JAK3

Summary

JAK3 (Janus kinase 3, HGNC:6193) is a protein-coding gene on chromosome 19p13.11, encoding Tyrosine-protein kinase JAK3 (P52333). Non-receptor tyrosine kinase involved in various processes such as cell growth, development, or differentiation.

The protein encoded by this gene is a member of the Janus kinase (JAK) family of tyrosine kinases involved in cytokine receptor-mediated intracellular signal transduction. It is predominantly expressed in immune cells and transduces a signal in response to its activation via tyrosine phosphorylation by interleukin receptors. Mutations in this gene are associated with autosomal SCID (severe combined immunodeficiency disease).

Source: NCBI Gene 3718 — RefSeq curated summary.

At a glance

• Gene–disease (curated): T-B+ severe combined immunodeficiency due to JAK3 deficiency (Definitive, ClinGen)
• Clinical variants (ClinVar): 1,408 total — 86 pathogenic, 45 likely-pathogenic
• Phenotypes (HPO): 40
• Druggable target: yes — 91 molecules with ChEMBL bioactivity
• Cancer driver (intOGen): activating (oncogene-like) across 1 cancer types
• MANE Select transcript: NM_000215

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6193
Approved symbol	JAK3
Name	Janus kinase 3
Location	19p13.11
Locus type	gene with protein product
Status	Approved
Aliases	L-JAK, JAKL, LJAK, JAK3_HUMAN, JAK-3
Ensembl gene	ENSG00000105639
Ensembl biotype	protein_coding
OMIM	600173
Entrez	3718

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 6 retained_intron, 3 protein_coding, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000458235, ENST00000526008, ENST00000527031, ENST00000527670, ENST00000528293, ENST00000528705, ENST00000534444, ENST00000696967, ENST00000696968, ENST00000696969, ENST00000696970

RefSeq mRNA: 1 — MANE Select: NM_000215 NM_000215

CCDS: CCDS12366

Canonical transcript exons

ENST00000458235 — 24 exons

Exon	Start	End
ENSE00000689791	17830108	17830218
ENSE00000689794	17830503	17830620
ENSE00000689798	17831228	17831400
ENSE00000689802	17831674	17831798
ENSE00000689806	17834571	17834721
ENSE00000689809	17834852	17835003
ENSE00000689811	17835083	17835215
ENSE00000689813	17835924	17836051
ENSE00000689815	17837129	17837213
ENSE00000871053	17832519	17832708
ENSE00000871054	17832790	17832929
ENSE00001355889	17824782	17826910
ENSE00003473538	17841640	17841762
ENSE00003479629	17837932	17838063
ENSE00003486977	17844234	17844430
ENSE00003513921	17843777	17843900
ENSE00003521716	17841389	17841546
ENSE00003554568	17840230	17840341
ENSE00003558414	17839477	17839663
ENSE00003575305	17838263	17838390
ENSE00003601257	17843380	17843491
ENSE00003615184	17842316	17842610
ENSE00003686647	17843027	17843172
ENSE00003897402	17847946	17847982

Expression profiles

Bgee: expression breadth ubiquitous, 219 present calls, max score 95.63.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 11.4831 / max 222.3135, expressed in 952 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
179896	10.1377	905
179897	1.2743	375
179891	0.0711	31

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	95.63	gold quality
blood	UBERON:0000178	95.39	gold quality
spleen	UBERON:0002106	93.30	gold quality
lymph node	UBERON:0000029	92.26	gold quality
leukocyte	CL:0000738	88.23	gold quality
monocyte	CL:0000576	88.22	gold quality
vermiform appendix	UBERON:0001154	88.07	gold quality
mononuclear cell	CL:0000842	87.97	gold quality
ileal mucosa	UBERON:0000331	85.20	silver quality
caecum	UBERON:0001153	85.01	gold quality
left ovary	UBERON:0002119	84.92	gold quality
right ovary	UBERON:0002118	84.78	gold quality
epithelium of nasopharynx	UBERON:0001951	84.30	gold quality
superficial temporal artery	UBERON:0001614	84.28	gold quality
tonsil	UBERON:0002372	83.23	gold quality
bone marrow cell	CL:0002092	82.19	gold quality
upper lobe of left lung	UBERON:0008952	81.91	gold quality
bone marrow	UBERON:0002371	81.67	gold quality
upper lobe of lung	UBERON:0008948	81.40	gold quality
ovary	UBERON:0000992	81.28	gold quality
pancreatic ductal cell	CL:0002079	80.02	silver quality
small intestine Peyer’s patch	UBERON:0003454	79.97	gold quality
caput epididymis	UBERON:0004358	79.13	gold quality
tibialis anterior	UBERON:0001385	79.01	silver quality
right lung	UBERON:0002167	78.99	gold quality
trabecular bone tissue	UBERON:0002483	78.20	gold quality
omental fat pad	UBERON:0010414	78.02	gold quality
peritoneum	UBERON:0002358	77.98	gold quality
right coronary artery	UBERON:0001625	77.67	gold quality
small intestine	UBERON:0002108	77.58	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	13.35
E-MTAB-6379	no	533.67
E-MTAB-7606	no	361.29

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ETS1, ETS2, SP1, STAT3, STAT5A, TBX21

miRNA regulators (miRDB)

81 targeting JAK3, 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-3613-3P	100.00	76.36	7965
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-3134	100.00	66.43	777
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-9-3P	99.96	70.88	2068
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-1323	99.83	69.89	2471
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-6842-5P	99.80	67.54	1587
HSA-MIR-7110-5P	99.80	67.84	1712
HSA-MIR-1273H-5P	99.77	66.32	2471
HSA-MIR-623	99.76	68.16	1170
HSA-MIR-548O-3P	99.74	69.30	2228
HSA-MIR-4524A-3P	99.72	66.85	2406
HSA-MIR-1296-3P	99.72	64.04	636
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-30B-3P	99.70	65.76	2325
HSA-MIR-3689A-3P	99.70	65.73	2306
HSA-MIR-3689B-3P	99.70	65.71	2311
HSA-MIR-3689C	99.70	65.71	2311
HSA-MIR-6779-5P	99.70	65.76	2363
HSA-MIR-1197	99.70	67.75	1027

Literature-anchored findings (GeneRIF, showing 40)

• mutations in severe combined immune deficiency (SCID) due to JAK3 deficiency (PMID:11668610)
• eleven novel mutations in patients with severe combined immunodeficiency-including the first patients with mutations in the kinase domain (PMID:11668621)
• In the T cell line HUT-78, JAK3 was found to be highly phosphorylated. These results suggest that SHP-1 might be involved in maintaining the IL-2R/JAK3 signaling pathway under control and point towards a role of SHP-1 in the pathogenesis of the disease. (PMID:12145687)
• JAK3 is associated with a pre-phosphorylated IL-4Ralpha and CD40. This novel “heterotrimer” (p-IL-4Ralpha, CD40/JAK3) is functional and controls STAT3 phosphorylation and CD40 expression. (PMID:12207328)
• the JH2 domain contributes to both the uninduced and ligand-induced Jak-receptor complex, where it acts as a cytokine-inducible switch to regulate signal transduction (PMID:12351625)
• newly described sequence corrects the previous published genomic sequence from Jak3 spanning introns 10 and 11 rather than identifying an insertion or translocation specific to these ALL (PMID:12613524)
• Data suggest there is no defect in the JAK/STAT pathway in the tested melanoma cell lines, and that interferon resistance must be mediated through other components. (PMID:12777975)
• The Jak3 promoter is found 60 bp upstream of a large (roughly 3500 bp) intron in the nontranslated 5’ protion of Jak3 mRNA; it is active in primary lymphocytes, Jurkat T cells, and NK3.3 cells, but not in COS or HeLa cells. (PMID:12794134)
• A highly selective and potent JAK3 inhibitor is effective in a nonhuman primate model of transplant rejection (PMID:14593182)
• mutations all resulted in abnormal B-cell Janus kinase 3 (JAK3)-dependent interleukin-2 (IL-2)-induced signal transducer and activator of transcription-5 (STAT5) phosphorylation. (PMID:14615376)
• Findings support a model in which JAK3 signaling enhances IL-10 production in monocytes/macrophages leading to down-regulation of IL-1 beta converting enzyme (ICE) activation and suppression of IL-1 beta processing and release. (PMID:15067075)
• Review. Jak3 mediates signal transduction via the gamma common chain of lymphokine surface receptors. Its structural and genetic features are discussed. (PMID:15584866)
• CXCL12 signaling is independent of Jak2 and Jak3 (PMID:15611059)
• phosphate group on pTyr981 in the activation loop is in part coordinated by an arginine residue in the regulatory C-helix, suggesting a direct mechanism by which the active position of the C-helix is induced by phosphorylation of the activation loop (PMID:15831699)
• We conclude that Jak3 activation is predominantly restricted to ALK-positive ALCL tumors. Most likely. (PMID:16153455)
• Inhibition of JAK3 signaling in colon carcinoma tumors and cell lines induces apoptosis and cell cycle arrest of colon carcinoma cells. (PMID:16192633)
• JAK3 is a highly significant, prognostic immunohistochemical marker in CRC. This study proves that cDNA microarrays, plotted by a small number of genes from a few samples, are both practical and useful. (PMID:16308103)
• WHI-P154, an inhibitor of Janus protein tyrosine kinase (JAK3), Hck and Syk, prevented PDGF-induced neurite outgrowth. (PMID:16515549)
• IL-9/Jak3 signaling plays a significant role in the pathogenesis of ALK+ anaplastic large-cell lymphoma (PMID:16763206)
• The transforming activity of JAK3(V674A) was confirmed by its introduction into 32Dcl3-mCAT. Sequencing of the original JAK3 cDNA derived from the patient, however, failed to detect the V674A mutation. (PMID:16790275)
• Loss of SHP1 enhances JAK3/STAT3 signaling and decreases proteosome degradation of JAK3 and NPM-ALK in ALK+ anaplastic large-cell lymphoma. (PMID:16825495)
• Findings illustrate the biological importance of gain-of-function JAK3 mutations in leukemogenesis. (PMID:16843266)
• evidence of VEGF production in cutaneous T-cell lymphoma, which is promoted by aberrant activation of Jak3 and the JNKs (PMID:16932349)
• These results suggest that oncostatin M inhibits adiponectin expression by inducing dedifferentiation of adipocytes through signaling pathways involving JAK3 and MEK, but not JAK2. (PMID:17081797)
• 4 types of JAK3 mutations were found in acute megakaryoblastic leukemia & transient myeloproliferative disorder patients, all in the pseudokinase domain or receptor-binding domain. I87T is in the common-gamma-subunit-binding domain. (PMID:17252020)
• data suggest that both gain-, and loss-of function mutations of jak3 can be acquired in Down syndrome -transient myeloproliferative disorder /acute megakaryoblastic leukaemia (DS-TMD/AMKL) (PMID:17456055)
• a novel pathway in intestinal enterocytes in which IL-2 enhances intestinal wound repair through mechanisms involving Jak3 and its interactions with villin. (PMID:17537734)
• the effect of IL-15 and IL-21, which are closely related to IL-2 and share the usage of the common gamma chain and of its JAK3-associated pathway. (PMID:17938255)
• 2 new Tyr phosphorylation sites within Jak3, Y904 & Y939, are conserved among Jak family proteins. Y904 and Y939 were required for optimal ATP usage by Jak3, while phosphorylation of Y939 preferentially promoted Stat5 activity in intact cells. (PMID:18250158)
• review of roles of Jak2, Jak3, and MPL mutations in signal transduction and etiology of myeloid malignancies (PMID:18297515)
• the JAK3 activating mutation is an early event during leukaemogenesis in Down syndrome (PMID:18397343)
• Some of the JAK1 and JAK3 mutations may to be functional and contributes to cancer development, especially to T-ALL development. (PMID:18559588)
• In a series of human AMKL samples from both Down syndrome and non-Down syndrome patients, mutations were identified within KIT, FLT3, JAK2, JAK3, and MPL genes, with a higher frequency in DS than in non-DS patients. (PMID:18755984)
• Jak-3 was expressed at higher levels in patients with diabetic nephropathy than in control subjects. (PMID:19017763)
• Constitutively expressed recombinant human JAK3A572V induces an aggressive, fatal, transplantable lymphoproliferative disorder of CD8(+)TCRalphabeta(+)CD44(+)CD122(+)Ly-6C(+) T cells in mice. (PMID:19139084)
• IL-7 stimulates chondrocyte secretion of S100A4 via activation of JAK/STAT signaling, and then S100A4 acts in an autocrine manner to stimulate MMP-13 production via RAGE. (PMID:19248116)
• Genetic polymorphisms in the Jak-Stat signaling pathway are associated with an increased risk of new cardiovascular events in incident dialysis patients. (PMID:19282076)
• The JAK3/ERK pathway may play an important role in epidermal growth factor induced MMP-9 expression in SKBR3 cells. (PMID:19385051)
• Genomic resequencing of JAK1, JAK2, JAK3, and TYK2 in 187 diagnostic samples from a high risk B-progenitor ALL cohort that had available DNA and gene expression profiling data identified mutations in JAK1, JAK2, and JAK3 in 20 patients (10.7%). (PMID:19470474)
• Data show that IL-4 receptors are functionally competent in pancreatic beta-cells and that they signal via PI3K and JAK/STAT pathways. (PMID:19531027)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Jak3	ENSMUSG00000031805
rattus_norvegicus	Jak3	ENSRNOG00000018669

Paralogs (32): FGR (ENSG00000000938), MATK (ENSG00000007264), BTK (ENSG00000010671), FYN (ENSG00000010810), STYK1 (ENSG00000060140), TNK2 (ENSG00000061938), TXK (ENSG00000074966), JAK2 (ENSG00000096968), ABL1 (ENSG00000097007), PTK6 (ENSG00000101213), HCK (ENSG00000101336), BMX (ENSG00000102010), CSK (ENSG00000103653), TYK2 (ENSG00000105397), FRK (ENSG00000111816), ITK (ENSG00000113263), ZAP70 (ENSG00000115085), PTK2B (ENSG00000120899), SRMS (ENSG00000125508), TEC (ENSG00000135605), BLK (ENSG00000136573), ABL2 (ENSG00000143322), FER (ENSG00000151422), JAK1 (ENSG00000162434), SYK (ENSG00000165025), PTK2 (ENSG00000169398), TNK1 (ENSG00000174292), YES1 (ENSG00000176105), FES (ENSG00000182511), LCK (ENSG00000182866), SRC (ENSG00000197122), LYN (ENSG00000254087)

Protein

Protein identifiers

Tyrosine-protein kinase JAK3 — P52333 (reviewed: P52333)

Alternative names: Janus kinase 3, Leukocyte janus kinase

All UniProt accessions (2): P52333, A0A0S2Z4R7

UniProt curated annotations — full annotation on UniProt →

Function. Non-receptor tyrosine kinase involved in various processes such as cell growth, development, or differentiation. Mediates essential signaling events in both innate and adaptive immunity and plays a crucial role in hematopoiesis during T-cells development. In the cytoplasm, plays a pivotal role in signal transduction via its association with type I receptors sharing the common subunit gamma such as IL2R, IL4R, IL7R, IL9R, IL15R and IL21R. Following ligand binding to cell surface receptors, phosphorylates specific tyrosine residues on the cytoplasmic tails of the receptor, creating docking sites for STATs proteins. Subsequently, phosphorylates the STATs proteins once they are recruited to the receptor. Phosphorylated STATs then form homodimer or heterodimers and translocate to the nucleus to activate gene transcription. For example, upon IL2R activation by IL2, JAK1 and JAK3 molecules bind to IL2R beta (IL2RB) and gamma chain (IL2RG) subunits inducing the tyrosine phosphorylation of both receptor subunits on their cytoplasmic domain. Then, STAT5A and STAT5B are recruited, phosphorylated and activated by JAK1 and JAK3. Once activated, dimerized STAT5 translocates to the nucleus and promotes the transcription of specific target genes in a cytokine-specific fashion.

Subunit / interactions. Interacts with STAM2 and MYO18A. Interacts with SHB. Interacts with CD69.

Subcellular location. Endomembrane system. Cytoplasm.

Tissue specificity. In NK cells and an NK-like cell line but not in resting T-cells or in other tissues. The S-form is more commonly seen in hematopoietic lines, whereas the B-form is detected in cells both of hematopoietic and epithelial origins.

Post-translational modifications. Tyrosine phosphorylated in response to IL-2 and IL-4. Dephosphorylation of Tyr-980 and Tyr-981 by PTPN2 negatively regulates cytokine-mediated signaling.

Disease relevance. Severe combined immunodeficiency autosomal recessive T-cell-negative/B-cell-positive/NK-cell-negative (T(-)B(+)NK(-) SCID) [MIM:600802] A form of severe combined immunodeficiency (SCID), 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 present in infancy 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. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. Possesses two phosphotransferase domains. The second one probably contains the catalytic domain, while the presence of slight differences suggest a different role for domain 1.

Miscellaneous. May be inactive as it lacks some part of the kinase domain.

Similarity. Belongs to the protein kinase superfamily. Tyr protein kinase family. JAK subfamily.

Isoforms (3)

UniProt ID	Names	Canonical?
P52333-1	2, JAK3S, Spleen-JAK3	yes
P52333-2	1, JAK3B, Breast-JAK3
P52333-4	3

RefSeq proteins (1): NP_000206* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000299	FERM_domain	Domain
IPR000719	Prot_kinase_dom	Domain
IPR000980	SH2	Domain
IPR001245	Ser-Thr/Tyr_kinase_cat_dom	Domain
IPR008266	Tyr_kinase_AS	Active_site
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR011993	PH-like_dom_sf	Homologous_superfamily
IPR016251	Tyr_kinase_non-rcpt_Jak/Tyk2	Family
IPR017441	Protein_kinase_ATP_BS	Binding_site
IPR019749	Band_41_domain	Domain
IPR020635	Tyr_kinase_cat_dom	Domain
IPR020775	Tyr_kinase_non-rcpt_Jak3	Family
IPR036860	SH2_dom_sf	Homologous_superfamily
IPR041046	FERM_F2	Domain
IPR041155	FERM_F1	Domain
IPR041381	JAK1-3/TYK2_PHL_dom	Domain
IPR051286	JAK	Family

Pfam: PF07714, PF17887, PF18377, PF18379, PF21990

Enzyme classification (BRENDA):

• EC 2.7.10.2 — non-specific protein-tyrosine kinase (BRENDA: 41 organisms, 396 substrates, 479 inhibitors, 43 Km, 32 kcat entries)

Substrate kinetics (BRENDA)

6 substrates with measured Km, best-characterized 6. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ATP	0.014–17.64	12
[KDSRC KINASE]-L-TYROSINE	0.0057–0.24	12
POLY(GLU4-TYR)	0.018–0.659	10
EEEEYIQ[DP]-8-HYDROXY-5-(N,N-DIMETHYLSULFONAMIDO	0.057	1
S1 PEPTIDE	0.037	1
EEEEY	—	0

Catalyzed reactions (Rhea), 1 shown:

• L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+) (RHEA:10596)

UniProt features (82 total): sequence variant 17, helix 16, sequence conflict 13, strand 13, modified residue 6, domain 4, mutagenesis site 4, splice variant 3, binding site 2, chain 1, region of interest 1, active site 1, turn 1

Structure

Experimental structures (PDB)

42 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
5LWM	X-RAY DIFFRACTION	1.55
5LWN	X-RAY DIFFRACTION	1.6
6DUD	X-RAY DIFFRACTION	1.66
6DB4	X-RAY DIFFRACTION	1.66
6GL9	X-RAY DIFFRACTION	1.7
5TTU	X-RAY DIFFRACTION	1.72
3LXL	X-RAY DIFFRACTION	1.74
7Q6H	X-RAY DIFFRACTION	1.75
4QPS	X-RAY DIFFRACTION	1.8
9R5Z	X-RAY DIFFRACTION	1.8
4HVD	X-RAY DIFFRACTION	1.85
4I6Q	X-RAY DIFFRACTION	1.85
6GLA	X-RAY DIFFRACTION	1.92
5TTV	X-RAY DIFFRACTION	1.93
7APF	X-RAY DIFFRACTION	1.95
6DB3	X-RAY DIFFRACTION	1.97
5TOZ	X-RAY DIFFRACTION	1.98
7C3N	X-RAY DIFFRACTION	1.98
3LXK	X-RAY DIFFRACTION	2
6GLB	X-RAY DIFFRACTION	2
7UYV	X-RAY DIFFRACTION	2.15
3PJC	X-RAY DIFFRACTION	2.2
4HVH	X-RAY DIFFRACTION	2.3
6NY4	X-RAY DIFFRACTION	2.33
5TTS	X-RAY DIFFRACTION	2.34
8EXM	X-RAY DIFFRACTION	2.35
3ZEP	X-RAY DIFFRACTION	2.35
4HVI	X-RAY DIFFRACTION	2.4
4QT1	X-RAY DIFFRACTION	2.4
7APG	X-RAY DIFFRACTION	2.4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P52333-F1	86.20	0.64

Functional residue map

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

Catalytic / active sites (1): 949 (proton acceptor)

Ligand- & substrate-binding residues (2): 828–836; 855

Post-translational modifications (6): 785, 904, 939, 980, 981, 17

Mutagenesis-validated functional residues (4):

Position	Phenotype
785	strong decrease of jak3 phosphorylation.
855	more than 90% loss of stat5a activation.
904	about 40% loss of stat5a activation.
939	about 80% loss of stat5a activation.

Function

Pathways and Gene Ontology

Reactome pathways

24 pathways

ID	Pathway
R-HSA-1266695	Interleukin-7 signaling
R-HSA-201556	Signaling by ALK
R-HSA-5673001	RAF/MAP kinase cascade
R-HSA-6785807	Interleukin-4 and Interleukin-13 signaling
R-HSA-8854691	Interleukin-20 family signaling
R-HSA-8983432	Interleukin-15 signaling
R-HSA-8985947	Interleukin-9 signaling
R-HSA-9020558	Interleukin-2 signaling
R-HSA-9020958	Interleukin-21 signaling
R-HSA-912526	Interleukin receptor SHC signaling
R-HSA-9679191	Potential therapeutics for SARS
R-HSA-1280215	Cytokine Signaling in Immune system
R-HSA-162582	Signal Transduction
R-HSA-1643685	Disease
R-HSA-168256	Immune System
R-HSA-449147	Signaling by Interleukins
R-HSA-451927	Interleukin-2 family signaling
R-HSA-512988	Interleukin-3, Interleukin-5 and GM-CSF signaling
R-HSA-5663205	Infectious disease
R-HSA-5683057	MAPK family signaling cascades
R-HSA-5684996	MAPK1/MAPK3 signaling
R-HSA-9006934	Signaling by Receptor Tyrosine Kinases
R-HSA-9679506	SARS-CoV Infections
R-HSA-9824446	Viral Infection Pathways

MSigDB gene sets: 500 (showing top): PID_SHP2_PATHWAY, MORF_RAGE, GOBP_REGULATION_OF_CELL_ACTIVATION, REACTOME_INTERLEUKIN_2_FAMILY_SIGNALING, CREL_01, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_NEGATIVE_REGULATION_OF_CELL_DEVELOPMENT, GOBP_NEGATIVE_REGULATION_OF_ADAPTIVE_IMMUNE_RESPONSE, GOBP_REGULATION_OF_ALPHA_BETA_T_CELL_ACTIVATION, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_RESPONSE_TO_INTERLEUKIN_4, GOBP_RESPONSE_TO_PEPTIDE, GOBP_REGULATION_OF_LEUKOCYTE_APOPTOTIC_PROCESS, GOBP_B_CELL_ACTIVATION, GOBP_T_CELL_ACTIVATION_INVOLVED_IN_IMMUNE_RESPONSE

GO Biological Process (37): adaptive immune response (GO:0002250), negative regulation of dendritic cell cytokine production (GO:0002731), enzyme-linked receptor protein signaling pathway (GO:0007167), cell surface receptor signaling pathway via JAK-STAT (GO:0007259), tyrosine phosphorylation of STAT protein (GO:0007260), negative regulation of glycoprotein biosynthetic process (GO:0010561), cytokine-mediated signaling pathway (GO:0019221), cell differentiation (GO:0030154), B cell differentiation (GO:0030183), negative regulation of interleukin-10 production (GO:0032693), negative regulation of interleukin-12 production (GO:0032695), intracellular signal transduction (GO:0035556), interleukin-15-mediated signaling pathway (GO:0035723), interleukin-4-mediated signaling pathway (GO:0035771), interleukin-2-mediated signaling pathway (GO:0038110), interleukin-7-mediated signaling pathway (GO:0038111), interleukin-9-mediated signaling pathway (GO:0038113), regulation of apoptotic process (GO:0042981), T cell homeostasis (GO:0043029), innate immune response (GO:0045087), negative regulation of T-helper 1 cell differentiation (GO:0045626), regulation of receptor signaling pathway via JAK-STAT (GO:0046425), negative regulation of T cell activation (GO:0050868), growth hormone receptor signaling pathway via JAK-STAT (GO:0060397), regulation of T cell apoptotic process (GO:0070232), negative regulation of thymocyte apoptotic process (GO:0070244), response to interleukin-2 (GO:0070669), response to interleukin-4 (GO:0070670), response to interleukin-15 (GO:0070672), response to interleukin-9 (GO:0071104), negative regulation of T-helper 17 cell lineage commitment (GO:2000329), immune system process (GO:0002376), protein phosphorylation (GO:0006468), regulation of cell-cell adhesion (GO:0022407), regulation of alpha-beta T cell activation (GO:0046634), regulation of cell activation (GO:0050865), regulation of leukocyte cell-cell adhesion (GO:1903037)

GO Molecular Function (10): protein tyrosine kinase activity (GO:0004713), non-membrane spanning protein tyrosine kinase activity (GO:0004715), growth hormone receptor binding (GO:0005131), ATP binding (GO:0005524), protein phosphatase binding (GO:0019903), nucleotide binding (GO:0000166), protein kinase activity (GO:0004672), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (10): endosome (GO:0005768), cytosol (GO:0005829), plasma membrane (GO:0005886), cytoplasmic side of plasma membrane (GO:0009898), extrinsic component of plasma membrane (GO:0019897), extrinsic component of cytoplasmic side of plasma membrane (GO:0031234), cytoplasm (GO:0005737), cytoskeleton (GO:0005856), endomembrane system (GO:0012505), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-10 pathways:

Category	Pathways
Signaling by Interleukins	5
Interleukin-2 family signaling	5
Signaling by Receptor Tyrosine Kinases	1
MAPK1/MAPK3 signaling	1
Interleukin-3, Interleukin-5 and GM-CSF signaling	1
SARS-CoV Infections	1
Immune System	1
Cytokine Signaling in Immune system	1
Disease	1
Signal Transduction	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cytokine-mediated signaling pathway	5
cellular anatomical structure	4
plasma membrane	3
immune response	2
cell surface receptor signaling pathway	2
negative regulation of cytokine production	2
intracellular anatomical structure	2
dendritic cell cytokine production	1
negative regulation of leukocyte mediated immunity	1
negative regulation of cytokine production involved in immune response	1
regulation of dendritic cell cytokine production	1
cell surface receptor signaling pathway via STAT	1
cell surface receptor signaling pathway via JAK-STAT	1
peptidyl-tyrosine phosphorylation	1
glycoprotein biosynthetic process	1
negative regulation of macromolecule biosynthetic process	1
regulation of glycoprotein biosynthetic process	1
negative regulation of glycoprotein metabolic process	1
cellular response to cytokine stimulus	1
cellular developmental process	1
lymphocyte differentiation	1
B cell activation	1
interleukin-10 production	1
regulation of interleukin-10 production	1
interleukin-12 production	1
regulation of interleukin-12 production	1
signal transduction	1
cellular response to interleukin-15	1
cellular response to interleukin-4	1
cellular response to interleukin-2	1
cellular response to interleukin-7	1
cellular response to interleukin-9	1
apoptotic process	1
regulation of programmed cell death	1
lymphocyte homeostasis	1
defense response to symbiont	1
protein kinase activity	1
protein tyrosine kinase activity	1
cytokine receptor binding	1
hormone receptor binding	1

Protein interactions and networks

STRING

3429 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
JAK3	IL2RG	P31785	998
JAK3	IL2	P01585	996
JAK3	IL7	P13232	994
JAK3	IL9	P15248	993
JAK3	IL15	P40933	993
JAK3	IL4	P05112	986
JAK3	JAK1	P23458	983
JAK3	STAT5A	P42229	972
JAK3	STAT3	P40763	967
JAK3	IL2RA	P01589	957
JAK3	STAT5B	P51692	956
JAK3	IL7R	P16871	919
JAK3	STAT1	P42224	904
JAK3	STAM2	O75886	869
JAK3	TYK2	P29597	864

IntAct

52 interactions, top by confidence:

A	B	Type	Score
MAGED2	JAK3	psi-mi:“MI:0915”(physical association)	0.710
JAK3	NAP1L1	psi-mi:“MI:0915”(physical association)	0.620
JAK3	LNX1	psi-mi:“MI:0915”(physical association)	0.490
LNX1	JAK3	psi-mi:“MI:0915”(physical association)	0.490
FBXW7	JAK3	psi-mi:“MI:2364”(proximity)	0.470
SMAD4	JAK3	psi-mi:“MI:2364”(proximity)	0.470
JAK3	SMARCA4	psi-mi:“MI:2364”(proximity)	0.470
SMARCA4	JAK3	psi-mi:“MI:2364”(proximity)	0.470
JAK3	BRAF	psi-mi:“MI:2364”(proximity)	0.470
JAK3	SMAD4	psi-mi:“MI:0915”(physical association)	0.470
BRAF	JAK3	psi-mi:“MI:0915”(physical association)	0.470
JAK3	SMARCA4	psi-mi:“MI:0915”(physical association)	0.470
JAK3	FBXW7	psi-mi:“MI:0915”(physical association)	0.470
JAK3	Stat5a	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
JAK3	NFATC1	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
JAK3	ERBB3	psi-mi:“MI:0407”(direct interaction)	0.440
JAK3	PKM	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
JAK3	ROCK2	psi-mi:“MI:0915”(physical association)	0.400
JAK3	KHDRBS1	psi-mi:“MI:0915”(physical association)	0.400
UHRF2	JAK3	psi-mi:“MI:0915”(physical association)	0.400
CDK1	JAK3	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (149): BAG2 (Affinity Capture-MS), CCT2 (Affinity Capture-MS), CCT3 (Affinity Capture-MS), CCT4 (Affinity Capture-MS), CCT6A (Affinity Capture-MS), CCT8 (Affinity Capture-MS), GNAS (Affinity Capture-MS), GPATCH8 (Affinity Capture-MS), MAGED2 (Affinity Capture-MS), NAP1L1 (Affinity Capture-MS), NAP1L4 (Affinity Capture-MS), RNPS1 (Affinity Capture-MS), SRRM2 (Affinity Capture-MS), TCP1 (Affinity Capture-MS), TUBB1 (Affinity Capture-MS)

ESM2 similar proteins: A0A0U1RPR8, O02740, O08644, O09127, O15197, O19179, O73875, O73878, P0C0K6, P0C0K7, P14616, P16067, P20594, P21709, P26770, P29317, P29322, P35590, P46197, P51839, P51840, P51841, P51842, P52333, P52785, P54753, P54754, P54760, P54761, P55203, P55205, Q02846, Q03146, Q06805, Q06806, Q08345, Q1KL86, Q5JZY3, Q5SDA5, Q60750

Diamond homologs: F1N9Y5, O12990, O19064, O42127, O54967, O60674, P00522, P00533, P00534, P00535, P06239, P07948, P07949, P08103, P08630, P08631, P0CY46, P11273, P11362, P13388, P16092, P18460, P18461, P21709, P21802, P21803, P21804, P22182, P22455, P22607, P23458, P24786, P25911, P29597, P35739, P42683, P42685, P42690, P43403, P43404

SIGNOR signaling

40 interactions.

A	Effect	B	Mechanism
JAK3	up-regulates	SIGLEC10	phosphorylation
JAK3	unknown	SIGLEC10	phosphorylation
PTPN2	“down-regulates activity”	JAK3	dephosphorylation
JAK1	up-regulates	JAK3	phosphorylation
JAK3	up-regulates	JAK1	phosphorylation
JAK3	up-regulates	JAK3	phosphorylation
JAK3	up-regulates	STAT5A	phosphorylation
JAK3	up-regulates	PLD2	phosphorylation
IL2RG	up-regulates	JAK3	binding
AT9283	down-regulates	JAK3	“chemical inhibition”
ruxolitinib	down-regulates	JAK3	“chemical inhibition”
TG101209	down-regulates	JAK3	“chemical inhibition”
“tofacitinib citrate”	down-regulates	JAK3	“chemical inhibition”
SOCS1	“down-regulates activity”	JAK3	binding
SOCS3	“down-regulates activity”	JAK3	binding
IL15RA	up-regulates	JAK3	phosphorylation
IL15RA	up-regulates	JAK3
JAK3	up-regulates	STAT3	phosphorylation
JAK3	“up-regulates activity”	NFATC1	phosphorylation
JAK3	“up-regulates activity”	CTNNB1	phosphorylation
JAK3	“up-regulates activity”	EZH2	phosphorylation
IL4R	up-regulates	JAK3
JAK3	down-regulates	JAK3	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 35 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling	5	15.1×	3e-03
PIP3 activates AKT signaling	5	10.4×	8e-03
RAF/MAP kinase cascade	5	9.5×	8e-03

GO biological processes:

GO term	Partners	Fold	FDR
epidermal growth factor receptor signaling pathway	5	37.5×	1e-04
phosphatidylinositol 3-kinase/protein kinase B signal transduction	5	31.9×	1e-04
positive regulation of MAPK cascade	5	12.2×	4e-03
positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	5	11.9×	4e-03
protein stabilization	5	10.1×	7e-03
positive regulation of gene expression	8	9.4×	2e-04
protein ubiquitination	6	7.5×	7e-03

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: activating (oncogene-like) across 1 cancer types — ALL.

Clinical variants and AI predictions

ClinVar

1408 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	86
Likely pathogenic	45
Uncertain significance	392
Likely benign	686
Benign	109

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1074842	NM_000215.4(JAK3):c.1142+1G>C	Pathogenic
1323133	NM_000215.4(JAK3):c.1254+2T>A	Pathogenic
1339536	NM_000215.4(JAK3):c.2324G>A (p.Arg775His)	Pathogenic
1390045	NC_000019.9:g.(?17940897)(17943758_?)del	Pathogenic
1404557	NM_000215.4(JAK3):c.1383dup (p.Leu462fs)	Pathogenic
1453819	NM_000215.4(JAK3):c.3032G>A (p.Trp1011Ter)	Pathogenic
1456683	NM_000215.4(JAK3):c.1178dup (p.Ser394fs)	Pathogenic
1459771	NM_000215.4(JAK3):c.2311C>T (p.Arg771Ter)	Pathogenic
1508758	NM_000215.4(JAK3):c.1701+2T>A	Pathogenic
1705246	NM_000215.4(JAK3):c.3085dup (p.Ser1029fs)	Pathogenic
191101	NM_000215.4(JAK3):c.913C>T (p.Gln305Ter)	Pathogenic
191102	NM_000215.4(JAK3):c.308G>A (p.Arg103His)	Pathogenic
2131140	NM_000215.4(JAK3):c.1701+1G>A	Pathogenic
2152312	NM_000215.4(JAK3):c.2350G>A (p.Asp784Asn)	Pathogenic
2577241	NM_000215.4(JAK3):c.2141C>T (p.Thr714Met)	Pathogenic
2692977	NM_000215.4(JAK3):c.2319_2325dup (p.Asp776delinsHisSerTer)	Pathogenic
2696185	NM_000215.4(JAK3):c.3371_3372insTTTTTTTTTTTTTTTTTTTTNNNNNNNNNNTGCCCTGGGCCGCAGCGCAGCCGCGCAAACCACCACCCGCGGCCACCATGGCCGGACAGTATAATTTCCCCTGTCCTTTTC (p.Ser1124_Ter1125insPhePhePhePhePhePheXaaXaaXaaXaaAlaLeuGlyArgSerAlaAlaAlaGlnThrThrThrArgGlyHisHisGlyArgThrValTer)	Pathogenic
2701655	NM_000215.4(JAK3):c.548del (p.Glu183fs)	Pathogenic
2704615	NM_000215.4(JAK3):c.2272C>T (p.Gln758Ter)	Pathogenic
2707279	NM_000215.4(JAK3):c.904_908dup (p.Lys304fs)	Pathogenic
2736842	NM_000215.4(JAK3):c.3008TCT[1] (p.Phe1004del)	Pathogenic
2736843	NM_000215.4(JAK3):c.2787T>G (p.Tyr929Ter)	Pathogenic
2736845	NM_000215.4(JAK3):c.1786+3G>T	Pathogenic
2747421	NM_000215.4(JAK3):c.2350+1G>T	Pathogenic
2759186	NM_000215.4(JAK3):c.958_959del (p.Val320fs)	Pathogenic
2759221	NM_000215.4(JAK3):c.2419C>T (p.Gln807Ter)	Pathogenic
2762708	NM_000215.4(JAK3):c.235_242dup (p.Trp81fs)	Pathogenic
2762790	NM_000215.4(JAK3):c.1142+1G>T	Pathogenic
2764602	NM_000215.4(JAK3):c.3071_3072delinsAA (p.Cys1024Ter)	Pathogenic
2767886	NM_000215.4(JAK3):c.664_670del (p.Arg222fs)	Pathogenic

SpliceAI

3426 predictions. Top by Δscore:

Variant	Effect	Δscore
19:17830496:GAC:G	donor_loss	1.0000
19:17830497:ACTC:A	donor_loss	1.0000
19:17830498:C:CG	donor_loss	1.0000
19:17830499:T:TA	donor_loss	1.0000
19:17830500:CA:C	donor_loss	1.0000
19:17830501:A:AC	donor_gain	1.0000
19:17830501:ACGG:A	donor_gain	1.0000
19:17830501:ACGGC:A	donor_gain	1.0000
19:17830502:C:CG	donor_gain	1.0000
19:17830502:CG:C	donor_gain	1.0000
19:17830502:CGG:C	donor_gain	1.0000
19:17830502:CGGC:C	donor_gain	1.0000
19:17830502:CGGCC:C	donor_gain	1.0000
19:17830616:CATAC:C	acceptor_gain	1.0000
19:17830618:TAC:T	acceptor_gain	1.0000
19:17830619:ACCTG:A	acceptor_loss	1.0000
19:17831265:A:AC	donor_gain	1.0000
19:17831294:G:C	donor_gain	1.0000
19:17831399:CC:C	acceptor_gain	1.0000
19:17831400:CC:C	acceptor_gain	1.0000
19:17831400:CCT:C	acceptor_loss	1.0000
19:17831422:G:C	acceptor_gain	1.0000
19:17831668:TCGCA:T	donor_loss	1.0000
19:17831669:CGCAC:C	donor_loss	1.0000
19:17831670:GCAC:G	donor_loss	1.0000
19:17831671:CACCT:C	donor_loss	1.0000
19:17831672:ACCTT:A	donor_loss	1.0000
19:17831673:C:CT	donor_loss	1.0000
19:17831794:GCGGC:G	acceptor_gain	1.0000
19:17831795:CGGC:C	acceptor_gain	1.0000

AlphaMissense

7305 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:17831305:G:C	D967E	1.000
19:17831305:G:T	D967E	1.000
19:17831306:T:A	D967V	1.000
19:17831306:T:G	D967A	1.000
19:17831307:C:G	D967H	1.000
19:17831344:G:C	N954K	1.000
19:17831344:G:T	N954K	1.000
19:17831360:T:A	D949V	1.000
19:17831360:T:G	D949A	1.000
19:17832634:T:A	K855N	1.000
19:17832634:T:G	K855N	1.000
19:17832635:T:A	K855I	1.000
19:17832700:A:C	F833L	1.000
19:17832700:A:T	F833L	1.000
19:17832702:A:G	F833L	1.000
19:17830563:G:C	S1012R	0.999
19:17830563:G:T	S1012R	0.999
19:17830565:T:G	S1012R	0.999
19:17830568:A:G	W1011R	0.999
19:17830568:A:T	W1011R	0.999
19:17830587:G:C	F1004L	0.999
19:17830587:G:T	F1004L	0.999
19:17830589:A:G	F1004L	0.999
19:17831229:A:G	W993R	0.999
19:17831229:A:T	W993R	0.999
19:17831306:T:C	D967G	0.999
19:17831318:A:T	V963D	0.999
19:17831345:T:A	N954I	0.999
19:17831345:T:G	N954T	0.999
19:17831346:T:C	N954D	0.999

dbSNP variants (sampled 300 via entrez): RS1000200380 (19:17836472 G>A), RS1000260310 (19:17829394 G>A), RS1000350704 (19:17830103 C>T), RS1000368007 (19:17825210 G>T), RS1000493604 (19:17835318 A>C), RS1000952575 (19:17840593 C>A,T), RS1000957625 (19:17840221 T>C), RS1001058164 (19:17840828 T>C), RS1001064641 (19:17833894 G>T), RS1001100735 (19:17846443 C>A,T), RS1001258187 (19:17845598 A>T), RS1001268865 (19:17829404 C>T), RS1001375856 (19:17824644 G>A), RS1001425164 (19:17824924 G>C), RS1001612528 (19:17824534 C>T)

Disease associations

OMIM: gene MIM:600173 | disease phenotypes: MIM:600802, MIM:303350, MIM:102700, MIM:601457

GenCC curated gene-disease

Disease	Classification	Inheritance
T-B+ severe combined immunodeficiency due to JAK3 deficiency	Definitive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
T-B+ severe combined immunodeficiency due to JAK3 deficiency	Definitive	AR

Mondo (6): T-B+ severe combined immunodeficiency due to JAK3 deficiency (MONDO:0010938), hereditary spastic paraplegia (MONDO:0019064), severe combined immunodeficiency (MONDO:0015974), severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-negative, due to adenosine deaminase deficiency (MONDO:0007064), severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-positive (MONDO:0011086), NK-cell enteropathy (MONDO:0016996)

Orphanet (6): T-B+ severe combined immunodeficiency due to JAK3 deficiency (Orphanet:35078), Hereditary spastic paraplegia (Orphanet:685), Severe combined immunodeficiency (Orphanet:183660), Severe combined immunodeficiency due to adenosine deaminase deficiency (Orphanet:277), Severe combined immunodeficiency due to complete RAG1/2 deficiency (Orphanet:331206), NK-cell enteropathy (Orphanet:263665)

HPO phenotypes

40 total (30 of 40 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000143	Rectovaginal fistula
HP:0000371	Acute otitis media
HP:0000403	Recurrent otitis media
HP:0000953	Hyperpigmentation of the skin
HP:0000988	Skin rash
HP:0001287	Meningitis
HP:0001433	Hepatosplenomegaly
HP:0001508	Failure to thrive
HP:0001531	Failure to thrive in infancy
HP:0001888	Decreased total lymphocyte count
HP:0001999	Abnormal facial shape
HP:0002028	Chronic diarrhea
HP:0002090	Pneumonia
HP:0002205	Recurrent respiratory infections
HP:0002783	Recurrent lower respiratory tract infections
HP:0002788	Recurrent upper respiratory tract infections
HP:0002850	Decreased circulating total IgM
HP:0002965	Cutaneous anergy
HP:0003139	Panhypogammaglobulinemia
HP:0003347	Impaired lymphocyte transformation with phytohemagglutinin
HP:0003593	Infantile onset
HP:0004315	Decreased circulating IgG concentration
HP:0004429	Recurrent viral infections
HP:0004430	Severe combined immunodeficiency
HP:0004798	Recurrent infection of the gastrointestinal tract
HP:0005214	Intestinal obstruction
HP:0005354	Absent cellular immunity
HP:0005372	Abnormal B cell physiology
HP:0005390	Recurrent opportunistic infections

GWAS associations

0 associations (top):

MeSH disease descriptors (5)

Descriptor	Name	Tree numbers
D016511	Severe Combined Immunodeficiency	C16.320.798.750; C16.614.815; C18.452.284.800; C20.673.795.750
D015419	Spastic Paraplegia, Hereditary	C10.500.300.820; C10.574.500.495.820; C10.668.829.800.300.820; C16.131.666.300.820; C16.320.400.375.820
C563311	Severe Combined Immunodeficiency, Autosomal Recessive, T Cell-Negative, B Cell-Negative, NK Cell-Positive (supp.)
C563440	Severe Combined Immunodeficiency, Autosomal Recessive, T Cell-Negative, B Cell-Positive, NK Cell-Negative (supp.)
C531816	Severe combined immunodeficiency due to adenosine deaminase deficiency (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (5): CHEMBL2148 (SINGLE PROTEIN), CHEMBL2363062 (PROTEIN FAMILY), CHEMBL3038491 (PROTEIN COMPLEX), CHEMBL4802035 (PROTEIN FAMILY), CHEMBL6066057 (PROTEIN-PROTEIN INTERACTION)

Molecules with ChEMBL bioactivity

91 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 220,679 (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
CHEMBL1078178	MOMELOTINIB	4	3,481
CHEMBL1287853	FEDRATINIB	4	3,554
CHEMBL1289926	AXITINIB	4	15,732
CHEMBL1336	SORAFENIB	4	86,060
CHEMBL1789941	RUXOLITINIB	4	11,547
CHEMBL1795071	RUXOLITINIB PHOSPHATE	4	3,220
CHEMBL180022	NERATINIB	4	9,404
CHEMBL1873475	IBRUTINIB	4	7,994
CHEMBL189963	PALBOCICLIB	4	13,102
CHEMBL1983268	ENTRECTINIB	4	3,510
CHEMBL2035187	PACRITINIB	4	3,345
CHEMBL2103743	TOFACITINIB CITRATE	4	1,672
CHEMBL2105759	BARICITINIB	4	6,741
CHEMBL2110732	DACOMITINIB ANHYDROUS	4	6,578
CHEMBL221959	TOFACITINIB	4	10,408
CHEMBL2403108	CERITINIB	4	8,551
CHEMBL288441	BOSUTINIB	4	12,255
CHEMBL3137308	PEFICITINIB	4	1,722
CHEMBL3301607	FILGOTINIB	4	2,905
CHEMBL3353410	OSIMERTINIB	4	8,898
CHEMBL3622821	UPADACITINIB	4
CHEMBL3655081	ABROCITINIB	4
CHEMBL3707348	ACALABRUTINIB	4
CHEMBL3936761	ZANUBRUTINIB	4
CHEMBL4085457	RITLECITINIB	4
CHEMBL4435170	DEUCRAVACITINIB	4
CHEMBL477772	PAZOPANIB	4
CHEMBL502835	NINTEDANIB	4
CHEMBL535	SUNITINIB	4
CHEMBL5416410	DASATINIB	4

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — Janus kinase (JakA) family

Most potent curated ligand interactions (59 total), top 25:

Ligand	Action	Affinity	Parameter
nezulcitinib	Inhibition	10.2	pKi
abivertinib	Inhibition	10.05	pIC50
ritlecitinib	Inhibition	9.52	pIC50
modzatinib	Inhibition	9.28	pIC50
izencitinib	Inhibition	9.0	pKi
AT-9283	Inhibition	8.96	pIC50
SJ988497	Binding	8.85	pKd
vexicitinib	Inhibition	8.84	pIC50
JAK inhibitor 17b	Inhibition	8.78	pIC50
PF-956980	Inhibition	8.55	pIC50
LASW1393	Inhibition	8.46	pIC50
JAK inhibitor I	Inhibition	8.3	pIC50
compound 2 [PMID: 15546730]	Inhibition	8.22	pIC50
cerdulatinib	Inhibition	8.1	pIC50
lepzacitinib	Inhibition	8.0	pIC50
JAK3 inhibitor 32	Inhibition	7.96	pIC50
delgocitinib	Inhibition	7.89	pIC50
compound 1d [PMID: 21493067]	Inhibition	7.82	pIC50
lazertinib	Inhibition	7.7	pIC50
GDC-0214	Inhibition	7.68	pKi
PRN694	Inhibition	7.52	pIC50
ibrutinib	Inhibition	7.49	pIC50
compound 18e [PMID: 31670517]	Inhibition	7.41	pIC50
ilginatinib	Inhibition	7.41	pIC50
compound 8l [PMID: 36053746]	Inhibition	7.34	pIC50

Binding affinities (BindingDB)

3465 measured of 4177 human assays (4180 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
N-methyl-N-[4-[[3-(2-methylpropoxy)piperidin-1-yl]sulfonylmethyl]cyclohexyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine	IC50	0.00133 nM	US-8633206: Pyrrolo[2,3-D]pyrimidine compounds
N-[4-[[3-(2-methoxyethoxy)piperidin-1-yl]sulfonylmethyl]cyclohexyl]-N-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine	IC50	0.00125 nM	US-8633206: Pyrrolo[2,3-D]pyrimidine compounds
[(3R,4R)-4-methyl-1-[[4-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclohexyl]methylsulfonyl]pyrrolidin-3-yl]methanol	IC50	0.00199 nM	US-8633206: Pyrrolo[2,3-D]pyrimidine compounds
US20260001898, Example A1	KD	0.004 nM	US-20260001898: Heteroaryl compounds as inhibitors of TYK2/JAK1, composition and application thereof
[(3S)-1-[[(1S,3R,4S)-3-methyl-4-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclohexyl]methylsulfonyl]pyrrolidin-3-yl]methanol	IC50	0.00508 nM	US-8633206: Pyrrolo[2,3-D]pyrimidine compounds
3-methyl-1-[[4-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclohexyl]methylsulfonyl]pyrrolidin-3-ol	IC50	0.00777 nM	US-8633206: Pyrrolo[2,3-D]pyrimidine compounds
1-methylsulfonyl-N-[3-(5H-pyrrolo[2,3-b]pyrazin-2-yl)-2-pyridinyl]azepan-4-amine	IC50	0.0089 nM	US-8618103: Inhibitors of JAK
methyl 3-[[3-(5H-pyrrolo[2,3-b]pyrazin-2-yl)-2-pyridinyl]amino]azepane-1-carboxylate	IC50	0.0106 nM	US-8618103: Inhibitors of JAK
N-[(3S)-1-methylsulfonylpyrrolidin-3-yl]-3-(5H-pyrrolo[2,3-b]pyrazin-2-yl)pyridin-2-amine	IC50	0.0108 nM	US-8618103: Inhibitors of JAK
N-[(3S)-1-(3,3-dimethylbutylsulfonyl)piperidin-3-yl]-2-(4-methylpiperazin-1-yl)-5-(5H-pyrrolo[2,3-b]pyrazin-2-yl)pyrimidin-4-amine	IC50	0.0172 nM	US-8618103: Inhibitors of JAK
1-[3-[[3-(5H-pyrrolo[2,3-b]pyrazin-2-yl)-2-pyridinyl]amino]azepan-1-yl]ethanone	IC50	0.0191 nM	US-8618103: Inhibitors of JAK
4-N-[(3S)-1-(2-methylpropylsulfonyl)piperidin-3-yl]-5-(5H-pyrrolo[2,3-b]pyrazin-2-yl)pyrimidine-2,4-diamine	IC50	0.0196 nM	US-8618103: Inhibitors of JAK
(3R,4R)-1-methylsulfonyl-3-[[3-(5H-pyrrolo[2,3-b]pyrazin-2-yl)-2-pyridinyl]amino]piperidin-4-ol	IC50	0.0201 nM	US-8618103: Inhibitors of JAK
1-methylsulfonyl-N-[3-(5H-pyrrolo[2,3-b]pyrazin-2-yl)-2-pyridinyl]azepan-3-amine	IC50	0.0209 nM	US-8618103: Inhibitors of JAK
2-[1-[4-[[(3S)-1-methylsulfonylpiperidin-3-yl]amino]-5-(5H-pyrrolo[2,3-b]pyrazin-2-yl)pyrimidin-2-yl]piperidin-4-yl]acetamide	IC50	0.0221 nM	US-8618103: Inhibitors of JAK
[(3R)-1-[[4-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclohexyl]methylsulfonyl]piperidin-3-yl] 2,2-dimethylpropanoate	IC50	0.0227 nM	US-8633206: Pyrrolo[2,3-D]pyrimidine compounds
1-[(3R)-3-[[3-(5H-pyrrolo[2,3-b]pyrazin-2-yl)-2-pyridinyl]amino]piperidin-1-yl]ethanone	IC50	0.0228 nM	US-8618103: Inhibitors of JAK
diethyl [(3R)-1-[[4-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclohexyl]methylsulfonyl]piperidin-3-yl] phosphate	IC50	0.0235 nM	US-8633206: Pyrrolo[2,3-D]pyrimidine compounds
N-[(3S)-1-(2,2-dimethylpropylsulfonyl)piperidin-3-yl]-3-(5H-pyrrolo[2,3-b]pyrazin-2-yl)pyridin-2-amine	IC50	0.0245 nM	US-8618103: Inhibitors of JAK
N-methyl-N-[4-[(4-methylpiperazin-1-yl)sulfonylmethyl]cyclohexyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine	IC50	0.0245 nM	US-8633206: Pyrrolo[2,3-D]pyrimidine compounds
[(3R)-1-[[4-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclohexyl]methylsulfonyl]piperidin-3-yl] dihydrogen phosphate	IC50	0.0263 nM	US-8633206: Pyrrolo[2,3-D]pyrimidine compounds
methyl (3S)-3-[[3-(5H-pyrrolo[2,3-b]pyrazin-2-yl)-2-pyridinyl]amino]pyrrolidine-1-carboxylate	IC50	0.0276 nM	US-8618103: Inhibitors of JAK
N-[(3R)-1-methylsulfonylpiperidin-3-yl]-3-(5H-pyrrolo[2,3-b]pyrazin-2-yl)pyridin-2-amine	IC50	0.0292 nM	US-8618103: Inhibitors of JAK
N-[(3S)-1-(3,3-dimethylbutylsulfonyl)piperidin-3-yl]-2-methylsulfanyl-5-(5H-pyrrolo[2,3-b]pyrazin-2-yl)pyrimidin-4-amine	IC50	0.0293 nM	US-8618103: Inhibitors of JAK
N-[(3R)-1-methylsulfonylpyrrolidin-3-yl]-3-(5H-pyrrolo[2,3-b]pyrazin-2-yl)pyridin-2-amine	IC50	0.0296 nM	US-8618103: Inhibitors of JAK
2-[(3S,5S)-3-methyl-5-[[3-(5H-pyrrolo[2,3-b]pyrazin-2-yl)-2-pyridinyl]amino]piperidin-1-yl]sulfonylacetonitrile	IC50	0.0332 nM	US-8618103: Inhibitors of JAK
3-(5H-pyrrolo[2,3-b]pyrazin-2-yl)-N-[(3S)-1-(2,2,2-trifluoroethyl)piperidin-3-yl]pyridin-2-amine	IC50	0.035 nM	US-8618103: Inhibitors of JAK
N-[(3S)-1-methylsulfonylpiperidin-3-yl]-3-(5H-pyrrolo[2,3-b]pyrazin-2-yl)pyrazin-2-amine	IC50	0.0359 nM	US-8618103: Inhibitors of JAK
3-(7-methyl-5H-pyrrolo[2,3-b]pyrazin-2-yl)-N-[(3S)-1-methylsulfonylpiperidin-3-yl]pyridin-2-amine	IC50	0.0367 nM	US-8618103: Inhibitors of JAK
3-(7-cyclopropyl-5H-pyrrolo[2,3-b]pyrazin-2-yl)-N-[(3S)-1-methylsulfonylpiperidin-3-yl]pyridin-2-amine	IC50	0.0384 nM	US-8618103: Inhibitors of JAK
1-[(3S)-3-[[3-(5H-pyrrolo[2,3-b]pyrazin-2-yl)-2-pyridinyl]amino]pyrrolidin-1-yl]ethanone	IC50	0.0397 nM	US-8618103: Inhibitors of JAK
3-(7-chloro-5H-pyrrolo[2,3-b]pyrazin-2-yl)-N-[(3S)-1-methylsulfonylpiperidin-3-yl]pyridin-2-amine	IC50	0.0398 nM	US-8618103: Inhibitors of JAK
N-[(3S)-1-(cyclopropylmethylsulfonyl)piperidin-3-yl]-3-(5H-pyrrolo[2,3-b]pyrazin-2-yl)pyridin-2-amine	IC50	0.0413 nM	US-8618103: Inhibitors of JAK
(2S)-2-[[4-[[(3S)-1-methylsulfonylpiperidin-3-yl]amino]-5-(5H-pyrrolo[2,3-b]pyrazin-2-yl)pyrimidin-2-yl]amino]butan-1-ol	IC50	0.0432 nM	US-8618103: Inhibitors of JAK
6-methyl-N-(1-methylsulfonylpiperidin-3-yl)-3-(5H-pyrrolo[2,3-b]pyrazin-2-yl)pyridin-2-amine	IC50	0.0464 nM	US-8618103: Inhibitors of JAK
methyl 4-[[3-(5H-pyrrolo[2,3-b]pyrazin-2-yl)-2-pyridinyl]amino]piperidine-1-carboxylate	IC50	0.047 nM	US-8618103: Inhibitors of JAK
1-[4-[[(3S)-1-methylsulfonylpiperidin-3-yl]amino]-5-(5H-pyrrolo[2,3-b]pyrazin-2-yl)pyrimidin-2-yl]azetidine-3-carbonitrile	IC50	0.0485 nM	US-8618103: Inhibitors of JAK
N-[(3S)-1-(2-methylpropylsulfonyl)piperidin-3-yl]-2-morpholin-4-yl-5-(5H-pyrrolo[2,3-b]pyrazin-2-yl)pyrimidin-4-amine	IC50	0.049 nM	US-8618103: Inhibitors of JAK
(S)-(3-(dimethylamino)-3-methylazetidin-1-yl)(2-(6-(2-ethyl-5-fluoro-4-hydroxyphenyl)-1H-indazol-3-yl)-5-propyl-4,5,6,7-tetrahydro-3H-imidazo[4,5-c]pyridin-6-yl)methanone	KI	0.05 nM	US-10196393: JAK inhibitors containing a 4-membered heterocyclic amide
BDBM431910	KI	0.05 nM	US-10196393: JAK inhibitors containing a 4-membered heterocyclic amide
US10196393, Example 8-20	KI	0.05 nM	US-10196393: JAK inhibitors containing a 4-membered heterocyclic amide
(S)-(3-(dimethylamino)-3-methylazetidin-1-yl)(5-ethyl-2-(6-(2-ethyl-5-fluoro-4-hydroxyphenyl)-1H-indazol-3-yl)-4,5,6,7-tetrahydro-3H-imidazo[4,5-c]pyridin-6-yl)methanone	KI	0.05 nM	US-10196393: JAK inhibitors containing a 4-membered heterocyclic amide
(2R)-2-[[4-[[(3S)-1-methylsulfonylpiperidin-3-yl]amino]-5-(5H-pyrrolo[2,3-b]pyrazin-2-yl)pyrimidin-2-yl]amino]butan-1-ol	IC50	0.054 nM	US-8618103: Inhibitors of JAK
2-N,2-N-dimethyl-4-N-[(3S)-1-(2-methylpropylsulfonyl)piperidin-3-yl]-5-(5H-pyrrolo[2,3-b]pyrazin-2-yl)pyrimidine-2,4-diamine	IC50	0.0549 nM	US-8618103: Inhibitors of JAK
6-[methyl-[(3R)-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)pyrrolidin-3-yl]amino]pyridine-3-sulfonamide	IC50	0.055 nM	US-9346810: Pyrrolopyrimidine compounds and uses thereof
2-fluoro-4-[methyl-[(3R)-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)pyrrolidin-3-yl]amino]benzonitrile	IC50	0.055 nM	US-9346810: Pyrrolopyrimidine compounds and uses thereof
4-[(3R)-3-[methyl(methylsulfamoyl)amino]pyrrolidin-1-yl]-7H-pyrrolo[2,3-d]pyrimidine	IC50	0.055 nM	US-9346810: Pyrrolopyrimidine compounds and uses thereof
2-cyano-N-methyl-N-[(3R)-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)pyrrolidin-3-yl]acetamide	IC50	0.055 nM	US-9346810: Pyrrolopyrimidine compounds and uses thereof
2-methoxy-6-[methyl-[(3R)-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)pyrrolidin-3-yl]amino]pyridine-3-carbonitrile	IC50	0.055 nM	US-9346810: Pyrrolopyrimidine compounds and uses thereof
5-chloro-N-methyl-N-[(3R)-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)pyrrolidin-3-yl]pyridin-2-amine	IC50	0.055 nM	US-9346810: Pyrrolopyrimidine compounds and uses thereof

ChEMBL bioactivities

6100 potent at pChembl≥5 of 6100 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.98	IC50	0.01051	nM	CHEMBL3665184
10.98	IC50	0.01047	nM	CHEMBL3665122
10.98	Ki	0.01046	nM	CHEMBL3335689
10.98	Ki	0.01055	nM	CHEMBL3335699
10.97	IC50	0.01071	nM	CHEMBL3665193
10.97	Ki	0.01081	nM	CHEMBL3665213
10.97	Ki	0.01074	nM	CHEMBL3665173
10.96	IC50	0.01096	nM	CHEMBL3665200
10.93	IC50	0.01175	nM	CHEMBL3665172
10.93	Ki	0.01167	nM	CHEMBL3665209
10.93	Ki	0.01179	nM	CHEMBL3665167
10.90	IC50	0.01251	nM	CHEMBL3665206
10.90	Ki	0.01253	nM	CHEMBL3665201
10.89	IC50	0.013	nM	CHEMBL3650991
10.89	Ki	0.01291	nM	CHEMBL3665203
10.89	IC50	0.013	nM	CHEMBL3651021
10.89	IC50	0.01281	nM	CHEMBL3665123
10.87	IC50	0.01359	nM	CHEMBL3665207
10.87	Ki	0.01339	nM	CHEMBL3665217
10.87	Ki	0.01356	nM	CHEMBL3665189
10.82	Ki	0.01504	nM	CHEMBL3665197
10.82	Ki	0.01517	nM	CHEMBL3665144
10.82	IC50	0.01512	nM	CHEMBL3335697
10.81	IC50	0.01559	nM	CHEMBL3335699
10.81	Ki	0.01553	nM	CHEMBL3335688
10.80	IC50	0.016	nM	CHEMBL3651050
10.79	Ki	0.01631	nM	CHEMBL3665191
10.79	Ki	0.01631	nM	CHEMBL3665215
10.79	Ki	0.01634	nM	CHEMBL3665211
10.78	IC50	0.01676	nM	CHEMBL3665150
10.76	IC50	0.01721	nM	CHEMBL3335695
10.76	IC50	0.01735	nM	CHEMBL3665171
10.76	Ki	0.01754	nM	CHEMBL3665153
10.75	IC50	0.01794	nM	CHEMBL3665128
10.75	IC50	0.01787	nM	CHEMBL3335694
10.73	IC50	0.01863	nM	CHEMBL3335698
10.73	Ki	0.01878	nM	CHEMBL3335693
10.72	Ki	0.01905	nM	CHEMBL3665141
10.72	IC50	0.0192	nM	CHEMBL3683258
10.71	Ki	0.01969	nM	CHEMBL3665151
10.71	IC50	0.01937	nM	CHEMBL3665146
10.70	Ki	0.01979	nM	CHEMBL3665195
10.70	IC50	0.02	nM	CHEMBL3651041
10.70	Ki	0.01988	nM	CHEMBL3665149
10.70	IC50	0.02	nM	CHEMBL3651060
10.69	IC50	0.02038	nM	CHEMBL3335689
10.67	Ki	0.02131	nM	CHEMBL3665205
10.67	IC50	0.0215	nM	CHEMBL3665173
10.66	IC50	0.02164	nM	CHEMBL3665213
10.64	IC50	0.02299	nM	CHEMBL3665167

PubChem BioAssay actives

2834 with measured affinity, of 6100 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
(E)-2-cyano-3-[5-(3-cyclohexyl-3,5,8,10-tetrazatricyclo[7.3.0.02,6]dodeca-1,4,6,8,11-pentaen-4-yl)furan-2-yl]-N,N-dimethylprop-2-enamide	1802149: Kinase HotSpot Assay from Article 10.1016/j.chembiol.2016.10.008: “Selective JAK3 Inhibitors with a Covalent Reversible Binding Mode Targeting a New Induced Fit Binding Pocket.”	ic50	0.0001	uM
2-cyano-3-[5-(3-cyclohexyl-3,5,8,10-tetrazatricyclo[7.3.0.02,6]dodeca-1,4,6,8,11-pentaen-4-yl)furan-2-yl]-N,N-dimethylprop-2-enamide	1497450: Inhibition of human JAK3 using GEEEEYFELVKKKK as substrate in presence of 10 uM [gamma33P]ATP by radiometric method	ic50	0.0001	uM
N-[3-[[6-[[1-(2-methoxyethyl)pyrazol-4-yl]amino]pyrazolo[3,4-d]pyrimidin-1-yl]methyl]phenyl]prop-2-enamide	1679033: Inhibition of human JAK3 expressed in baculovirus expression system using TK-substrate-biotin as substrate preincubated for 5 mins followed by ATP and substrate addition and measured after 60 mins by HTRF method	ic50	0.0001	uM
3-(1H-indol-3-yl)-4-[2-nitro-5-(4-prop-2-ynoylpiperazin-1-yl)phenyl]pyrrole-2,5-dione	1536109: Inhibition of human N-terminal His-tagged JAK3 (795 to 1124 residues) expressed in baculovirus expression system in presence of 6 uM ATP by HTRF assay	ic50	0.0001	uM
(2S,3R,4R,6R)-3-methoxy-2-methyl-4-(methylamino)-29-oxa-1,7,17-triazaoctacyclo[12.12.2.12,6.07,28.08,13.015,19.020,27.021,26]nonacosa-8,10,12,14,19,21,23,25,27-nonaen-16-one	1350981: Inhibition of JAK3 (unknown origin)	ic50	0.0001	uM
3-[(3R,4R)-4-methyl-3-(3,8,10-triazatricyclo[7.3.0.02,6]dodeca-1,4,6,8,11-pentaen-3-yl)piperidin-1-yl]-3-oxopropanenitrile	1940830: Inhibition of human JAK3 kinase domain using biotin-Lyn-substrate-2 as substrate incubated for 1 hr by ELISA	ic50	0.0001	uM
3-[(3R,4R)-1-(2-cyanoacetyl)-4-methylpiperidin-3-yl]-3,8,10-triazatricyclo[7.3.0.02,6]dodeca-1,4,6,8,11-pentaene-12-carbonitrile	1940830: Inhibition of human JAK3 kinase domain using biotin-Lyn-substrate-2 as substrate incubated for 1 hr by ELISA	ic50	0.0001	uM
N-[(2R)-1-(3-cyanoazetidin-1-yl)-3,3-dimethyl-1-oxobutan-2-yl]-2-cyclopropyl-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide	726510: Binding affinity to JAK3 (unknown origin)	kd	0.0001	uM
(E)-2-cyano-N,N-dimethyl-3-[5-[3-[(1S,2R)-2-methylcyclohexyl]-3,5,8,10-tetrazatricyclo[7.3.0.02,6]dodeca-1,4,6,8,11-pentaen-4-yl]furan-2-yl]prop-2-enamide	1802149: Kinase HotSpot Assay from Article 10.1016/j.chembiol.2016.10.008: “Selective JAK3 Inhibitors with a Covalent Reversible Binding Mode Targeting a New Induced Fit Binding Pocket.”	ic50	0.0002	uM
(E)-3-[5-(3-cyclohexyl-3,5,8,10-tetrazatricyclo[7.3.0.02,6]dodeca-1,4,6,8,11-pentaen-4-yl)furan-2-yl]prop-2-enenitrile	1497450: Inhibition of human JAK3 using GEEEEYFELVKKKK as substrate in presence of 10 uM [gamma33P]ATP by radiometric method	ic50	0.0002	uM
4-[2-amino-8-[[(1R,5S)-8-azabicyclo[3.2.1]octan-3-yl]amino]quinazolin-6-yl]-5-ethyl-2-fluorophenol	1824614: Inhibition of GST-fused human JAK3 (810 to 1100 residues) expressed in insect cells using ULight-JAK-1 Tyr1023 peptide as substrate preincubated for 30 mins followed by substrate addition and further incubated for 20 mins in presence of ATP by FRET assay	ic50	0.0002	uM
4-[2-amino-8-[[(3S)-1-methylpiperidin-3-yl]amino]quinazolin-6-yl]-5-ethyl-2-fluorophenol	1824614: Inhibition of GST-fused human JAK3 (810 to 1100 residues) expressed in insect cells using ULight-JAK-1 Tyr1023 peptide as substrate preincubated for 30 mins followed by substrate addition and further incubated for 20 mins in presence of ATP by FRET assay	ic50	0.0002	uM
3-[(3R,4R)-4-methyl-3-(4-methyl-3,8,10-triazatricyclo[7.3.0.02,6]dodeca-1,4,6,8,11-pentaen-3-yl)piperidin-1-yl]-3-oxopropanenitrile	1940830: Inhibition of human JAK3 kinase domain using biotin-Lyn-substrate-2 as substrate incubated for 1 hr by ELISA	ic50	0.0002	uM
N-[3-(1H-pyrrolo[2,3-b]pyridin-3-yl)phenyl]prop-2-enamide	1872698: Inhibition of recombinant JAK3 (unknown origin)	ic50	0.0002	uM
Ritlecitinib	1365118: Inhibition of JAK3 (unknown origin)	ic50	0.0003	uM
N-[3-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)phenyl]prop-2-enamide	1438276: Inhibition of recombinant human GST-tagged cytoplasmic JAK3 catalytic domain (781 to 1124 residues) expressed in baculovirus expression system using FITC-KGGEEEEYFELVKK as substrate in presence of 4 uM ATP by microfluidic assay	ic50	0.0003	uM
[4-[[4-[3-(prop-2-enoylamino)anilino]-5-(trifluoromethyl)pyrimidin-2-yl]amino]phenyl]boronic acid	1650544: Inhibition of recombinant human N-terminal His-tagged JAK3 (795 to 1124 residues) expressed in baculovirus expression system using Ulight-Poly GT as substrate incubated for 2 hrs by Lanthascreen TR-FRET assay	ic50	0.0003	uM
4-[8-methoxy-2-[(1-methylpyrazol-4-yl)amino]quinazolin-6-yl]phenol	1824614: Inhibition of GST-fused human JAK3 (810 to 1100 residues) expressed in insect cells using ULight-JAK-1 Tyr1023 peptide as substrate preincubated for 30 mins followed by substrate addition and further incubated for 20 mins in presence of ATP by FRET assay	ic50	0.0003	uM
N-[(1R)-2-[(3R)-3-cyanopyrrolidin-1-yl]-1-cyclopropyl-2-oxoethyl]-2-cyclopropyl-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide	726698: Inhibition of JAK3 (unknown origin)-mediated phosphorylation of Biotin-KAIETDKEYYTVKD incubated for 10 mins prior to substrate addition measured after 30 mins by scintillation counting analysis in presence of [gamma-33P]ATP	ic50	0.0003	uM
4-[[(3S,4R)-1-(5-cyano-2-pyridinyl)-3-fluoropiperidin-4-yl]amino]-1H-pyrrolo[2,3-b]pyridine-5-carboxamide	1234588: Inhibition of human JAK3 kinase domain using biotin-Lyn-substrate-2 as substrate incubated for 1 hr by ELISA method	ic50	0.0003	uM
2-(6-chloro-1-methylindazol-3-yl)-N-[(1R)-2-(3-cyanoazetidin-1-yl)-1-cyclopropyl-2-oxoethyl]-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide	745000: Inhibition of JAK3 (unknown origin) using [33gammaP]ATP and Biotin-KAIETDKEYYTVKD as substrate incubated for 10 mins prior to substrate addition measured after 30 mins by filtration assay	ic50	0.0003	uM
N-[(2R)-1-(3-cyanoazetidin-1-yl)-1-oxopropan-2-yl]-2-(6-fluoroimidazo[1,5-a]pyridin-1-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide	745000: Inhibition of JAK3 (unknown origin) using [33gammaP]ATP and Biotin-KAIETDKEYYTVKD as substrate incubated for 10 mins prior to substrate addition measured after 30 mins by filtration assay	ic50	0.0003	uM
4-[[(1R,3S)-3-amino-2,2,3-trimethylcyclopentyl]amino]-6-(3-methoxyphenyl)pyrrolo[1,2-b]pyridazine-3-carboxamide	1485443: Inhibition of JAK3 (unknown origin) using CSKtide as substrate after 30 mins in presence of [gamma33P]ATP by liquid scintillation counting method	ic50	0.0004	uM
4-[[(1R,3S)-3-amino-2,2,3-trimethylcyclopentyl]amino]-6-(6-fluoro-3-pyridinyl)pyrrolo[1,2-b]pyridazine-3-carboxamide	1485443: Inhibition of JAK3 (unknown origin) using CSKtide as substrate after 30 mins in presence of [gamma33P]ATP by liquid scintillation counting method	ic50	0.0004	uM
1-[(3aR,7aR)-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-3,3a,4,5,7,7a-hexahydro-2H-pyrrolo[2,3-c]pyridin-6-yl]prop-2-en-1-one	1438276: Inhibition of recombinant human GST-tagged cytoplasmic JAK3 catalytic domain (781 to 1124 residues) expressed in baculovirus expression system using FITC-KGGEEEEYFELVKK as substrate in presence of 4 uM ATP by microfluidic assay	ic50	0.0004	uM
ethyl 4-[2-fluoro-5-(prop-2-enoylamino)phenyl]-7H-pyrrolo[2,3-d]pyrimidine-5-carboxylate	1365118: Inhibition of JAK3 (unknown origin)	ic50	0.0004	uM
2-[[5-(3-cyclohexyl-3,5,8,10-tetrazatricyclo[7.3.0.02,6]dodeca-1,4,6,8,11-pentaen-4-yl)furan-2-yl]methylidene]propanedinitrile	1497450: Inhibition of human JAK3 using GEEEEYFELVKKKK as substrate in presence of 10 uM [gamma33P]ATP by radiometric method	ic50	0.0004	uM
3-(1H-indol-3-yl)-4-[2-nitro-5-(4-prop-2-enoylpiperazin-1-yl)phenyl]pyrrole-2,5-dione	1536109: Inhibition of human N-terminal His-tagged JAK3 (795 to 1124 residues) expressed in baculovirus expression system in presence of 6 uM ATP by HTRF assay	ic50	0.0004	uM
3-[5-[4-(2-chloroacetyl)piperazin-1-yl]-2-(trifluoromethyl)phenyl]-4-(1H-indol-3-yl)pyrrole-2,5-dione	1536109: Inhibition of human N-terminal His-tagged JAK3 (795 to 1124 residues) expressed in baculovirus expression system in presence of 6 uM ATP by HTRF assay	ic50	0.0004	uM
N-[3-[3-[4-(1H-indol-3-yl)-2,5-dioxopyrrol-3-yl]-N-methyl-4-nitroanilino]propyl]prop-2-enamide	1536109: Inhibition of human N-terminal His-tagged JAK3 (795 to 1124 residues) expressed in baculovirus expression system in presence of 6 uM ATP by HTRF assay	ic50	0.0004	uM
N-[3-[[2-[(1-hydroxy-3H-2,1-benzoxaborol-5-yl)amino]-5-(trifluoromethyl)pyrimidin-4-yl]amino]phenyl]prop-2-enamide	1650544: Inhibition of recombinant human N-terminal His-tagged JAK3 (795 to 1124 residues) expressed in baculovirus expression system using Ulight-Poly GT as substrate incubated for 2 hrs by Lanthascreen TR-FRET assay	ic50	0.0004	uM
4-[[1-(5-cyano-2-pyridinyl)piperidin-4-yl]amino]-6-[(2-methylpyrimidin-4-yl)amino]pyridine-3-carboxamide	1629468: Inhibition of human JAK3 assessed as reduction in phosphorylation of Biotin-Lyn-Substrate-2 after 1 hr in presence of ATP by ELISA	ic50	0.0004	uM
4-[[(3S,4R)-1-(5-cyano-2-pyridinyl)-3-fluoropiperidin-4-yl]amino]-6-[(2-methylpyrimidin-4-yl)amino]pyridine-3-carboxamide	1629468: Inhibition of human JAK3 assessed as reduction in phosphorylation of Biotin-Lyn-Substrate-2 after 1 hr in presence of ATP by ELISA	ic50	0.0004	uM
N-[(1R)-2-(3-cyanoazetidin-1-yl)-1-cyclopropyl-2-oxoethyl]-2-cyclopropyl-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide	726698: Inhibition of JAK3 (unknown origin)-mediated phosphorylation of Biotin-KAIETDKEYYTVKD incubated for 10 mins prior to substrate addition measured after 30 mins by scintillation counting analysis in presence of [gamma-33P]ATP	ic50	0.0004	uM
N-[(1R)-2-[(3S)-3-cyanopyrrolidin-1-yl]-1-cyclopropyl-2-oxoethyl]-2-cyclopropyl-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide	726698: Inhibition of JAK3 (unknown origin)-mediated phosphorylation of Biotin-KAIETDKEYYTVKD incubated for 10 mins prior to substrate addition measured after 30 mins by scintillation counting analysis in presence of [gamma-33P]ATP	ic50	0.0004	uM
4-[(5-hydroxy-2-adamantyl)amino]-1H-pyrrolo[2,3-b]pyridine-5-carboxamide	1399997: Inhibition of recombinant human N-terminal His-tagged JAK3 catalytic domain (795 to 1124 residues) expressed in baculovirus expression system using Biotin-Lyn-Substrate2 after 1 hr by ELISA	ic50	0.0004	uM
N-[(2R)-1-(3-cyanoazetidin-1-yl)-1-oxopropan-2-yl]-2-(3,4,5-trimethoxyphenyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide	745000: Inhibition of JAK3 (unknown origin) using [33gammaP]ATP and Biotin-KAIETDKEYYTVKD as substrate incubated for 10 mins prior to substrate addition measured after 30 mins by filtration assay	ic50	0.0004	uM
2-(6-chloro-1-methylindazol-3-yl)-N-[(2R)-1-(3-cyanoazetidin-1-yl)-1-oxobutan-2-yl]-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide	745000: Inhibition of JAK3 (unknown origin) using [33gammaP]ATP and Biotin-KAIETDKEYYTVKD as substrate incubated for 10 mins prior to substrate addition measured after 30 mins by filtration assay	ic50	0.0004	uM
4-[[(1R,3S)-3-amino-2,2,3-trimethylcyclopentyl]amino]-6-(6-propan-2-yloxy-3-pyridinyl)pyrrolo[1,2-b]pyridazine-3-carboxamide	1485443: Inhibition of JAK3 (unknown origin) using CSKtide as substrate after 30 mins in presence of [gamma33P]ATP by liquid scintillation counting method	ic50	0.0005	uM
N-[3-[[[2-[[1-(1-acetylpiperidin-4-yl)pyrazol-4-yl]amino]-5-chloropyrimidin-4-yl]amino]methyl]phenyl]prop-2-enamide	1239421: Inhibition of JAK3 (unknown origin) by Z’-Lyte assay	ic50	0.0005	uM
N-[3-[[[5-chloro-2-[[1-(2-morpholin-4-ylethyl)pyrazol-4-yl]amino]pyrimidin-4-yl]amino]methyl]phenyl]prop-2-enamide	1239421: Inhibition of JAK3 (unknown origin) by Z’-Lyte assay	ic50	0.0005	uM
N-[3-[[[5-chloro-2-[[1-(2-ethoxyethyl)pyrazol-4-yl]amino]pyrimidin-4-yl]amino]methyl]phenyl]prop-2-enamide	1239421: Inhibition of JAK3 (unknown origin) by Z’-Lyte assay	ic50	0.0005	uM
N-[3-[[[5-chloro-2-[[1-(2-propan-2-yloxyethyl)pyrazol-4-yl]amino]pyrimidin-4-yl]amino]methyl]phenyl]prop-2-enamide	1239421: Inhibition of JAK3 (unknown origin) by Z’-Lyte assay	ic50	0.0005	uM
N-[3-[[[5-chloro-2-[[1-(2-hydroxyethyl)pyrazol-4-yl]amino]pyrimidin-4-yl]amino]methyl]phenyl]prop-2-enamide	1239421: Inhibition of JAK3 (unknown origin) by Z’-Lyte assay	ic50	0.0005	uM
N-[3-[[[5-chloro-2-[[1-(2,2-difluoroethyl)pyrazol-4-yl]amino]pyrimidin-4-yl]amino]methyl]phenyl]prop-2-enamide	1239421: Inhibition of JAK3 (unknown origin) by Z’-Lyte assay	ic50	0.0005	uM
N-[3-[[[5-chloro-2-[[1-(2-methoxyethyl)pyrazol-4-yl]amino]pyrimidin-4-yl]amino]methyl]phenyl]prop-2-enamide	1239421: Inhibition of JAK3 (unknown origin) by Z’-Lyte assay	ic50	0.0005	uM
N-[3-[[[5-chloro-2-[[1-[2-(dimethylamino)ethyl]pyrazol-4-yl]amino]pyrimidin-4-yl]amino]methyl]phenyl]prop-2-enamide	1239421: Inhibition of JAK3 (unknown origin) by Z’-Lyte assay	ic50	0.0005	uM
N-[3-[[[5-chloro-2-[[1-[2-oxo-2-(2,2,2-trifluoroethylamino)ethyl]pyrazol-4-yl]amino]pyrimidin-4-yl]amino]methyl]phenyl]prop-2-enamide	1239421: Inhibition of JAK3 (unknown origin) by Z’-Lyte assay	ic50	0.0005	uM
N-[3-[[[5-chloro-2-[[1-[2-(methylamino)-2-oxoethyl]pyrazol-4-yl]amino]pyrimidin-4-yl]amino]methyl]phenyl]prop-2-enamide	1239421: Inhibition of JAK3 (unknown origin) by Z’-Lyte assay	ic50	0.0005	uM
1-[6-[5-(2-methoxyethyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-2,3-dihydro-1,4-benzoxazin-4-yl]prop-2-en-1-one	1419128: Inhibition of recombinant human GST-tagged JAK3 JH1 domain using KAIETDKEYYTVKD-NH2 as substrate in presence of ATP at Km concentration by coupled PK/LDH assay	ic50	0.0005	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
tofacitinib	decreases reaction, increases activity, increases phosphorylation, decreases activity	6
Particulate Matter	decreases methylation, increases abundance, increases expression	3
Acetaminophen	increases expression	2
Air Pollutants	increases expression, decreases methylation, increases abundance	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Tobacco Smoke Pollution	decreases expression	2
Triclosan	decreases expression, increases methylation	2
Valproic Acid	affects cotreatment, decreases expression	2
baricitinib	decreases reaction, increases activity, increases phosphorylation	1
bisphenol F	decreases methylation	1
sotorasib	affects cotreatment, decreases expression	1
tubocapsenolide A	decreases phosphorylation, decreases reaction	1
bufotalin	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases methylation	1
mono-(2-ethylhexyl)phthalate	increases abundance, increases expression, decreases methylation	1
afimoxifene	decreases response to substance	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
enterotoxin A, Staphylococcal	increases secretion, affects reaction	1
benzo(e)pyrene	decreases methylation	1
epigallocatechin gallate	decreases expression	1
2-ethyl-5-carboxypentyl phthalate	increases abundance, increases expression	1
pervanadate	decreases phosphorylation, decreases reaction	1
mono(2-ethyl-5-oxohexyl)phthalate	increases expression, increases abundance	1
RTKI cpd	decreases activity, decreases phosphorylation	1
WHI P154	decreases activity, decreases phosphorylation	1
WHI P131	decreases activity, decreases phosphorylation	1
entinostat	increases expression	1
2,2’,4,6,6’-pentachlorobiphenyl	increases phosphorylation, decreases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1

ChEMBL screening assays

1461 unique, capped per target: 1400 binding, 37 functional, 22 admet, 2 toxicity

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1009896	Binding	Inhibition of JAK3	Fragment-based discovery of the pyrazol-4-yl urea (AT9283), a multitargeted kinase inhibitor with potent aurora kinase activity. — J Med Chem
CHEMBL1963742	Functional	PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: JAK3	PubChem BioAssay data set
CHEMBL4023732	ADMET	Inhibition of recombinant human catalytic GST-tagged JAK3 expressed in baculovirus at 1 uM by Z’-LYTE assay	Discovery of GDC-0853: A Potent, Selective, and Noncovalent Bruton’s Tyrosine Kinase Inhibitor in Early Clinical Development. — J Med Chem

Cellosaurus cell lines

18 cell lines: 14 cancer cell line, 4 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B8IZ	Abcam HCT 116 JAK3 KO	Cancer cell line	Male
CVCL_B8XV	Abcam MCF-7 JAK3 KO	Cancer cell line	Female
CVCL_B9LA	Abcam A-549 JAK3 KO	Cancer cell line	Male
CVCL_D8NS	Ubigene HCT 116 JAK3 KO	Cancer cell line	Male
CVCL_E0WK	Ubigene Jurkat, Clone E6-1 JAK3 KO	Cancer cell line	Male
CVCL_E8ED	HEK-Blue CD122/CD132	Transformed cell line	Female
CVCL_E8EI	HEK-Blue IL-7	Transformed cell line	Female
CVCL_E8EJ	HEK-Blue IL-9	Transformed cell line	Female
CVCL_F0K0	JXQ-3D-783R1	Cancer cell line	Female
CVCL_F0K1	JXQ-3D-783R2	Cancer cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT07542548	PHASE4	COMPLETED	D-Cycloserine for Serine Palmitoyltransferase Inhibition
NCT00220766	PHASE3	COMPLETED	Rapid Infusion of Immune Globulin Intravenous (Human) In Primary Immunodeficiency Patients
NCT01420627	PHASE3	COMPLETED	EZN-2279 in Patients With ADA-SCID
NCT06940570	PHASE3	SUSPENDED	Methadone as an Alternative Treatment for Children Underdoing HSCT
NCT03961906	PHASE2	COMPLETED	Physiotherapy in Hereditary Spastic Paraplegia
NCT04768166	PHASE2	COMPLETED	Testing Miglustat Administration in Subjects With Spastic Paraplegia 11
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
NCT06117020	PHASE1	COMPLETED	Single and Multiple Ascending Dose Study of MTR-601 in Healthy Individuals
NCT00008450	PHASE1	COMPLETED	Total-Body Irradiation Followed By Cyclosporine and Mycophenolate Mofetil in Treating Patients With Severe Combined Immunodeficiency Undergoing Donor Bone Marrow Transplant
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
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
NCT02604186	PHASE2/PHASE3	COMPLETED	Effects of Botulinum Toxin Injections in Patients With Hereditary Spastic Paraplegia
NCT05518188	PHASE1/PHASE2	RECRUITING	Melpida: Recombinant Adeno-associated Virus (serotype 9) Encoding a Codon Optimized Human AP4M1 Transgene (hAP4M1opt)
NCT06948019	PHASE1/PHASE2	NOT_YET_RECRUITING	Safety and Efficacy of AAV9/AP4B1 (BFB-101) For Patients With AP4B1-related Hereditary Spastic Paraplegia Type 47 (SPG47)
NCT06478238	EARLY_PHASE1	RECRUITING	Calcium Folinate Treatment of Spastic Paraplegia 56
NCT00023075	Not specified	COMPLETED	Nuclear Magnetic Spectroscopy Imaging to Evaluate Primary Lateral Sclerosis, Hereditary Spastic Paraplegia and Amyotrophic Lateral Sclerosis
NCT00136630	Not specified	COMPLETED	Natural History, Genetic Bases and Phenotype-genotype Correlations in Autosomal Dominant Spinocerebellar Degenerations
NCT00140829	Not specified	COMPLETED	SPATAX: Clinical and Genetic Analysis of Cerebellar Ataxias and Spastic Paraplegias
NCT00677768	Not specified	COMPLETED	Validation of Biomarkers in Amyotrophic Lateral Sclerosis (ALS)
NCT01568658	Not specified	ACTIVE_NOT_RECRUITING	Genetic and Physical Study of Childhood Nerve and Muscle Disorders
NCT02327845	Not specified	ENROLLING_BY_INVITATION	Phenotype, Genotype & Biomarkers in ALS and Related Disorders
NCT02852278	Not specified	COMPLETED	A Patient Centric Motor Neuron Disease Activities of Daily Living Scale
NCT02859428	Not specified	TERMINATED	Disease Natural History and Biomarkers of SPG3A, SPG4A, and SPG31
NCT03104088	Not specified	COMPLETED	Studying Cognition in SPG4
NCT03206190	Not specified	RECRUITING	The preSPG4 Study - Studying the Prodromal and Early Phase of SPG4
NCT03627416	Not specified	COMPLETED	Repetitive Transcranial Magnetic Stimulation as Therapy in Hereditary Spastic Paraplegia and Adrenomyeloneuropathy
NCT03981276	Not specified	RECRUITING	Phenotypes, Biomarkers and Pathophysiology in Hereditary Spastic Paraplegias and Related Disorders
NCT04006418	Not specified	RECRUITING	A Registered Cohort Study on Spastic Paraplegia
NCT04180098	Not specified	COMPLETED	Improving Gait Adaptability in Hereditary Spastic Paraplegia
NCT04256681	Not specified	COMPLETED	SNAP: Measurement of the Subjective Perception of the Symptom in Hereditary Spastic Paraparesis (HSP)
NCT04712812	Not specified	RECRUITING	Registry and Natural History Study for Early Onset Hereditary Spastic Paraplegia
NCT04875416	Not specified	ACTIVE_NOT_RECRUITING	Phenotype, Genotype and Biomarkers 2