ADA2

Summary

ADA2 (adenosine deaminase 2, HGNC:1839) is a protein-coding gene on chromosome 22q11.1, encoding Adenosine deaminase 2 (Q9NZK5). Adenosine deaminase that may contribute to the degradation of extracellular adenosine, a signaling molecule that controls a variety of cellular responses.

This gene encodes a member of a subfamily of the adenosine deaminase protein family. The encoded protein is one of two adenosine deaminases found in humans, which regulate levels of the signaling molecule, adenosine. The encoded protein is secreted from monocytes undergoing differentiation and may regulate cell proliferation and differentiation. This gene may be responsible for some of the phenotypic features associated with cat eye syndrome. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 51816 — RefSeq curated summary.

At a glance

• Gene–disease (curated): deficiency of adenosine deaminase 2 (Strong, GenCC) — +3 more curated relationships
• GWAS associations: 1
• Clinical variants (ClinVar): 693 total — 91 pathogenic, 34 likely-pathogenic (top 5% of genes corpus-wide)
• GTEx eGene: eQTL in 50 tissues, sQTL in 32 (q < 0.05)
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 0.88 (unconstrained)
• MANE Select transcript: NM_001282225

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1839
Approved symbol	ADA2
Name	adenosine deaminase 2
Location	22q11.1
Locus type	gene with protein product
Status	Approved
Aliases	ADGF
Ensembl gene	ENSG00000093072
Ensembl biotype	protein_coding
OMIM	607575
Entrez	51816

Gene structure

Transcript identifiers

Ensembl transcripts: 33 — 22 protein_coding, 6 retained_intron, 3 nonsense_mediated_decay, 2 protein_coding_CDS_not_defined

MANE Select: ENST00000399837

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 2, TSL 2: 3, TSL 3: 1, TSL 4: 1, TSL 5: 2

ENST00000399837, ENST00000262607, ENST00000330232, ENST00000399839, ENST00000449907, ENST00000469063, ENST00000480276, ENST00000543038, ENST00000610390, ENST00000648061, ENST00000648343, ENST00000648668, ENST00000649310, ENST00000649540, ENST00000649746, ENST00000649915, ENST00000650635, ENST00000696189, ENST00000696196, ENST00000696197, ENST00000696198, ENST00000696218, ENST00000696220, ENST00000696221, ENST00000696222, ENST00000696223, ENST00000696224, ENST00000696225, ENST00000696226, ENST00000696227, ENST00000885358, ENST00000885359, ENST00001105598

RefSeq mRNA: 6 — MANE Select: NM_001282225 NM_001282225, NM_001282226, NM_001282227, NM_001282228, NM_001282229, NM_177405

CCDS: CCDS13742, CCDS13743, CCDS63395, CCDS74809

Canonical transcript exons

ENST00000399837 — 10 exons

Exon	Start	End
ENSE00000650248	17181820	17182022
ENSE00000650252	17188339	17188447
ENSE00000650260	17189942	17190032
ENSE00000650274	17203563	17203773
ENSE00000650281	17207071	17207290
ENSE00001540382	17178790	17181576
ENSE00001540384	17219356	17219435
ENSE00003508775	17191683	17191810
ENSE00003966413	17209356	17209723
ENSE00003966554	17182604	17182761

Expression profiles

Bgee: expression breadth ubiquitous, 254 present calls, max score 98.88.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 15.5150 / max 452.3044, expressed in 1105 samples.

Highest expression (Bgee): monocyte, mononuclear cell, leukocyte, granulocyte, bone marrow cell.

Genetic regulation across tissues (GTEx eQTL / sQTL)

ADA2 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 50 tissues and its splicing (sQTL) in 32 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 82 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Cells Cultured fibroblasts	eqtl	2.1e-198	+1.10	22:17199629:A:C
Nerve Tibial	eqtl	5.1e-198	+0.98	22:17199629:A:C
Esophagus Muscularis	eqtl	6.2e-138	+1.08	22:17199629:A:C
Muscle Skeletal	eqtl	3.3e-136	+0.81	22:17199629:A:C
Skin Sun Exposed Lower leg	eqtl	2.7e-125	+0.79	22:17199629:A:C
Thyroid	eqtl	1.2e-114	+0.82	22:17199629:A:C
Heart Atrial Appendage	eqtl	8.2e-111	+0.99	22:17199629:A:C
Esophagus Mucosa	eqtl	1.3e-106	+0.95	22:17199629:A:C
Heart Left Ventricle	eqtl	8.5e-102	+1.04	22:17199629:A:C
Skin Not Sun Exposed Suprapubic	eqtl	1.9e-101	+0.77	22:17199629:A:C
Artery Tibial	eqtl	2.2e-100	+0.57	22:17199629:A:C
Adipose Subcutaneous	eqtl	4.2e-98	+0.55	22:17199629:A:C
Pancreas	eqtl	4.5e-96	+1.15	22:17199629:A:C
Breast Mammary Tissue	eqtl	4.3e-93	+0.88	22:17199629:A:C
Pituitary	eqtl	4.5e-93	+1.18	22:17199629:A:C
Esophagus Gastroesophageal Junction	eqtl	9.0e-89	+1.15	22:17199629:A:C
Colon Sigmoid	eqtl	1.1e-88	+0.92	22:17199629:A:C
Adipose Visceral Omentum	eqtl	1.3e-76	+0.63	22:17199629:A:C
Artery Aorta	eqtl	2.6e-71	+0.86	22:17199629:A:C
Colon Transverse	eqtl	6.1e-71	+0.62	22:17199629:A:C

FANTOM5 promoters

8 alternative TSS:

Promoter ID	TPM avg	Samples expressed
193076	12.0018	469
193075	3.1815	776
193077	0.1223	75
193083	0.0907	36
193073	0.0731	16
193074	0.0211	4
193082	0.0183	6
193078	0.0061	1

Top tissues by expression

showing 100 of 285 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
monocyte	CL:0000576	98.88	gold quality
mononuclear cell	CL:0000842	98.87	gold quality
leukocyte	CL:0000738	98.86	gold quality
granulocyte	CL:0000094	98.21	gold quality
bone marrow cell	CL:0002092	96.94	gold quality
right uterine tube	UBERON:0001302	96.16	gold quality
spleen	UBERON:0002106	96.11	gold quality
blood	UBERON:0000178	95.42	gold quality
lymph node	UBERON:0000029	95.10	gold quality
thymus	UBERON:0002370	94.40	gold quality
sperm	CL:0000019	93.96	silver quality
gall bladder	UBERON:0002110	93.86	gold quality
vermiform appendix	UBERON:0001154	93.65	gold quality
colonic epithelium	UBERON:0000397	92.95	gold quality
rectum	UBERON:0001052	92.86	gold quality
heart right ventricle	UBERON:0002080	92.74	gold quality
palpebral conjunctiva	UBERON:0001812	92.16	gold quality
male germ cell	CL:0000015	92.06	silver quality
caecum	UBERON:0001153	91.77	gold quality
right lung	UBERON:0002167	91.65	gold quality
ileal mucosa	UBERON:0000331	91.59	gold quality
cardiac muscle of right atrium	UBERON:0003379	91.52	gold quality
decidua	UBERON:0002450	91.37	gold quality
epithelium of bronchus	UBERON:0002031	91.09	gold quality
bronchus	UBERON:0002185	90.90	gold quality
apex of heart	UBERON:0002098	90.89	gold quality
trabecular bone tissue	UBERON:0002483	90.71	gold quality
bone marrow	UBERON:0002371	90.65	gold quality
bronchial epithelial cell	CL:0002328	90.46	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	90.43	gold quality
heart left ventricle	UBERON:0002084	90.33	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	90.29	gold quality
cardiac ventricle	UBERON:0002082	90.28	gold quality
right testis	UBERON:0004534	90.12	gold quality
spinal cord	UBERON:0002240	89.96	gold quality
right atrium auricular region	UBERON:0006631	89.34	gold quality
left testis	UBERON:0004533	89.33	gold quality
cardiac atrium	UBERON:0002081	89.31	gold quality
tonsil	UBERON:0002372	88.95	gold quality
lung	UBERON:0002048	88.85	gold quality
islet of Langerhans	UBERON:0000006	88.84	gold quality
upper lobe of left lung	UBERON:0008952	88.64	gold quality
lower lobe of lung	UBERON:0008949	88.56	silver quality
eye	UBERON:0000970	88.54	gold quality
heart	UBERON:0000948	88.52	gold quality
upper lobe of lung	UBERON:0008948	88.45	gold quality
visceral pleura	UBERON:0002401	88.40	gold quality
testis	UBERON:0000473	88.02	gold quality
pituitary gland	UBERON:0000007	87.78	gold quality
fallopian tube	UBERON:0003889	87.76	gold quality
layer of synovial tissue	UBERON:0007616	87.71	gold quality
smooth muscle tissue	UBERON:0001135	87.64	gold quality
small intestine Peyer’s patch	UBERON:0003454	87.46	gold quality
small intestine	UBERON:0002108	87.27	gold quality
endometrium	UBERON:0001295	87.15	gold quality
myocardium	UBERON:0002349	87.06	gold quality
mucosa of sigmoid colon	UBERON:0004993	86.55	gold quality
descending thoracic aorta	UBERON:0002345	86.46	gold quality
right coronary artery	UBERON:0001625	86.41	gold quality
cervix squamous epithelium	UBERON:0006922	86.25	gold quality
pleura	UBERON:0000977	85.99	gold quality
trigeminal ganglion	UBERON:0001675	85.97	gold quality
left ventricle myocardium	UBERON:0006566	85.93	gold quality
duodenum	UBERON:0002114	85.91	gold quality
jejunal mucosa	UBERON:0000399	85.86	gold quality
oviduct epithelium	UBERON:0004804	85.85	gold quality
trachea	UBERON:0003126	85.61	gold quality
adenohypophysis	UBERON:0002196	85.32	gold quality
superficial temporal artery	UBERON:0001614	84.85	gold quality
inferior vagus X ganglion	UBERON:0005363	84.67	silver quality
parietal pleura	UBERON:0002400	84.65	gold quality
thoracic aorta	UBERON:0001515	84.22	gold quality
renal glomerulus	UBERON:0000074	84.08	gold quality
ascending aorta	UBERON:0001496	84.04	gold quality
esophagus squamous epithelium	UBERON:0006920	84.03	gold quality
substantia nigra	UBERON:0002038	83.88	gold quality
right hemisphere of cerebellum	UBERON:0014890	83.86	gold quality
nasal cavity mucosa	UBERON:0001826	83.83	gold quality
cerebellar hemisphere	UBERON:0002245	83.74	gold quality
hypothalamus	UBERON:0001898	83.58	gold quality
cerebellar cortex	UBERON:0002129	83.56	gold quality
epithelium of esophagus	UBERON:0001976	83.54	gold quality
urinary bladder	UBERON:0001255	83.45	gold quality
midbrain	UBERON:0001891	83.37	gold quality
uterus	UBERON:0000995	83.26	gold quality
subthalamic nucleus	UBERON:0001906	83.18	silver quality
skin of hip	UBERON:0001554	83.16	gold quality
pylorus	UBERON:0001166	83.03	gold quality
prostate gland	UBERON:0002367	82.99	gold quality
intestine	UBERON:0000160	82.98	gold quality
ganglionic eminence	UBERON:0004023	82.88	gold quality
epithelium of nasopharynx	UBERON:0001951	82.83	gold quality
nasopharynx	UBERON:0001728	82.82	gold quality
cerebellum	UBERON:0002037	82.82	gold quality
pancreas	UBERON:0001264	82.81	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	82.78	gold quality
metanephric glomerulus	UBERON:0004736	82.68	gold quality
left uterine tube	UBERON:0001303	82.54	gold quality
right lobe of thyroid gland	UBERON:0001119	82.47	gold quality
right adrenal gland	UBERON:0001233	82.41	gold quality

Single-cell (SCXA)

Detected in 7 experiment(s), a significant marker in 6.

Experiment	Marker?	Max mean expression
E-MTAB-6678	yes	23.88
E-MTAB-8498	yes	11.65
E-GEOD-93593	yes	7.77
E-MTAB-9801	yes	6.56
E-MTAB-9543	yes	4.58
E-MTAB-8060	no	52.43
E-ANND-3	no	0.00

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 150 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM
Spleen	tissue	106.4
Tonsil	tissue	60.5
Thymus	tissue	52.8
Lung	tissue	52.7
Lymph node	tissue	47.8
Fallopian tube	tissue	42.4
Appendix	tissue	37.8
Choroid plexus	tissue	37.3
Heart muscle	tissue	36.4
Midbrain	tissue	35.4
Spinal cord	tissue	35.3
Pons	tissue	34.8
Urinary bladder	tissue	33.9
Thalamus	tissue	33.7
Corpus callosum	tissue	33.4
Medulla oblongata	tissue	33.2
Rectum	tissue	32.9
Superior colliculi	tissue	32.4
Cerebral cortex	tissue	32.1
Somatosensory cortex	tissue	32.1
Occipital cortex	tissue	31.7
Hypothalamus	tissue	31.3
Periaqueductal gray	tissue	31.3
Gallbladder	tissue	30.8
Substantia nigra	tissue	30.8
Substantia nigra	tissue	30.2
Spinal cord	tissue	30.2
Septum	tissue	30.2
Hippocampal formation	tissue	29.9
Prefrontal cortex	tissue	29.8
Motor cortex	tissue	29.7
Putamen	tissue	29.4
Retrosplenial and cingulate cortex	tissue	29.2
Retrosplenial cortex	tissue	29.0
Entorhinal cortex	tissue	28.7
Hypothalamus	tissue	28.3
Periaqueductal gray	tissue	27.7
Medulla oblongata	tissue	27.6
Cerebellum	tissue	27.5
Ventral forebrain	tissue	27.4
Temporal cortex	tissue	27.4
Corpus callosum	tissue	27.2
Basal ganglia	tissue	26.9
Insular cortex	tissue	25.6
Small intestine	tissue	25.2
Septum	tissue	24.8
Olfactory bulb	tissue	24.6
Colon	tissue	24.0
Amygdala	tissue	23.9
Pons	tissue	23.3
Midbrain	tissue	23.1
Bone marrow	tissue	23.1
Putamen	tissue	22.8
Smooth muscle	tissue	21.6
Ventral pallidum	tissue	20.7
Cervix	tissue	20.4
Thalamus	tissue	20.3
Frontal cortex	tissue	20.1
Amygdala	tissue	20.0
Liver	tissue	20.0

Brain sub-regions (HPA Brain Atlas): detected in 378; highest nTPM — Lateral funiculus (white matter) (40.9), Ventral spinal cord (35.3), Anterior funiculus (white matter) (34.4), White matter (33.4), Dorsal funiculus (white matter) (32.9).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting ADA2 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 92 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-3689D	100.00	66.14	1181
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-4745-5P	99.98	65.95	1028
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-4487	99.96	64.58	1252
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-10395-5P	99.86	67.35	676
HSA-MIR-3934-3P	99.76	65.51	1351
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-6752-3P	99.72	66.71	1587
HSA-MIR-4524A-3P	99.72	66.85	2406
HSA-MIR-5004-5P	99.68	66.63	1294
HSA-MIR-4756-3P	99.62	66.30	1319
HSA-MIR-4516	99.61	67.78	3390
HSA-MIR-6832-5P	99.58	64.82	1132
HSA-MIR-4524A-5P	99.57	71.73	1193
HSA-MIR-4524B-5P	99.57	71.68	1195
HSA-MIR-7844-5P	99.55	68.56	1428
HSA-MIR-5584-5P	99.49	68.22	2814
HSA-MIR-4696	99.48	67.48	1040
HSA-MIR-1224-5P	99.48	65.59	803
HSA-MIR-3123	99.47	67.15	2693

Functional genomics

gnomAD constraint: pLI 5.39e-06, LOEUF 0.879, missense Z 0.325 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000399837 — one region, missense o/e 0.99.

Literature-anchored findings (GeneRIF, showing 40)

• findings show ADA2 is encoded by the CECR1 gene & belongs to novel family of ADA-related growth factors;ADA2 may be active in sites of inflammation during hypoxia & in areas of tumour growth where adenosine is elevated & extracellular pH is acidic (PMID:15926889)
• The crystal structures of ADA2 and ADA2 bound to a transition state analogue presented here reveal the structural basis of the catalytic/signaling activity of adenosine deaminase growth factor/ADA2 proteins. (PMID:20147294)
• Plasma AD2 may have a role in determining tumour response to treatment. (PMID:22558798)
• Increased ADA2 expression and activity are identified in human and porcine retinas with diabetes. (PMID:23685153)
• Loss-of-function mutations in CECR1 were associated with a spectrum of vascular and inflammatory phenotypes, ranging from early-onset recurrent stroke to systemic vasculopathy or vasculitis. (PMID:24552284)
• Recessive loss-of-function mutations of ADA2, a growth factor that is the major extracellular adenosine deaminase, can cause polyarteritis nodosa vasculopathy with highly varied clinical expression. (PMID:24552285)
• We report on a 5-year-old girl with a severe vasculopathy who carried two novel mutations in CECR1. (PMID:24737293)
• ADA2 (CECR1) may act as a regulator of neutrophil activation, and that a reduction of ADA2 activity results in significant endothelial damage via a neutrophil-driven process. (PMID:25278816)
• Ectopic expression of miR-146b-3p suppressed ADA2 expression, activity, and TNF-alpha release in the AGA-treated human macrophages (PMID:25815338)
• In patients with unexplained young-onset lacunar stroke accompanied by systemic inflammation and a positive family history suspicious of recessively inherited disease, ADA2 deficiency needs to be considered in the differential diagnosis. (PMID:25888558)
• IL-17 receptor A and adenosine deaminase 2 deficiency due to deletion mutations was found in siblings with chronic mucocutaneous candidiasis and chronic systemic inflammation. (PMID:26607704)
• This case series revealed large phenotypic variability in patients with ADA2 deficiency though they were homozygous for the same R169Q mutation in CECR1. (PMID:26867732)
• Deficiency of ADA2 causes IgA-IgG antibody deficiencies in a family. (PMID:26922074)
• The clinical manifestations of adenosine deaminase 2 deficiency ranged in severity from limited cutaneous involvement to severe multisystemic vasculitis; one-third of our cases (5 of 15) were currently asymptomatic, and required close monitoring. We recommend CECR1 screening for unaffected siblings of index cases, cases of familial vasculitis, and cases of PAN that is resistant to standard treatment (PMID:27059682)
• Adenosine deaminase type 2 deficiency with a homozygous premature stop codon masquerading as GATA2 deficiency: successful haploidentical sibling hematopoietic stem cell transplantation. (PMID:27130863)
• We discuss three newly described monogenic autoinflammatory diseases [deficiency of adenosine deaminase 2 (DADA2), a subtype of macrophage activation syndrome (MAS), and stimulator of interferon genes (STING)-associated vasculopathy with onset in infancy (SAVI)], discuss the possibilities of somatic mosaicism and digenic inheritance, and give an update on new concepts in pathways involved in familial Mediterranean fever (PMID:27362340)
• Deficiency of Adenosine Deaminase 2 (DADA2) is a new autoinflammatory disease secondary to autosomal recessive mutations of CECR1 (Cat Eye Syndrome Chromosome Region 1) gene, mapped to chromosome 22q11.1. (PMID:27609179)
• High CECR1 activity is associated with brain tumor. (PMID:28453746)
• Findings indicate that ADA2 deficiency presents not only with vasculopathy but also with an immunodeficiency of the B cell compartment. Therefore, patients with antibody deficiency should be screened for ADA2 deficiency. (PMID:28493328)
• CECR1 function in (M2-like) macrophages mediates cross talk between macrophages and pericytes in GBM via paracrine PDGFB-PDGFRbeta signaling, promoting pericyte recruitment and migration, and tumor angiogenesis. (PMID:28534507)
• Data show that 2 patients required a second transplant for engraftment failure were discovered to carry the deleterious ADA2 adenosine deaminase (CECR1) mutations and be ADA2 deficient. (PMID:28974505)
• We imposed no clinical selection or criteria before testing but collected uniform clinical data for each patient. Therefore, this series exactly reflects the context of requests for sequencing the ADA2 gene we receive in our laboratory (PMID:29681619)
• Our work identifies not only a new set of causal mutations but more generally demonstrates the importance of N-glycosylation for normal ADA2 function. To our knowledge, this is the first report of an autoinflammatory disease caused by a defect in glycosylation. (PMID:29936104)
• Case Report: describe phenotype of patient with ADA2 deficiency. (PMID:30148442)
• this study reports two ADA2 deficiency patients in whom recalcitrant warts and mollusca were a predominant phenotype (PMID:30386947)
• ADA2 activity in plasma reliably distinguishes adult Sneddon’s syndrome of unknown cause patients from healthy controls. (PMID:30645994)
• In children with deficiency of ADA2 (DADA2) (5 with polyarteritis nodosa, 3 with unclassifiable vasculitis, and 1 with ANCA-associated vasculitis), 1 patient had no rare variants in the coding region of ADA2 and 8 had biallelic, rare variants (minor allele frequency <0.01) with a known association with DADA2 (p.Gly47Arg and p.Gly47Ala) or a novel association (p.Arg9Trp, p.Leu351Gln, and p.Ala357Thr). (PMID:31008556)
• These results suggest that neutrophils may play a pathogenic role in DADA2. Modulation of adenosine-mediated NET formation may contribute a novel and directed therapeutic approach in the treatment of DADA2 and potentially other inflammatory diseases. (PMID:31015188)
• Description of three families with the same homozygous splice site mutation in ADA2 and observed a novel combination of manifestations resembling Behcet’s disease. (PMID:31856934)
• Role of adenosine deaminase 2 gene variants in pediatric deficiency of adenosine deaminase 2: A structural biological approach. (PMID:31974608)
• Two cases of ADA2 deficiency presenting as childhood polyarteritis nodosa: novel ADA2 variant, atypical CNS manifestations, and literature review. (PMID:32535845)
• Deficiency of Adenosine Deaminase 2 (DADA2): Hidden Variants, Reduced Penetrance, and Unusual Inheritance. (PMID:32638197)
• Dysregulation in B-cell responses and T follicular helper cell function in ADA2 deficiency patients. (PMID:32707604)
• Sequence-Based Screening of Patients With Idiopathic Polyarteritis Nodosa, Granulomatosis With Polyangiitis, and Microscopic Polyangiitis for Deleterious Genetic Variants in ADA2. (PMID:33021335)
• Novel ADA2 Compound Heterozygous Mutations Resulting in Deficiency of Adenosine Deaminase 2 in a Pair of Siblings. (PMID:33517505)
• Detailed analysis of Japanese patients with adenosine deaminase 2 deficiency reveals characteristic elevation of type II interferon signature and STAT1 hyperactivation. (PMID:33529688)
• Adult-onset deficiency of adenosine deaminase 2-a case report and literature review. (PMID:33638065)
• Expanding spectrum of DADA2: a review of phenotypes, genetics, pathogenesis and treatment. (PMID:33791889)
• Targeting Adenosine with Adenosine Deaminase 2 to Inhibit Growth of Solid Tumors. (PMID:33863778)
• Macrophage-Derived Adenosine Deaminase 2 Correlates with M2 Macrophage Phenotype in Triple Negative Breast Cancer. (PMID:33916440)

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
danio_rerio	ada2b	ENSDARG00000015623
danio_rerio	ada2a	ENSDARG00000051746
drosophila_melanogaster	Adgf-E	FBGN0033952
drosophila_melanogaster	Adgf-B	FBGN0036751
drosophila_melanogaster	Adgf-A	FBGN0036752
drosophila_melanogaster	Adgf-D	FBGN0038172
drosophila_melanogaster	Adgf-C	FBGN0038173
drosophila_melanogaster	Adgf-A2	FBGN0043025

Paralogs (2): MAPDA (ENSG00000168803), ADA (ENSG00000196839)

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
Cupriavidus taiwanensis LMG 19424	B3R3T1	97.4%	Diamond
Pseudomonas [fluorescens] SBW25	C3K8W2	97.2%	Diamond
Pongo abelii	Q5RC46	96.9%	Diamond
Cupriavidus pinatubonensis JMP134	Q46YJ3	94.3%	Diamond
Ralstonia pickettii 12J	B2U7U6	94.2%	Diamond
Ralstonia pseudosolanacearum GMI1000	Q8XXL5	94.2%	Diamond
Cupriavidus metallidurans CH34	Q1LQ00	91.4%	Diamond
Trichlorobacter lovleyi SZ	B3E600	82.2%	Diamond
Sus scrofa	P58780	71.2%	Diamond
Chelativorans sp. BNC1	Q11C48	71.2%	Diamond
Phlebotomus duboscqi	Q06K61	71.0%	Diamond
Lutzomyia longipalpis	Q9NC65	71.0%	Diamond
Acinetobacter baylyi ADP1	Q6FCU0	67.9%	Diamond
Wolinella succinogenes DSM 1740	Q7M9R5	63.1%	Diamond
Crocosphaera subtropica ATCC 51142	B1WR40	61.2%	Diamond
Streptomyces coelicolor A3(2)	Q9RDE5	61.2%	Diamond
Vibrio parahaemolyticus RIMD 2210633	Q87GM3	61.0%	Diamond
Zymomonas mobilis subsp. mobilis ZM4 = ATCC 31821	Q5NNW5	60.9%	Diamond
Pelodictyon luteolum DSM 273	Q3B2Q0	60.7%	Diamond
Xenopus laevis	Q2VQV9	58.6%	Diamond
Campylobacter lari RM2100	B9KE87	58.2%	Diamond
Aedes albopictus	Q5MIX2	51.4%	Diamond
Opitutus terrae PB90-1	B1ZYW1	42.6%	Diamond
Aplysia californica	P15287	41.5%	Diamond
Acidothermus cellulolyticus 11B	A0LRH8	39.4%	Diamond
Dictyostelium discoideum	Q553U5	39.2%	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
LINC01664	ncRNA	100996342
TMEM121B	protein-coding	27439
HDHD5	protein-coding	27440
HDHD5-AS1	ncRNA	100130717
IL17RA	protein-coding	23765
CECR3	ncRNA	27442
CECR2	protein-coding	27443

Protein

Protein identifiers

Adenosine deaminase 2 — Q9NZK5 (reviewed: Q9NZK5)

Alternative names: Cat eye syndrome critical region protein 1

All UniProt accessions (13): A0A087X0I3, A0A3B3IRN1, A0A3B3IRR5, A0A3B3IT96, A0A8Q3SIG4, A0A8Q3SIK1, A0A8Q3WL33, A0A8Q3WL39, A0A8Q3WM36, Q9NZK5, A0A8Q3WMB0, B4E3Q4, F5H7J3

UniProt curated annotations — full annotation on UniProt →

Function. Adenosine deaminase that may contribute to the degradation of extracellular adenosine, a signaling molecule that controls a variety of cellular responses. Requires elevated adenosine levels for optimal enzyme activity. Binds to cell surfaces via proteoglycans and may play a role in the regulation of cell proliferation and differentiation, independently of its enzyme activity.

Subunit / interactions. Homodimer. Interacts with adenosine receptors. Binds heparin.

Subcellular location. Secreted.

Tissue specificity. Detected in blood plasma (at protein level). Widely expressed, with most abundant expression in human adult heart, lung, lymphoblasts, and placenta as well as fetal lung, liver, and kidney. In embryo, expressed in the outflow tract and atrium of the developing heart, the VII/VIII cranial nerve ganglion, and the notochord.

Disease relevance. Vasculitis, autoinflammation, immunodeficiency, and hematologic defects syndrome (VAIHS) [MIM:615688] An autosomal recessive, systemic necrotizing vasculitis that affects medium and small arteries. The ensuing tissue ischemia can affect any organ, including the skin, musculoskeletal system, kidneys, gastrointestinal tract, and the cardiovascular and nervous systems. Organ involvement and disease severity are highly variable. Clinical features include recurrent ischemic stroke affecting the small vessels of the brain and resulting in neurologic dysfunction, recurrent fever, myalgias, livedoid rash, gastrointestinal pain and hepatosplenomegaly. The disease is caused by variants affecting the gene represented in this entry. Sneddon syndrome (SNDNS) [MIM:182410] An autosomal recessive, systemic non-inflammatory thrombotic vasculopathy characterized by the association of livedo racemosa, and in some cases livedo reticularis, with cerebrovascular disease. Livedo racemosa is a persistent net-like violaceous-cyanotic, mottled discoloration of the skin affecting the legs, the arms, the buttocks and the trunk; livedo reticularis is limited to the extremities and is visible only in the cold. Cerebrovascular features include recurrent transient ischemic attacks, infarcts, and rarely spinal strokes or intracranial or subarachnoid hemorrhages. Headache and vertigo may precede the onset of livedo racemosa and cerebrovascular manifestations by several years. Rare neurologic symptoms include seizures, chorea, or myelopathies. The disease is caused by variants affecting the gene represented in this entry.

Cofactor. Binds 1 zinc ion per subunit.

Domain organisation. The PRB domain is involved in receptor binding, and may be responsible for the cytokine-like growth factor activity due to its sharing of several structural properties with chemokines. High-affinity binding to heparin/glycosaminoclycan (GAG) is mediated by a large, highly positively charged surface at the interface of dimer’s subunits involving approximately residues 30-45, 389-396, and 422-428.

Miscellaneous. Candidate gene for the Cat Eye Syndrome (CES), a developmental disorder associated with the duplication of a 2 Mb region of 22q11.2. Duplication usually takes in the form of a surpernumerary bisatellited isodicentric chromosome, resulting in four copies of the region (represents an inv dup(22)(q11)). CES is characterized clinically by the combination of coloboma of the iris and anal atresia with fistula, downslanting palpebral fissures, preauricular tags and/or pits, frequent occurrence of heart and renal malformations, and normal or near-normal mental development.

Similarity. Belongs to the metallo-dependent hydrolases superfamily. Adenosine and AMP deaminases family. ADGF subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9NZK5-1	1	yes
Q9NZK5-2	2

RefSeq proteins (6): NP_001269154, NP_001269155, NP_001269156, NP_001269157, NP_001269158, NP_803124 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001365	A_deaminase_dom	Domain
IPR006330	Ado/ade_deaminase	Family
IPR006331	ADGF	Family
IPR013659	A_deaminase_N	Domain
IPR032466	Metal_Hydrolase	Homologous_superfamily

Pfam: PF00962, PF08451

Enzyme classification (BRENDA)

• EC 3.5.4.4 — adenosine deaminase (BRENDA: 55 organisms, 135 substrates, 272 inhibitors, 117 Km, 44 kcat entries)

Substrate kinetics (BRENDA)

11 substrates with measured Km, best-characterized 11. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ADENOSINE	—	69
2’-DEOXYADENOSINE	0.004–0.56	18
5’-METHYLTHIOADENOSINE	0.0044–0.376	14
2’,3’-ISOPROPYLIDENE ADENOSINE	0.29	1
6-CHLOROPURINE RIBOSIDE	0.31	1
6-CHLOROPURINRIBOSIDE	0.277	1
6-METHOXYPURINRIBOSIDE	0.081	1
ADENINE	0.032	1
ADENOSINE-3’-MONOPHOSPHATE	2	1
AMP	0.17	1
CAMP	0.5	1

Catalyzed reactions (Rhea)

• adenosine + H2O + H(+) = inosine + NH4(+) (RHEA:24408)

UniProt features (84 total): helix 31, strand 12, sequence variant 11, binding site 9, glycosylation site 4, turn 4, region of interest 2, splice variant 2, mutagenesis site 2, sequence conflict 2, active site 2, signal peptide 1, chain 1, disulfide bond 1

Structure

Experimental structures (PDB)

2 structures by resolution:

PDB	Title	Method	Resolution (Å)
3LGD	Crystal structure of human adenosine deaminase growth factor, adenosine deaminase type 2 …	X-RAY DIFFRACTION	2
3LGG	Crystal structure of human adenosine deaminase growth factor, adenosine deaminase type 2 …	X-RAY DIFFRACTION	2.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NZK5-F1	96.03	0.95

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Hydrolases, Metabolic proteins, Predicted secreted proteins, Predicted intracellular proteins, Plasma proteins, Disease related genes, Potential drug targets, Human disease related genes

Protein evidence: Evidence at protein level

Antibody reliability (HPA): IH uncertain

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 (2)

Position	Role
359	proton donor
384	proton acceptor

Ligand- & substrate-binding residues (9)

Position	Role
293	substrate
326	substrate
356	Zn(2+)
441	Zn(2+)
442	substrate
112	Zn(2+)
114	Zn(2+)
115	substrate
204–211	substrate

Disulfide bonds (1)

Type	Positions
Disulfide bond	137–159

Glycosylation sites (4)

Type	Positions
N-linked (glcnac…) asparagine	127, 174, 185, 378

Mutagenesis-validated functional residues (2)

Position	Phenotype
137	abolishes secretion.
362	reduces dimerization and enzyme activity.

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-6798695	Neutrophil degranulation	curated
R-HSA-5683826	Surfactant metabolism	curated
R-HSA-168256	Immune System	—
R-HSA-168249	Innate Immune System	—
R-HSA-392499	Metabolism of proteins	—

MSigDB gene sets: 562 (showing top): WALLACE_PROSTATE_CANCER_RACE_UP, REACTOME_INNATE_IMMUNE_SYSTEM, MCLACHLAN_DENTAL_CARIES_UP, GOCC_SECRETORY_GRANULE, GOBP_CARBOHYDRATE_DERIVATIVE_CATABOLIC_PROCESS, GOMF_GROWTH_FACTOR_ACTIVITY, WIELAND_UP_BY_HBV_INFECTION, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_NUCLEOBASE_CONTAINING_SMALL_MOLECULE_METABOLIC_PROCESS, GOBP_SMALL_MOLECULE_BIOSYNTHETIC_PROCESS, GNF2_MCL1, GNF2_CD1D, HOSHIDA_LIVER_CANCER_SUBCLASS_S3, GOBP_CARBOHYDRATE_DERIVATIVE_BIOSYNTHETIC_PROCESS, MODULE_301

GO Biological Process (3): adenosine catabolic process (GO:0006154), inosine biosynthetic process (GO:0046103), signal transduction (GO:0007165)

GO Molecular Function (10): adenosine deaminase activity (GO:0004000), growth factor activity (GO:0008083), heparin binding (GO:0008201), zinc ion binding (GO:0008270), adenosine receptor binding (GO:0031685), protein homodimerization activity (GO:0042803), proteoglycan binding (GO:0043394), hydrolase activity (GO:0016787), deaminase activity (GO:0019239), metal ion binding (GO:0046872)

GO Cellular Component (2): extracellular region (GO:0005576), azurophil granule lumen (GO:0035578)

Reactome top-level categories

3 top-level categories:

Category	Pathways
Metabolism of proteins	1
Innate Immune System	1
Immune System	1

GO top-level categories

27 GO namespaces:

Category	Terms
adenosine metabolic process	1
purine ribonucleoside catabolic process	1
inosine metabolic process	1
purine ribonucleoside biosynthetic process	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in cyclic amidines	1
deaminase activity	1
receptor ligand activity	1
glycosaminoglycan binding	1
sulfur compound binding	1
transition metal ion binding	1
G protein-coupled receptor binding	1
identical protein binding	1
protein dimerization activity	1
protein binding	1
carbohydrate derivative binding	1
catalytic activity	1
hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds	1
cation binding	1
cellular anatomical structure	1
vacuolar lumen	1
secretory granule lumen	1
azurophil granule	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 6 of 16 annotations. The rest are phylogenetic / computational / electronic (IEA).

6 experimentally-supported GO terms:

GO term	NS	Evidence
adenosine catabolic process	BP	direct assay
adenosine deaminase activity	MF	direct assay
adenosine receptor binding	MF	direct assay
protein homodimerization activity	MF	physical interaction
proteoglycan binding	MF	direct assay
zinc ion binding	MF	direct assay

Protein interactions and networks

STRING

showing 16 of 1,340 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ADA2	ADA	P00813	922
ADA2	HDHD5	Q9BXW7	458
ADA2	MAPDA	Q6DHV7	457
ADA2	PNP	P00491	452
ADA2	CECR2	Q9BXF3	427
ADA2	MEFV	O15553	426
ADA2	XKR3	Q5GH77	403
ADA2	AMPD2	Q01433	396
ADA2	MVK	Q03426	390
ADA2	PSTPIP1	O43586	387
ADA2	ADK	P55263	380
ADA2	P2RY4	P51582	367
ADA2	OXER1	Q8TDS5	367
ADA2	GART	P22102	363
ADA2	FAM151A	Q8WW52	361
ADA2	TSR2	Q969E8	361

IntAct

Human interaction partners of ADA2 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

1 partners by confidence:

Partner	Interaction type	MIscore	Records
TRIO	association	0.350	1

Disease & clinical

Genetic variants

Variant evidence for ADA2: 693 ClinVar records (125 pathogenic / likely pathogenic); 1 GWAS association. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	91
Likely pathogenic	34
Uncertain significance	273
Likely benign	192
Benign	31

Top pathogenic / likely-pathogenic (15)

Showing the 15 best-reviewed of 125 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
541735	NM_001282225.2(ADA2):c.973-2A>G	Pathogenic	criteria provided, multiple submitters, no conflicts	17
120301	NM_001282225.2(ADA2):c.140G>C (p.Gly47Ala)	Pathogenic	criteria provided, multiple submitters, no conflicts	12
1076271	NM_001282225.2(ADA2):c.139G>C (p.Gly47Arg)	Pathogenic	criteria provided, multiple submitters, no conflicts	11
420337	NM_001282225.2(ADA2):c.1072G>A (p.Gly358Arg)	Pathogenic	criteria provided, multiple submitters, no conflicts	7
541731	NM_001282225.2(ADA2):c.139G>T (p.Gly47Trp)	Pathogenic	criteria provided, multiple submitters, no conflicts	7
189342	NM_001282225.2(ADA2):c.1078A>G (p.Thr360Ala)	Pathogenic	criteria provided, multiple submitters, no conflicts	6
640066	NM_001282225.2(ADA2):c.144del (p.Arg49fs)	Pathogenic	criteria provided, multiple submitters, no conflicts	4
852411	NM_001282225.2(ADA2):c.934C>T (p.Arg312Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	4
1027880	NM_001282225.2(ADA2):c.882-2A>G	Pathogenic	criteria provided, multiple submitters, no conflicts	3
1285514	NM_001282225.2(ADA2):c.158del (p.Asn53fs)	Pathogenic	criteria provided, multiple submitters, no conflicts	2
1407177	NM_001282225.2(ADA2):c.2T>C (p.Met1Thr)	Pathogenic	criteria provided, multiple submitters, no conflicts	2
2889771	NM_001282225.2(ADA2):c.660C>A (p.Tyr220Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	2
2892125	NM_001282225.2(ADA2):c.1303_1319del (p.His434_Pro435insTer)	Pathogenic	criteria provided, multiple submitters, no conflicts	2
3587771	NM_001282225.2(ADA2):c.794C>G (p.Ser265Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	2
636596	NM_001282225.2(ADA2):c.916C>T (p.Arg306Ter)	Likely pathogenic	criteria provided, multiple submitters, no conflicts	2

Per-variant reference — Sugi Variant

Explore ADA2’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.

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

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

2 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	1.6e-05
Lung Adenocarcinoma (TCGA)	favorable	2.8e-05

Disease associations

OMIM: gene MIM:607575 | disease phenotypes: MIM:615688, MIM:182410, MIM:613953

GenCC curated gene-disease

4 curated gene-disease records:

Disease	Classification	Inheritance	Records
deficiency of adenosine deaminase 2	Strong	Autosomal recessive	4
polyarteritis nodosa	Moderate	Autosomal recessive
Sneddon syndrome	Moderate	Autosomal recessive	2
Diamond-Blackfan anemia	Supportive	Autosomal dominant

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (9 panels, 8 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

9 panels:

Panel	Rating
Autoinflammatory disorders	green
COVID-19 research	green
Cytopenia - NOT Fanconi anaemia	green
Cytopenias and congenital anaemias	green
Hereditary neuropathy or pain disorder	green
Primary immunodeficiency or monogenic inflammatory bowel disease	green
Rare anaemia	green
Rare genetic inflammatory skin disorders	green
Cerebral vascular malformations	amber

Mondo (7): deficiency of adenosine deaminase 2 (MONDO:0014306), Sneddon syndrome (MONDO:0008436), autoinflammatory syndrome (MONDO:0019751), immunodeficiency 51 (MONDO:0013500), neurodevelopmental disorder (MONDO:0700092), polyarteritis nodosa (MONDO:0019170), Diamond-Blackfan anemia (MONDO:0015253)

Orphanet (5): Deficiency of adenosine deaminase 2 (Orphanet:404553), Sneddon syndrome (Orphanet:820), Autoinflammatory syndrome (Orphanet:93665), Chronic mucocutaneous candidiasis (Orphanet:1334), Polyarteritis nodosa (Orphanet:767)

GWAS associations

1 associations:

Study	Trait	p-value
GCST002701_35	Verbal declarative memory	1e-6

EFO canonical traits (from GWAS)

2 canonical traits:

EFO ID	Trait name
EFO:0004874	memory performance
EFO:0006805	word list delayed recall measurement

MeSH disease descriptors

4 disease descriptors:

Descriptor	Name	Tree numbers
D029503	Anemia, Diamond-Blackfan	C15.378.050.085.080.090; C15.378.050.750.500; C15.378.190.223.500.500.090; C16.320.077.090
D065886	Neurodevelopmental Disorders	F03.625
D010488	Polyarteritis Nodosa	C14.907.940.090.720; C14.907.940.897.500; C17.800.862.625
D018860	Sneddon Syndrome	C10.228.140.300.750; C14.907.253.774; C17.800.862.775

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (CPIC guideline: no)

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases expression, affects cotreatment, decreases expression	9
trichostatin A	decreases expression	2
Phenylmercuric Acetate	decreases expression, affects cotreatment	2
Aflatoxin B1	affects methylation, decreases methylation, increases methylation	2
GSK-J4	decreases expression	1
methylmercuric chloride	decreases expression	1
2,5,2’,5’-tetrachlorobiphenyl	increases expression	1
sodium arsenite	increases expression	1
benzo(e)pyrene	increases methylation	1
aflatoxin B2	increases methylation	1
entinostat	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
(+)-JQ1 compound	decreases expression	1
Vorinostat	decreases expression	1
Amiodarone	increases expression	1
Arsenic	affects methylation	1
Benzo(a)pyrene	affects methylation	1
Doxorubicin	decreases expression	1
Methapyrilene	increases methylation	1
Naled	affects expression	1
Nickel	increases expression	1
Smoke	decreases expression	1
Thimerosal	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Tretinoin	decreases expression	1
Triclosan	decreases expression	1
Isotretinoin	increases expression	1
1-Methyl-4-phenylpyridinium	increases expression	1
Antirheumatic Agents	decreases expression	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_E1CN	Ubigene THP-1 ADA2 KO	Cancer cell line	Male

Clinical trials (associated diseases)

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

showing 60 of 359 trials:

NCT	Phase	Status	Title
NCT00307671	Phase 4	COMPLETED	Treatment of Necrotizing Vasculitides for Patients Older Than 65 Years
NCT00400075	Phase 4	UNKNOWN	CHUSPAN PAN BP Treatment of Polyarteritis Nodosa and Microscopic Polyangiitis Without Poor-Prognosis Factors
NCT00673608	Phase 4	COMPLETED	Magnetic Resonance Imaging (MRI) Assessments of the Heart and Liver Iron Load in Patients With Transfusion Induced Iron Overload
NCT05879419	Phase 4	ACTIVE_NOT_RECRUITING	Recombinant Herpes Zoster Vaccine in Patients With Autoimmune Rheumatic Diseases
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,
NCT00647166	Phase 3	COMPLETED	Association Corticosteroid/Azathioprine in Microscopic Polyangiitis/ Polyarteritis Nodosa or Eosinophilic Granulomatosis With Polyangiitis (Churg Strauss Syndrome)
NCT00235391	Phase 3	COMPLETED	Expanded Access of Deferasirox to Patients With Congenital Disorders of Red Blood Cells and Chronic Iron Overload
NCT00995709	Phase 3	COMPLETED	Phase III Study in Refractory Behcet’s Disease
NCT01532570	Phase 3	COMPLETED	Clinical Study of TA-650 in Patients With Behcet’s Disease (BD) With Special Lesions
NCT02307513	Phase 3	COMPLETED	A Phase 3 Randomized, Double-blind Study to Evaluate the Efficacy and Safety of Apremilast (CC-10004) in Subjects With Active Behçet’s Disease
NCT02505568	Phase 3	COMPLETED	A Study to Evaluate Efficacy and Safety of Infliximab in Participant With Moderate-to-Severe Refractory Intestinal Behcet’s Disease
NCT03209219	Phase 3	COMPLETED	Interferon α2a Versus Cyclosporine for Refractory Behçet’s Disease Uveitis
NCT04528082	Phase 3	RECRUITING	Apremilast Pediatric Study in Children With Active Oral Ulcers Associated With Behçet’s Disease
NCT05767047	Phase 3	RECRUITING	A Study of Apremilast in Children With Oral Ulcers Associated With Behçet’s Disease or Juvenile Psoriatic Arthritis
NCT06145893	Phase 3	RECRUITING	A Study of Efficacy and Safety of Hemay005 Tablets in Patients With Behçet’s Disease
NCT06780462	Phase 3	RECRUITING	Randomized Controlled Multicenter Study Comparing Steroid Therapy Plus Anticoagulants to Steroid Therapy Alone in Deep Venous Thrombosis of Behçet’s Syndrome
NCT06925698	Phase 3	NOT_YET_RECRUITING	Immunosuppressive Therapy Alone Versus Plus Oral Anticoagulation in the Treatment of VT Associated With Behcet’s Disease
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
NCT00001457	Phase 2	COMPLETED	Lamivudine for Chronic Hepatitis B
NCT00751517	Phase 2	UNKNOWN	Cyclophosphamide Versus Methotrexate for Remission Maintenance in Systemic Necrotizing Vasculitides
NCT03482479	Phase 2	COMPLETED	Low Dose Naltrexone to Improve Physical Health in Patients With Vasculitis
NCT05168475	Phase 2	TERMINATED	Biologics in Refractory Vasculitis: A Trial of Biologic Therapy for Refractory Primary Non-ANCA Associated Vasculitis
NCT00001962	Phase 2	TERMINATED	A Study to Determine Whether Therapy With Daclizumab Will Benefit Patients With Bone Marrow Failure
NCT00011505	Phase 2	COMPLETED	Mobilization of Stem Cells With G-CSF for Collection From Patients With Diamond-Blackfan Anemia
NCT00301834	Phase 2	COMPLETED	Alemtuzumab, Fludarabine, and Busulfan Followed By Donor Stem Cell Transplant in Treating Young Patients With Hematologic Disorders
NCT00957931	Phase 2	COMPLETED	Allo-HCT MUD for Non-malignant Red Blood Cell (RBC) Disorders: Sickle Cell, Thal, and DBA: Reduced Intensity Conditioning, Co-tx MSCs
NCT01529827	Phase 2	COMPLETED	Fludarabine Phosphate, Melphalan, and Low-Dose Total-Body Irradiation Followed by Donor Peripheral Blood Stem Cell Transplant in Treating Patients With Hematologic Malignancies
NCT02386267	Phase 2	UNKNOWN	L-leucine in Diamond Blackfan Anemia Patients
NCT02512679	Phase 2	TERMINATED	Related Hematopoietic Stem Cell Transplantation (HSCT) for Genetic Diseases of Blood Cells
NCT03333486	Phase 2	TERMINATED	Fludarabine Phosphate, Cyclophosphamide, Total Body Irradiation, and Donor Stem Cell Transplant in Treating Patients With Blood Cancer
NCT04099966	Phase 2	RECRUITING	AlloSCT for Malignant and Non-malignant Hematologic Diseases Utilizing Alpha/Beta T Cell and CD19+ B Cell Depletion
NCT04965597	Phase 2	COMPLETED	Treosulfan-Based Conditioning Regimen Before a Blood or Bone Marrow Transplant for the Treatment of Bone Marrow Failure Diseases (BMT CTN 1904)
NCT00442182	Phase 2	UNKNOWN	The Efficacy and Safety of ITF2357 in AIS
NCT00001865	Phase 2	COMPLETED	HAT in Eye Complications of Behcet’s Disease
NCT00483184	Phase 2	COMPLETED	Low Dose Interferon Alpha Treatment for Oral Ulcers of Behcet’s Disease
NCT00664599	Phase 2	COMPLETED	Rituximab for the Treatment of Severe Ocular Manifestations of Behcet’s Disease
NCT00700297	Phase 2	COMPLETED	Colchicine Randomized Double-Blind Controlled Crossover Study in Behcet’s Disease
NCT00866359	Phase 2	COMPLETED	A Study to Evaluate the Efficacy and Safety of Apremilast (CC-10004) in the Treatment of Behçet Disease
NCT01693653	Phase 2	TERMINATED	Tocilizumab for the Treatment of Behcet’s Syndrome
NCT02648581	Phase 2	COMPLETED	Efficacy and Safety of Ustekinumab, a Human Monoclonal Anti-IL-12/IL-23 Antibody, in Patients With Behçet Disease
NCT02756650	Phase 2	COMPLETED	1 Year of Treatment With Canakinumab in Behçet’s Disease Patients With Neurologic or Vascular Involvement
NCT03554161	Phase 2	TERMINATED	Tocilizumab for the Treatment of Refractory Behcet’s Uveitis
NCT04186559	Phase 2	UNKNOWN	Topical Pentoxifylline Gel on Behcet’s Disease Genital Ulcers
NCT04218565	Phase 2	TERMINATED	Golimumab for the Treatment of Refractory Behcet’s Uveitis
NCT04609397	Phase 2	TERMINATED	A Study to Evaluate the Efficacy and Safety of Hemay005 in the Treatment of Behçet Disease
NCT06386744	Phase 2	COMPLETED	Dusquetide for the Treatment of Behcet’s Disease
NCT06794008	Phase 2	RECRUITING	BCMA-CD19 CAR-T Therapy for Refractory Autoimmune Diseases
NCT07080346	Phase 2	COMPLETED	Upadacitinib for Refractory Behcet’s Syndrome
NCT07634848	Phase 2	WITHDRAWN	Ivarmacitinib for Refractory Behcet’s Syndrome
NCT07833163	Phase 2	NOT_YET_RECRUITING	Corticotropin for Behçet’s Disease: A Multicenter Randomized Controlled TrialAcronym.
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
NCT01586455	Phase 1	COMPLETED	Human Placental-Derived Stem Cell Transplantation
NCT01917708	Phase 1	COMPLETED	Bone Marrow Transplant With Abatacept for Non-Malignant Diseases
NCT00550498	Phase 1	TERMINATED	Stem Cell Transplantation in Ocular Lesions of Behcet’s Disease