Tool: Measuring Outcomes for CHAnge
NCT03232489	Not specified	UNKNOWN	Study for the Evaluation of the Feasibility of Applying Advanced MRI Scanning in Pediatric Clinical Practice
NCT03381027	Not specified	COMPLETED	BABY SMART (Study of Massage Therapy, Sleep And neurodevelopMenT)
NCT03388294	Not specified	COMPLETED	Evaluation of a Novel Intervention for Infants At Risk for Neurodevelopmental Disorders
NCT03410810	Not specified	UNKNOWN	Childhood Outcomes of Preterm Brain Abnormalities
NCT03492060	Not specified	RECRUITING	Longitudinal Study of Neurogenetic Disorders
NCT03577756	Not specified	COMPLETED	Neurodevelopmental Assessment of Infants With Cystic Fibrosis
NCT03654248	Not specified	COMPLETED	Let’s Get Organized in Adult Psychiatric/habilitation Care
NCT03659279	Not specified	COMPLETED	Let’s Get Organized Feasibility Study
NCT03722615	Not specified	COMPLETED	Epidemiology of Congenital Cytomegalovirus in a High HIV Prevalence Setting, South Africa