ADA

Summary

ADA (adenosine deaminase, HGNC:186) is a protein-coding gene on chromosome 20q13.12, encoding Adenosine deaminase (P00813). Catalyzes the hydrolytic deamination of adenosine and 2-deoxyadenosine.

This gene encodes an enzyme that catalyzes the hydrolysis of adenosine to inosine in the purine catabolic pathway. Various mutations have been described for this gene and have been linked to human diseases related to impaired immune function such as severe combined immunodeficiency disease (SCID) which is the result of a deficiency in the ADA enzyme. In ADA-deficient individuals there is a marked depletion of T, B, and NK lymphocytes, and consequently, a lack of both humoral and cellular immunity. Conversely, elevated levels of this enzyme are associated with congenital hemolytic anemia.

Source: NCBI Gene 100 — RefSeq curated summary.

At a glance

• Gene–disease (curated): severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-negative, due to adenosine deaminase deficiency (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 6
• Clinical variants (ClinVar): 769 total — 69 pathogenic, 79 likely-pathogenic
• Phenotypes (HPO): 74
• Druggable target: yes — 3 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_000022

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:186
Approved symbol	ADA
Name	adenosine deaminase
Location	20q13.12
Locus type	gene with protein product
Status	Approved
Aliases	ADA1
Ensembl gene	ENSG00000196839
Ensembl biotype	protein_coding
OMIM	608958
Entrez	100

Gene structure

Transcript identifiers

Ensembl transcripts: 64 — 28 protein_coding, 22 retained_intron, 14 nonsense_mediated_decay

ENST00000372874, ENST00000464097, ENST00000492931, ENST00000535573, ENST00000536076, ENST00000536532, ENST00000537820, ENST00000539235, ENST00000545776, ENST00000695889, ENST00000695890, ENST00000695891, ENST00000695927, ENST00000695949, ENST00000695956, ENST00000695957, ENST00000695991, ENST00000695992, ENST00000695993, ENST00000695994, ENST00000695995, ENST00000695996, ENST00000695997, ENST00000696003, ENST00000696004, ENST00000696005, ENST00000696006, ENST00000696007, ENST00000696008, ENST00000696009, ENST00000696010, ENST00000696017, ENST00000696034, ENST00000696035, ENST00000696036, ENST00000696037, ENST00000696038, ENST00000696039, ENST00000696058, ENST00000696059, ENST00000696060, ENST00000696061, ENST00000696062, ENST00000696063, ENST00000696064, ENST00000696065, ENST00000696072, ENST00000696073, ENST00000696074, ENST00000696075, ENST00000696076, ENST00000696077, ENST00000696078, ENST00000696079, ENST00000696080, ENST00000696081, ENST00000696082, ENST00000696083, ENST00000696084, ENST00000696104, ENST00000696105, ENST00000903022, ENST00000903023, ENST00000921861

RefSeq mRNA: 3 — MANE Select: NM_000022 NM_000022, NM_001322050, NM_001322051

CCDS: CCDS13335, CCDS82618

Canonical transcript exons

ENST00000372874 — 12 exons

Exon	Start	End
ENSE00003463626	44626456	44626599
ENSE00003478001	44636227	44636288
ENSE00003512095	44622829	44622930
ENSE00003524429	44621018	44621147
ENSE00003526755	44623007	44623078
ENSE00003551087	44622588	44622652
ENSE00003572076	44620299	44620401
ENSE00003645967	44629047	44629169
ENSE00003659075	44624202	44624329
ENSE00003691626	44625569	44625684
ENSE00003965374	44619522	44619847
ENSE00003965375	44651575	44651699

Expression profiles

Bgee: expression breadth ubiquitous, 202 present calls, max score 99.53.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 13.7815 / max 1599.7343, expressed in 1617 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
187353	10.8030	1421
187354	2.3118	1100
187352	0.6354	312
187355	0.0313	14

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
jejunal mucosa	UBERON:0000399	99.53	gold quality
duodenum	UBERON:0002114	97.09	gold quality
thymus	UBERON:0002370	95.40	gold quality
granulocyte	CL:0000094	93.72	gold quality
body of stomach	UBERON:0001161	92.35	gold quality
oocyte	CL:0000023	91.05	gold quality
stomach	UBERON:0000945	89.51	gold quality
secondary oocyte	CL:0000655	89.44	gold quality
right atrium auricular region	UBERON:0006631	89.33	gold quality
apex of heart	UBERON:0002098	89.23	gold quality
mucosa of stomach	UBERON:0001199	88.30	gold quality
subcutaneous adipose tissue	UBERON:0002190	88.26	gold quality
cardiac atrium	UBERON:0002081	87.81	gold quality
vermiform appendix	UBERON:0001154	87.55	gold quality
lymph node	UBERON:0000029	87.16	gold quality
blood	UBERON:0000178	86.57	gold quality
leukocyte	CL:0000738	86.42	gold quality
fundus of stomach	UBERON:0001160	86.14	gold quality
monocyte	CL:0000576	86.13	gold quality
mononuclear cell	CL:0000842	86.11	gold quality
spleen	UBERON:0002106	86.11	gold quality
omental fat pad	UBERON:0010414	85.82	gold quality
adipose tissue of abdominal region	UBERON:0007808	85.72	gold quality
peritoneum	UBERON:0002358	85.70	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	85.60	gold quality
adipose tissue	UBERON:0001013	85.32	gold quality
parietal pleura	UBERON:0002400	85.15	gold quality
heart left ventricle	UBERON:0002084	84.79	gold quality
bone marrow	UBERON:0002371	84.74	gold quality
connective tissue	UBERON:0002384	84.57	gold quality

Single-cell (SCXA)

Detected in 11 experiment(s), a significant marker in 8.

Experiment	Marker?	Max mean expression
E-MTAB-9067	yes	1361.20
E-CURD-112	yes	628.32
E-MTAB-10432	yes	607.51
E-ANND-5	yes	600.43
E-MTAB-7249	yes	144.96
E-HCAD-4	yes	52.19
E-ANND-3	yes	10.39
E-MTAB-9801	yes	6.63
E-CURD-79	no	1608.65
E-MTAB-6379	no	1080.03
E-HCAD-6	no	622.87

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CDX1, ESR1, GATA4, ONECUT2, PDX1, RARA, RUNX1, SP1, TFAP2A, TFAP2C, TP53, TP63, TP73, YY1

miRNA regulators (miRDB)

14 targeting ADA, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-3064-3P	100.00	70.09	1254
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-4715-3P	99.98	66.03	670
HSA-MIR-30A-3P	99.87	69.74	2928
HSA-MIR-30D-3P	99.87	69.92	2917
HSA-MIR-30E-3P	99.87	69.68	2942
HSA-MIR-3663-3P	99.84	70.39	798
HSA-MIR-4495	99.82	72.08	3080
HSA-MIR-6815-3P	99.13	68.98	1530
HSA-MIR-4758-3P	99.12	63.96	869
HSA-MIR-10B-3P	99.04	66.98	988
HSA-MIR-6501-5P	97.41	68.24	712
HSA-MIR-6872-3P	97.08	66.99	750

Literature-anchored findings (GeneRIF, showing 40)

• Clustered charged amino acids of human adenosine deaminase comprise a functional epitope for binding the adenosine deaminase complexing protein CD26/dipeptidyl peptidase IV (PMID:11901152)
• Relationship between plasma malondialdehyde levels and adenosine deaminase activities in preeclampsia. (PMID:12104097)
• serum adenosine deaminase-2 (but not adenosine deaminase-1) and cytidine deaminase levels were significantly higher in systemic lupus erythematosus patients (PMID:12113294)
• In humans, ADA1 was mainly purified concomitant with ADA-binding protein and dipeptidyl peptidase IV, was not adsorbed in adenosine-Sepharose, but was adsorbed in IgG anti-ADA1-Sepharose column; properties compared with chicken ADA1 (PMID:12381379)
• The activity of this enzyme was studied in tissues, erythrocytes, and blood plasma of patients with peptic ulcer both in its uncomplicated course and in the development of complications. (PMID:12712614)
• The activity of ADA was determined in lymphocytes, esoinophils and blood serum in patients with bronchial asthma. (PMID:12774669)
• ADA was analyzed by linkage disequilibrium and no correlation was found between hot spots of equal and unequal homologous recombination. (PMID:12809673)
• Adenosine deaminase binding is diminished by mutation of ADA residues known to interact with CD26. (PMID:15016824)
• adenosine-related gene variants do not appear to alter susceptibility to the disease in this group of essential hypertensives (PMID:15257174)
• adenosine deaminase contributes to the clinical manifestations of type 2 diabetes and probably also have a marginal influence on susceptibility to the disease (PMID:15281007)
• The adenosine deaminase (ADA) gene was highly up-regulated in Ara-C-resistant cells, while equilibrative nucleoside transporter 1 (ENT1) and several cell-cycle-related genes were down-regulated. (PMID:15632314)
• ADA colocalizing with adenosine receptors on dendritic cells interact with CD26 expressed on lymphocytes. (PMID:15983379)
• Adenosine deaminase activity was abnormal in active nephrotic syndrome, and lymphocyte ADA demonstrated change both in active as well as remission stage of the disease. (PMID:16133068)
• We tested whether p63 is implicated in transcriptional events related to sustaining cell proliferation by transactivation of antiapoptotic and cell survival target genes such as Adenosine Deaminase (ADA), an important gene involved in cell proliferation. (PMID:16410722)
• During acute hypoxia associated with vascular leakage and excessive inflammation, ADA inhibition may serve as therapeutic strategy. (PMID:16670267)
• Findings suggest a possible role for a low-activity genotype of adenosine deaminase in the pathogenesis of mild mental retardation. No significant differences were found when comparing the group with moderate or severe mental retardation and controls. (PMID:16970880)
• the ADA c7C/T mutation was estimated to be approximately 7,100 years old (PMID:17181544)
• Increased adenosine deaminase is associated with hydatidiform mole (PMID:17243920)
• ADA*2 allele may decrease genetic susceptibility to coronary artery disease. (PMID:17287605)
• G22A polymorphism plays a minimal role in susceptibility to autism in North American families (PMID:17340203)
• The measurement of adenosine deaminase activity in ascites represents a diagnostic advance in tuberculous peritonitis among end-stage renal failure patients. (PMID:17397971)
• the transition-state structures of PfADA, HsADA, and bovine ADA (BtADA) solved using competitive kinetic isotope effects (KIE) and density functional calculations (PMID:17536804)
• This study shows that adenosine elimination on human airway epithelia is mediated by ADA1, CNT2, and CNT3, which constitute important regulators of adenosine-mediated inflammation. (PMID:17696452)
• CD4(+) T cells from ADA-severe combined immunodeficiency patients have severely compromised T cell receptor/CD28-driven proliferation and cytokine production, both at the transcriptional and protein levels. (PMID:18218852)
• Results describe the activities of ectonucleotide pyrophosphatase/phosphodiesterase and adenosine deaminase in patients with uterine cervix neoplasia. (PMID:18222177)
• the primary mechanism in men with ischemic stroke might involve the reduction of ADA1 activity (PMID:18302529)
• Suggest that adenosine deaminase can be used to distinguish between tuberculous and malignant pleural effusions. (PMID:18357489)
• Negative association between coronary artery disease and ADA*2 allele is only present in males (PMID:18560234)
• the increased level of ADA activity in the subararachnoid hemorrhage patients with the poor clinical and consciousness level may have resulted from the ischemic cerebral insult (PMID:18597230)
• Elevated serum adenosine deaminase in patients with hyperemesis gravidarum may relate to high levels of E2 and progesterone. (PMID:18673094)
• Human ADA, apart from reducing the adenosine concentration and thus preventing A(1)R desensitization, binds to A(1)R behaving as an allosteric effector that markedly enhances agonist affinity and increases receptor functionality. (PMID:18680557)
• Zygotes with low adenosine deaminase locus 1 activity and low F activity may experience the most favourable intrauterine conditions for a balanced development of the feto-placental unit. (PMID:18768081)
• heterozygosity for the 22G>A variant of ADA, although reducing catalytic activity, does not enhance forearm reactive hyperaemia (PMID:18794722)
• Findings suggest that adenosine deaminase might play a crucial role in the development of aspirin-intolerant-asthma by mediation of A1 and A2A receptors. (PMID:19019667)
• Results hypothesized that altered ADA activity may be associated with altered immunity. (PMID:19026999)
• Serum adenosine deaminase activity was significantly higher in eclamptic pregnant women when compared with healthy pregnant women and non-pregnant women. (PMID:19172437)
• ADA may have a role in the cytokine network of the inflammatory cascade of familial Mediterranean fever; elevated ADA levels may be a part of the activated Th1 response in the disease (PMID:19237091)
• serum catalytic concentration elevated in pregnancy, no difference between gestational diabetes and normal pregnancy (PMID:19521708)
• Decreased paraoxonase activity as well as increased adenosine deaminase and xanthine oxidase activities and nitrite levels indicate that oxidative stress is increased and purine metabolism is altered in pseudoexfoliation syndrome. (PMID:19628957)
• ADA-deficient SCID is associated with a specific microenvironment and bone phenotype characterized by RANKL/OPG imbalance and osteoblast insufficiency. (PMID:19633200)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	ada	ENSDARG00000003113
mus_musculus	Ada	ENSMUSG00000017697
rattus_norvegicus	Ada	ENSRNOG00000010265
caenorhabditis_elegans		WBGENE00015551

Paralogs (2): ADA2 (ENSG00000093072), MAPDA (ENSG00000168803)

Protein

Protein identifiers

Adenosine deaminase — P00813 (reviewed: P00813)

Alternative names: Adenosine aminohydrolase

All UniProt accessions (37): A0A0S2Z381, A0A0S2Z3B9, A0A0S2Z3T6, A0A8Q3SI46, A0A8Q3SI64, A0A8Q3SI69, A0A8Q3SIA9, A0A8Q3SIC0, A0A8Q3SIC7, A0A8Q3SIE4, A0A8Q3SIG8, A0A8Q3SIH0, A0A8Q3SJ25, A0A8Q3SJ50, A0A8Q3SJ57, A0A8Q3SJ63, A0A8Q3WKW4, A0A8Q3WKX5, A0A8Q3WKX8, A0A8Q3WKY2, A0A8Q3WKZ1, A0A8Q3WKZ4, A0A8Q3WKZ5, P00813, A0A8Q3WKZ6, A0A8Q3WKZ9, A0A8Q3WL01, A0A8Q3WL06, A0A8Q3WL32, A0A8Q3WLJ0, A0A8Q3WLK2, A0A8Q3WM09, A0A8Q3WM58, A0A8Q3WM84, F5GWI4, F5GXW0, F5GYD4

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the hydrolytic deamination of adenosine and 2-deoxyadenosine. Plays an important role in purine metabolism and in adenosine homeostasis. Modulates signaling by extracellular adenosine, and so contributes indirectly to cellular signaling events. Acts as a positive regulator of T-cell coactivation, by binding DPP4. Its interaction with DPP4 regulates lymphocyte-epithelial cell adhesion. Enhances dendritic cell immunogenicity by affecting dendritic cell costimulatory molecule expression and cytokines and chemokines secretion. Enhances CD4+ T-cell differentiation and proliferation. Acts as a positive modulator of adenosine receptors ADORA1 and ADORA2A, by enhancing their ligand affinity via conformational change. Stimulates plasminogen activation. Plays a role in male fertility. Plays a protective role in early postimplantation embryonic development. Also responsible for the deamination of cordycepin (3’-deoxyadenosine), a fungal natural product that shows antitumor, antibacterial, antifungal, antivirus, and immune regulation properties.

Subunit / interactions. Interacts with DPP4 (via extracellular domain). Interacts with PLG (via Kringle 4 domain); the interaction stimulates PLG activation when in complex with DPP4.

Subcellular location. Cell membrane. Cell junction. Cytoplasmic vesicle lumen. Cytoplasm. Lysosome.

Tissue specificity. Found in all tissues, occurs in large amounts in T-lymphocytes. Expressed at the time of weaning in gastrointestinal tissues.

Disease relevance. Severe combined immunodeficiency autosomal recessive T-cell-negative/B-cell-negative/NK-cell-negative due to adenosine deaminase deficiency (ADASCID) [MIM:102700] An autosomal recessive disorder accounting for about 50% of non-X-linked SCIDs. SCID refers to a genetically and clinically heterogeneous group of rare congenital disorders characterized by impairment of both humoral and cell-mediated immunity, leukopenia, and low or absent antibody levels. Patients with SCID present in infancy with recurrent, persistent infections by opportunistic organisms. The common characteristic of all types of SCID is absence of T-cell-mediated cellular immunity due to a defect in T-cell development. ADA deficiency has been diagnosed in chronically ill teenagers and adults (late or adult onset). Population and newborn screening programs have also identified several healthy individuals with normal immunity who have partial ADA deficiency. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Inhibited by Cu(2+) and Hg(2+), coformycin, deoxycoformycin (dCF), 2-deoxyadenosine, 6-methylaminopurine riboside, 2-3-iso-propylidene-adenosine, pentostatin, naringin and erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA).

Cofactor. Binds 1 zinc ion per subunit.

Induction. Up-regulated by hypoxia.

Polymorphism. There is a common allele, ADA*2, also known as the ADA 2 allozyme. It is associated with the reduced metabolism of adenosine to inosine. It specifically enhances deep sleep and slow-wave activity (SWA) during sleep.

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

RefSeq proteins (3): NP_000013, NP_001308979, NP_001308980 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001365	A_deaminase_dom	Domain
IPR006330	Ado/ade_deaminase	Family
IPR006650	A/AMP_deam_AS	Active_site
IPR028893	A_deaminase	Family
IPR032466	Metal_Hydrolase	Homologous_superfamily

Pfam: PF00962

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), 3 shown:

• adenosine + H2O + H(+) = inosine + NH4(+) (RHEA:24408)
• 2’-deoxyadenosine + H2O + H(+) = 2’-deoxyinosine + NH4(+) (RHEA:28190)
• cordycepin + H2O + H(+) = 3’-deoxyinosine + NH4(+) (RHEA:79047)

UniProt features (106 total): sequence variant 35, helix 24, mutagenesis site 15, strand 11, binding site 8, site 3, modified residue 3, turn 2, initiator methionine 1, chain 1, region of interest 1, active site 1, sequence conflict 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
3IAR	X-RAY DIFFRACTION	1.52
7RTG	X-RAY DIFFRACTION	2.59

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P00813-F1	96.81	0.97

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 (4): 58 (important for interaction with adenosine receptors and increasing their affinity for agonists); 62 (important for interaction with adenosine receptors and increasing their affinity for agonists); 238 (important for catalytic activity); 217 (proton donor)

Ligand- & substrate-binding residues (8): 295; 296; 15; 17; 17; 19; 184; 214

Post-translational modifications (3): 2, 54, 232

Mutagenesis-validated functional residues (15):

Position	Phenotype
58	decreases enzyme activity by reducing substrate affinity and maximum velocity; abolishes adora1 and adora2a modulator fu
60	moderately reduces enzyme activity; reduces adora1 and adora2a modulation.
61	decreases enzyme activity by reducing maximum velocity; reduces adora1 modulation.
62	decreases enzyme activity by reducing substrate affinity and maximum velocity; abolishes adora1 and adora2a modulator fu
64	moderately reduces enzyme activity; no change in adora1 and adora2a modulation.
65	decreases enzyme activity by reducing substrate affinity and maximum velocity; reduces adora1 and adora2a modulation.
66	no change in enzyme activity; no change in adora1 and adora2a modulation.
69	decreases enzyme activity by reducing maximum velocity; reduces adora2a modulation.
115	no change in enzyme activity; no change in adora1 and adora2a modulation.
118	moderately reduces enzyme activity; no change in adora1 and adora2a modulation.
155	decreases enzyme activity by reducing substrate affinity and maximum velocity.
157	moderately reduces enzyme activity; no change in adora1 and adora2a modulation.
184	moderately reduces enzyme activity.
185	moderately reduces enzyme activity.
194	no change in enzyme activity.

Function

Pathways and Gene Ontology

Reactome pathways

11 pathways

ID	Pathway
R-HSA-74217	Purine salvage
R-HSA-9734735	Defective ADA disrupts (deoxy)adenosine deamination
R-HSA-9755088	Ribavirin ADME
R-HSA-1430728	Metabolism
R-HSA-15869	Metabolism of nucleotides
R-HSA-1643685	Disease
R-HSA-5668914	Diseases of metabolism
R-HSA-8956321	Nucleotide salvage
R-HSA-9734207	Nucleotide salvage defects
R-HSA-9735804	Diseases of nucleotide metabolism
R-HSA-9748784	Drug ADME

MSigDB gene sets: 780 (showing top): GOBP_CIRCADIAN_RHYTHM, GOBP_REGULATION_OF_T_CELL_RECEPTOR_SIGNALING_PATHWAY, GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_REGULATION_OF_ANTIGEN_RECEPTOR_MEDIATED_SIGNALING_PATHWAY, GOBP_NEGATIVE_REGULATION_OF_REPRODUCTIVE_PROCESS, GOBP_G_PROTEIN_COUPLED_PURINERGIC_RECEPTOR_SIGNALING_PATHWAY, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_REGULATION_OF_LEUKOCYTE_PROLIFERATION, GOBP_HEPATICOBILIARY_SYSTEM_DEVELOPMENT, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_POSITIVE_REGULATION_OF_ADAPTIVE_IMMUNE_RESPONSE, GOBP_B_CELL_HOMEOSTASIS, GOBP_BEHAVIOR, GOBP_REGULATION_OF_CALCIUM_MEDIATED_SIGNALING, GOBP_REGULATION_OF_ALPHA_BETA_T_CELL_ACTIVATION

GO Biological Process (67): allantoin metabolic process (GO:0000255), response to hypoxia (GO:0001666), trophectodermal cell differentiation (GO:0001829), liver development (GO:0001889), placenta development (GO:0001890), germinal center B cell differentiation (GO:0002314), germinal center formation (GO:0002467), positive regulation of germinal center formation (GO:0002636), negative regulation of leukocyte migration (GO:0002686), mature B cell apoptotic process (GO:0002901), negative regulation of mature B cell apoptotic process (GO:0002906), adenosine catabolic process (GO:0006154), deoxyadenosine catabolic process (GO:0006157), AMP catabolic process (GO:0006196), xenobiotic metabolic process (GO:0006805), smooth muscle contraction (GO:0006939), cell adhesion (GO:0007155), positive regulation of heart rate (GO:0010460), response to purine-containing compound (GO:0014074), calcium-mediated signaling (GO:0019722), positive regulation of B cell proliferation (GO:0030890), purine nucleotide salvage (GO:0032261), GMP salvage (GO:0032263), T cell differentiation in thymus (GO:0033077), positive regulation of T cell differentiation in thymus (GO:0033089), regulation of cell-cell adhesion mediated by integrin (GO:0033632), B cell proliferation (GO:0042100), T cell activation (GO:0042110), penile erection (GO:0043084), purine-containing compound salvage (GO:0043101), hypoxanthine salvage (GO:0043103), obsolete amide catabolic process (GO:0043605), AMP salvage (GO:0044209), regulation of circadian sleep/wake cycle, sleep (GO:0045187), positive regulation of smooth muscle contraction (GO:0045987), dAMP catabolic process (GO:0046059), dATP catabolic process (GO:0046061), adenosine metabolic process (GO:0046085), inosine biosynthetic process (GO:0046103), xanthine biosynthetic process (GO:0046111)

GO Molecular Function (7): adenosine deaminase activity (GO:0004000), zinc ion binding (GO:0008270), deaminase activity (GO:0019239), 2’-deoxyadenosine deaminase activity (GO:0046936), protein binding (GO:0005515), hydrolase activity (GO:0016787), metal ion binding (GO:0046872)

GO Cellular Component (10): lysosome (GO:0005764), cytosol (GO:0005829), plasma membrane (GO:0005886), external side of plasma membrane (GO:0009897), cell surface (GO:0009986), membrane (GO:0016020), cytoplasmic vesicle lumen (GO:0060205), anchoring junction (GO:0070161), cytoplasm (GO:0005737), cytoplasmic vesicle (GO:0031410)

Reactome top-level categories

Rollup of top-8 pathways:

Category	Pathways
Nucleotide salvage	1
Nucleotide salvage defects	1
Drug ADME	1
Metabolism	1
Disease	1
Metabolism of nucleotides	1
Diseases of nucleotide metabolism	1
Diseases of metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
metabolic process	2
hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in cyclic amidines	2
deaminase activity	2
cytoplasm	2
response to stress	1
response to decreased oxygen levels	1
blastocyst formation	1
cell differentiation	1
gland development	1
hepaticobiliary system development	1
animal organ development	1
mature B cell differentiation involved in immune response	1
adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains	1
anatomical structure formation involved in morphogenesis	1
germinal center formation	1
regulation of germinal center formation	1
positive regulation of adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains	1
positive regulation of developmental process	1
negative regulation of immune system process	1
regulation of leukocyte migration	1
negative regulation of cell migration	1
leukocyte migration	1
B cell homeostasis	1
B cell apoptotic process	1
mature B cell apoptotic process	1
negative regulation of B cell apoptotic process	1
regulation of mature B cell apoptotic process	1
adenosine metabolic process	1
purine ribonucleoside catabolic process	1
deoxyadenosine metabolic process	1
2’-deoxyribonucleoside catabolic process	1
purine deoxyribonucleoside catabolic process	1
purine ribonucleotide catabolic process	1
purine ribonucleoside monophosphate catabolic process	1
AMP metabolic process	1
cellular response to xenobiotic stimulus	1
muscle contraction	1
cellular process	1
regulation of heart rate	1

Protein interactions and networks

STRING

3124 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ADA	DPP4	P27487	997
ADA	PNP	P00491	980
ADA	ADAR	P55265	952
ADA	ADA2	Q9NZK5	923
ADA	AMPD3	Q01432	910
ADA	AMPD2	Q01433	901
ADA	AMPD1	P23109	894
ADA	ADARB2	Q9NS39	887
ADA	ADK	P55263	875
ADA	ADORA2A	P29274	864
ADA	FAP	Q12884	849
ADA	ADARB1	P78555	833
ADA	AHCY	P23526	806
ADA	ADORA1	P30542	792
ADA	ITPA	Q9BY32	777

IntAct

13 interactions, top by confidence:

A	B	Type	Score
ADA	POTEF	psi-mi:“MI:0914”(association)	0.560
ADA	POTEF	psi-mi:“MI:0915”(physical association)	0.560
	AGPS	psi-mi:“MI:0915”(physical association)	0.400
	TK2	psi-mi:“MI:0915”(physical association)	0.400
TERF2IP	ADA	psi-mi:“MI:0915”(physical association)	0.370
ADA	TINF2	psi-mi:“MI:0915”(physical association)	0.370
SGCD	ADA	psi-mi:“MI:0915”(physical association)	0.370
ADA	PIAS2	psi-mi:“MI:0915”(physical association)	0.370
PLEKHA7	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
CER1	ADA	psi-mi:“MI:0914”(association)	0.350
MPI	ADA	psi-mi:“MI:0914”(association)	0.350

BioGRID (50): POTEF (Affinity Capture-MS), ACTB (Affinity Capture-MS), ADA (Affinity Capture-MS), ACP1 (Co-fractionation), APRT (Co-fractionation), ATXN2 (Co-fractionation), ATXN2L (Co-fractionation), SERPINB5 (Co-fractionation), ADA (Affinity Capture-MS), ADA (Affinity Capture-Western), ADA (Affinity Capture-Western), ADA (Affinity Capture-MS), CHEK1 (Negative Genetic), PTEN (Positive Genetic), POTEF (Affinity Capture-MS)

ESM2 similar proteins: A1A4M4, A4JPX7, A6TAC4, A7ZI99, A7ZWZ9, B1J0S7, B1LIN7, B2JQW0, B5XQJ4, B5Z2Q7, B6HZX8, B7L508, B7M300, B7MPB9, B7N8Q9, B7NK03, C1DF10, C1DRJ0, O95620, P00813, P03958, P51020, P56658, Q05AV0, Q0VC13, Q13QH6, Q13VU3, Q17R31, Q32M08, Q3U1C6, Q3Z554, Q46NW8, Q47B13, Q4V831, Q4V9P6, Q503T5, Q56Y42, Q5ZKP6, Q63ZU0, Q640V9

Diamond homologs: A0L2R5, A0PNJ1, A1ABG8, A1JML4, A1RDZ6, A1S1P1, A1T5H1, A3CYL9, A3QJD9, A4W9X4, A4YCD7, A5F4Q2, A5I0I2, A5N6F5, A6T9W8, A6WUH7, A7FHX5, A7FSN7, A7GC28, A7ZM83, A8A0G5, A8GE12, A9KWZ3, B0TT81, B1IHX4, B1IQD2, B1JKL9, B1KY93, B1LER3, B1XF88, B2HDU8, B2K4L5, B2U2C1, B2VK11, B4EVZ1, B4T5A0, B4THP5, B4TVC7, B5F6I4, B5FFC4

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
Pentostatin	“down-regulates activity”	ADA	“chemical inhibition”
Adechlorin	“down-regulates activity”	ADA	“chemical inhibition”
ADA	“up-regulates activity”	ADORA1	binding
ADA	“down-regulates quantity”	adenosine	“chemical modification”
ADA	“up-regulates quantity”	inosine	“chemical modification”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	69
Likely pathogenic	79
Uncertain significance	183
Likely benign	352
Benign	28

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1068992	NC_000020.10:g.(?43264848)(43264949_?)del	Pathogenic
1068993	NC_000020.10:g.(?43252823)(43255260_?)del	Pathogenic
1069449	NM_000022.4(ADA):c.421G>T (p.Glu141Ter)	Pathogenic
1070322	NM_000022.4(ADA):c.33+1G>A	Pathogenic
1339532	NM_000022.4(ADA):c.870C>A (p.Tyr290Ter)	Pathogenic
1346719	NM_000022.4(ADA):c.845+2T>C	Pathogenic
1370617	NM_000022.4(ADA):c.34-11_55del	Pathogenic
1396468	NM_000022.4(ADA):c.306C>G (p.Tyr102Ter)	Pathogenic
1437148	NM_000022.4(ADA):c.337G>T (p.Glu113Ter)	Pathogenic
1451616	NM_000022.4(ADA):c.1024G>T (p.Glu342Ter)	Pathogenic
1456866	NC_000020.10:g.(?43248475)(43280248_?)del	Pathogenic
1459560	NC_000020.10:g.(?43251625)(43255215_?)del	Pathogenic
193544	NM_000022.4(ADA):c.956_960del (p.Glu319fs)	Pathogenic
1956	NM_000022.4(ADA):c.302G>A (p.Arg101Gln)	Pathogenic
1957	NM_000022.4(ADA):c.632G>A (p.Arg211His)	Pathogenic
1959	NM_000022.4(ADA):c.986C>T (p.Ala329Val)	Pathogenic
1960	NC_000020.11:g.44649961_44653216del	Pathogenic
1968	NM_000022.4(ADA):c.646G>A (p.Gly216Arg)	Pathogenic
1969294	NM_000022.4(ADA):c.1009G>T (p.Glu337Ter)	Pathogenic
1970	NM_000022.4(ADA):c.466C>T (p.Arg156Cys)	Pathogenic
1975	NM_000022.4(ADA):c.781-3_781delinsTGGAAGAGCAGATCTGG	Pathogenic
1976	NM_000022.4(ADA):c.33+1G>C	Pathogenic
2034899	NM_000022.4(ADA):c.307del (p.Ser103fs)	Pathogenic
2130916	NM_000022.4(ADA):c.976-2A>G	Pathogenic
2138345	NM_000022.4(ADA):c.976-1G>C	Pathogenic
2161844	NM_000022.4(ADA):c.1019del (p.Lys340fs)	Pathogenic
2416243	NM_000022.4(ADA):c.394del (p.Ala131_Leu132insTer)	Pathogenic
265025	NM_000022.4(ADA):c.478+1G>A	Pathogenic
2680692	NM_000022.4(ADA):c.760C>T (p.Gln254Ter)	Pathogenic
2680706	NM_000022.4(ADA):c.482G>A (p.Trp161Ter)	Pathogenic

SpliceAI

2912 predictions. Top by Δscore:

Variant	Effect	Δscore
20:44589786:T:TA	acceptor_gain	1.0000
20:44589795:A:AG	acceptor_gain	1.0000
20:44589796:G:GG	acceptor_gain	1.0000
20:44589796:GA:G	acceptor_gain	1.0000
20:44614528:CCACA:C	acceptor_loss	1.0000
20:44614529:CACAG:C	acceptor_loss	1.0000
20:44614532:A:AG	acceptor_gain	1.0000
20:44614533:G:GG	acceptor_gain	1.0000
20:44614533:G:T	acceptor_loss	1.0000
20:44614533:GGC:G	acceptor_gain	1.0000
20:44614533:GGCCT:G	acceptor_gain	1.0000
20:44614638:G:GT	donor_gain	1.0000
20:44614649:GGCT:G	donor_gain	1.0000
20:44614650:GCTG:G	donor_gain	1.0000
20:44614657:GC:G	donor_gain	1.0000
20:44614664:G:GT	donor_gain	1.0000
20:44620412:C:CT	acceptor_gain	1.0000
20:44620427:CA:C	acceptor_gain	1.0000
20:44620428:A:AC	acceptor_gain	1.0000
20:44620428:A:C	acceptor_gain	1.0000
20:44620435:C:CT	acceptor_gain	1.0000
20:44620436:A:T	acceptor_gain	1.0000
20:44621014:TCA:T	donor_loss	1.0000
20:44621015:CA:C	donor_loss	1.0000
20:44621016:A:AC	donor_gain	1.0000
20:44621016:ACC:A	donor_loss	1.0000
20:44621016:ACCAG:A	donor_gain	1.0000
20:44621017:C:CC	donor_gain	1.0000
20:44621017:CCAG:C	donor_gain	1.0000
20:44621017:CCAGC:C	donor_gain	1.0000

AlphaMissense

2382 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:44621109:T:A	D295V	0.999
20:44621108:A:C	D295E	0.998
20:44621108:A:T	D295E	0.998
20:44621110:C:G	D295H	0.998
20:44622647:G:C	C262W	0.998
20:44621109:T:G	D295A	0.996
20:44621110:C:A	D295Y	0.996
20:44621114:G:C	N293K	0.996
20:44621114:G:T	N293K	0.996
20:44622635:G:C	S266R	0.996
20:44622635:G:T	S266R	0.996
20:44622637:T:G	S266R	0.996
20:44629070:A:C	F65L	0.996
20:44629070:A:T	F65L	0.996
20:44629072:A:G	F65L	0.996
20:44620392:C:G	A329P	0.995
20:44621109:T:C	D295G	0.995
20:44622895:G:C	H238Q	0.995
20:44622895:G:T	H238Q	0.995
20:44636273:G:C	H17D	0.995
20:44620388:G:T	A330D	0.994
20:44621105:G:C	D296E	0.994
20:44621105:G:T	D296E	0.994
20:44622648:C:T	C262Y	0.994
20:44636279:G:C	H15D	0.994
20:44621122:A:G	S291P	0.993
20:44622649:A:G	C262R	0.993
20:44622897:G:C	H238D	0.993
20:44623045:G:C	H214D	0.993
20:44626509:A:C	S103R	0.993

dbSNP variants (sampled 300 via entrez): RS1000084522 (20:44646633 G>A), RS1000158775 (20:44640238 A>C), RS1000232997 (20:44641268 G>A), RS1000455538 (20:44629463 C>G), RS1000477794 (20:44646342 G>A), RS1000521374 (20:44642460 C>T), RS1000634827 (20:44636622 G>A), RS1000694875 (20:44635294 G>A), RS1000735560 (20:44645808 C>T), RS1000844707 (20:44631448 G>A), RS1000953688 (20:44622733 CCCT>C), RS1001005035 (20:44619093 T>C), RS1001098479 (20:44619486 G>A,C), RS1001148971 (20:44652700 G>A), RS1001399284 (20:44624768 T>A,C)

Disease associations

OMIM: gene MIM:608958 | disease phenotypes: MIM:102700, MIM:601457

GenCC curated gene-disease

Disease	Classification	Inheritance
severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-negative, due to adenosine deaminase deficiency	Definitive	Autosomal recessive
Omenn syndrome	Supportive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-negative, due to adenosine deaminase deficiency	Definitive	AR

Mondo (4): severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-negative, due to adenosine deaminase deficiency (MONDO:0007064), severe combined immunodeficiency (MONDO:0015974), severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-positive (MONDO:0011086), Omenn syndrome (MONDO:0011338)

Orphanet (3): Severe combined immunodeficiency due to adenosine deaminase deficiency (Orphanet:277), Severe combined immunodeficiency (Orphanet:183660), Severe combined immunodeficiency due to complete RAG1/2 deficiency (Orphanet:331206)

HPO phenotypes

74 total (30 of 74 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000100	Nephrotic syndrome
HP:0000246	Sinusitis
HP:0000403	Recurrent otitis media
HP:0000821	Hypothyroidism
HP:0000907	Anterior rib cupping
HP:0000926	Platyspondyly
HP:0000944	Abnormal metaphysis morphology
HP:0000958	Dry skin
HP:0000969	Edema
HP:0000988	Skin rash
HP:0000989	Pruritus
HP:0001019	Erythroderma
HP:0001072	Thickened skin
HP:0001270	Motor delay
HP:0001442	Typified by somatic mosaicism
HP:0001508	Failure to thrive
HP:0001596	Alopecia
HP:0001744	Splenomegaly
HP:0001831	Short toe
HP:0001880	Increased total eosinophil count
HP:0001888	Decreased total lymphocyte count
HP:0001890	Autoimmune hemolytic anemia
HP:0001903	Anemia
HP:0001945	Fever
HP:0001954	Recurrent fever
HP:0001967	Diffuse mesangial sclerosis
HP:0001973	Autoimmune thrombocytopenia
HP:0001974	Increased total leukocyte count
HP:0002014	Diarrhea

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST001728_19	Ulcerative colitis	1.000000e-43
GCST004131_41	Inflammatory bowel disease	1.000000e-17
GCST004133_4	Ulcerative colitis	4.000000e-30
GCST012020_507	Serum metabolite levels	4.000000e-26
GCST012020_527	Serum metabolite levels	2.000000e-24
GCST012021_68	Serum metabolite levels	2.000000e-24

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D016511	Severe Combined Immunodeficiency	C16.320.798.750; C16.614.815; C18.452.284.800; C20.673.795.750
C563311	Severe Combined Immunodeficiency, Autosomal Recessive, T Cell-Negative, B Cell-Negative, NK Cell-Positive (supp.)
C531816	Severe combined immunodeficiency due to adenosine deaminase deficiency (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1910 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

3 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 105,043 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1580	PENTOSTATIN	4	103,826
CHEMBL441738	AFAMELANOTIDE	4	602
CHEMBL284483	COFORMYCIN	2	615

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

PharmGKB variants

5 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs244076	ADA		0.00	0
rs73598374	ADA		0.00	0
rs2057638	ADA		0.00	0
rs6017375	ADA		0.00	0
rs371927	ADA		0.00	0

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — Adenosine turnover

Most potent curated ligand interactions (2 total), top 2:

Ligand	Action	Affinity	Parameter
pentostatin	Inhibition	10.8	pIC50
EHNA	Inhibition	8.8	pKi

Binding affinities (BindingDB)

31 measured of 34 human assays (34 total across all organisms); most potent 31 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
Covidarabine	KI	0.033 nM
1-[(2R)-4-{5-[3-(4-chlorophenyl)propoxy]-1-methyl-1H-indol-3-yl}-1-hydroxybutan-2-yl]-1H-imidazole-4-carboxamide	KI	4.9 nM
1-[(2R)-4-{6-[(benzylcarbamoyl)amino]-1H-indol-1-yl}-1-hydroxybutan-2-yl]-1H-imidazole-4-carboxamide	KI	7.5 nM
1-[(2R)-1-hydroxy-4-{6-[3-(1-methyl-1H-1,3-benzodiazol-2-yl)propanamido]-1H-indol-1-yl}butan-2-yl]-1H-imidazole-4-carboxamide	KI	7.7 nM
1-[(3R,4S)-4-hydroxy-1-(naphthalen-2-yloxy)pentan-3-yl]-1H-imidazole-4-carboxamide	KI	9.8 nM
1-[(2R)-1-hydroxy-4-[6-(5-phenylpentanamido)-1H-indol-1-yl]butan-2-yl]-1H-imidazole-4-carboxamide	KI	11 nM
1-[(3R,4S)-4-hydroxy-1-(naphthalen-1-yl)pentan-3-yl]-1H-imidazole-4-carboxamide	KI	11 nM
1-[(2R)-1-hydroxy-4-[6-(4-phenylbutoxy)-1H-indol-1-yl]butan-2-yl]-1H-imidazole-4-carboxamide	KI	12 nM
1-[(2R)-4-{6-[3-(4-chlorophenyl)propoxy]-1H-indol-1-yl}-1-hydroxybutan-2-yl]-1H-imidazole-4-carboxamide	KI	13 nM
1-[(2R)-4-[5-(hexyloxy)-1-methyl-1H-indol-3-yl]-1-hydroxybutan-2-yl]-1H-imidazole-4-carboxamide	KI	13 nM
1-[(3R,4S)-1-(2,3-dichlorophenyl)-4-hydroxypentan-3-yl]-1H-imidazole-4-carboxamide	KI	13 nM
1-[(2R)-1-hydroxy-4-[6-(4-phenylbutanamido)-1H-indol-1-yl]butan-2-yl]-1H-imidazole-4-carboxamide	KI	16 nM
1-[(2R)-1-hydroxy-4-{6-[3-(pyridin-3-yl)propanamido]-1H-indol-1-yl}butan-2-yl]-1H-imidazole-4-carboxamide	KI	17 nM
1-[(2R)-1-hydroxy-4-[6-(3-phenylpropoxy)-1H-indol-1-yl]butan-2-yl]-1H-imidazole-4-carboxamide	KI	17 nM
1-[(2R)-4-(6-hexanamido-1H-indol-1-yl)-1-hydroxybutan-2-yl]-1H-imidazole-4-carboxamide	KI	24 nM
1-[(2R)-1-hydroxy-4-[1-methyl-5-(3-phenylpropoxy)-1H-indol-3-yl]butan-2-yl]-1H-imidazole-4-carboxamide	KI	26 nM
1-[(2R)-1-hydroxy-4-[6-(3-phenylpropanamido)-1H-indol-1-yl]butan-2-yl]-1H-imidazole-4-carboxamide	KI	30 nM
1-[(2R)-1-hydroxy-4-{6-[4-(4-methylphenyl)butanamido]-1H-indol-1-yl}butan-2-yl]-1H-imidazole-4-carboxamide	KI	34 nM
3-(6-amino-9H-purin-9-yl)nonan-2-ol	KI	37 nM
1-[(2R)-1-hydroxy-4-{6-[3-(4-methylphenyl)propanamido]-1H-indol-1-yl}butan-2-yl]-1H-imidazole-4-carboxamide	KI	38 nM
1-[(2R)-4-[6-(hexyloxy)-1H-indol-1-yl]-1-hydroxybutan-2-yl]-1H-imidazole-4-carboxamide	KI	55 nM
1-[(2R)-1-hydroxy-4-{6-[3-(4-methoxyphenyl)propanamido]-1H-indol-1-yl}butan-2-yl]-1H-imidazole-4-carboxamide	KI	57 nM
1-[(2R)-1-hydroxy-4-[6-(6-phenylhexanamido)-1H-indol-1-yl]butan-2-yl]-1H-imidazole-4-carboxamide	KI	91 nM
1-[(2R)-4-(6-butoxy-1H-indol-1-yl)-1-hydroxybutan-2-yl]-1H-imidazole-4-carboxamide	KI	240 nM
imidazole-4-carboxamide derivative, 3	KI	680 nM
2-(4-{5-[(1H-1,3-benzodiazol-2-ylamino)methyl]thiophen-2-yl}-1,3-thiazol-2-yl)guanidine	KI	1200 nM
1-[(2R)-4-(6-acetamido-1H-indol-1-yl)-1-hydroxybutan-2-yl]-1H-imidazole-4-carboxamide	KI	1300 nM
1-[(2R)-1-hydroxy-4-[5-(3-phenylpropoxy)-1H-indol-1-yl]butan-2-yl]-1H-imidazole-4-carboxamide	KI	1900 nM
1-(1-hydroxy-4-phenylbutan-2-yl)-1H-imidazole-4-carboxamide	KI	5900 nM
1-[(2R)-4-[5-(hexyloxy)-1H-indol-1-yl]-1-hydroxybutan-2-yl]-1H-imidazole-4-carboxamide	KI	6200 nM
1-(2-hydroxy-1-phenylethyl)-1H-imidazole-4-carboxamide	KI	54000 nM

ChEMBL bioactivities

255 potent at pChembl≥5 of 258 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
11.00	Ki	0.01	nM	COFORMYCIN
11.00	Ki	0.01	nM	CONFORMYCIN
11.00	Ki	0.01	nM	CHEMBL1651377
10.59	Ki	0.026	nM	PENTOSTATIN
10.48	Ki	0.033	nM	PENTOSTATIN
10.28	Ki	0.053	nM	CHEMBL1651379
10.00	Ki	0.1	nM	PENTOSTATIN
10.00	Ki	0.1	nM	COFORMYCIN
9.96	Ki	0.11	nM	COFORMYCIN
9.40	Ki	0.4	nM	EHNA
9.40	IC50	0.4	nM	CHEMBL5864154
9.30	Ki	0.5	nM	PENTOSTATIN
9.30	IC50	0.5	nM	CHEMBL5818178
9.22	IC50	0.6	nM	CHEMBL6005828
9.22	IC50	0.6	nM	CHEMBL5755688
9.15	IC50	0.7	nM	CHEMBL5813207
9.15	IC50	0.7	nM	CHEMBL6000417
9.05	IC50	0.9	nM	CHEMBL6063238
9.05	IC50	0.9	nM	CHEMBL6059148
9.05	IC50	0.9	nM	CHEMBL5868228
9.00	Ki	1	nM	(+)-EHNA
9.00	IC50	1	nM	CHEMBL5911082
9.00	IC50	1	nM	CHEMBL5805964
8.96	IC50	1.1	nM	CHEMBL5879972
8.92	IC50	1.2	nM	CHEMBL5785869
8.92	IC50	1.2	nM	CHEMBL5884259
8.89	IC50	1.3	nM	CHEMBL6004227
8.89	IC50	1.3	nM	CHEMBL5983193
8.85	IC50	1.4	nM	CHEMBL5956235
8.85	IC50	1.4	nM	CHEMBL5780320
8.82	IC50	1.5	nM	CHEMBL5783482
8.82	IC50	1.5	nM	CHEMBL5972430
8.80	IC50	1.6	nM	CHEMBL5759921
8.80	IC50	1.6	nM	CHEMBL5997347
8.77	IC50	1.7	nM	CHEMBL5809185
8.77	IC50	1.7	nM	CHEMBL5895135
8.74	IC50	1.8	nM	CHEMBL5998906
8.72	IC50	1.9	nM	CHEMBL5788860
8.72	IC50	1.9	nM	CHEMBL5785714
8.72	IC50	1.9	nM	CHEMBL5894696
8.70	Ki	2	nM	(+)-EHNA
8.70	IC50	2	nM	CHEMBL5941353
8.70	IC50	2	nM	CHEMBL5958825
8.70	IC50	2	nM	CHEMBL5767359
8.68	IC50	2.1	nM	CHEMBL5863520
8.66	IC50	2.2	nM	CHEMBL6039461
8.66	IC50	2.2	nM	CHEMBL5787523
8.66	IC50	2.2	nM	CHEMBL6051107
8.64	IC50	2.3	nM	CHEMBL6029118
8.64	IC50	2.3	nM	CHEMBL5814876

PubChem BioAssay actives

108 with measured affinity, of 170 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
(2R,3R,4S,5R)-2-[(8R)-8-hydroxy-7,8-dihydro-4H-imidazo[4,5-d][1,3]diazepin-3-yl]-5-(hydroxymethyl)oxolane-3,4-diol	1895861: Binding affinity to ADA (unknown origin) assessed as inhibition constant	ki	<0.0001	uM
Pentostatin	1578775: Inhibition of human erythrocytes ADA assessed as equilibrium dissociation constant by measuring reduction in formation of inosine using adenosine as substrate	ki	<0.0001	uM
(3S,4R,5S)-2-[(8R)-8-hydroxy-7,8-dihydro-6H-imidazo[4,5-b]azepin-3-yl]-5-(hydroxymethyl)oxolane-3,4-diol	33845: Binding affinity towards Adenosine deaminase	ki	<0.0001	uM
(2R,3R,4S,5R)-2-[(8R)-8-hydroxy-8H-imidazo[4,5-d][1,3]diazepin-3-yl]-5-(hydroxymethyl)oxolane-3,4-diol	554264: Inhibition of adenosine deaminase	ki	<0.0001	uM
(8R)-3-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-8H-imidazo[4,5-d][1,3]diazepin-8-ol	554264: Inhibition of adenosine deaminase	ki	<0.0001	uM
(8R)-3-[(2S,4R,5S)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-7,8-dihydro-6H-imidazo[4,5-b]azepin-8-ol	33845: Binding affinity towards Adenosine deaminase	ki	<0.0001	uM
(2R)-1-(4-aminopyrazolo[3,4-d]pyrimidin-2-yl)decan-2-ol	554264: Inhibition of adenosine deaminase	ki	0.0001	uM
(2R,3S)-3-(6-aminopurin-9-yl)nonan-2-ol	33846: Compound was evaluated for the inhibition of adenosine deaminase	ki	0.0004	uM
(2S,3R)-3-(6-aminopurin-9-yl)nonan-2-ol	1895861: Binding affinity to ADA (unknown origin) assessed as inhibition constant	ki	0.0010	uM
1-[(2R)-4-[5-[3-(4-chlorophenyl)propoxy]-1-methylindol-3-yl]-1-hydroxybutan-2-yl]imidazole-4-carboxamide	1798271: ADA Inhibition Assay from Article 10.1021/jm0306374: “Structure-based design, synthesis, and structure-activity relationship studies of novel non-nucleoside adenosine deaminase inhibitors.”	ki	0.0049	uM
3-(4-aminoimidazo[4,5-c]pyridin-1-yl)nonan-2-ol	33848: Inhibition constant (Ki) against Human erythrocyte adenosine deaminase	ki	0.0063	uM
1-[(2R)-4-[6-(benzylcarbamoylamino)indol-1-yl]-1-hydroxybutan-2-yl]imidazole-4-carboxamide	1798271: ADA Inhibition Assay from Article 10.1021/jm0306374: “Structure-based design, synthesis, and structure-activity relationship studies of novel non-nucleoside adenosine deaminase inhibitors.”	ki	0.0075	uM
1-[(2R)-1-hydroxy-4-[6-[3-(1-methylbenzimidazol-2-yl)propanoylamino]indol-1-yl]butan-2-yl]imidazole-4-carboxamide	1798269: ADA Inhibition Assay from Article 10.1021/ja038606l: “A highly potent non-nucleoside adenosine deaminase inhibitor: efficient drug discovery by intentional lead hybridization.”	ki	0.0077	uM
1-[(3R,4S)-1-[2-(4-chlorophenyl)-1,3-benzoxazol-7-yl]-4-hydroxypentan-3-yl]imidazole-4-carboxamide	240756: Inhibitory concentration against adenosine deaminase	ic50	0.0086	uM
1-[(3R,4S)-1-[2-(4-chlorophenyl)-1,3-benzoxazol-4-yl]-4-hydroxypentan-3-yl]imidazole-4-carboxamide	240756: Inhibitory concentration against adenosine deaminase	ic50	0.0087	uM
1-[(3R,4S)-4-hydroxy-1-naphthalen-2-yloxypentan-3-yl]imidazole-4-carboxamide	1798272: ADA Inhibition Assay from Article 10.1021/jm0499559: “Structure-based design and synthesis of non-nucleoside, potent, and orally bioavailable adenosine deaminase inhibitors.”	ki	0.0098	uM
1-[(2R)-1-hydroxy-4-[6-(5-phenylpentanoylamino)indol-1-yl]butan-2-yl]imidazole-4-carboxamide	1798271: ADA Inhibition Assay from Article 10.1021/jm0306374: “Structure-based design, synthesis, and structure-activity relationship studies of novel non-nucleoside adenosine deaminase inhibitors.”	ki	0.0110	uM
1-[(3R,4S)-4-hydroxy-1-naphthalen-1-ylpentan-3-yl]imidazole-4-carboxamide	1798272: ADA Inhibition Assay from Article 10.1021/jm0499559: “Structure-based design and synthesis of non-nucleoside, potent, and orally bioavailable adenosine deaminase inhibitors.”	ki	0.0110	uM
1-[(2R)-1-hydroxy-4-[6-(4-phenylbutoxy)indol-1-yl]butan-2-yl]imidazole-4-carboxamide	1798271: ADA Inhibition Assay from Article 10.1021/jm0306374: “Structure-based design, synthesis, and structure-activity relationship studies of novel non-nucleoside adenosine deaminase inhibitors.”	ki	0.0120	uM
1-[(2R)-4-(5-hexoxy-1-methylindol-3-yl)-1-hydroxybutan-2-yl]imidazole-4-carboxamide	1798271: ADA Inhibition Assay from Article 10.1021/jm0306374: “Structure-based design, synthesis, and structure-activity relationship studies of novel non-nucleoside adenosine deaminase inhibitors.”	ki	0.0130	uM
1-[(2R)-4-[6-[3-(4-chlorophenyl)propoxy]indol-1-yl]-1-hydroxybutan-2-yl]imidazole-4-carboxamide	1798271: ADA Inhibition Assay from Article 10.1021/jm0306374: “Structure-based design, synthesis, and structure-activity relationship studies of novel non-nucleoside adenosine deaminase inhibitors.”	ki	0.0130	uM
1-[(3R,4S)-1-(2,3-dichlorophenyl)-4-hydroxypentan-3-yl]imidazole-4-carboxamide	1798272: ADA Inhibition Assay from Article 10.1021/jm0499559: “Structure-based design and synthesis of non-nucleoside, potent, and orally bioavailable adenosine deaminase inhibitors.”	ki	0.0130	uM
1-[(2R)-1-hydroxy-4-[6-(4-phenylbutanoylamino)indol-1-yl]butan-2-yl]imidazole-4-carboxamide	1798271: ADA Inhibition Assay from Article 10.1021/jm0306374: “Structure-based design, synthesis, and structure-activity relationship studies of novel non-nucleoside adenosine deaminase inhibitors.”	ki	0.0160	uM
(4S)-4-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-acetamido-3-hydroxypropanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-hydroxypropanoyl]amino]hexanoyl]amino]-5-[[(2S)-1-[[(2R)-1-[[(2S)-1-[[(2S)-1-[[2-[[(2S)-6-amino-1-[(2S)-2-[[(2S)-1-amino-3-methyl-1-oxobutan-2-yl]carbamoyl]pyrrolidin-1-yl]-1-oxohexan-2-yl]amino]-2-oxoethyl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-(1H-imidazol-4-yl)-1-oxopropan-2-yl]amino]-5-oxopentanoic acid	33850: Inhibition of human adenosine deaminase (ADA)	ki	0.0160	uM
1-[(2R)-1-hydroxy-4-[6-(3-phenylpropoxy)indol-1-yl]butan-2-yl]imidazole-4-carboxamide	1798271: ADA Inhibition Assay from Article 10.1021/jm0306374: “Structure-based design, synthesis, and structure-activity relationship studies of novel non-nucleoside adenosine deaminase inhibitors.”	ki	0.0170	uM
1-[(2R)-1-hydroxy-4-[6-(3-pyridin-3-ylpropanoylamino)indol-1-yl]butan-2-yl]imidazole-4-carboxamide	1798271: ADA Inhibition Assay from Article 10.1021/jm0306374: “Structure-based design, synthesis, and structure-activity relationship studies of novel non-nucleoside adenosine deaminase inhibitors.”	ki	0.0170	uM
1-[(2R)-4-[6-(hexanoylamino)indol-1-yl]-1-hydroxybutan-2-yl]imidazole-4-carboxamide	1798271: ADA Inhibition Assay from Article 10.1021/jm0306374: “Structure-based design, synthesis, and structure-activity relationship studies of novel non-nucleoside adenosine deaminase inhibitors.”	ki	0.0240	uM
1-[(2R)-1-hydroxy-4-[1-methyl-5-(3-phenylpropoxy)indol-3-yl]butan-2-yl]imidazole-4-carboxamide	1798271: ADA Inhibition Assay from Article 10.1021/jm0306374: “Structure-based design, synthesis, and structure-activity relationship studies of novel non-nucleoside adenosine deaminase inhibitors.”	ki	0.0260	uM
1-[(2R)-1-hydroxy-4-[6-(3-phenylpropanoylamino)indol-1-yl]butan-2-yl]imidazole-4-carboxamide	1798271: ADA Inhibition Assay from Article 10.1021/jm0306374: “Structure-based design, synthesis, and structure-activity relationship studies of novel non-nucleoside adenosine deaminase inhibitors.”	ki	0.0300	uM
1-[(2R)-1-hydroxy-4-[6-[4-(4-methylphenyl)butanoylamino]indol-1-yl]butan-2-yl]imidazole-4-carboxamide	1798271: ADA Inhibition Assay from Article 10.1021/jm0306374: “Structure-based design, synthesis, and structure-activity relationship studies of novel non-nucleoside adenosine deaminase inhibitors.”	ki	0.0340	uM
3-(6-aminopurin-9-yl)nonan-2-ol	1798270: ADA Inhibition Assay from Article 10.1016/s0960-894x(03)00026-x: “Structure-based de novo design of non-nucleoside adenosine deaminase inhibitors.”	ki	0.0370	uM
1-[(2R)-1-hydroxy-4-[6-[3-(4-methylphenyl)propanoylamino]indol-1-yl]butan-2-yl]imidazole-4-carboxamide	1798271: ADA Inhibition Assay from Article 10.1021/jm0306374: “Structure-based design, synthesis, and structure-activity relationship studies of novel non-nucleoside adenosine deaminase inhibitors.”	ki	0.0380	uM
(2R,3S,4R,5R)-2-(hydroxymethyl)-5-(triazolo[4,5-d]pyrimidin-3-yl)oxolane-3,4-diol	554264: Inhibition of adenosine deaminase	ki	0.0400	uM
1-[(2R)-4-(6-hexoxyindol-1-yl)-1-hydroxybutan-2-yl]imidazole-4-carboxamide	1798271: ADA Inhibition Assay from Article 10.1021/jm0306374: “Structure-based design, synthesis, and structure-activity relationship studies of novel non-nucleoside adenosine deaminase inhibitors.”	ki	0.0550	uM
1-[(2R)-1-hydroxy-4-[6-[3-(4-methoxyphenyl)propanoylamino]indol-1-yl]butan-2-yl]imidazole-4-carboxamide	1798271: ADA Inhibition Assay from Article 10.1021/jm0306374: “Structure-based design, synthesis, and structure-activity relationship studies of novel non-nucleoside adenosine deaminase inhibitors.”	ki	0.0570	uM
(2S,3S)-3-(6-aminopurin-9-yl)nonan-2-ol	33846: Compound was evaluated for the inhibition of adenosine deaminase	ki	0.0800	uM
1-[(2R)-1-hydroxy-4-[6-(6-phenylhexanoylamino)indol-1-yl]butan-2-yl]imidazole-4-carboxamide	1798271: ADA Inhibition Assay from Article 10.1021/jm0306374: “Structure-based design, synthesis, and structure-activity relationship studies of novel non-nucleoside adenosine deaminase inhibitors.”	ki	0.0910	uM
(2R,3R,4S,5R)-2-(7-aminoimidazo[4,5-b]pyridin-3-yl)-5-(hydroxymethyl)oxolane-3,4-diol	554264: Inhibition of adenosine deaminase	ki	0.1000	uM
3-(7-aminoimidazo[4,5-b]pyridin-3-yl)nonan-2-ol	33848: Inhibition constant (Ki) against Human erythrocyte adenosine deaminase	ki	0.1200	uM
(2R,3R)-3-(6-aminopurin-9-yl)nonan-2-ol	33846: Compound was evaluated for the inhibition of adenosine deaminase	ki	0.1220	uM
1-[(2R)-4-(6-butoxyindol-1-yl)-1-hydroxybutan-2-yl]imidazole-4-carboxamide	1798271: ADA Inhibition Assay from Article 10.1021/jm0306374: “Structure-based design, synthesis, and structure-activity relationship studies of novel non-nucleoside adenosine deaminase inhibitors.”	ki	0.2400	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2147803: Binding affinity to human ADA incubated for 45 mins by Kinobead based pull down assay	kd	0.2462	uM
1-(1-hydroxy-4-naphthalen-1-ylbutan-2-yl)imidazole-4-carboxamide	240756: Inhibitory concentration against adenosine deaminase	ic50	0.5700	uM
2-[4-[5-[(1H-benzimidazol-2-ylamino)methyl]thiophen-2-yl]-1,3-thiazol-2-yl]guanidine	240756: Inhibitory concentration against adenosine deaminase	ic50	0.7000	uM
2-[4-[5-[(1H-indol-2-ylamino)methyl]thiophen-2-yl]-1,3-thiazol-2-yl]guanidine	33977: Binding affinity towards adenosine deaminase	ki	1.2000	uM
1-[(2R)-4-(6-acetamidoindol-1-yl)-1-hydroxybutan-2-yl]imidazole-4-carboxamide	1798271: ADA Inhibition Assay from Article 10.1021/jm0306374: “Structure-based design, synthesis, and structure-activity relationship studies of novel non-nucleoside adenosine deaminase inhibitors.”	ki	1.3000	uM
1-[(2R)-1-hydroxy-4-[5-(3-phenylpropoxy)indol-1-yl]butan-2-yl]imidazole-4-carboxamide	1798271: ADA Inhibition Assay from Article 10.1021/jm0306374: “Structure-based design, synthesis, and structure-activity relationship studies of novel non-nucleoside adenosine deaminase inhibitors.”	ki	1.9000	uM
(2R,3R,4R,5R)-2-[6-amino-2-(triazol-1-yl)purin-9-yl]-5-(hydroxymethyl)-3-methyloxolane-3,4-diol	626235: Inhibition of adenosine deaminase assessed as conversion of adenosine to inosine	ic50	3.7000	uM
1-(1-hydroxy-4-phenylbutan-2-yl)imidazole-4-carboxamide	1798269: ADA Inhibition Assay from Article 10.1021/ja038606l: “A highly potent non-nucleoside adenosine deaminase inhibitor: efficient drug discovery by intentional lead hybridization.”	ki	5.9000	uM
1-[(2R)-1-hydroxy-4-phenylbutan-2-yl]imidazole-4-carboxamide	33847: In vitro binding affinity towards human adenosine deaminase (ADA)	ki	5.9000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, affects expression	5
sodium arsenite	affects expression, decreases expression, increases abundance	3
Benzo(a)pyrene	increases expression	3
Tretinoin	increases expression	3
trichostatin A	decreases expression, affects cotreatment	2
cobaltous chloride	increases expression, decreases expression	2
perfluorooctane sulfonic acid	decreases expression	2
belinostat	decreases expression, affects cotreatment	2
Panobinostat	affects cotreatment, decreases expression	2
Cisplatin	affects expression, affects cotreatment, increases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Tobacco Smoke Pollution	affects expression	2
Cadmium Chloride	decreases expression, increases abundance	2
bisphenol F	affects cotreatment, increases expression	1
bisphenol A	decreases methylation	1
tris(2-butoxyethyl) phosphate	affects expression	1
beta-lapachone	decreases expression	1
afimoxifene	decreases expression	1
sulforaphane	decreases expression	1
perfluorooctanoic acid	decreases expression	1
potassium chromate(VI)	decreases expression	1
rutecarpine	decreases expression	1
cupric chloride	decreases expression	1
nickel sulfate	increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
beta-methylcholine	affects expression	1
tamibarotene	increases expression	1
di-n-butylphosphoric acid	affects expression	1
Am 580	increases expression	1
CGP 52608	affects binding, increases reaction	1

ChEMBL screening assays

40 unique, capped per target: 35 binding, 5 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1037328	Binding	Inhibition of AMP deaminase AMP binding site	Fructose-1,6-bisphosphatase Inhibitors. 2. Design, synthesis, and structure-activity relationship of a series of phosphonic acid containing benzimidazoles that function as 5’-adenosinemonophosphate (AMP) mimics. — J Med Chem
CHEMBL3110756	ADMET	Drug metabolism in human MOLT4 cells assessed as ADA-mediated inosine metabolite formation	Structure-activity relationships of synthetic cordycepin analogues as experimental therapeutics for African trypanosomiasis. — J Med Chem

Cellosaurus cell lines

39 cell lines: 20 transformed cell line, 11 finite cell line, 4 cancer cell line, 4 induced pluripotent stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_6G82	ID00017	Transformed cell line	Female
CVCL_7360	GM02605	Finite cell line	Male
CVCL_7365	GM02824	Finite cell line	Female
CVCL_8517	GM01390	Finite cell line	Male
CVCL_B8AV	Abcam HCT 116 ADA KO	Cancer cell line	Male
CVCL_B9CX	Abcam A-549 ADA KO	Cancer cell line	Male
CVCL_C104	ADA-iPS2	Induced pluripotent stem cell	Male
CVCL_C105	ADA-iPS3	Induced pluripotent stem cell	Male
CVCL_CZ12	GM01997	Finite cell line	Male
CVCL_CZ84	GM02294	Transformed cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01420627	PHASE3	COMPLETED	EZN-2279 in Patients With ADA-SCID
NCT00220766	PHASE3	COMPLETED	Rapid Infusion of Immune Globulin Intravenous (Human) In Primary Immunodeficiency Patients
NCT06940570	PHASE3	SUSPENDED	Methadone as an Alternative Treatment for Children Underdoing HSCT
NCT07284641	PHASE2	RECRUITING	Hematopoietic Stem Cell Transplantation (HSCT) for Common Variable Immunodeficiency (CVID) and Other Autoimmune Manifestations of Primary Immune Regulatory Disorders (PIRD)
NCT00000603	PHASE2	COMPLETED	Cord Blood Stem Cell Transplantation Study (COBLT)
NCT00794508	PHASE2	COMPLETED	MND-ADA Transduction of CD34+ Cells From Children With ADA-SCID
NCT01182675	PHASE2	TERMINATED	Hematopoietic Stem Cell Transplantation (HSCT) for Children With SCID Utilizing Alemtuzumab, Plerixafor & Filgrastim
NCT01529827	PHASE2	COMPLETED	Fludarabine Phosphate, Melphalan, and Low-Dose Total-Body Irradiation Followed by Donor Peripheral Blood Stem Cell Transplant in Treating Patients With Hematologic Malignancies
NCT01821781	PHASE2	ACTIVE_NOT_RECRUITING	Immune Disorder HSCT Protocol
NCT02177760	PHASE2	WITHDRAWN	Sirolimus Prophylaxis for aGVHD in TME SCID
NCT03619551	PHASE2	ACTIVE_NOT_RECRUITING	Conditioning SCID Infants Diagnosed Early
NCT00008450	PHASE1	COMPLETED	Total-Body Irradiation Followed By Cyclosporine and Mycophenolate Mofetil in Treating Patients With Severe Combined Immunodeficiency Undergoing Donor Bone Marrow Transplant
NCT02022696	PHASE1	COMPLETED	Treatment of SCID Due to ADA Deficiency With Autologous Transplantation of Cord Blood or Hematopoietic CD 34+ Cells After Addition of a Normal Human ADA cDNA by the EFS-ADA Lentiviral Vector
NCT00028236	PHASE1	COMPLETED	Stem Cell Gene Therapy to Treat X-Linked Severe Combined Immunodeficiency (XSCID)
NCT00152100	PHASE1	COMPLETED	Transplantation of Hematopoietic Cells in Children With Severe Combined Immunodeficiency Syndrome
NCT02860559	PHASE1	UNKNOWN	Safety and Early Efficacy Study of TBX-1400 in Patients With Severe Combined Immunodeficiency
NCT04140539	PHASE2/PHASE3	WITHDRAWN	A Clinical Study to Enable Process Validation of Commercial Grade OTL-101
NCT01279720	PHASE1/PHASE2	COMPLETED	Gene Therapy ADA Deficiency
NCT01380990	PHASE1/PHASE2	COMPLETED	Lentiviral (LV) Gene Therapy for Adenosine Deaminase (ADA) Deficiency
NCT01852071	PHASE1/PHASE2	COMPLETED	Autologous CD34+ Hematopoietic Stem Cells Transduced ex Vivo With Elongation Factor 1 Alpha Shortened (EFS) Lentiviral Vector Encoding for the Human ADA Gene
NCT02999984	PHASE1/PHASE2	COMPLETED	Efficacy and Safety of the Cryopreserved Formulation of OTL-101 in Subjects With ADA-SCID
NCT03765632	PHASE1/PHASE2	COMPLETED	Efficacy and Safety of the Cryopreserved Formulation of OTL-101 in Subjects With ADA-SCID
NCT01182857	Not specified	WITHDRAWN	Quality of Life and Neuropsychiatric Sequelae in Patients Treated With Gene Therapy for ADA-SCID and in Their Parents
NCT01186913	Not specified	ENROLLING_BY_INVITATION	Natural History Study of SCID Disorders
NCT01346150	Not specified	UNKNOWN	Patients Treated for SCID (1968-Present)
NCT03232203	Not specified	COMPLETED	Evaluating the Effectiveness of STRIMVELIS Risk Minimization Measures (RMMs)
NCT03655223	Not specified	ENROLLING_BY_INVITATION	Early Check: Expanded Screening in Newborns
NCT04049084	Not specified	ENROLLING_BY_INVITATION	An Observational LTFU Study for Patients Previously Treated With Autologous ex Vivo Gene Therapy for ADA-SCID
NCT04959890	Not specified	UNKNOWN	Methodology Study of Retroviral Insertion Site Analysis in Strimvelis Gene Therapy
NCT05300334	Not specified	UNKNOWN	Investigation of ADA Enzyme Deficiency
NCT05300347	Not specified	UNKNOWN	Observational Study Evaluating the Prevalence of Enzyme Deficiency in Pulmonology Clinics (ADA)
NCT05300373	Not specified	UNKNOWN	Evaluation of Adenosine Deaminase (ADA) Enzyme Deficiency in Patients With Lymphopenia and/or Elevated Immunoglobulin E
NCT01019876	PHASE2/PHASE3	COMPLETED	Risk-Adapted Allogeneic Stem Cell Transplantation For Mixed Donor Chimerism In Patients With Non-Malignant Diseases
NCT00228852	PHASE1/PHASE2	COMPLETED	IMM 0212: Busulfan With Fludarabine and Antithymocyte Globulin as Preparative Therapy for Hematopoietic Stem Cell Transplant for the Treatment of Severe Congenital T-Cell Immunodeficiency
NCT00579137	PHASE1/PHASE2	TERMINATED	Allogeneic SCT Of Pts With SCID And Other Primary Immunodeficiency Disorders
NCT01129544	PHASE1/PHASE2	COMPLETED	Gene Transfer for Severe Combined Immunodeficiency, X-linked (SCID-X1) Using a Self-inactivating (SIN) Gammaretroviral Vector
NCT01852370	PHASE1/PHASE2	ENROLLING_BY_INVITATION	Sequential Cadaveric Lung and Bone Marrow Transplant for Immune Deficiency Diseases
NCT02127892	PHASE1/PHASE2	TERMINATED	SCID Bu/Flu/ATG Study With T Cell Depletion
NCT02963064	PHASE1/PHASE2	TERMINATED	JSP191 Antibody Targeting Conditioning in SCID Patients
NCT03513328	PHASE1/PHASE2	COMPLETED	Conditioning Regimen for Allogeneic Hematopoietic Stem-Cell Transplantation