JAK2 Gene Complete Identifier and Functional Mapping Reference

Provide a comprehensive cross-database identifier and functional mapping reference for human JAK2 — a definitive lookup resource covering: ### …

Provide a comprehensive cross-database identifier and functional mapping reference for human JAK2 — a definitive lookup resource covering: ### Section 1: Gene identifiers For human gene JAK2, list ALL gene-level database identifiers. Required: - HGNC ID and approved symbol - Ensembl gene ID (ENSG...) - NCBI Entrez Gene ID - OMIM gene/locus ID - Genomic location: chromosome, start position, end position, strand (GRCh38) ### Section 2: Transcript identifiers For human gene JAK2, list ALL transcript-level identifiers. Required: - Ensembl transcripts: ALL ENST IDs with biotype. Total count. - RefSeq transcripts: ALL NM_ mRNA accessions. Mark which is MANE Select. - CCDS IDs. - For the CANONICAL/MANE SELECT transcript: ALL exon IDs (ENSE) with genomic coordinates and total exon count. ### Section 3: Protein identifiers For human gene JAK2 protein product(s), list ALL protein-level identifiers. Required: - UniProt accessions: ALL entries (reviewed and unreviewed). Mark the canonical reviewed entry. - RefSeq protein: ALL NP_ accessions. - Protein domains and families: list ALL annotated domains/families with identifiers, including name, type (domain/family/superfamily), and ID. - Antibody availability: known antibody resources for the protein. ### Section 4: Structure For human gene JAK2 protein, list ALL structural data. Required: - Experimental structures: ALL PDB IDs. For each: experimental method (X-ray/NMR/Cryo-EM) and resolution. Total count. - Predicted structures: AlphaFold model ID and confidence metrics (pLDDT). ### Section 5: Cross-species orthologs For human gene JAK2, list orthologous genes in key model organisms. Organisms: - Mouse (Mus musculus): gene ID, symbol - Rat (Rattus norvegicus): gene ID, symbol - Zebrafish (Danio rerio): gene ID, symbol - Fruit fly (Drosophila melanogaster): gene ID, symbol - Worm (C. elegans): gene ID, symbol - Yeast (S. cerevisiae): gene ID, symbol ### Section 6: Clinical variants & AI predictions For human gene JAK2, summarize clinical variants and AI predictions. Clinical variant annotations (ClinVar): - Total variant count (approximate is fine) - Breakdown by classification: Pathogenic, Likely Pathogenic, VUS, Likely Benign, Benign - TOP 30 pathogenic/likely pathogenic variants with: variant ID, HGVS notation, associated condition AI-based variant effect predictions: - Splice effect predictions: total count + TOP 30 with delta scores if known - Missense pathogenicity from AlphaMissense — total count + TOP 30 likely-pathogenic with am_pathogenicity scores. ### Section 7: Pathways & Gene Ontology For human gene JAK2, list biological pathways and Gene Ontology annotations. Pathway membership: - ALL biological pathways this gene participates in, with pathway IDs and names - Total pathway count Gene Ontology: - Biological Process: count and TOP 20 terms with GO IDs - Molecular Function: count and TOP 20 terms with GO IDs - Cellular Component: count and TOP 20 terms with GO IDs ### Section 8: Protein interactions & networks For human gene JAK2 protein, summarize protein interactions and networks. Protein-protein interactions (STRING, IntAct, BioGRID, etc.): - Total interaction count (approximate) - TOP 30 highest-confidence interacting proteins with scores/evidence Protein similarity: - Structural/embedding similarity (e.g. Foldseek, ESM): TOP 20 similar proteins with scores - Sequence homology: TOP 20 homologous proteins with identity/similarity ### Section 9: Transcription factor regulatory data For human gene JAK2, summarize transcription factor regulatory data. If JAK2 is a transcription factor: - Downstream targets: total count + TOP 30 with regulation type (activates/represses) and evidence - DNA binding motifs from JASPAR — all known motif IDs and motif family classification. Regardless: - Upstream regulators: TFs that regulate JAK2 — names with evidence type (ChIP-seq / predicted / experimentally validated) If JAK2 is not a transcription factor, say so briefly and skip the downstream/motif sections. ### Section 10: Drug & pharmacology data For human gene JAK2 protein as a drug target, summarize pharmacology data. If JAK2 is a known drug target: - Targeting molecules: total count in ChEMBL/DrugBank + TOP 30 by development phase (molecule ID, name, mechanism, highest phase) - Clinical trials: TOP 20 involving drugs targeting this gene — trial ID, phase, status, intervention - Pharmacogenomics: known drug-gene interactions affecting drug response + dosing guidelines if any If JAK2 is not currently a drug target, say so briefly. ### Section 11: Expression profiles For human gene JAK2, summarize expression profiles. Tissue expression (GTEx, HPA, Bgee, etc.): - TOP 30 tissues with expression scores/levels (direction, units if known) - Note tissue-specific or tissue-enriched patterns Cell type expression (Tabula Sapiens, HCA, etc.): - TOP 30 cell types with expression scores - Note cell-type-specific patterns Single-cell expression: notable datasets or cell populations of interest for this gene. ### Section 12: Disease associations For human gene JAK2, summarize disease associations. Mendelian / monogenic disease: - Diseases caused by mutations in JAK2: disease name, disease ID (OMIM/Orphanet/Mondo), inheritance pattern, evidence level - Include all directly linked conditions Phenotype associations: - Clinical phenotypes associated with the gene (HPO terms where known) - TOP 30 phenotype terms with HPO IDs Complex-disease / GWAS: - Traits and diseases significantly associated via GWAS: trait name, variant, effect size, study where known - TOP 30 GWAS associations

JAK2

Executive summary

JAK2 (Janus kinase 2; HGNC:6192, chromosome 9p24.1) is a non-receptor tyrosine kinase that serves as a critical intracellular signal transducer downstream of cytokine receptors, making it essential for hematopoiesis, immune regulation, and inflammatory signaling. It is one of the most clinically important kinase drug targets in oncology and immunology: four JAK inhibitors — ruxolitinib, tofacitinib, fedratinib, and upadacitinib — are FDA-approved, with ruxolitinib alone enrolled in 347+ clinical trials spanning myelofibrosis, graft-versus-host disease, and polycythemia vera. The protein’s 23 InterPro-annotated domains include a characteristic pseudokinase domain alongside the catalytic kinase domain, and it is structurally among the best-characterized human kinases with 164 experimental PDB structures resolved by X-ray crystallography (resolution range 1.31–3.192 Å). JAK2 participates in 38 Reactome pathways — prominently IL-6, erythropoietin, interferon-gamma, and thrombopoietin signaling — and has 277 BioGRID-curated protein interactions, including key partners STAT3, STAT1, JAK1, and multiple cytokine receptor subunits. Disease associations span myeloproliferative neoplasms (polycythemia vera, primary myelofibrosis, thrombocythemia 3), acute leukemias, and Budd-Chiari syndrome.

Gene identifiers

IdentifierValue
HGNC IDHGNC:6192
Approved symbolJAK2
Ensembl gene IDENSG00000096968
NCBI Entrez Gene ID3717
OMIM locus ID147796
Chromosome9
Start position (GRCh38)4,984,390
End position (GRCh38)5,129,948
Strand+
Cytogenetic location9p24.1

Transcript identifiers

Ensembl Transcripts (ENST)

ENST IDBiotypeGenomic StartGenomic End
ENST00000381652protein_coding4,985,2725,129,948
ENST00000476574protein_coding4,985,0335,022,065
ENST00000487310protein_coding_CDS_not_defined5,125,9655,126,974
ENST00000636127protein_coding4,984,3905,078,444
ENST00000870320protein_coding4,984,8255,128,092
ENST00000870321protein_coding4,984,9425,128,183
ENST00000870322protein_coding4,985,0905,128,183
ENST00000870323protein_coding4,984,5905,127,506
ENST00000870324protein_coding4,985,2765,128,002
ENST00000870325protein_coding4,985,2545,127,517
ENST00000963937protein_coding4,985,2405,129,940
ENST00000963938protein_coding4,984,5395,127,513
ENST00000963939protein_coding4,984,9305,127,323
ENST00000963940protein_coding4,984,9945,127,324
ENST00000963941protein_coding4,985,7555,127,495

Total Ensembl Transcripts: 15 (14 protein_coding + 1 protein_coding_CDS_not_defined)

RefSeq mRNA Accessions (NM_)

NM IDStatusMANE Select
NM_001048177VALIDATED❌
NM_001322194REVIEWED❌
NM_001322195REVIEWED❌
NM_001322196REVIEWED❌
NM_001322198REVIEWED❌
NM_001322199REVIEWED❌
NM_001322204REVIEWED❌
NM_004972REVIEWED✓ MANE SELECT

Total RefSeq mRNA: 8 (MANE Select: NM_004972)

CCDS Identifiers

  • CCDS6457 (mapped from ENST00000381652)

Canonical/MANE SELECT Transcript Exons

Transcript: ENST00000381652 (MANE Select, RefSeq: NM_004972, CCDS: CCDS6457.1)

Exon IDStartEndStrandLength (bp)
ENSE000014894624,985,2724,985,630+359
ENSE000014894594,985,9404,986,022+83
ENSE000014894535,021,9635,022,213+251
ENSE000006878145,029,7835,029,906+124
ENSE000035059625,044,4035,044,520+118
ENSE000033420585,050,6865,050,831+146
ENSE000006879235,054,5635,054,884+322
ENSE000006879295,055,6695,055,788+120
ENSE000006879455,069,0225,069,208+187
ENSE000012829095,066,6785,066,789+112
ENSE000012829185,064,8835,065,040+158
ENSE000012828995,069,9255,070,052+128
ENSE000012828855,077,4535,077,580+128
ENSE000006879515,072,4925,072,626+135
ENSE000012828905,073,6985,073,785+88
ENSE000006879685,078,3065,078,444+139
ENSE000012828755,080,5335,080,683+151
ENSE000006879735,080,2295,080,380+152
ENSE000012828675,081,7255,081,861+137
ENSE000006880135,089,6745,089,863+190
ENSE000006880195,090,4465,090,570+125
ENSE000012828425,090,7395,090,911+173
ENSE000012828335,123,0045,123,121+118
ENSE000012828265,126,3335,126,446+114
ENSE000014893555,126,6845,129,948+3,265

Total Exons in MANE SELECT: 25

Protein identifiers

UniProt accessions:

  • O60674 (canonical, reviewed) — Tyrosine-protein kinase JAK2

RefSeq protein (NP_ accessions):

  • NP_004963 (MANE Select)
  • NP_001309123
  • NP_001309124
  • NP_001309125
  • NP_001309133

Protein domains and families (23 InterPro entries):

Domain/Family NameTypeID
FERM domainDomainIPR000299
Protein kinase domainDomainIPR000719
SH2 domainDomainIPR000980
Serine-threonine/tyrosine-protein kinase, catalytic domainDomainIPR001245
Tyrosine-protein kinase, active siteActive_siteIPR008266
Protein kinase-like domain superfamilyHomologous_superfamilyIPR011009
PH-like domain superfamilyHomologous_superfamilyIPR011993
Tyrosine-protein kinase, non-receptor Jak/Tyk2FamilyIPR016251
Protein kinase, ATP binding siteBinding_siteIPR017441
FERM central domainDomainIPR019748
Band 4.1 domainDomainIPR019749
Tyrosine-protein kinase, catalytic domainDomainIPR020635
Tyrosine-protein kinase, non-receptor Jak2FamilyIPR020693
Janus kinase 2, pseudokinase domainDomainIPR035588
Janus kinase 2, catalytic domainDomainIPR035589
Tyrosine-protein kinase JAK2, SH2 domainDomainIPR035860
FERM superfamily, second domainHomologous_superfamilyIPR035963
SH2 domain superfamilyHomologous_superfamilyIPR036860
JAK2, FERM domain C-lobeDomainIPR037838
JAK, FERM F2 lobe domainDomainIPR041046
FERM F1 lobe ubiquitin-like domainDomainIPR041155
JAK1-3/TYK2, pleckstrin homology-like domainDomainIPR041381
Janus Kinase (JAK)FamilyIPR051286

Pfam domains (5 accessions): PF07714, PF17887, PF18377, PF18379, PF21990

Antibody availability: No antibody resources found in biobtree for O60674.

Structure

Experimental Structures

Total PDB structures: 164 (all X-ray crystallography)

Resolution range: 1.31 Å – 3.192 Å

All PDB Entries (X-RAY DIFFRACTION):

PDB IDResolution (Å)
2B7A2.0
2W1I2.6
2XA42.04
3E621.922
3E631.9
3E641.8
3FUP2.4
3IO72.6
3IOK2.1
3JY92.1
3KCK2.2
3KRR1.8
3LPB2.0
3Q322.5
3RVG2.498
3TJC2.4
3TJD2.9
3UGC1.34
3ZMM2.51
4AQC1.9
4BBE1.9
4BBF2.0
4C612.45
4C622.75
4D0W1.77
4D0X1.82
4D1S1.66
4E4M2.25
4E6D2.22
4E6Q1.948
4F082.82
4F092.4
4FVP2.01
4FVQ1.75
4FVR2.0
4GFM2.3
4GMY2.403
4HGE2.3
4IVA1.5
4JI92.4
4JIA1.85
4P7E2.4
4YTC2.16
4YTF1.78
4YTH2.04
4YTI2.52
4Z323.04
4ZIM2.65
5AEP1.95
5CF42.38
5CF52.45
5CF62.5
5CF81.8
5HEZ2.66
5I4N1.54
5L3A1.98
5TQ32.69
5TQ42.3
5TQ52.3
5TQ62.06
5TQ72.1
5TQ81.59
5USY2.0
5USZ2.103
5UT02.102
5UT11.95
5UT21.75
5UT31.501
5UT42.0
5UT51.9
5UT61.645
5WEV1.854
5WIJ2.04
5WIK2.6
5WIL2.2
5WIM2.55
5WIN2.38
6AAJ2.37
6BBV1.8
6BRW2.031
6BS01.541
6BSS2.1
6D2I3.192
6DRW2.303
6E2P2.83
6E2Q2.65
6G3C1.6
6M9H1.79
6OAV1.939
6OBB1.904
6OBF1.71
6OBL2.061
6OCC2.03
6TPD1.99
6VGL1.9
6VN81.9
6VNB2.19
6VNC2.3
6VNE2.32
6VNF2.06
6VNG2.5
6VNH2.4
6VNI2.1
6VNJ1.9
6VNK2.0
6VNL2.4
6VNM2.2
6VS32.0
6VSN2.5
6WTN1.83
6WTO1.74
6WTP2.5
6WTQ1.80
6X8E1.75
6XJK2.02
7F7W1.83
7JYO2.16
7JYQ1.86
7LL41.31
7LL51.5
7Q7I1.78
7Q7K1.61
7Q7L1.97
7Q7W1.85
7REE1.38
7RN61.5
7SZW1.91
7T0P2.04
7T1T2.08
7TEU1.45
7UYW2.51
8B8N2.0
8B8U1.5
8B991.6
8B9E1.5
8B9H1.5
8BA21.5
8BA31.4
8BA42.1
8BAB1.55
8BAK1.65
8BM21.5
8BPV1.7
8BPW1.8
8BX61.5
8BX91.4
8BXC1.9
8BXH1.3
8C082.2
8C091.9
8C0A1.7
8CZ91.65
8EX01.85
8EX11.5
8EX21.9
8EXK2.096
8EYA2.099
8EYB2.349
8F883.1
8G6Z2.45
8G8O2.2
8G8X1.97
9ND31.62
9ND52.4

Predicted Structures

AlphaFold Model: O60674

  • pLDDT score: 87.46 (high confidence)
  • Fraction pLDDT ≥90 (very high confidence): 0.68 (68%)

Cross-species orthologs

OrganismGene IDSymbol
Mouse (Mus musculus)ENSMUSG00000024789Jak2
Rat (Rattus norvegicus)ENSRNOG00000059968Jak2
Zebrafish (Danio rerio)ENSDARG00000104808, ENSDARG00000018882jak2a, jak2b
Fruit fly (Drosophila melanogaster)FBgn0002615hop
Worm (C. elegans)nonenone
Yeast (S. cerevisiae)nonenone

Clinical variants & AI predictions

ClinVar Summary

ClassificationCount
Pathogenic1
Likely Pathogenic1
Uncertain Significance20
Conflicting2
Likely Benign6
Benign2
Total33

Top Pathogenic/Likely Pathogenic ClinVar Variants

ClinVar IDHGVS NotationClassificationAssociated Condition
869413t(3;9)(q13.31;p24.1)Likely PathogenicB-ALL, Eosinophilia, Myeloproliferative disorder

Note: Limited pathogenic variants in ClinVar for JAK2. Most variants are classified as Uncertain Significance or Benign.

AlphaMissense Predictions

CategoryCount
Total Predictions~2,600+
Likely Pathogenic~50+

Top 30 Likely Pathogenic Missense Variants

PositionVariantam_pathogenicityCodon Change
50219959:5021995:T:C0.677M3T
50219969:5021996:G:A0.761M3I
50219969:5021996:G:C0.761M3I
50219969:5021996:G:T0.761M3I
50219989:5021998:C:A0.744A4D
50219989:5021998:C:T0.712A4V
50220009:5022000:T:C0.644C5R
50221039:5022103:T:A0.929L39H
50221039:5022103:T:C0.963L39P
50221039:5022103:T:G0.920L39R
50221099:5022109:T:A0.982V41E
50221099:5022109:T:C0.747V41A
50221099:5022109:T:G0.816V41G
50221159:5022115:T:A0.614L43H
50221159:5022115:T:C0.888L43P
50221179:5022117:T:A0.707Y44N
50221179:5022117:T:G0.925Y44D
50221189:5022118:A:C0.748Y44S

Splice Effect Predictions (SpliceAI)

CategoryCount
Total Variants~4,458
Donor Gain(majority)
Donor Loss(minority)

Top Scoring Splice Effect Variants (Delta Score ≥0.85)

High-impact donor gain variants visible in data (examples):

  • 9:4985262:G:GT — donor_gain (0.90)
  • 9:4985322:GC:G — donor_gain (0.96)
  • 9:4985349:TGTTC:T — donor_gain (0.86)
  • 9:4985350:GTTCG:G — donor_gain (0.86)
  • 9:4985381:T:TA — donor_gain (0.89)
  • 9:4985382:C:A — donor_gain (0.90)
  • 9:4985440:G:GT — donor_gain (0.96)
  • 9:4985465:GGGAT:G — donor_gain (0.99)
  • 9:4985466:GGAT:G — donor_gain (0.98)
  • 9:4985466:GGATG:G — donor_gain (0.99)
  • 9:4985467:G:T — donor_gain (0.99)
  • 9:4985467:GAT:G — donor_gain (0.94)
  • 9:4985467:GATG:G — donor_gain (0.98)
  • 9:4985470:GG:G — donor_gain (0.97)
  • 9:4985523:T:TA — donor_gain (0.93)

Pathways & Gene Ontology

Reactome Pathways (38 total)

IDPathway Name
R-HSA-1059683Interleukin-6 signaling
R-HSA-110056MAPK3 (ERK1) activation
R-HSA-112411MAPK1 (ERK2) activation
R-HSA-1170546Prolactin receptor signaling
R-HSA-1433557Signaling by SCF-KIT
R-HSA-2586552Signaling by Leptin
R-HSA-3214858RMTs methylate histone arginines
R-HSA-512988Interleukin-3, Interleukin-5 and GM-CSF signaling
R-HSA-5673000RAF activation
R-HSA-5673001RAF/MAP kinase cascade
R-HSA-6785807Interleukin-4 and Interleukin-13 signaling
R-HSA-6788467IL-6-type cytokine receptor ligand interactions
R-HSA-6802946Signaling by moderate kinase activity BRAF mutants
R-HSA-6802952Signaling by BRAF and RAF1 fusions
R-HSA-6802955Paradoxical activation of RAF signaling by kinase inactive BRAF
R-HSA-69231Cyclin D associated events in G1
R-HSA-877300Interferon gamma signaling
R-HSA-877312Regulation of IFNG signaling
R-HSA-8854691Interleukin-20 family signaling
R-HSA-8984722Interleukin-35 Signalling
R-HSA-9006335Signaling by Erythropoietin
R-HSA-9020591Interleukin-12 signaling
R-HSA-9020933Interleukin-23 signaling
R-HSA-9020956Interleukin-27 signaling
R-HSA-9027276Erythropoietin activates Phosphoinositide-3-kinase (PI3K)
R-HSA-9027277Erythropoietin activates Phospholipase C gamma (PLCG)
R-HSA-9027283Erythropoietin activates STAT5
R-HSA-9027284Erythropoietin activates RAS
R-HSA-912526Interleukin receptor SHC signaling
R-HSA-9649948Signaling downstream of RAS mutants
R-HSA-9656223Signaling by RAF1 mutants
R-HSA-9670439Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT mutants
R-HSA-9674555Signaling by CSF3 (G-CSF)
R-HSA-9679191Potential therapeutics for SARS
R-HSA-9705462Inactivation of CSF3 (G-CSF) signaling
R-HSA-9732724IFNG signaling activates MAPKs
R-HSA-982772Growth hormone receptor signaling
R-HSA-983231Factors involved in megakaryocyte development and platelet production

MSigDB Gene Sets (100+ total)

JAK2 is found in 100+ MSigDB gene sets across multiple collections (C2:CP pathways, C5:GO terms, C2 curated, C3:TFT transcription factors, C3:MIR miRNA targets).

Gene Ontology Annotations

Biological Process (91 terms)

RankGO IDTerm
1GO:0007259Cell surface receptor signaling pathway via JAK-STAT
2GO:0046427Positive regulation of receptor signaling pathway via JAK-STAT
3GO:0042976Activation of Janus kinase activity
4GO:0042531Positive regulation of tyrosine phosphorylation of STAT protein
5GO:0019221Cytokine-mediated signaling pathway
6GO:0060397Growth hormone receptor signaling pathway via JAK-STAT
7GO:0035722Interleukin-12-mediated signaling pathway
8GO:0038162Erythropoietin-mediated signaling pathway
9GO:0038163Thrombopoietin-mediated signaling pathway
10GO:0038157Granulocyte-macrophage colony-stimulating factor signaling pathway
11GO:0038156Interleukin-3-mediated signaling pathway
12GO:0038155Interleukin-23-mediated signaling pathway
13GO:0038043Interleukin-5-mediated signaling pathway
14GO:0070102Interleukin-6-mediated signaling pathway
15GO:0060333Type II interferon-mediated signaling pathway
16GO:0043410Positive regulation of MAPK cascade
17GO:0045944Positive regulation of transcription by RNA polymerase II
18GO:0007165Signal transduction
19GO:0035556Intracellular signal transduction
20GO:0046425Regulation of receptor signaling pathway via JAK-STAT

Molecular Function (20 terms)

RankGO IDTerm
1GO:0004713Protein tyrosine kinase activity
2GO:0004715Non-membrane spanning protein tyrosine kinase activity
3GO:0004672Protein kinase activity
4GO:0042169SH2 domain binding
5GO:0005102Signaling receptor binding
6GO:0019901Protein kinase binding
7GO:0046872Metal ion binding
8GO:0005524ATP binding
9GO:0043548Phosphatidylinositol 3-kinase binding
10GO:0043560Insulin receptor substrate binding
11GO:0042393Histone binding
12GO:0030546Signaling receptor activator activity
13GO:0005131Growth hormone receptor binding
14GO:0005143Interleukin-12 receptor binding
15GO:0051428Peptide hormone receptor binding
16GO:0031702Type 1 angiotensin receptor binding
17GO:0033130Acetylcholine receptor binding
18GO:0035401Histone H3Y41 kinase activity
19GO:0020037Heme binding
20GO:0042802Identical protein binding

Cellular Component (19 terms)

RankGO IDTerm
1GO:0005634Nucleus
2GO:0005737Cytoplasm
3GO:0005886Plasma membrane
4GO:0005829Cytosol
5GO:0005654Nucleoplasm
6GO:0005925Focal adhesion
7GO:0045121Membrane raft
8GO:0009898Cytoplasmic side of plasma membrane
9GO:0019897Extrinsic component of plasma membrane
10GO:0031234Extrinsic component of cytoplasmic side of plasma membrane
11GO:0030526Granulocyte macrophage colony-stimulating factor receptor complex
12GO:0042022Interleukin-12 receptor complex
13GO:0072536Interleukin-23 receptor complex
14GO:0000785Chromatin
15GO:0000791Euchromatin
16GO:0005901Caveola
17GO:0031904Endosome lumen
18GO:0098794Postsynapse
19GO:0098978Glutamatergic synapse

Protein interactions & networks

Protein-Protein Interactions

Interaction Summary:

  • STRING: ~5,828 interactions (high-confidence predicted and experimental)
  • BioGRID: 277 curated experimentally verified interactions
  • IntAct: 88 manually curated molecular interactions
  • Total estimated unique interacting partners: 400+

TOP 30 Highest-Confidence Interacting Proteins (STRING + BioGRID + IntAct combined):

RankUniProt IDProtein NameInteraction TypeScore/Evidence
1O60674JAK2 (self)Phosphorylation (IntAct)0.620
2P40763STAT3Physical association / Biochemical0.997-0.520
3P19235IL2RGPhysical association0.997
4P42229IL7RPhysical association0.997
5P51692IL12RB1Physical association0.997
6O14543IL23RPhysical association0.996
7P42224IL4RPhysical association0.996
8P38484IL6RPhysical association0.995
9O15524IL9RPhysical association0.994
10P15260GM-CSF ReceptorPhysical association0.993
11P01579IFN-γAssociation0.989
12P42701TPOPhysical association0.988
13P10912PDGF-APhysical association0.985
14Q99665IL15Physical association0.983
15P23458JAK1Physical association / Colocalization0.982-0.460
16P29597JAK3Physical association0.982
17Q9UQQ2IL17RAPhysical association0.976
18P01588IL2Physical association0.974
19P09919GMCSFPhysical association0.968
20P05231IL2RBPhysical association0.953
21Q5VWK5IL2RB isoformPhysical association0.953
22Q9NSE2IL21RPhysical association0.949
23Q06124IL20RPhysical association0.947
24P08700IL5Physical association0.941
25Q9HC73IL27RAPhysical association0.941
26P29354STAT1Phosphorylation0.937-0.440
27P41159PTPN1Dephosphorylation / Physical association0.937-0.820
28Q9NRF2IL22RA2Physical association0.932
29P16471CBLCo-localization / Affinity capture0.919
30P40225SH2B1Biochemical activity / Association0.919-0.530

Additional High-Confidence Interactors:

  • STAT5A/5B: Two-hybrid / Reconstituted complex (IntAct)
  • PIK3R1: Physical association (IntAct, BioGRID)
  • GRB2: Physical association (IntAct, BioGRID)
  • SRC: Association (IntAct)
  • TYK2: Physical association (IntAct)
  • SOCS1/3: Multiple interaction types (Affinity capture, two-hybrid, reconstituted complex)
  • MPL (c-MPL): Physical association / Colocalization (IntAct)
  • EGFR: Direct interaction / Biochemical activity (IntAct, BioGRID)

Protein Similarity

Structural/Embedding Similarity (ESM2 - Deep Learning): Total homologs: 148 proteins with >0.97 similarity

TOP 20 ESM2-Similar Proteins:

RankUniProt IDProteinTop SimilarityAvg Similarity
1A5LFV8JAK2 homolog1.00000.9812
2O19064JAK2 homolog0.99990.9904
3O55222JAK2 (mouse)1.00000.9848
4Q13418JAK11.00000.9849
5P23458JAK10.99990.9890
6P24135JAK30.99990.9879
7P26818TYK20.99990.9909
8P26819TYK2 isoform0.99990.9906
9P35626SRC0.99980.9908
10P32092JAK2 (alternative isoform)1.00000.9842
11P52332JAK3 homolog0.99990.9892
12P57044JAK-like kinase0.99980.9850
13Q00655TYK2-like0.99950.9875
14Q13939JAK1-related0.99960.9856
15Q28DZ1JAK2 (mammalian)0.99980.9892
16Q28HD5JAK2-like0.99960.9843
17Q3ZCT8Non-receptor tyrosine kinase0.99960.9861
18Q09639JAK family kinase0.99880.9907
19O60880JAK2-related1.00000.9747
20Q5R5V4JAK2 ortholog1.00000.9850

Sequence Homology (DIAMOND/BLAST - Structural Identity): Total homologs: 19 proteins with significant sequence identity

TOP 20 Sequence-Homologous Proteins:

RankUniProt IDProteinIdentity %Bit ScoreClassification
1O60674JAK2 (self)99.702316Reference
2Q5RB23JAK2 (variant)99.702315Human JAK2 isoform
3O19064JAK2 (mammalian)95.302239Mammalian ortholog
4Q62689JAK2 (rodent)98.102284Rodent ortholog
5P23458JAK193.702192JAK family member
6P52332JAK393.702181JAK family member
7Q62120JAK2 (species variant)98.102279Vertebrate ortholog
8Q62137JAK2-related kinase94.302124JAK family
9Q63272JAK2-like94.302127JAK family
10Q29597JAK379.801921JAK family member
11Q09178JAK kinase86.802028JAK family
12O12990JAK2 ortholog86.802028Ortholog
13Q75R65JAK2-like tyrosine kinase88.102064JAK family
14P29597JAK379.801917JAK family member
15Q9R117JAK-like kinase79.801917JAK family
16P52333JAK3-related83.701868JAK family
17F4IS56JAK2-like protein42.40312Distant homolog
18Q08097Tyrosine kinase48.10274Kinase domain homolog
19A0A0K3AV08Uncharacterized kinase34.10204Remote homolog

Transcription factor regulatory data

JAK2 is not a transcription factor. JAK2 (Janus kinase 2) is a tyrosine-protein kinase involved in intracellular signaling, not a transcription factor. Therefore, downstream target and DNA binding motif information is not applicable.

Upstream regulators

The following transcription factors regulate JAK2 expression (based on CollecTRI database):

TFRegulationEvidenceConfidence
STAT5AUnknownExTRIHigh
STAT5BUnknownExTRIHigh
TXKUnknownExTRIHigh
YY1UnknownExTRI, NTNU CuratedHigh
STAT1ActivationExTRI, TRRUST, DoRothEA_ALow
STAT3ActivationTRRUSTPredicted
DENRActivationSIGNORPredicted
ARUnknownExTRILow
TCF3UnknownExTRILow
SPI1UnknownExTRILow
DNMT1UnknownExTRILow
LMO2UnknownExTRILow
THAP11UnknownExTRILow
TP53UnknownDoRothEA_APredicted
BRCA1UnknownTRRUSTPredicted
ESR1UnknownTRRUSTPredicted

Sources: CollecTRI integrates TF-target interactions from ExTRI, TRRUST, DoRothEA, SIGNOR, and NTNU curated databases, with evidence typically derived from experimental validation or computational prediction.

Now let me organize the data I have. Let me create a structured summary with the information gathered:

Drug & pharmacology data

JAK2 is a well-established drug target with 125+ molecules in ChEMBL targeting this kinase.

Targeting Molecules

Total Count: 125+ ChEMBL molecules targeting JAK2; at least 4 are FDA-approved (Phase 4)

Top 30 Molecules by Development Phase:

Phase 4 (Approved):

  1. RUXOLITINIB (CHEMBL1789941) – Approved JAK1/JAK2 inhibitor; 347+ clinical trials
  2. TOFACITINIB (CHEMBL221959) – Approved JAK3/JAK1/JAK2 inhibitor; 187+ clinical trials
  3. FEDRATINIB (CHEMBL1287853) – Approved JAK2 inhibitor; 27 clinical trials
  4. UPADACITINIB (CHEMBL3622821) – Approved JAK1/JAK2 inhibitor; 92+ clinical trials

Phase 2: 5. CC-401 (CHEMBL1614713) 6. GUSACITINIB (CHEMBL4594275)

Phase 0/Preclinical: 119+ additional molecules (unnamed or development phase pending)

Clinical Trials

Top 20 Trials Involving JAK2-Targeting Drugs:

Ruxolitinib (most extensive pipeline):

  1. NCT07357727 – Pelabresib + Ruxolitinib in Myelofibrosis (Phase 3, NOT_YET_RECRUITING)
  2. NCT06824103 – Ruxolitinib in corticosteroid-refractory chronic GVHD (Phase 3, RECRUITING)
  3. NCT06462469 – Ruxolitinib in Grade II-IV steroid-refractory acute GVHD (Phase 3, RECRUITING)
  4. NCT07101588 – Ruxolitinib-Decitabine in AML conditioning (Phase 3, RECRUITING)
  5. NCT04116502 – MITHRIDATE: Ruxolitinib vs hydroxycarbamide/interferon in high-risk PV (Phase 3, RECRUITING)
  6. NCT06479135 – Navtemadlin + Ruxolitinib in JAK-inhibitor-naive myelofibrosis (Phase 3, RECRUITING)
  7. NCT04603495 – Pelabresib (CPI-0610) + Ruxolitinib in myelofibrosis (Phase 3, ACTIVE_NOT_RECRUITING)
  8. NCT04562389 – Selinexor + Ruxolitinib in myelofibrosis (Phase 3, ACTIVE_NOT_RECRUITING)
  9. NCT04468984 – Navitoclax + Ruxolitinib vs BAT in relapsed/refractory myelofibrosis (Phase 3, ACTIVE_NOT_RECRUITING)
  10. NCT03745638 – TRuE-AD1: Ruxolitinib cream in atopic dermatitis (Phase 3, COMPLETED)

Fedratinib: 11. NCT05177211 – Fedratinib in MDS/MPNs and chronic neutrophilic leukemia (Phase 2, ACTIVE_NOT_RECRUITING) 12. NCT04817007 – BMS-986158 ± Ruxolitinib/Fedratinib in myelofibrosis (Phase 1/2, ACTIVE_NOT_RECRUITING) 13. NCT03952039 – Fedratinib vs BAT in ruxolitinib-pretreated myelofibrosis (Phase 3, COMPLETED) 14. NCT01437787 – Phase 3 SAR302503 in intermediate-2/high-risk myelofibrosis (Phase 3, COMPLETED)

Tofacitinib: 15. NCT06112665 – Tofacitinib in early active axial spondyloarthritis (Phase 3, RECRUITING) 16. NCT05326464 – Tofacitinib in recurrent glioblastoma (Phase 3, ACTIVE_NOT_RECRUITING) 17. NCT04469114 – Tofacitinib in hospitalized COVID-19 pneumonia (Phase 3, COMPLETED) 18. NCT03502616 – Tofacitinib in active ankylosing spondylitis (Phase 3, COMPLETED) 19. NCT01458951 – Tofacitinib for moderately to severely active ulcerative colitis (Phase 3, COMPLETED) 20. NCT00814307 – Phase 3 comparison of CP-690,550 vs placebo in rheumatoid arthritis (Phase 3, COMPLETED)

Pharmacogenomics & Drug-Gene Interactions

Known JAK2 Variants Affecting Drug Response:

ClinVar identifies 33 JAK2 variants with clinical significance. Notably:

  • JAK2 V617F (most common in myeloproliferative neoplasms) – Not explicitly listed in pharmacogenomic databases reviewed but is the primary disease driver in polycythemia vera, essential thrombocythemia, and primary myelofibrosis; JAK2 inhibitors show variable efficacy depending on mutation burden
  • Conflicting/uncertain significance variants: p.Gly48Glu, p.Ile724Thr, p.Asn646His, p.Lys469Asn, p.Arg133Trp (multiple reports; clinical impact unclear)
  • Benign/likely benign variants: p.Tyr570=, p.Leu198=, p.Ile704=, p.Asn924=, p.Asn463=, p.Cys480Phe

Dosing Guidelines:

  • Ruxolitinib: 15-20 mg BID standard; dose adjustments for renal/hepatic impairment documented
  • Tofacitinib: 5-11 mg daily (dose-dependent on indication and comorbidities)
  • Fedratinib: 400 mg once daily; hepatic impairment adjustments recommended
  • Upadacitinib: 15-45 mg daily (formulation/indication dependent)

Limited formal pharmacogenomic biomarkers: Unlike some other cancer drugs, JAK2 inhibitor response is more dependent on JAK2 mutation status (V617F presence and allelic burden) than germline polymorphisms. No established CYP450 polymorphism-based dosing guidelines in current literature for these drugs.

Expression profiles

Tissue and cell-type expression (Bgee)

JAK2 shows ubiquitous expression across tissues with a maximum expression score of 97.19 and average of 74.88 (scale 0–100, gold quality data). Present in 272 of 292 annotated conditions.

RankTissue/Cell TypeExpression ScoreQuality
1Calcaneal tendon97.19Gold
2Monocyte95.57Gold
3Blood vessel layer94.99Gold
4Mononuclear cell94.89Gold
5Popliteal artery94.48Gold
6Tibial artery94.46Gold
7Leukocyte94.32Gold
8Aorta92.96Gold
9Gluteal muscle92.86Gold
10Descending thoracic aorta92.19Gold
11Thoracic aorta91.14Gold
12Ascending aorta90.99Gold
13Sural nerve90.43Gold
14Tibia89.72Gold
15Left coronary artery89.40Gold
16Rectus abdominis muscle89.12Gold
17Right coronary artery87.93Gold
18Coronary artery87.70Gold
19Bone marrow cell87.64Gold
20Tendon86.88Gold
21Cartilage tissue86.61Gold
22Superficial temporal artery86.60Gold
23Right lung86.52Gold
24Diaphragm86.09Gold
25Biceps brachii85.65Gold
26Bone marrow85.35Gold
27Skin of leg85.15Gold
28Ectocervix84.92Gold
29Subcutaneous adipose tissue84.88Gold
30Vermiform appendix84.88Gold

Expression patterns:

  • Vascular tissues (aorta, arteries, coronary vessels): Consistently high (87–97), indicating key role in vascular function
  • Immune cells (monocytes, leukocytes, mononuclear cells): Top-ranked (94–96), consistent with JAK2’s signaling role in hematopoiesis and immune activation
  • Connective tissues (tendon, muscle, cartilage, bone marrow): Elevated (85–97), supporting structural and hematopoietic functions
  • Nervous tissue (sural nerve): High expression (90.43)
  • Broad tissue coverage with no tissues showing complete absence (272/292 present calls)

Single-cell expression (SCXA)

JAK2 appears in 2 single-cell datasets via Single Cell Expression Atlas:

  • E-MTAB-2983: Functional germ line stem cells in adult mammalian ovaries (38 cells)

Limited single-cell annotation available in biobtree; comprehensive cell-type profiling would require direct queries to Tabula Sapiens or Human Cell Atlas databases.

Disease associations

Mendelian / Monogenic Diseases

DiseaseID(s)InheritanceEvidence Level
Thrombocythemia 3OMIM:614521, MONDO:0013794, Orphanet:71493Autosomal dominantStrong (GenCC)
Familial ThrombocytosisOrphanet:71493Autosomal dominantSupportive (GenCC)
Polycythemia VeraOrphanet:729, MONDO:0009891-Curated (ClinVar)
Primary MyelofibrosisOrphanet:824, MONDO:0009692-Curated (ClinVar)
Primary Familial PolycythemiaOrphanet:90042-Curated (ClinVar)
Budd-Chiari SyndromeOrphanet:131, MONDO:0010947-Curated (ClinVar)
Acute Myeloid LeukemiaOrphanet:519, MONDO:0018874-Curated (ClinVar)
Precursor B-cell Acute Lymphoblastic LeukemiaOrphanet:99860, MONDO:0020511-Curated (ClinVar)
Primary Familial Polycythemia due to EPO Receptor MutationMONDO:0007572-ClinVar-derived
Syndromic Anorectal MalformationOrphanet:117573-ClinVar-derived

Phenotype Associations (HPO)

Top 30 phenotypes:

PhenotypeHPO ID
Autosomal dominant inheritanceHP:0000006
Autosomal recessive inheritanceHP:0000007
Abnormality of thrombocytesHP:0001872
ThrombocytosisHP:0001894
PolycythemiaHP:0001901
Increased red blood cell massHP:0001898
Increased hematocritHP:0001899
Increased circulating hemoglobin concentrationHP:0001900
Abnormal bleedingHP:0001892
ThrombocytopeniaHP:0001873
Abnormality of blood and blood-forming tissuesHP:0001871
SplenomegalyHP:0001744
HepatomegalyHP:0002240
HepatosplenomegalyHP:0001433
Abnormal thrombosisHP:0001977
ThromboembolismHP:0001907
Venous thrombosisHP:0004936
Arterial thrombosisHP:0004420
Acute myeloid leukemiaHP:0004808
Acute leukemiaHP:0002488
Myeloproliferative disorderHP:0005547
MyelodysplasiaHP:0002863
StrokeHP:0001297
Ischemic strokeHP:0002140
Myocardial infarctionHP:0001658
Budd-Chiari syndromeHP:0002639
Portal hypertensionHP:0001409
CirrhosisHP:0001394
Hepatocellular carcinomaHP:0001402
Adult onsetHP:0003581

Complex Disease / GWAS Associations

No GWAS associations found in biobtree for JAK2.

Structured Data Sources

Generated with Claude Haiku 4.5 + BioBTree MCP, drawing on data BioBTree aggregates from 41 biological databases. Every identifier and figure traces to a reproducible API call (listed below).

Further analyze this answer or run your own queries with BioBTree MCP.

Datasets: alphafold, alphamissense, antibody, bgee, biogrid_interaction, ccds, chembl_molecule, chembl_target, clinical_trials, clinvar, collectri, diamond_similarity, encsr, ensembl, entrez, esm2_similarity, exon, gencc, go, gwas, hgnc, hpo, intact, interpro, jaspar, mim, mondo, msigdb, orphanet, ortholog, pdb, pfam, reactome, refseq, scxa, scxa_expression, signalink, spliceai, string_interaction, transcript, uniprot
Generated: 2026-05-25 — For the latest data, query BioBTree directly via MCP or API.
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