JAK2

Summary

JAK2 (Janus kinase 2, HGNC:6192) is a protein-coding gene on chromosome 9p24.1, encoding Tyrosine-protein kinase JAK2 (O60674). Non-receptor tyrosine kinase involved in various processes such as cell growth, development, differentiation or histone modifications. In precision oncology, JAK2 V617F confers sensitivity to Peginterferon Alfa-2b in Polycythemia Vera (CIViC Level B); 4 further curated variant–drug associations are listed below.

This gene encodes a non-receptor tyrosine kinase that plays a central role in cytokine and growth factor signalling. The primary isoform of this protein has an N-terminal FERM domain that is required for erythropoietin receptor association, an SH2 domain that binds STAT transcription factors, a pseudokinase domain and a C-terminal tyrosine kinase domain. Cytokine binding induces autophosphorylation and activation of this kinase. This kinase then recruits and phosphorylates signal transducer and activator of transcription (STAT) proteins. Growth factors like TGF-beta 1 also induce phosphorylation and activation of this kinase and translocation of downstream STAT proteins to the nucleus where they influence gene transcription. Mutations in this gene are associated with numerous inflammatory diseases and malignancies. This gene is a downstream target of the pleiotropic cytokine IL6 that is produced by B cells, T cells, dendritic cells and macrophages to produce an immune response or inflammation. Disregulation of the IL6/JAK2/STAT3 signalling pathways produces increased cellular proliferation and myeloproliferative neoplasms of hematopoietic stem cells. A nonsynonymous mutation in the pseudokinase domain of this gene disrupts the domains inhibitory effect and results in constitutive tyrosine phosphorylation activity and hypersensitivity to cytokine signalling. This gene and the IL6/JAK2/STAT3 signalling pathway is a therapeutic target for the treatment of excessive inflammatory responses to viral infections. Alternative splicing results in multiple transcript variants encoding distinct isoforms.

Source: NCBI Gene 3717 — RefSeq curated summary.

At a glance

• Gene–disease (curated): thrombocythemia 3 (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 57
• Clinical variants (ClinVar): 49 total — 1 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 125
• Druggable target: yes — 100 molecules with ChEMBL bioactivity
• Precision-oncology evidence (CIViC): 5 curated variant–drug associations
• Cancer driver (intOGen): activating (oncogene-like) across 5 cancer types
• MANE Select transcript: NM_004972

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6192
Approved symbol	JAK2
Name	Janus kinase 2
Location	9p24.1
Locus type	gene with protein product
Status	Approved
Aliases	JTK10
Ensembl gene	ENSG00000096968
Ensembl biotype	protein_coding
OMIM	147796
Entrez	3717

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 14 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000381652, ENST00000476574, ENST00000487310, ENST00000636127, ENST00000870320, ENST00000870321, ENST00000870322, ENST00000870323, ENST00000870324, ENST00000870325, ENST00000963937, ENST00000963938, ENST00000963939, ENST00000963940, ENST00000963941

RefSeq mRNA: 7 — MANE Select: NM_004972 NM_001322194, NM_001322195, NM_001322196, NM_001322198, NM_001322199, NM_001322204, NM_004972

CCDS: CCDS6457

Canonical transcript exons

ENST00000381652 — 25 exons

Exon	Start	End
ENSE00000687814	5029783	5029906
ENSE00000687923	5054563	5054884
ENSE00000687929	5055669	5055788
ENSE00000687945	5069022	5069208
ENSE00000687951	5072492	5072626
ENSE00000687968	5078306	5078444
ENSE00000687973	5080229	5080380
ENSE00000688013	5089674	5089863
ENSE00000688019	5090446	5090570
ENSE00001282826	5126333	5126446
ENSE00001282833	5123004	5123121
ENSE00001282842	5090739	5090911
ENSE00001282867	5081725	5081861
ENSE00001282875	5080533	5080683
ENSE00001282885	5077453	5077580
ENSE00001282890	5073698	5073785
ENSE00001282899	5069925	5070052
ENSE00001282909	5066678	5066789
ENSE00001282918	5064883	5065040
ENSE00001489355	5126684	5129948
ENSE00001489453	5021963	5022213
ENSE00001489459	4985940	4986022
ENSE00001489462	4985272	4985630
ENSE00003342058	5050686	5050831
ENSE00003505962	5044403	5044520

Expression profiles

Bgee: expression breadth ubiquitous, 272 present calls, max score 97.19.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 15.4319 / max 1145.3604, expressed in 1747 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
95928	9.0161	1444
95926	2.3553	993
95925	1.6798	866
95924	0.7391	409
95929	0.5718	302
95927	0.4292	239
205417	0.3783	179
205418	0.2622	104

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	97.19	gold quality
monocyte	CL:0000576	95.57	gold quality
blood vessel layer	UBERON:0004797	94.99	gold quality
mononuclear cell	CL:0000842	94.89	gold quality
popliteal artery	UBERON:0002250	94.48	gold quality
tibial artery	UBERON:0007610	94.46	gold quality
leukocyte	CL:0000738	94.32	gold quality
aorta	UBERON:0000947	92.96	gold quality
gluteal muscle	UBERON:0002000	92.86	gold quality
descending thoracic aorta	UBERON:0002345	92.19	gold quality
thoracic aorta	UBERON:0001515	91.14	gold quality
ascending aorta	UBERON:0001496	90.99	gold quality
sural nerve	UBERON:0015488	90.43	gold quality
tibia	UBERON:0000979	89.72	gold quality
left coronary artery	UBERON:0001626	89.40	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	89.12	gold quality
right coronary artery	UBERON:0001625	87.93	gold quality
coronary artery	UBERON:0001621	87.70	gold quality
bone marrow cell	CL:0002092	87.64	gold quality
tendon	UBERON:0000043	86.88	gold quality
cartilage tissue	UBERON:0002418	86.61	gold quality
superficial temporal artery	UBERON:0001614	86.60	gold quality
right lung	UBERON:0002167	86.52	gold quality
diaphragm	UBERON:0001103	86.09	gold quality
biceps brachii	UBERON:0001507	85.65	gold quality
bone marrow	UBERON:0002371	85.35	gold quality
skin of leg	UBERON:0001511	85.15	gold quality
ectocervix	UBERON:0012249	84.92	gold quality
vermiform appendix	UBERON:0001154	84.88	gold quality
subcutaneous adipose tissue	UBERON:0002190	84.88	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-6678	yes	8.05
E-ANND-3	yes	5.25

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
MYC	Activation

Upstream regulators (CollecTRI, top): AR, BRCA1, DENR, DNMT1, ESR1, LMO2, SPI1, STAT1, STAT3, STAT5A, STAT5B, TCF3, THAP11, TP53, TXK, YY1

miRNA regulators (miRDB)

103 targeting JAK2, 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-8485	100.00	77.57	4731
HSA-MIR-3163	100.00	77.23	8605
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-433-3P	99.98	69.37	1203
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-101-3P	99.94	75.03	2230
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867

Literature-anchored findings (GeneRIF, showing 40)

• increase in cyclin d-1 promoter activity is predominantly mediated by the Jak2/Stat5 signaling pathway (PMID:11923474)
• Phosphorylation of STAT-3 in response to basic fibroblast growth factor occurs through a mechanism involving platelet-activating factor, JAK-2, and Src in human umbilical vein endothelial cells (PMID:11940567)
• The mechanisms by which HNF-4 is modified after injury involve the activation of Janus kinase 2 (JAK2) signal transduction pathways, but the direct or indirect interaction of JAK2 with HNF-4 remains to be defined. (PMID:12106016)
• requirement in interferon-gamma-mediated inhibition in human chondrocytes (PMID:12223098)
• 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)
• Jak2 mediates the increase in c-Myc expression that is induced by Bcr-Abl. (PMID:12370803)
• theoretical model of Janus kinase 2 comprising all seven Janus homology domains (PMID:12456871)
• JAK2 has an important pathologic role in Hodgkin’s lymphoma (PMID:12478664)
• JAK2 phosphorylation is suppressed by estrogen, which inhibits growth hormone signaling (PMID:12552091)
• 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)
• Janus kinase 2 ubiquitination/degradation downstream of the prolactin receptor is regulated by SHP-2 and mediated by SOCS-1 (PMID:14522994)
• Jak2 is required for Ang II-induced ERK2 inactivation via induction of MKP-1 gene expression. (PMID:14551204)
• Janus kinase 2 and calcium are required for angiotensin II-dependent activation of steroidogenic acute regulatory protein transcription (PMID:14565954)
• Although the methylation frequency of SOCS-1 is low, the data of Fujitake et al. indicate role of JAK/STAT/SOCS pathway in gastrointestinal tumorigenesis. (PMID:15198092)
• Protein tyrosine phosphatase 1-B levels increased with introduction of wt p53 and may be involved in the dephosphorylation of JAK2 (PMID:15358195)
• review of Jak2 tyrosine kinase at the molecular, cellular, and physiological levels [review] (PMID:15475610)
• Jak2 activation is sufficient for GTPCH I upregulation in response to IFN-gamma and its synergy with TNF-alpha. (PMID:15604419)
• CXCL12 signaling is independent of Jak2 and Jak3 (PMID:15611059)
• The N-terminal part of the 1st intracellular loop (ICL) is needed to activate Jak2 after SDF-1alpha binding to CXCR4, leading to phosphorylation of only one cytoplasmic Tyr, present at the C terminus of the 2nd (ICL), which triggers STAT3 activation. (PMID:15615703)
• Jak2 is novel pathway in Ang II-dependent activation of StAR expression and steroidogenesis in adrenocortical cells and is requirement for ongoing protein synthesis in Ang II-mediated StAR transcription. (PMID:15666812)
• tel-jak2a fusion oncoprotein based on that seen in a case of chronic myeloid leukemia in zebrafish caused revealed disruption of normal embryonic hematopoiesis, including perturbation of the myeloid and erythroid lineages. (PMID:15676212)
• In human nonfailing myocytes, high glucose allows Angiotensin II to activate JAK2 signaling. (PMID:15677497)
• Similar to SOCS-1, Tkip peptide binds to the autophosphorylation site of JAK2. (PMID:15688010)
• A single acquired mutation of JAK2 was noted in more than half of patients with a myeloproliferative disorder. (PMID:15781101)
• a clonal and recurrent mutation in the JH2 pseudo-kinase domain of the Janus kinase 2 (JAK2) gene in most (> 80%) polycythaemia vera patients (PMID:15793561)
• A somatic mutation JAK2V617F was found in granulocyte DNA from 121 of 164 polycythemia vera patients, from 37 of 115 essential thrombocythemia patients, and from 16 of 46 myeloid metaplasia with myelofibrosis patients. (PMID:15837627)
• A high proportion of patients with myeloproliferative disorders carry a dominant gain-of-function mutation of JAK2. (PMID:15858187)
• current observation strengthens the specific association between JAK2 V617F and classic MPD, but also suggests an infrequent occurrence in other myeloid disorders (PMID:15860661)
• a gain-of-function mutation of JAK may explain the hypersensitivity of polycythemia vera progenitor cells to growth factors and cytokines (PMID:15863514)
• Data show that medroxyprogesterone acetate treatment of mammary tumor cells up-regulated Stat3 protein expression and induced rapid, nongenomic Stat3, Jak1, and Jak2 tyrosine phosphorylation. (PMID:15923602)
• Leptin enhances ADP-induced caalcium increases via JAK2 and tyrosine kinases in a megakaryoblast cell line. (PMID:15927298)
• mutated in polycythemia vera (PMID:15985214)
• Presence of the Jak2V617F mutation was very highly correlated with polycythemia rubra vera 1 overexpression (PMID:15985544)
• JAK1 and JAK2 must work cooperatively and not independently and that their actions are dependent on having normal kinase activity to trigger downstream signals leading to Interleukin-3 independent proliferation (PMID:15988755)
• The rearrangement created by the t(8;9)(p22;p24)used dual-colour FISH on metaphases from patient cells using labelled-BAC clones centred on JAK2. (PMID:16034466)
• JAK2 Val617Phe activating tyrosine kinase mutation is associated with juvenile myelomonocytic leukemia (PMID:16079889)
• mutated in myeloproliferative disorders and hematologic cancers. (review) (PMID:16084028)
• CaM binds to the membrane-proximal EpoR cytoplasmic region and plays an essential role in activation of Jak2-mediated EpoR signaling (PMID:16084495)
• A genetic translocation in atypical chronic myeloid leukemia yields a new PCM1-JAK2 fusion gene. (PMID:16091753)
• crystal structure of the active conformation of the JAK2 PTK domain in complex with a high-affinity, pan-JAK inhibitor that appears to bind via an induced fit mechanism (PMID:16174768)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	jak2b	ENSDARG00000018882
danio_rerio	jak2a	ENSDARG00000104808
mus_musculus	Jak2	ENSMUSG00000024789
rattus_norvegicus	Jak2	ENSRNOG00000059968

Paralogs (32): FGR (ENSG00000000938), MATK (ENSG00000007264), BTK (ENSG00000010671), FYN (ENSG00000010810), STYK1 (ENSG00000060140), TNK2 (ENSG00000061938), TXK (ENSG00000074966), ABL1 (ENSG00000097007), PTK6 (ENSG00000101213), HCK (ENSG00000101336), BMX (ENSG00000102010), CSK (ENSG00000103653), TYK2 (ENSG00000105397), JAK3 (ENSG00000105639), 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 JAK2 — O60674 (reviewed: O60674)

Alternative names: Janus kinase 2

All UniProt accessions (3): O60674, A0A1B0GTR9, A0A1B0GVR5

UniProt curated annotations — full annotation on UniProt →

Function. Non-receptor tyrosine kinase involved in various processes such as cell growth, development, differentiation or histone modifications. Mediates essential signaling events in both innate and adaptive immunity. In the cytoplasm, plays a pivotal role in signal transduction via its association with type I receptors such as growth hormone (GHR), prolactin (PRLR), leptin (LEPR), erythropoietin (EPOR), thrombopoietin receptor (MPL/TPOR); or type II receptors including IFN-alpha, IFN-beta, IFN-gamma and multiple interleukins. 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, cell stimulation with erythropoietin (EPO) during erythropoiesis leads to JAK2 autophosphorylation, activation, and its association with erythropoietin receptor (EPOR) that becomes phosphorylated in its cytoplasmic domain. Then, STAT5 (STAT5A or STAT5B) is recruited, phosphorylated and activated by JAK2. Once activated, dimerized STAT5 translocates into the nucleus and promotes the transcription of several essential genes involved in the modulation of erythropoiesis. Part of a signaling cascade that is activated by increased cellular retinol and that leads to the activation of STAT5 (STAT5A or STAT5B). In addition, JAK2 mediates angiotensin-2-induced ARHGEF1 phosphorylation. Plays a role in cell cycle by phosphorylating CDKN1B. Cooperates with TEC through reciprocal phosphorylation to mediate cytokine-driven activation of FOS transcription. In the nucleus, plays a key role in chromatin by specifically mediating phosphorylation of ‘Tyr-41’ of histone H3 (H3Y41ph), a specific tag that promotes exclusion of CBX5 (HP1 alpha) from chromatin. Up-regulates the potassium voltage-gated channel activity of KCNA3.

Subunit / interactions. Interacts with EPOR, LYN, SIRPA, SH2B1 and TEC. Interacts with IL23R. Interacts with SKB1. Interacts with STAM2. Interacts with IFNGR2 (via intracellular domain). Interacts with LEPR (Isoform B). Interacts with HSP90AB1; promotes functional activation in a heat shock-dependent manner. Interacts with STRA6. Interacts with RHEX; this interaction occurs in a erythropoietin (EPO)-dependent manner. Interacts with ASB2; the interaction targets JAK2 for Notch-induced proteasomal degradation. Interacts with MPL/TPOR.

Subcellular location. Endomembrane system. Cytoplasm. Nucleus.

Tissue specificity. Ubiquitously expressed throughout most tissues.

Post-translational modifications. Autophosphorylated, leading to regulate its activity. Leptin promotes phosphorylation on tyrosine residues, including phosphorylation on Tyr-813. Autophosphorylation on Tyr-119 in response to EPO down-regulates its kinase activity. Autophosphorylation on Tyr-868, Tyr-966 and Tyr-972 in response to growth hormone (GH) are required for maximal kinase activity. Also phosphorylated by TEC. Phosphorylated on tyrosine residues in response to interferon gamma signaling. Phosphorylated on tyrosine residues in response to a signaling cascade that is activated by increased cellular retinol. Undergoes Notch-induced ubiquitination and subsequent proteasomal degradation which is mediated by ASB1 or ASB2, the substrate-recognition components of probable ECS E3 ubiquitin-protein ligase complexes.

Disease relevance. Chromosomal aberrations involving JAK2 are found in both chronic and acute forms of eosinophilic, lymphoblastic and myeloid leukemia. Translocation t(8;9)(p22;p24) with PCM1 links the protein kinase domain of JAK2 to the major portion of PCM1. Translocation t(9;12)(p24;p13) with ETV6. Budd-Chiari syndrome (BDCHS) [MIM:600880] A syndrome caused by obstruction of hepatic venous outflow involving either the hepatic veins or the terminal segment of the inferior vena cava. Obstructions are generally caused by thrombosis and lead to hepatic congestion and ischemic necrosis. Clinical manifestations observed in the majority of patients include hepatomegaly, right upper quadrant pain and abdominal ascites. Budd-Chiari syndrome is associated with a combination of disease states including primary myeloproliferative syndromes and thrombophilia due to factor V Leiden, protein C deficiency and antithrombin III deficiency. Budd-Chiari syndrome is a rare but typical complication in patients with polycythemia vera. Disease susceptibility is associated with variants affecting the gene represented in this entry. Polycythemia vera (PV) [MIM:263300] A myeloproliferative disorder characterized by abnormal proliferation of all hematopoietic bone marrow elements, erythroid hyperplasia, an absolute increase in total blood volume, but also by myeloid leukocytosis, thrombocytosis and splenomegaly. The disease is caused by variants affecting the gene represented in this entry. Thrombocythemia 3 (THCYT3) [MIM:614521] A myeloproliferative disorder characterized by excessive platelet production, resulting in increased numbers of circulating platelets. It can be associated with spontaneous hemorrhages and thrombotic episodes. The disease may be caused by variants affecting the gene represented in this entry. Myelofibrosis (MYELOF) [MIM:254450] A disorder characterized by replacement of the bone marrow by fibrous tissue, occurring in association with a myeloproliferative disorder. Clinical manifestations may include anemia, pallor, splenomegaly, hypermetabolic state, petechiae, ecchymosis, bleeding, lymphadenopathy, hepatomegaly, portal hypertension. The disease is caused by variants affecting the gene represented in this entry. Leukemia, acute myelogenous (AML) [MIM:601626] A subtype of acute leukemia, a cancer of the white blood cells. AML is a malignant disease of bone marrow characterized by maturational arrest of hematopoietic precursors at an early stage of development. Clonal expansion of myeloid blasts occurs in bone marrow, blood, and other tissue. Myelogenous leukemias develop from changes in cells that normally produce neutrophils, basophils, eosinophils and monocytes. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Regulated by autophosphorylation, can both activate or decrease activity. Heme regulates its activity by enhancing the phosphorylation on Tyr-1007 and Tyr-1008.

Cofactor. Mn(2+) was used in the in vitro kinase assay but Mg(2+) is likely to be the in vivo cofactor.

Domain organisation. Possesses 2 protein kinase domains. The second one probably contains the catalytic domain, while the presence of slight differences suggest a different role for protein kinase 1.

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

RefSeq proteins (7): NP_001309123, NP_001309124, NP_001309125, NP_001309127, NP_001309128, NP_001309133, NP_004963* (*=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
IPR019748	FERM_central	Domain
IPR019749	Band_41_domain	Domain
IPR020635	Tyr_kinase_cat_dom	Domain
IPR020693	Tyr_kinase_non-rcpt_Jak2	Family
IPR035588	PTK_Jak2_rpt1	Domain
IPR035589	PTKc_Jak2_rpt2	Domain
IPR035860	JAK2_SH2	Domain
IPR035963	FERM_2	Homologous_superfamily
IPR036860	SH2_dom_sf	Homologous_superfamily
IPR037838	JAK2_FERM_C-lobe	Domain
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 (148 total): helix 51, strand 44, sequence variant 13, turn 12, modified residue 11, site 5, domain 4, sequence conflict 2, binding site 2, chain 1, mutagenesis site 1, region of interest 1, active site 1

Structure

Experimental structures (PDB)

164 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
8BXH	X-RAY DIFFRACTION	1.3
7LL4	X-RAY DIFFRACTION	1.31
3UGC	X-RAY DIFFRACTION	1.34
7REE	X-RAY DIFFRACTION	1.38
8BA3	X-RAY DIFFRACTION	1.4
8BX9	X-RAY DIFFRACTION	1.4
7TEU	X-RAY DIFFRACTION	1.45
4IVA	X-RAY DIFFRACTION	1.5
7LL5	X-RAY DIFFRACTION	1.5
7RN6	X-RAY DIFFRACTION	1.5
8B8U	X-RAY DIFFRACTION	1.5
8B9E	X-RAY DIFFRACTION	1.5
8B9H	X-RAY DIFFRACTION	1.5
8BA2	X-RAY DIFFRACTION	1.5
8BM2	X-RAY DIFFRACTION	1.5
8BX6	X-RAY DIFFRACTION	1.5
8EX1	X-RAY DIFFRACTION	1.5
5UT3	X-RAY DIFFRACTION	1.5
5I4N	X-RAY DIFFRACTION	1.54
6BS0	X-RAY DIFFRACTION	1.54
8BAB	X-RAY DIFFRACTION	1.55
5TQ8	X-RAY DIFFRACTION	1.59
6G3C	X-RAY DIFFRACTION	1.6
8B99	X-RAY DIFFRACTION	1.6
7Q7K	X-RAY DIFFRACTION	1.61
9ND3	X-RAY DIFFRACTION	1.62
5UT6	X-RAY DIFFRACTION	1.65
8BAK	X-RAY DIFFRACTION	1.65
8CZ9	X-RAY DIFFRACTION	1.65
4D1S	X-RAY DIFFRACTION	1.66

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O60674-F1	87.46	0.68

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 (6): 442–443 (breakpoint for translocation to form pcm1-jak2 fusion protein); 450–451 (breakpoint for translocation to form pcm1-jak2 fusion protein); 504–505 (breakpoint for translocation to form pcm1-jak2 fusion protein); 710–711 (breakpoint for translocation to form pcm1-jak2 fusion protein); 976 (proton acceptor); 352–353 (breakpoint for translocation to form pcm1-jak2 fusion protein)

Ligand- & substrate-binding residues (2): 855–863; 882

Post-translational modifications (11): 119, 372, 373, 523, 570, 813, 868, 966, 972, 1007, 1008

Mutagenesis-validated functional residues (1):

Position	Phenotype
882	loss of ability to up-regulate potassium voltage-gated channel activity of kcna3.

Function

Pathways and Gene Ontology

Reactome pathways

66 pathways

ID	Pathway
R-HSA-1059683	Interleukin-6 signaling
R-HSA-110056	MAPK3 (ERK1) activation
R-HSA-112411	MAPK1 (ERK2) activation
R-HSA-1170546	Prolactin receptor signaling
R-HSA-1433557	Signaling by SCF-KIT
R-HSA-2586552	Signaling by Leptin
R-HSA-3214858	RMTs methylate histone arginines
R-HSA-512988	Interleukin-3, Interleukin-5 and GM-CSF signaling
R-HSA-5673000	RAF activation
R-HSA-5673001	RAF/MAP kinase cascade
R-HSA-6785807	Interleukin-4 and Interleukin-13 signaling
R-HSA-6788467	IL-6-type cytokine receptor ligand interactions
R-HSA-6802946	Signaling by moderate kinase activity BRAF mutants
R-HSA-6802952	Signaling by BRAF and RAF1 fusions
R-HSA-6802955	Paradoxical activation of RAF signaling by kinase inactive BRAF
R-HSA-69231	Cyclin D associated events in G1
R-HSA-877300	Interferon gamma signaling
R-HSA-877312	Regulation of IFNG signaling
R-HSA-8854691	Interleukin-20 family signaling
R-HSA-8984722	Interleukin-35 Signalling
R-HSA-9006335	Signaling by Erythropoietin
R-HSA-9020591	Interleukin-12 signaling
R-HSA-9020933	Interleukin-23 signaling
R-HSA-9020956	Interleukin-27 signaling
R-HSA-9027276	Erythropoietin activates Phosphoinositide-3-kinase (PI3K)
R-HSA-9027277	Erythropoietin activates Phospholipase C gamma (PLCG)
R-HSA-9027283	Erythropoietin activates STAT5
R-HSA-9027284	Erythropoietin activates RAS
R-HSA-912526	Interleukin receptor SHC signaling
R-HSA-9649948	Signaling downstream of RAS mutants

MSigDB gene sets: 1031 (showing top): PID_SHP2_PATHWAY, GOBP_MYELOID_CELL_DIFFERENTIATION, GSE45365_NK_CELL_VS_BCELL_UP, GOBP_PLATELET_DERIVED_GROWTH_FACTOR_RECEPTOR_SIGNALING_PATHWAY, GOBP_SMAD_PROTEIN_SIGNAL_TRANSDUCTION, GOBP_REGULATION_OF_CELL_ACTIVATION, REACTOME_INTERLEUKIN_2_FAMILY_SIGNALING, REACTOME_INTERLEUKIN_6_SIGNALING, ELVIDGE_HYPOXIA_DN, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_REGULATION_OF_LEUKOCYTE_PROLIFERATION, GOBP_NEGATIVE_REGULATION_OF_NEURON_APOPTOTIC_PROCESS, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_REGULATION_OF_EPITHELIAL_CELL_APOPTOTIC_PROCESS, GOBP_REGULATION_OF_ALPHA_BETA_T_CELL_ACTIVATION

GO Biological Process (114): microglial cell activation (GO:0001774), adaptive immune response (GO:0002250), transcription by RNA polymerase II (GO:0006366), apoptotic process (GO:0006915), immune response (GO:0006955), cell adhesion (GO:0007155), signal transduction (GO:0007165), enzyme-linked receptor protein signaling pathway (GO:0007167), positive regulation of cytosolic calcium ion concentration (GO:0007204), cell surface receptor signaling pathway via JAK-STAT (GO:0007259), mesoderm development (GO:0007498), negative regulation of cell population proliferation (GO:0008285), intrinsic apoptotic signaling pathway in response to oxidative stress (GO:0008631), positive regulation of platelet activation (GO:0010572), negative regulation of cardiac muscle cell apoptotic process (GO:0010667), positive regulation of cell-substrate adhesion (GO:0010811), cytokine-mediated signaling pathway (GO:0019221), negative regulation of cell-cell adhesion (GO:0022408), actin filament polymerization (GO:0030041), cell differentiation (GO:0030154), erythrocyte differentiation (GO:0030218), positive regulation of cell migration (GO:0030335), axon regeneration (GO:0031103), lipopolysaccharide-mediated signaling pathway (GO:0031663), nuclear receptor-mediated mineralocorticoid signaling pathway (GO:0031959), positive regulation of insulin secretion (GO:0032024), positive regulation of type II interferon production (GO:0032729), positive regulation of interleukin-1 beta production (GO:0032731), positive regulation of interleukin-17 production (GO:0032740), positive regulation of tumor necrosis factor production (GO:0032760), positive regulation of natural killer cell proliferation (GO:0032819), response to hydroperoxide (GO:0033194), tumor necrosis factor-mediated signaling pathway (GO:0033209), symbiont-induced defense-related programmed cell death (GO:0034050), response to tumor necrosis factor (GO:0034612), post-embryonic hemopoiesis (GO:0035166), intracellular signal transduction (GO:0035556), interleukin-12-mediated signaling pathway (GO:0035722), cellular response to interleukin-3 (GO:0036016), interleukin-5-mediated signaling pathway (GO:0038043)

GO Molecular Function (24): protein kinase activity (GO:0004672), protein tyrosine kinase activity (GO:0004713), non-membrane spanning protein tyrosine kinase activity (GO:0004715), signaling receptor binding (GO:0005102), growth hormone receptor binding (GO:0005131), interleukin-12 receptor binding (GO:0005143), ATP binding (GO:0005524), protein kinase binding (GO:0019901), heme binding (GO:0020037), signaling receptor activator activity (GO:0030546), type 1 angiotensin receptor binding (GO:0031702), acetylcholine receptor binding (GO:0033130), histone H3Y41 kinase activity (GO:0035401), SH2 domain binding (GO:0042169), histone binding (GO:0042393), identical protein binding (GO:0042802), phosphatidylinositol 3-kinase binding (GO:0043548), insulin receptor substrate binding (GO:0043560), metal ion binding (GO:0046872), peptide hormone receptor binding (GO:0051428), nucleotide binding (GO:0000166), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (23): chromatin (GO:0000785), euchromatin (GO:0000791), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), plasma membrane (GO:0005886), caveola (GO:0005901), focal adhesion (GO:0005925), cytoplasmic side of plasma membrane (GO:0009898), extrinsic component of plasma membrane (GO:0019897), granulocyte macrophage colony-stimulating factor receptor complex (GO:0030526), extrinsic component of cytoplasmic side of plasma membrane (GO:0031234), endosome lumen (GO:0031904), interleukin-12 receptor complex (GO:0042022), membrane raft (GO:0045121), interleukin-23 receptor complex (GO:0072536), postsynapse (GO:0098794), glutamatergic synapse (GO:0098978), endosome (GO:0005768), cytoskeleton (GO:0005856), endomembrane system (GO:0012505), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-14 pathways:

Category	Pathways
Signaling by Interleukins	3
Oncogenic MAPK signaling	3
Interleukin-6 family signaling	2
RAF-independent MAPK1/3 activation	2
Cytokine Signaling in Immune system	1
Signaling by Receptor Tyrosine Kinases	1
Signal Transduction	1
Chromatin modifying enzymes	1
RAF/MAP kinase cascade	1
MAPK1/MAPK3 signaling	1
G1 Phase	1
Interferon Signaling	1
Interferon gamma signaling	1
Interleukin-12 family signaling	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein binding	5
cellular anatomical structure	5
plasma membrane signaling receptor complex	3
cellular process	2
cell surface receptor signaling pathway	2
protein tyrosine kinase activity	2
cytokine receptor binding	2
hormone receptor binding	2
plasma membrane	2
synapse	2
leukocyte activation involved in inflammatory response	1
macrophage activation	1
glial cell activation	1
immune response	1
DNA-templated transcription	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
immune system process	1
response to stimulus	1
cell communication	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
regulation of biological quality	1
cell surface receptor signaling pathway via STAT	1
tissue development	1
cell population proliferation	1
regulation of cell population proliferation	1
negative regulation of cellular process	1
intrinsic apoptotic signaling pathway	1
regulation of platelet activation	1
platelet activation	1
positive regulation of cell activation	1
cardiac muscle cell apoptotic process	1
negative regulation of striated muscle cell apoptotic process	1
regulation of cardiac muscle cell apoptotic process	1
regulation of cell-substrate adhesion	1
cell-substrate adhesion	1
positive regulation of cell adhesion	1

Protein interactions and networks

STRING

5828 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
JAK2	STAT3	P40763	999
JAK2	EPOR	P19235	997
JAK2	STAT5B	P51692	997
JAK2	STAT5A	P42229	997
JAK2	SOCS3	O14543	996
JAK2	STAT1	P42224	996
JAK2	IFNGR2	P38484	995
JAK2	SOCS1	O15524	994
JAK2	IFNGR1	P15260	993
JAK2	IFNG	P01579	989
JAK2	IL12RB1	P42701	988
JAK2	GHR	P10912	985
JAK2	IL12RB2	Q99665	983
JAK2	JAK1	P23458	982
JAK2	TYK2	P29597	982

IntAct

88 interactions, top by confidence:

A	B	Type	Score
PTPN1	JAK2	psi-mi:“MI:0203”(dephosphorylation reaction)	0.820
JAK2	PTPN1	psi-mi:“MI:0915”(physical association)	0.820
PTPN1	JAK2	psi-mi:“MI:0915”(physical association)	0.820
JAK2	JAK2	psi-mi:“MI:0217”(phosphorylation reaction)	0.620
CSF2RB	JAK2	psi-mi:“MI:0915”(physical association)	0.560
CSF2RB	JAK2	psi-mi:“MI:0914”(association)	0.560
SH2B1	JAK2	psi-mi:“MI:0914”(association)	0.530
MPL	JAK2	psi-mi:“MI:0915”(physical association)	0.520
MPL	JAK2	psi-mi:“MI:0403”(colocalization)	0.520
MPL	JAK2	psi-mi:“MI:2364”(proximity)	0.520
JAK2	MPL	psi-mi:“MI:2364”(proximity)	0.520
JAK2	Slc40a1	psi-mi:“MI:0915”(physical association)	0.520
IL5RA	JAK2	psi-mi:“MI:0915”(physical association)	0.500
IL5RA	JAK2	psi-mi:“MI:0914”(association)	0.500
JAK1	JAK2	psi-mi:“MI:0915”(physical association)	0.460

BioGRID (281): EMD (Affinity Capture-MS), KPNB1 (Affinity Capture-MS), NAP1L1 (Affinity Capture-MS), RCN1 (Affinity Capture-MS), SLC2A1 (Affinity Capture-MS), UBP1 (Affinity Capture-MS), JAK2 (Biochemical Activity), EGFR (Biochemical Activity), STAT3 (Biochemical Activity), PIK3R1 (Negative Genetic), STAT3 (Biochemical Activity), JAK2 (Reconstituted Complex), ARL11 (Two-hybrid), HSFY1 (Two-hybrid), JAK2 (Affinity Capture-Western)

ESM2 similar proteins: A0A078BQP2, A8WPG9, A8XQC7, B1Q257, E7EAU8, G5EFQ0, G5EGT9, H2L002, N1NVB7, O16544, O16715, O19064, O60674, O62026, O62179, P11528, P16065, P23897, P25092, P55204, P55205, P70106, P91550, Q07553, Q09435, Q10028, Q10029, Q18163, Q18331, Q19187, Q19768, Q23310, Q23681, Q23682, Q2HWD6, Q3UWA6, Q5RB23, Q62120, Q62689, Q6DNF3

Diamond homologs: A0A0K3AV08, A7J1T0, A7J1T2, A7MBB4, A8X775, D3ZG83, G5EE56, H2KZW3, O01700, O19064, O22558, O43283, O54967, O60674, P00529, P00533, P00534, P00535, P03949, P04412, P06239, P06240, P08069, P08922, P08941, P09760, P09769, P11273, P11362, P13388, P14234, P14616, P14617, P16092, P16591, P18461, P21802, P21803, P21804, P22607

SIGNOR signaling

157 interactions.

A	Effect	B	Mechanism
PTPN12	down-regulates	JAK2	dephosphorylation
SOCS1	“down-regulates quantity by destabilization”	JAK2	ubiquitination
PTPN1	down-regulates	JAK2	dephosphorylation
IL3RA	up-regulates	JAK2	binding
IFNGR1	up-regulates	JAK2	binding
JAK2	up-regulates	STAT4	phosphorylation
MAPK3	down-regulates	JAK2	phosphorylation
“erlotinib hydrochloride”	down-regulates	JAK2	“chemical inhibition”
IL31RA	up-regulates	JAK2	binding
JAK2	up-regulates	ARHGEF1	phosphorylation
JAK2	down-regulates	PRMT5	phosphorylation
JAK2	“down-regulates activity”	JAK2	phosphorylation
JAK2	up-regulates	GAB2	phosphorylation
JAK2	down-regulates	MAP3K5	phosphorylation
AT9283	down-regulates	JAK2	“chemical inhibition”
“AZ 960”	down-regulates	JAK2	“chemical inhibition”
AZD1480	down-regulates	JAK2	“chemical inhibition”
N-(cyanomethyl)-4-[2-[4-(4-morpholinyl)anilino]-4-pyrimidinyl]benzamide	down-regulates	JAK2	“chemical inhibition”
LY2784544	down-regulates	JAK2	“chemical inhibition”
“NVP-BSK805 dihydrochloride”	down-regulates	JAK2	“chemical inhibition”
JAK2	down-regulates	EZH2	phosphorylation
NIN	down-regulates	JAK2	binding
ruxolitinib	down-regulates	JAK2	“chemical inhibition”
N-tert-butyl-3-[[5-methyl-2-[4-[2-(1-pyrrolidinyl)ethoxy]anilino]-4-pyrimidinyl]amino]benzenesulfonamide	down-regulates	JAK2	“chemical inhibition”
TG101209	down-regulates	JAK2	“chemical inhibition”
JAK2	up-regulates	STAT1	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 56 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
Signaling by CSF3 (G-CSF)	7	85.0×	3e-10
Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT mutants	6	66.3×	4e-08
Downstream signal transduction	8	64.8×	2e-10
Growth hormone receptor signaling	6	60.7×	5e-08
Signaling by ALK	5	60.7×	5e-07
Regulation of IFNA/IFNB signaling	6	56.1×	5e-08
Inactivation of CSF3 (G-CSF) signaling	6	56.1×	5e-08
Interleukin receptor SHC signaling	6	52.1×	7e-08

GO biological processes:

GO term	Partners	Fold	FDR
negative regulation of insulin receptor signaling pathway	5	36.0×	3e-05
cell surface receptor signaling pathway via JAK-STAT	6	33.5×	5e-06
epidermal growth factor receptor signaling pathway	7	33.4×	7e-07
cellular response to UV	5	28.4×	1e-04
phosphatidylinositol 3-kinase/protein kinase B signal transduction	7	28.4×	2e-06
cytokine-mediated signaling pathway	11	27.6×	2e-10
insulin receptor signaling pathway	6	25.6×	2e-05
cellular response to insulin stimulus	5	16.4×	7e-04

Disease & clinical

Cancer significance

From CIViC — curated cancer-variant interpretation:

JAK2 is a kinase that is misregulated or mutated in a number of myeloproliferative diseases and cancers. The mutation V617F is the most clinically relevant variant, and is seen in around half of myeloproliferative disorders. The variant is a known activating mutation, and activated JAK2 is sufficient to drive myeloproliferative disorders in mouse models. V617F, while most recurrent, is not the only mechanism by which JAK2 can be activated in patients. JAK2 is now one of the first diagnostic markers tested upon diagnosis with a myeloproliferative disorder.

From intOGen — cancer-driver classification: activating (oncogene-like) across 5 cancer types — ALL, AML, BLADDER, BRCA, NSCLC.

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	1
Uncertain significance	29
Likely benign	8
Benign	4

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
14663	NM_004972.4(JAK2):c.1821G>C (p.Lys607Asn)	Pathogenic
869413	t(3;9)(q13.31;p24.1)	Likely pathogenic

SpliceAI

4458 predictions. Top by Δscore:

Variant	Effect	Δscore
9:5021957:TTACA:T	acceptor_loss	1.0000
9:5021960:CA:C	acceptor_loss	1.0000
9:5021961:A:AG	acceptor_gain	1.0000
9:5021962:G:GT	acceptor_gain	1.0000
9:5021962:GGC:G	acceptor_gain	1.0000
9:5021962:GGCA:G	acceptor_gain	1.0000
9:5021962:GGCAA:G	acceptor_gain	1.0000
9:5022209:TTGTG:T	donor_gain	1.0000
9:5022210:TGTG:T	donor_gain	1.0000
9:5022210:TGTGG:T	donor_loss	1.0000
9:5022211:GTG:G	donor_gain	1.0000
9:5022211:GTGG:G	donor_gain	1.0000
9:5022212:TG:T	donor_gain	1.0000
9:5022212:TGG:T	donor_loss	1.0000
9:5022212:TGGT:T	donor_gain	1.0000
9:5022213:GG:G	donor_gain	1.0000
9:5022214:G:GG	donor_gain	1.0000
9:5022215:T:A	donor_loss	1.0000
9:5029777:TTCTA:T	acceptor_loss	1.0000
9:5029778:TCTA:T	acceptor_loss	1.0000
9:5029779:CTAGG:C	acceptor_loss	1.0000
9:5029780:TAGG:T	acceptor_loss	1.0000
9:5029781:A:C	acceptor_loss	1.0000
9:5044398:TGTA:T	acceptor_loss	1.0000
9:5044399:GTA:G	acceptor_loss	1.0000
9:5044400:TAG:T	acceptor_loss	1.0000
9:5044401:A:AG	acceptor_gain	1.0000
9:5044401:AGAT:A	acceptor_loss	1.0000
9:5044402:G:GA	acceptor_gain	1.0000
9:5044402:GA:G	acceptor_gain	1.0000

AlphaMissense

7572 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:5089680:T:C	F860L	1.000
9:5089682:T:A	F860L	1.000
9:5089682:T:G	F860L	1.000
9:5089684:G:A	G861E	1.000
9:5089741:C:A	A880D	1.000
9:5089747:A:T	K882I	1.000
9:5089748:A:C	K882N	1.000
9:5089748:A:T	K882N	1.000
9:5090752:T:C	L967P	1.000
9:5090772:C:G	H974D	1.000
9:5090776:G:C	R975T	1.000
9:5090776:G:T	R975M	1.000
9:5090777:G:C	R975S	1.000
9:5090777:G:T	R975S	1.000
9:5090778:G:C	D976H	1.000
9:5090779:A:C	D976A	1.000
9:5090779:A:G	D976G	1.000
9:5090779:A:T	D976V	1.000
9:5090780:T:A	D976E	1.000
9:5090780:T:G	D976E	1.000
9:5090782:T:A	L977Q	1.000
9:5090782:T:C	L977P	1.000
9:5090791:G:C	R980T	1.000
9:5090791:G:T	R980I	1.000
9:5090793:A:G	N981D	1.000
9:5090794:A:C	N981T	1.000
9:5090795:T:A	N981K	1.000
9:5090795:T:G	N981K	1.000
9:5090821:T:A	V990D	1.000
9:5090832:G:C	D994H	1.000

dbSNP variants (sampled 300 via entrez): RS1000043085 (9:4995488 T>G), RS1000084644 (9:5085251 C>A,T), RS1000092136 (9:5040011 T>G), RS1000096910 (9:5063855 A>G), RS1000138589 (9:5088193 A>G), RS1000156895 (9:5116522 G>C), RS1000158426 (9:5115798 A>G), RS1000179472 (9:5105379 G>A), RS1000216432 (9:5035466 T>C), RS1000258206 (9:5120425 T>A), RS1000279916 (9:5101454 G>A), RS1000280464 (9:5048597 G>C), RS1000285751 (9:5053257 G>A), RS1000291198 (9:5101298 T>A,C), RS1000297362 (9:5008480 G>C)

Disease associations

OMIM: gene MIM:147796 | disease phenotypes: MIM:614521, MIM:133100, MIM:254450, MIM:263300, MIM:600880, MIM:601626

GenCC curated gene-disease

Disease	Classification	Inheritance
thrombocythemia 3	Strong	Autosomal dominant
familial thrombocytosis	Supportive	Autosomal dominant

Mondo (9): thrombocythemia 3 (MONDO:0013794), primary familial polycythemia due to EPO receptor mutation (MONDO:0007572), primary myelofibrosis (MONDO:0009692), acquired polycythemia vera (MONDO:0009891), Budd-Chiari syndrome (MONDO:0010947), acute myeloid leukemia (MONDO:0018874), precursor B-cell acute lymphoblastic leukemia (MONDO:0020511), hereditary breast ovarian cancer syndrome (MONDO:0003582), familial thrombocytosis (MONDO:0019111)

Orphanet (8): Budd-Chiari syndrome (Orphanet:131), Acute myeloid leukemia (Orphanet:519), Polycythemia vera (Orphanet:729), Primary myelofibrosis (Orphanet:824), Primary familial polycythemia (Orphanet:90042), Syndromic anorectal malformation (Orphanet:117573), Precursor B-cell acute lymphoblastic leukemia (Orphanet:99860), Hereditary breast and/or ovarian cancer syndrome (Orphanet:145)

HPO phenotypes

125 total (30 of 125 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000083	Renal insufficiency
HP:0000225	Gingival bleeding
HP:0000360	Tinnitus
HP:0000421	Epistaxis
HP:0000504	Abnormality of vision
HP:0000505	Visual impairment
HP:0000822	Hypertension
HP:0000952	Jaundice
HP:0000967	Petechiae
HP:0000975	Hyperhidrosis
HP:0000978	Bruising susceptibility
HP:0000979	Purpura
HP:0000980	Pallor
HP:0000989	Pruritus
HP:0001028	Hemangioma
HP:0001050	Plethora
HP:0001082	Cholecystitis
HP:0001123	Visual field defect
HP:0001250	Seizure
HP:0001260	Dysarthria
HP:0001279	Syncope
HP:0001297	Stroke
HP:0001342	Cerebral hemorrhage
HP:0001394	Cirrhosis
HP:0001402	Hepatocellular carcinoma
HP:0001409	Portal hypertension
HP:0001433	Hepatosplenomegaly
HP:0001442	Typified by somatic mosaicism

GWAS associations

57 associations (top):

Study	Trait	p-value
GCST000207_12	Crohn’s disease	3.000000e-09
GCST000357_1	Myeloproliferative neoplasms	4.000000e-20
GCST000529_4	Ulcerative colitis	1.000000e-06
GCST000624_6	Ulcerative colitis	1.000000e-06
GCST000879_49	Crohn’s disease	1.000000e-13
GCST000964_13	Ulcerative colitis	2.000000e-25
GCST001725_99	Inflammatory bowel disease	8.000000e-45
GCST001785_10	Crohn’s disease	5.000000e-06
GCST002840_1	Myeloproliferative neoplasms	1.000000e-10
GCST003097_16	Pediatric autoimmune diseases	9.000000e-08
GCST003270_3	Psoriatic arthritis	3.000000e-07
GCST003622_19	Systemic lupus erythematosus	2.000000e-17
GCST003622_63	Systemic lupus erythematosus	1.000000e-06
GCST003622_9	Systemic lupus erythematosus	4.000000e-14
GCST004603_84	Platelet count	6.000000e-28
GCST004603_85	Platelet count	7.000000e-18
GCST004603_86	Platelet count	2.000000e-09
GCST004606_6	Eosinophil count	4.000000e-16
GCST004607_176	Plateletcrit	2.000000e-30
GCST004607_177	Plateletcrit	1.000000e-13
GCST004607_178	Plateletcrit	8.000000e-10
GCST004624_130	Sum eosinophil basophil counts	1.000000e-15
GCST005038_119	Allergic disease (asthma, hay fever or eczema)	3.000000e-10
GCST005537_171	Chronic inflammatory diseases (ankylosing spondylitis, Crohn’s disease, psoriasis, primary sclerosing cholangitis, ulcerative colitis) (pleiotropy)	5.000000e-43
GCST006611_81	HDL cholesterol	1.000000e-19
GCST006612_116	LDL cholesterol	9.000000e-14
GCST006614_9	Total cholesterol levels	1.000000e-18
GCST008483_5	Ulcerative colitis	2.000000e-09
GCST008839_227	Height	9.000000e-09
GCST009465_3	Platelet count	3.000000e-12

EFO canonical traits (14, from GWAS)

EFO ID	Trait name
EFO:0004251	myeloproliferative disorder
EFO:0004309	platelet count
EFO:0004842	eosinophil count
EFO:0007985	platelet crit
EFO:0005090	basophil count
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0004574	total cholesterol measurement
EFO:0007991	eosinophil percentage of leukocytes
EFO:0004527	mean corpuscular hemoglobin
EFO:0007989	monocyte percentage of leukocytes
EFO:0010701	mean reticulocyte volume
EFO:0004833	neutrophil count
EFO:0004305	erythrocyte count

MeSH disease descriptors (5)

Descriptor	Name	Tree numbers
D006502	Budd-Chiari Syndrome	C06.552.347; C14.907.355.830.925.275
D061325	Hereditary Breast and Ovarian Cancer Syndrome	C04.588.180.483; C04.588.322.455.431; C04.700.517; C12.050.351.500.056.630.705.431; C12.050.351.937.418.685.431; C12.100.250.056.630.705.431; C12.900.418.685.431; C16.320.700.517; C17.800.090.500.483; C19.344.410.431; C19.391.630.705.431
D015470	Leukemia, Myeloid, Acute	C04.557.337.539.275; C15.378.508.539.275
D011087	Polycythemia Vera	C04.588.448.200.500; C15.378.190.250.500; C15.378.190.636.753; C15.378.400.200.500
D055728	Primary Myelofibrosis	C15.378.190.636.765

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (9): CHEMBL2363062 (PROTEIN FAMILY), CHEMBL2971 (SINGLE PROTEIN), CHEMBL3038492 (PROTEIN COMPLEX), CHEMBL3301390 (PROTEIN COMPLEX), CHEMBL3301392 (PROTEIN COMPLEX), CHEMBL4630750 (PROTEIN-PROTEIN INTERACTION), CHEMBL4742263 (PROTEIN-PROTEIN INTERACTION), CHEMBL4802035 (PROTEIN FAMILY), CHEMBL5482983 (PROTEIN COMPLEX)

Molecules with ChEMBL bioactivity

100 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 130,263 (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
CHEMBL1287853	FEDRATINIB	4	3,554
CHEMBL1789941	RUXOLITINIB	4	11,547
CHEMBL221959	TOFACITINIB	4	10,408
CHEMBL3622821	UPADACITINIB	4	2,726
CHEMBL1078178	MOMELOTINIB	4	3,481
CHEMBL1171837	PONATINIB	4	8,955
CHEMBL1289926	AXITINIB	4	15,732
CHEMBL1448	NICLOSAMIDE	4	14,322
CHEMBL1795071	RUXOLITINIB PHOSPHATE	4	3,220
CHEMBL1834657	INFIGRATINIB PHOSPHATE	4	285
CHEMBL1852688	INFIGRATINIB	4	2,209
CHEMBL1983268	ENTRECTINIB	4	3,510
CHEMBL2028663	DABRAFENIB	4	12,430
CHEMBL2035187	PACRITINIB	4	3,345
CHEMBL2103743	TOFACITINIB CITRATE	4	1,672
CHEMBL2105759	BARICITINIB	4	6,741
CHEMBL2403108	CERITINIB	4	8,551
CHEMBL288441	BOSUTINIB	4	12,255
CHEMBL3137308	PEFICITINIB	4	1,722
CHEMBL3286830	LORLATINIB	4	3,598
CHEMBL3301607	FILGOTINIB	4
CHEMBL3545311	BRIGATINIB	4
CHEMBL3655081	ABROCITINIB	4
CHEMBL4298138	REPOTRECTINIB	4
CHEMBL4435170	DEUCRAVACITINIB	4
CHEMBL4582651	PRALSETINIB	4
CHEMBL4596392	CRAVACITINIB	4
CHEMBL477772	PAZOPANIB	4
CHEMBL502835	NINTEDANIB	4
CHEMBL535	SUNITINIB	4

Clinical evidence (CIViC)

Drug × variant × indication: 5 predictive associations from 5 curated evidence items; also 4 diagnostic.

Variant	Therapy	Indication	Effect	Level	CIViC
JAK2 V617F	Peginterferon Alfa-2b	Polycythemia Vera	Sensitivity/Response	CIViC B	EID19
JAK2 F694L	Ruxolitinib	Childhood B-cell Acute Lymphoblastic Leukemia	Sensitivity/Response	CIViC C	EID7021
JAK2 Splice Site (c.1641+2T>G)	Pembrolizumab	Melanoma	Resistance	CIViC C	EID4825
JAK2 c.1641+1dup	Pembrolizumab	Skin Melanoma	Resistance	CIViC C	EID1568
JAK2 V617F	Fedratinib	Polycythemia Vera	Sensitivity/Response	CIViC D	EID20

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

PharmGKB variants

2 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs12343867	INSL6, JAK2		0.00	0
rs77375493	INSL6, JAK2		0.00	0

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — Janus kinase (JakA) family

Most potent curated ligand interactions (74 total), top 25:

Ligand	Action	Affinity	Parameter
nezulcitinib	Inhibition	10.51	pKi
izencitinib	Inhibition	10.0	pKi
SJ988497	Binding	9.47	pKd
AZ960	Inhibition	9.35	pKi
GDC-0214	Inhibition	9.21	pKi
compound 18e [PMID: 31670517]	Inhibition	9.15	pIC50
ilginatinib	Inhibition	9.14	pIC50
tinengotinib	Inhibition	9.12	pIC50
JAK inhibitor I	Inhibition	9.0	pIC50
BMS-911543	Inhibition	9.0	pIC50
compound 1d [PMID: 21493067]	Inhibition	9.0	pIC50
repotrectinib	Inhibition	8.98	pIC50
soficitinib	Inhibition	8.92	pIC50
AT-9283	Inhibition	8.92	pIC50
momelotinib	Inhibition	8.85	pIC50
LASW1393	Inhibition	8.82	pIC50
compound 25ap [PMID: 37796543]	Inhibition	8.74	pIC50
CEP-33779	Inhibition	8.74	pIC50
XL019	Inhibition	8.66	pIC50
delgocitinib	Inhibition	8.59	pIC50
compound 13ac [PMID: 33256400]	Inhibition	8.52	pIC50
fedratinib	Inhibition	8.52	pIC50
compound 19a [PMID: 24359159]	Inhibition	8.52	pIC50
JAK inhibitor 17b	Inhibition	8.45	pIC50
gandotinib	Inhibition	8.4	pIC50

Binding affinities (BindingDB)

5522 measured of 6100 human assays (6100 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
2,2,2-trifluoroethyl 4-[4-carbamoyl-3-[[6-(1H-pyrazol-4-yl)-3-pyridinyl]amino]pyrazol-1-yl]-4-(cyanomethyl)piperidine-1-carboxylate	IC50	0.01 nM	US-9328099: Cyanomethylpyrazole carboxamides as janus kinase inhibitors
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
1-[1-(cyanomethyl)-4-(2,2,2-trifluoroethylamino)cyclohexyl]-3-[4-(difluoromethylsulfonyl)anilino]pyrazole-4-carboxamide	IC50	0.02 nM	US-9328099: Cyanomethylpyrazole carboxamides as janus kinase inhibitors
(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
US9328099, 40-63	IC50	0.03 nM	US-9328099: Cyanomethylpyrazole carboxamides as janus kinase inhibitors
2,2,2-trifluoroethyl 4-[4-carbamoyl-3-[[6-(1-methylpyrazol-4-yl)-3-pyridinyl]amino]pyrazol-1-yl]-4-(cyanomethyl)piperidine-1-carboxylate	IC50	0.03 nM	US-9328099: Cyanomethylpyrazole carboxamides as janus kinase inhibitors
1-[1-(cyanomethyl)-4-(2,4-difluoroanilino)cyclohexyl]-3-[(2-fluoro-4-pyridinyl)amino]pyrazole-4-carboxamide	IC50	0.03 nM	US-9328099: Cyanomethylpyrazole carboxamides as janus kinase inhibitors
1-[4-[(2-chlorophenyl)methylamino]-1-(cyanomethyl)cyclohexyl]-3-[(2-fluoro-4-pyridinyl)amino]pyrazole-4-carboxamide	IC50	0.03 nM	US-9328099: Cyanomethylpyrazole carboxamides as janus kinase inhibitors
2,2-difluoroethyl (3S,4S)-4-[4-carbamoyl-3-[(2-fluoro-4-pyridinyl)amino]pyrazol-1-yl]-4-(cyanomethyl)-3-fluoropiperidine-1-carboxylate	IC50	0.03 nM	US-9328099: Cyanomethylpyrazole carboxamides as janus kinase inhibitors
1-[(3R,4S)-4-cyanooxan-3-yl]-3-[4-[(2S)-1,1-difluoro-2-hydroxypropan-2-yl]anilino]pyrazole-4-carboxamide	IC50	0.03 nM	US-9394282: Pyrazole carboxamides as Janus kinase inhibitors
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
1-[(1S,2S,4R)-4-(azetidin-1-yl)-2-cyanocyclohexyl]-3-[4-[(2R)-1,1,1-trifluoro-2-hydroxypropan-2-yl]anilino]pyrazole-4-carboxamide	IC50	0.04 nM	US-8962608: Cycloalkylnitrile pyrazole carboxamides as janus kinase inhibitors
1-[4-(cyanomethyl)-1-[(3-hydroxyphenyl)methyl]piperidin-4-yl]-3-[(2-fluoro-4-pyridinyl)amino]pyrazole-4-carboxamide	IC50	0.04 nM	US-9328099: Cyanomethylpyrazole carboxamides as janus kinase inhibitors
1-[1-(cyanomethyl)-4-(2-fluoroanilino)cyclohexyl]-3-[(2-fluoro-4-pyridinyl)amino]pyrazole-4-carboxamide	IC50	0.04 nM	US-9328099: Cyanomethylpyrazole carboxamides as janus kinase inhibitors
1-[1-(cyanomethyl)-4-(2,2-difluoroethylamino)cyclohexyl]-3-[4-(difluoromethylsulfonyl)anilino]pyrazole-4-carboxamide	IC50	0.04 nM	US-9328099: Cyanomethylpyrazole carboxamides as janus kinase inhibitors
1-[4-(benzylamino)-1-(cyanomethyl)cyclohexyl]-3-(4-fluoroanilino)pyrazole-4-carboxamide	IC50	0.04 nM	US-9328099: Cyanomethylpyrazole carboxamides as janus kinase inhibitors
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

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
10.97	IC50	0.0108	nM	CHEMBL3665128
10.97	IC50	0.0106	nM	CHEMBL3665130
10.89	Ki	0.013	nM	CHEMBL6036273
10.89	Ki	0.013	nM	CHEMBL5776613
10.89	Ki	0.013	nM	CHEMBL5997591
10.80	Ki	0.016	nM	CHEMBL5956972
10.80	Ki	0.016	nM	CHEMBL5979950
10.80	Ki	0.016	nM	CHEMBL5813467
10.80	Ki	0.016	nM	CHEMBL5905186
10.78	IC50	0.0165	nM	CHEMBL3652404
10.76	IC50	0.0172	nM	CHEMBL3665202
10.72	IC50	0.0191	nM	CHEMBL3665129
10.71	IC50	0.0196	nM	CHEMBL3665180
10.70	IC50	0.0201	nM	CHEMBL3665176
10.70	IC50	0.0199	nM	CHEMBL3652402
10.70	Ki	0.02	nM	CHEMBL5979950
10.70	Ki	0.02	nM	CHEMBL5956972
10.70	Ki	0.02	nM	CHEMBL5791141
10.70	Ki	0.02	nM	CHEMBL5851343
10.70	Ki	0.02	nM	CHEMBL6064118
10.70	Ki	0.02	nM	CHEMBL5993958
10.68	IC50	0.0209	nM	CHEMBL3665131
10.66	IC50	0.0221	nM	CHEMBL3665199
10.66	Kd	0.022	nM	CHEMBL5090416
10.64	IC50	0.0228	nM	CHEMBL3665123
10.61	IC50	0.0245	nM	CHEMBL3335690
10.60	Ki	0.025	nM	CHEMBL5744137
10.60	Ki	0.025	nM	CHEMBL5792137
10.60	Ki	0.025	nM	CHEMBL5828027
10.56	IC50	0.0276	nM	CHEMBL3665127
10.53	IC50	0.0296	nM	CHEMBL3665122
10.53	IC50	0.0293	nM	CHEMBL3665188
10.53	IC50	0.0292	nM	CHEMBL3665119
10.52	Ki	0.03	nM	CHEMBL5993958
10.52	Ki	0.03	nM	CHEMBL6064937
10.52	Ki	0.03	nM	CHEMBL5984979
10.52	Ki	0.03	nM	CHEMBL5957273
10.52	Ki	0.03	nM	CHEMBL5948963
10.52	Ki	0.03	nM	CHEMBL5879480
10.52	Ki	0.03	nM	CHEMBL5836552
10.52	Ki	0.03	nM	CHEMBL5894302
10.52	Ki	0.03	nM	CHEMBL5775383
10.52	IC50	0.03	nM	CHEMBL5957755
10.52	Ki	0.03	nM	CHEMBL5783241
10.52	Ki	0.03	nM	CHEMBL5952598
10.52	Ki	0.03	nM	CHEMBL5819815
10.49	Ki	0.032	nM	CHEMBL5753964
10.49	Ki	0.032	nM	CHEMBL5881510
10.49	Ki	0.032	nM	CHEMBL6062038
10.49	Ki	0.032	nM	NEZULCITINIB

PubChem BioAssay actives

2913 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
2-amino-N-[5-[5-chloro-2-(difluoromethoxy)phenyl]-1H-pyrazol-4-yl]pyrazolo[1,5-a]pyrimidine-3-carboxamide	1672519: Inhibition of recombinant human JAK2 (812 to 1132 residues) expressed in insect cells using Y1-B as substrate incubated for 30 mins by microfluidic mobility shift assay	ki	<0.0001	uM
N-[5-[5-bromo-2-(difluoromethoxy)phenyl]-1H-pyrazol-4-yl]pyrazolo[1,5-a]pyrimidine-3-carboxamide	1672519: Inhibition of recombinant human JAK2 (812 to 1132 residues) expressed in insect cells using Y1-B as substrate incubated for 30 mins by microfluidic mobility shift assay	ki	<0.0001	uM
N-[5-[2-(difluoromethoxy)-5-iodophenyl]-1H-pyrazol-4-yl]pyrazolo[1,5-a]pyrimidine-3-carboxamide	1672519: Inhibition of recombinant human JAK2 (812 to 1132 residues) expressed in insect cells using Y1-B as substrate incubated for 30 mins by microfluidic mobility shift assay	ki	<0.0001	uM
N-[4-[[4-(1-but-3-enylpyrazol-4-yl)-7H-pyrrolo[2,3-d]pyrimidin-2-yl]amino]phenyl]-N’-hydroxyoctanediamide	1396956: Inhibition of human JAK2 using poly[Glu:Tyr] (4:1) as substrate in presence of [gamma-33P]ATP	ic50	<0.0001	uM
N-[4-[[4-[1-(2-cyanoethyl)pyrazol-4-yl]-7H-pyrrolo[2,3-d]pyrimidin-2-yl]amino]phenyl]-N’-hydroxyoctanediamide	1396956: Inhibition of human JAK2 using poly[Glu:Tyr] (4:1) as substrate in presence of [gamma-33P]ATP	ic50	<0.0001	uM
4-[[4-[1-[3-(cyanomethyl)-1-ethylsulfonylazetidin-3-yl]pyrazol-4-yl]-7H-pyrrolo[2,3-d]pyrimidin-2-yl]amino]-N-[3-[4-[4-(2,6-dioxopiperidin-3-yl)phenyl]piperazin-1-yl]propyl]benzamide	1827307: Binding affinity to JAK2 (unknown origin)	kd	<0.0001	uM
Ruxolitinib	2031086: Inhibition of JAK2 (unknown origin)	ic50	<0.0001	uM
N-[5-[5-chloro-2-(difluoromethoxy)phenyl]-1H-pyrazol-4-yl]pyrazolo[1,5-a]pyrimidine-3-carboxamide	1672519: Inhibition of recombinant human JAK2 (812 to 1132 residues) expressed in insect cells using Y1-B as substrate incubated for 30 mins by microfluidic mobility shift assay	ki	0.0001	uM
3-[(1R,5S)-3-[[7-[(5-methyl-1H-pyrazol-3-yl)amino]-1,6-naphthyridin-5-yl]amino]-8-azabicyclo[3.2.1]octan-8-yl]propanenitrile	2066937: Inhibition of human recombinant JAK2	ki	0.0001	uM
N-[5-[5-chloro-2-(difluoromethoxy)phenyl]-1H-pyrazol-4-yl]imidazo[1,2-b]pyridazine-3-carboxamide	1672519: Inhibition of recombinant human JAK2 (812 to 1132 residues) expressed in insect cells using Y1-B as substrate incubated for 30 mins by microfluidic mobility shift assay	ki	0.0001	uM
N-[5-[2-(difluoromethoxy)-5-methylsulfanylphenyl]-1H-pyrazol-4-yl]imidazo[1,2-b]pyridazine-3-carboxamide	1934118: Binding affinity to human recombinant JAK2 assessed as inhibition constant incubated for 30 mins by microtiter plate reader analysis	ki	0.0001	uM
N-[5-[5-chloro-2-(difluoromethoxy)phenyl]-1H-pyrazol-4-yl]-6-ethynylimidazo[1,2-b]pyridazine-3-carboxamide	1672519: Inhibition of recombinant human JAK2 (812 to 1132 residues) expressed in insect cells using Y1-B as substrate incubated for 30 mins by microfluidic mobility shift assay	ki	0.0001	uM
N-[5-[3-(difluoromethoxy)naphthalen-2-yl]-1H-pyrazol-4-yl]pyrazolo[1,5-a]pyrimidine-3-carboxamide	1672519: Inhibition of recombinant human JAK2 (812 to 1132 residues) expressed in insect cells using Y1-B as substrate incubated for 30 mins by microfluidic mobility shift assay	ki	0.0001	uM
N-[5-[6-(difluoromethoxy)-1H-indazol-5-yl]-1H-pyrazol-4-yl]pyrazolo[1,5-a]pyrimidine-3-carboxamide	1672519: Inhibition of recombinant human JAK2 (812 to 1132 residues) expressed in insect cells using Y1-B as substrate incubated for 30 mins by microfluidic mobility shift assay	ki	0.0001	uM
N-[5-[5-chloro-2-(difluoromethoxy)phenyl]-1H-pyrazol-4-yl]-5-methylpyrazolo[1,5-a]pyrimidine-3-carboxamide	1672519: Inhibition of recombinant human JAK2 (812 to 1132 residues) expressed in insect cells using Y1-B as substrate incubated for 30 mins by microfluidic mobility shift assay	ki	0.0001	uM
N-[5-[5-chloro-2-(difluoromethoxy)phenyl]-1H-pyrazol-4-yl]-[1,2]thiazolo[4,3-b]pyridine-3-carboxamide	1672519: Inhibition of recombinant human JAK2 (812 to 1132 residues) expressed in insect cells using Y1-B as substrate incubated for 30 mins by microfluidic mobility shift assay	ki	0.0001	uM
N’-hydroxy-N-[4-[[4-(1-propylpyrazol-4-yl)-7H-pyrrolo[2,3-d]pyrimidin-2-yl]amino]phenyl]octanediamide	1396956: Inhibition of human JAK2 using poly[Glu:Tyr] (4:1) as substrate in presence of [gamma-33P]ATP	ic50	0.0001	uM
(3S)-3-cyclopentyl-3-[4-[2-(4-piperidin-4-ylanilino)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]pyrazol-1-yl]propanenitrile	1709011: Inhibition of human JAK2 by radiometric assay	ic50	0.0001	uM
(3R)-3-cyclopentyl-3-[4-[2-(4-piperidin-4-ylanilino)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]pyrazol-1-yl]propanenitrile	1709011: Inhibition of human JAK2 by radiometric assay	ic50	0.0001	uM
3-[4-[2-(4-piperidin-4-ylanilino)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]pyrazol-1-yl]propanenitrile	1709011: Inhibition of human JAK2 by radiometric assay	ic50	0.0001	uM
N-[5-[5-chloro-2-(difluoromethoxy)-4-hydroxyphenyl]-1H-pyrazol-4-yl]pyrazolo[1,5-a]pyrimidine-3-carboxamide	1672519: Inhibition of recombinant human JAK2 (812 to 1132 residues) expressed in insect cells using Y1-B as substrate incubated for 30 mins by microfluidic mobility shift assay	ki	0.0001	uM
3-cyclopentyl-3-[4-[2-(4-piperidin-4-ylanilino)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]pyrazol-1-yl]propanenitrile	1709011: Inhibition of human JAK2 by radiometric assay	ic50	0.0001	uM
4-[[4-[1-[3-(cyanomethyl)-1-ethylsulfonylazetidin-3-yl]pyrazol-4-yl]-7H-pyrrolo[2,3-d]pyrimidin-2-yl]amino]-N-[4-[4-(2,6-dioxopiperidin-3-yl)phenoxy]butyl]benzamide	1827307: Binding affinity to JAK2 (unknown origin)	kd	0.0001	uM
N-[5-(2,2-dimethyl-3H-[1,4]dioxino[2,3-b]pyridin-6-yl)-4-[(4-methoxy-6-methylsulfonyl-2-pyridinyl)amino]-2-pyridinyl]acetamide	2029558: Inhibition of JAK2/TYK2 signal transduction pathway in human NK92 cells assessed as IL-12 induced STAT4 phosphorylation	ic50	0.0001	uM
6-(2,6-difluorophenyl)-4-[(5-morpholin-4-yl-2-pyridinyl)amino]pyridazine-3-carboxamide	2029514: Inhibition of JAK2/TYK2 signal transduction pathway in human NK92 cells assessed as IL-2 induced IFNgamma expression incubated for 24 hrs by ELISA 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	1715309: Inhibition of human JAK2 using poly[Glu:Tyr] (4:1) as substrate by [gamma-33P]-ATP assay	ic50	0.0001	uM
4-(2-chloro-6-fluorophenyl)-15-fluoro-3,5,10-triazatetracyclo[11.4.0.02,6.07,12]heptadeca-1(13),2(6),4,7(12),8,14,16-heptaen-11-one	317363: Inhibition of human JAK2	ic50	0.0002	uM
N-[5-(6-methoxy-1H-indazol-5-yl)-1H-pyrazol-4-yl]pyrazolo[1,5-a]pyrimidine-3-carboxamide	1672519: Inhibition of recombinant human JAK2 (812 to 1132 residues) expressed in insect cells using Y1-B as substrate incubated for 30 mins by microfluidic mobility shift assay	ki	0.0002	uM
N-[5-[5-chloro-2-(difluoromethoxy)phenyl]-1H-pyrazol-4-yl]-[1,3]thiazolo[5,4-c]pyridine-7-carboxamide	1672519: Inhibition of recombinant human JAK2 (812 to 1132 residues) expressed in insect cells using Y1-B as substrate incubated for 30 mins by microfluidic mobility shift assay	ki	0.0002	uM
N-[4-[[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]amino]butyl]-4-[[4-(1-propylpyrazol-4-yl)-7H-pyrrolo[2,3-d]pyrimidin-2-yl]amino]benzamide	1710172: PROTAC activity at CRBN/JAK2 in human MHHCALL4 cells assessed as protein degradation by immunoblot analysis	ec50	0.0002	uM
4-[8-methoxy-2-[(1-methylpyrazol-4-yl)amino]quinazolin-6-yl]phenol	1824613: Inhibition of GST-tagged recombinant human JAK2 (808 to 1132 residues) expressed in baculovirus expression system 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
N-[5-[5-chloro-2-(difluoromethylsulfanyl)phenyl]-1H-pyrazol-4-yl]pyrazolo[1,5-a]pyrimidine-3-carboxamide	1672519: Inhibition of recombinant human JAK2 (812 to 1132 residues) expressed in insect cells using Y1-B as substrate incubated for 30 mins by microfluidic mobility shift assay	ki	0.0002	uM
N-[5-(5-chloro-4-hydroxy-2-methoxyphenyl)-1H-pyrazol-4-yl]pyrazolo[1,5-a]pyrimidine-3-carboxamide	1672519: Inhibition of recombinant human JAK2 (812 to 1132 residues) expressed in insect cells using Y1-B as substrate incubated for 30 mins by microfluidic mobility shift assay	ki	0.0002	uM
N-[5-[2-(difluoromethoxy)-5-ethylphenyl]-1H-pyrazol-4-yl]pyrazolo[1,5-a]pyrimidine-3-carboxamide	1672519: Inhibition of recombinant human JAK2 (812 to 1132 residues) expressed in insect cells using Y1-B as substrate incubated for 30 mins by microfluidic mobility shift assay	ki	0.0002	uM
N-[5-[3-chloro-6-(difluoromethoxy)-2-fluorophenyl]-1H-pyrazol-4-yl]pyrazolo[1,5-a]pyrimidine-3-carboxamide	1672519: Inhibition of recombinant human JAK2 (812 to 1132 residues) expressed in insect cells using Y1-B as substrate incubated for 30 mins by microfluidic mobility shift assay	ki	0.0002	uM
3-[6-[[(1R)-1-(4-fluorophenyl)ethyl]amino]pyrimidin-4-yl]pyrazolo[1,5-a]pyrimidin-2-amine	446109: Inhibition of JAK2 by radiometric assay	ic50	0.0002	uM
[2-[6-(2-ethyl-5-fluoro-4-hydroxyphenyl)-1H-indazol-3-yl]-3,4,6,7-tetrahydroimidazo[4,5-c]pyridin-5-yl]-(4-fluorophenyl)methanone	1436130: Inhibition of GST tagged human recombinant JAK2 catalytic domain expressed in baculovirus using peptide substrate preincubated for 60 mins followed by substrate addition and measured after 60 mins by microfluidic assay	ic50	0.0003	uM
N-[5-(3-methoxynaphthalen-2-yl)-1H-pyrazol-4-yl]pyrazolo[1,5-a]pyrimidine-3-carboxamide	1672519: Inhibition of recombinant human JAK2 (812 to 1132 residues) expressed in insect cells using Y1-B as substrate incubated for 30 mins by microfluidic mobility shift assay	ki	0.0003	uM
N-[5-[2-(difluoromethoxy)-5-methylphenyl]-1H-pyrazol-4-yl]pyrazolo[1,5-a]pyrimidine-3-carboxamide	1672519: Inhibition of recombinant human JAK2 (812 to 1132 residues) expressed in insect cells using Y1-B as substrate incubated for 30 mins by microfluidic mobility shift assay	ki	0.0003	uM
4-(1-but-3-enylpyrazol-4-yl)-N-(4-piperidin-4-ylphenyl)-7H-pyrrolo[2,3-d]pyrimidin-2-amine	1709011: Inhibition of human JAK2 by radiometric assay	ic50	0.0003	uM
2-[4-[[5-chloro-4-[(2,5-difluorophenyl)methylamino]pyrimidin-2-yl]amino]pyrazol-1-yl]ethanol	1666678: Inhibition of JAK2 (unknown origin)	ic50	0.0003	uM
N-[5-(3-chloro-2-fluoro-6-methoxyphenyl)-1H-pyrazol-4-yl]pyrazolo[1,5-a]pyrimidine-3-carboxamide	1672519: Inhibition of recombinant human JAK2 (812 to 1132 residues) expressed in insect cells using Y1-B as substrate incubated for 30 mins by microfluidic mobility shift assay	ki	0.0003	uM
6-(2,6-difluorophenyl)-4-[[5-(3-oxomorpholin-4-yl)-2-pyridinyl]amino]pyridazine-3-carboxamide	2029514: Inhibition of JAK2/TYK2 signal transduction pathway in human NK92 cells assessed as IL-2 induced IFNgamma expression incubated for 24 hrs by ELISA assay	ic50	0.0003	uM
Baricitinib	1709011: Inhibition of human JAK2 by radiometric assay	ic50	0.0003	uM
6-N-[(1S)-1-(4-fluorophenyl)ethyl]-4-(1-methylpyrazol-4-yl)-2-N-pyrazin-2-ylpyridine-2,6-diamine	1875944: Inhibition of JAK 2 (unknown origin)	ic50	0.0003	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	1940831: Inhibition of human JAK2 kinase domain using biotin-Lyn-substrate-2 as substrate incubated for 1 hr by ELISA	ic50	0.0003	uM
5-chloro-2-N-[(1S)-1-(5-fluoropyrimidin-2-yl)ethyl]-4-N-(5-methyl-1H-pyrazol-3-yl)pyrimidine-2,4-diamine	1941950: Competitive inhibition of JAK2 (unknown origin) in the presence of ATP	ic50	0.0004	uM
(3S,5R)-4-[[5-(1H-pyrazol-4-yl)-1H-pyrrolo[2,3-b]pyridin-4-yl]amino]adamantan-1-ol	1989290: Inhibition of recombinant JAK2 (unknown origin) using GFP-STAT1 as substrate incubated for 1 hr by TR-FRET Lanthascreen assay	ic50	0.0004	uM
6-(2-chloro-6-fluorophenyl)-4-(4-morpholin-4-ylanilino)pyridazine-3-carboxamide	2029514: Inhibition of JAK2/TYK2 signal transduction pathway in human NK92 cells assessed as IL-2 induced IFNgamma expression incubated for 24 hrs by ELISA assay	ic50	0.0004	uM
5-fluoro-2-[[(1S)-1-(4-fluorophenyl)ethyl]amino]-6-[(5-methyl-1H-pyrazol-3-yl)amino]pyridine-3-carbonitrile	1629279: Inhibition of JAK2 V617F mutant (unknown origin) using L-Ahx-IPTSPITTTYFFFKKK-COOH as substrate in presence of ATP	ki	0.0004	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
alpha-cyano-(3,4-dihydroxy)-N-benzylcinnamide	decreases expression, decreases response to substance, decreases phosphorylation, increases activity, increases phosphorylation (+4 more)	8
Arsenic Trioxide	decreases expression, increases reaction, decreases phosphorylation, affects cotreatment, decreases reaction (+3 more)	6
Estradiol	affects cotreatment, decreases activity, decreases reaction, decreases expression, increases phosphorylation (+1 more)	6
Resveratrol	increases expression, decreases reaction, increases phosphorylation, decreases phosphorylation, affects cotreatment	5
bisphenol A	affects cotreatment, decreases activity, decreases reaction, decreases expression, decreases methylation (+1 more)	4
sodium arsenite	affects cotreatment, decreases expression, increases abundance, increases expression, decreases reaction (+2 more)	4
tofacitinib	affects response to substance, decreases reaction, increases phosphorylation, increases activity, decreases activity	4
Nickel	affects expression, decreases expression, increases expression, decreases reaction	4
pervanadate	decreases phosphorylation, decreases reaction	3
ruxolitinib	affects response to substance, affects cotreatment, decreases phosphorylation, decreases activity	3
Arsenic	increases abundance, affects methylation, increases phosphorylation, affects cotreatment, decreases expression	3
Curcumin	decreases expression, increases reaction, decreases reaction, increases phosphorylation	3
Doxorubicin	decreases expression	3
Quercetin	affects cotreatment, decreases phosphorylation, increases expression	3
Rotenone	increases reaction, decreases phosphorylation, decreases reaction, increases activity, increases phosphorylation	3
Cyclosporine	increases expression	3
baricitinib	decreases reaction, increases activity, increases phosphorylation, decreases activity	2
gingerenone A	decreases activity, increases response to substance	2
CDM-3008	decreases phosphorylation, decreases reaction, increases phosphorylation	2
fucoxanthin	decreases reaction, increases phosphorylation, affects binding, decreases phosphorylation	2
perfluorooctane sulfonic acid	decreases expression, increases phosphorylation	2
linderalactone	affects activity, affects expression, affects phosphorylation, decreases expression, decreases phosphorylation	2
WP1066	decreases phosphorylation, increases degradation	2
pacritinib	decreases reaction, increases phosphorylation, decreases phosphorylation	2
(+)-JQ1 compound	decreases expression, decreases phosphorylation	2
CEP 33779	decreases activity	2
Decitabine	decreases expression, decreases methylation	2
Acetylcysteine	decreases reaction, increases phosphorylation, decreases phosphorylation	2
Daunorubicin	decreases expression	2
Hydrogen Peroxide	decreases expression, decreases phosphorylation	2

ChEMBL screening assays

2018 unique, capped per target: 1911 binding, 51 functional, 48 admet, 4 unclassified, 4 toxicity

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1218226	Binding	Inhibition of JAK-mediated interferon-gamma/anisomycin-induced Stat1 phosphorylation in human U937 cells by Phospho-Flow cytometry	High-content single-cell drug screening with phosphospecific flow cytometry. — Nat Chem Biol
CHEMBL1613998	Functional	PUBCHEM_BIOASSAY: Luminescent counterscreen for inhibitors of the Janus kinase 2 mutant JAK2V617F: dose response cell-based high throughput screening assay for inhibitors of parental Ba/F3 cell viability. (Class of assay: confirmatory) [Rel	PubChem BioAssay data set
CHEMBL1738019	Unclassified	PUBCHEM_BIOASSAY: Late stage results from the probe development effort to identify inhibitors of the Janus kinase 2 mutant JAK2V617F. (Class of assay: screening) [Related pubchem assays (depositor defined):AID1446, AID1486, AID1520, AID1521	PubChem BioAssay data set

Cellosaurus cell lines

62 cell lines: 34 cancer cell line, 26 induced pluripotent stem cell, 2 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_0001	HEL	Cancer cell line	Male
CVCL_0104	UKE-1	Cancer cell line	Female
CVCL_0H70	SMF No.5	Induced pluripotent stem cell	Female
CVCL_0H71	SMF No.6	Induced pluripotent stem cell	Female
CVCL_0H73	SMF No.8	Induced pluripotent stem cell	Female
CVCL_0H74	SMF No.9	Induced pluripotent stem cell	Female
CVCL_0H76	SMF No.15	Induced pluripotent stem cell	Female
CVCL_0H80	SMF No.21	Induced pluripotent stem cell	Female
CVCL_2130	MUTZ-8	Cancer cell line	Female
CVCL_2187	SET-2	Cancer cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01558739	PHASE4	COMPLETED	Exploratory Phase II Study of INC424 Patients With Primary Myelofibrosis (PMF) or Post Polycythaemia Myelofibrosis (PPV MF) or Post Essential Thrombocythaemia Myelofibrosis (PET-MF)
NCT02386800	PHASE4	ACTIVE_NOT_RECRUITING	CINC424A2X01B Rollover Protocol
NCT05853458	PHASE4	TERMINATED	Evaluation of HU-resistance in Adult Patients With Polycythemia Vera Who Meet PV-AIM Predictors
NCT06290765	PHASE4	NOT_YET_RECRUITING	Efficacy and Safety of Ropeginterferon Alfa 2b (P1101) for Patients With Polycythemia Vera
NCT00799461	PHASE3	COMPLETED	Internet-Based Program With or Without Telephone-Based Problem-Solving Training in Helping Long-Term Survivors of Hematopoietic Stem Cell Transplant Cope With Late Complications
NCT01178281	PHASE3	COMPLETED	Study of Pomalidomide in Persons With Myeloproliferative-Neoplasm-Associated Myelofibrosis and RBC-Transfusion-Dependence
NCT01387763	PHASE3	COMPLETED	A Study of Low Dose Interferon Alpha Versus Hydroxyurea in Treatment of Chronic Myeloid Neoplasms
NCT01773187	PHASE3	TERMINATED	Pacritinib Versus Best Available Therapy to Treat Myelofibrosis
NCT01969838	PHASE3	COMPLETED	Momelotinib Versus Ruxolitinib in Subjects With Myelofibrosis
NCT02055781	PHASE3	TERMINATED	Pacritinib Versus Best Available Therapy to Treat Patients With Myelofibrosis and Thrombocytopenia
NCT02087059	PHASE3	COMPLETED	A Clinical Study of Ruxolitinib in Patients With Primary Myelofibrosis (PM), Post-polycythemia Vera (PV) Myelofibrosis, or Post-essential Thrombocythemia (ET) Myelofibrosis
NCT02101268	PHASE3	COMPLETED	Efficacy of Momelotinib Versus Best Available Therapy in Anemic or Thrombocytopenic Subjects With Primary Myelofibrosis (MF), Post-polycythemia Vera MF, or Post-essential Thrombocythemia MF
NCT03165734	PHASE3	ACTIVE_NOT_RECRUITING	A Phase 3 Study of Pacritinib in Patients With Primary Myelofibrosis, Post Polycythemia Vera Myelofibrosis, or Post-Essential Thrombocythemia Myelofibrosis
NCT03755518	PHASE3	TERMINATED	A Trial of Fedratinib in Subjects With DIPSS, Intermediate or High-Risk Primary Myelofibrosis, Post-Polycythemia Vera Myelofibrosis, or Post-Essential Thrombocythemia Myelofibrosis and Previously Treated With Ruxolitinib
NCT03952039	PHASE3	COMPLETED	An Efficacy and Safety Study of Fedratinib Compared to Best Available Therapy in Subjects With DIPSS-intermediate or High-risk Primary Myelofibrosis, Post-polycythemia Vera Myelofibrosis, or Post-essential Thrombocythemia Myelofibrosis and Previously Treated With Ruxolitinib
NCT04173494	PHASE3	COMPLETED	A Study of Momelotinib Versus Danazol in Symptomatic and Anemic Myelofibrosis Participants (MOMENTUM)
NCT04551053	PHASE3	TERMINATED	To Evaluate Efficacy and Safety of Parsaclisib and Ruxolitinib in Participants With Myelofibrosis Who Have Suboptimal Response to Ruxolitinib (LIMBER-304)
NCT04551066	PHASE3	TERMINATED	To Evaluate the Efficacy and Safety of Parsaclisib and Ruxolitinib in Participants With Myelofibrosis (LIMBER-313)
NCT04603495	PHASE3	ACTIVE_NOT_RECRUITING	Phase 3 Study of Pelabresib (CPI-0610) in Myelofibrosis (MF) (MANIFEST-2)
NCT04717414	PHASE3	ACTIVE_NOT_RECRUITING	An Efficacy and Safety Study of Luspatercept (ACE-536) Versus Placebo in Subjects With Myeloproliferative Neoplasm-Associated Myelofibrosis on Concomitant JAK2 Inhibitor Therapy and Who Require Red Blood Cell Transfusions
NCT06351631	PHASE3	RECRUITING	A Study to Evaluate Safety and Efficacy of Bomedemstat (MK-3543-017)
NCT06468033	PHASE3	RECRUITING	P1101 in Treating Patients With Early PMF or Overt PMF at Low or Intermediate-1 Risk
NCT06479135	PHASE3	RECRUITING	Study of Navtemadlin add-on to Ruxolitinib in JAK Inhibitor-Naïve Patients With Myelofibrosis Who Have a Suboptimal Response to Ruxolitinib
NCT07357727	PHASE3	RECRUITING	A Phase 3 Study of Pelabresib (DAK539) and Ruxolitinib in Myelofibrosis (MF)
NCT01243944	PHASE3	COMPLETED	Study of Efficacy and Safety in Polycythemia Vera Subjects Who Are Resistant to or Intolerant of Hydroxyurea: JAK Inhibitor INC424 (INCB018424) Tablets Versus Best Available Care: (The RESPONSE Trial)
NCT01632904	PHASE3	COMPLETED	Randomized Switch Study From Hydroxyurea to Ruxolitinib for RELIEF of Polycythemia Vera Symptoms: The Relief Study
NCT01645124	PHASE3	TERMINATED	Large-scale Trial Testing the Intensity of CYTOreductive Therapy in Polycythemia Vera (PV)
NCT01949805	PHASE3	COMPLETED	Pegylated Interferon Alpha-2b Versus Hydroxyurea in Polycythemia Vera
NCT02038036	PHASE3	COMPLETED	Ruxolitinib Efficacy and Safety in Patients With HU Resistant or Intolerant Polycythemia Vera vs Best Available Therapy.
NCT02218047	PHASE3	COMPLETED	AOP2014 vs. BAT in Patients With Polycythemia Vera Who Previously Participated in the PROUD-PV Study.
NCT02292446	PHASE3	COMPLETED	Expanded Treatment Protocol (ETP) of Ruxolitinib in Patients With Polycythemia Vera Who Were Hydroxyurea Resistant or Intolerant and for Whom no Treatment Alternatives Was Available.
NCT02523638	PHASE3	COMPLETED	Study to Assess the Self-administration of AOP2014 Using a Pen, Developed for the Treatment of Polycythemia Vera Patients
NCT04116502	PHASE3	RECRUITING	MITHRIDATE: Ruxolitinib Versus Hydroxycarbamide or Interferon as First Line Therapy in High Risk Polycythemia Vera
NCT04655092	PHASE3	RECRUITING	Extension Study of P1101 After Completion of Phase 2 Study in PV Patients or Phase 3 Study in ET Patients
NCT05198960	PHASE3	RECRUITING	AVAJAK: Apixaban/Rivaroxaban Versus Aspirin for Primary Prevention of Thrombo-embolic Complications in JAK2V617F-positive Myeloproliferative Neoplasms
NCT05210790	PHASE3	ACTIVE_NOT_RECRUITING	A Phase 3 Study of Rusfertide in Patients With Polycythemia Vera
NCT05481151	PHASE3	ACTIVE_NOT_RECRUITING	A Study to Assess Efficacy, Safety, and Tolerability of P1101 in Adult Patients With PV
NCT06002490	PHASE3	COMPLETED	A Study to Evaluate P1101 in Japanese PV Patients
NCT06033586	PHASE3	ACTIVE_NOT_RECRUITING	Study to Evaluate the Long-term Safety of Rusfertide (PTG-300) in Subjects With Polycythemia Vera
NCT06093672	PHASE3	RECRUITING	Study on Efficacy and Safety of Givinostat Versus Hydroxyurea in Patients With Polycythemia Vera