Protein Dossier — JAK2 (Tyrosine-protein kinase JAK2)
MR feasibility tier: A — Published pQTL-MR estimates exist for this protein (retrieved below - not computed here).
1. Published MR estimates (retrieved, not computed)
| Outcome |
beta |
se |
p |
method |
nSNP |
cis/trans |
coloc |
| Eye problems or disorders: Glaucoma |
0.262 |
0.0678 |
1.09e-04 |
Wald ratio |
1 |
trans |
NA |
| Eye problems or disorders: Injury or trauma resulting in loss of vision |
0.362 |
0.0965 |
1.72e-04 |
Wald ratio |
1 |
trans |
NA |
| Diagnoses - main ICD10: K60 Fissure and fistula of anal and rectal regions |
0.394 |
0.106 |
1.99e-04 |
Wald ratio |
1 |
trans |
NA |
| Squamous cell lung cancer |
-0.448 |
0.128 |
4.65e-04 |
Wald ratio |
1 |
trans |
NA |
| Forced vital capacity (FVC) |
0.027 |
0.00861 |
0.00172 |
Wald ratio |
1 |
trans |
NA |
| Packed cell volume |
-0.296 |
0.112 |
0.00814 |
Wald ratio |
1 |
trans |
NA |
| Haemoglobin concentration |
-0.0973 |
0.037 |
0.00848 |
Wald ratio |
1 |
trans |
NA |
| Height |
0.0382 |
0.0157 |
0.015 |
Wald ratio |
1 |
trans |
NA |
| Percent emphysema |
-0.0965 |
0.0416 |
0.0205 |
Wald ratio |
1 |
trans |
NA |
| Forced expiratory volume in 1-second (FEV1) |
0.0208 |
0.00908 |
0.0218 |
Wald ratio |
1 |
trans |
NA |
| Non-cancer illness code self-reported: diverticular disease or diverticulitis |
-0.311 |
0.139 |
0.0246 |
Wald ratio |
1 |
trans |
NA |
| Serum creatinine (eGFRcrea) |
0.00935 |
0.00425 |
0.0278 |
Wald ratio |
1 |
trans |
NA |
| …and 84 more outcomes (see JSON) |
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2. pQTL instrument availability (Tier-B probe)
| Dataset |
Trait |
Author |
Year |
prot-c-4998_50_1 |
JAK2 |
Suhre K |
2019 |
3. GWAS Catalog results — traits with signal at this locus
346 association rows across 160 traits (325 genome-wide significant rows). Associations are loci, not causal claims; the mapped gene at a locus is not necessarily the effector gene.
| Trait |
best p |
lead SNP |
n assoc |
study |
MR status |
| Myeloproliferative disease (PheCode 200) |
1e-323 |
rs77375493 |
4 |
GCST90475608 |
no MR -> candidate analysis |
| Polycythemia vera (PheCode 200.1) |
1e-323 |
rs77375493 |
3 |
GCST90479825 |
no MR -> candidate analysis |
| red cell diameter width (RDW, mean, inv-norm transformed) |
1e-323 |
rs77375493 |
3 |
GCST90476361 |
no MR -> candidate analysis |
| red cell diameter width (RDW, maximum, inv-norm transformed) |
9e-308 |
rs77375493 |
3 |
GCST90476357 |
no MR -> candidate analysis |
| red cell diameter width (RDW, minimum, inv-norm transformed) |
2e-264 |
rs77375493 |
3 |
GCST90476365 |
no MR -> candidate analysis |
| platelet count (maximum, inv-norm transformed) |
5e-234 |
rs77375493 |
2 |
GCST90480650 |
no MR -> candidate analysis |
| Other diseases of blood and blood-forming organs (PheCode 28 |
2e-199 |
rs77375493 |
3 |
GCST90479994 |
no MR -> candidate analysis |
| monocyte (fraction, mean, inv-norm transformed) |
8e-171 |
rs77375493 |
3 |
GCST90475511 |
no MR -> candidate analysis |
| red blood cell count (RBC, maximum, inv-norm transformed) |
4e-165 |
rs77375493 |
3 |
GCST90476345 |
no MR -> candidate analysis |
| white blood cell count (WBC, mean, inv-norm transformed) |
2e-160 |
rs77375493 |
3 |
GCST90476454 |
no MR -> candidate analysis |
| mean corpuscular hemoglobin concentration (MCHC, minimum, in |
1e-157 |
rs77375493 |
3 |
GCST90475462 |
no MR -> candidate analysis |
| lymphocyte (fraction, mean, inv-norm transformed) |
8e-155 |
rs77375493 |
3 |
GCST90475435 |
no MR -> candidate analysis |
| …and 148 more traits (see JSON) |
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|
|
4. Phenome map — where this gene is a genetic locus, vs. where MR exists
Top diseases by Open Targets association (of 1636 total). Associations are loci, not causal claims. The causal-status column is a four-state triage per pair: established (curated) = a curated clinical assertion exists (ClinGen/G2P/GEL/Orphanet/ClinVar — any validity level, MR adds little); exploratory rare-variant signal = ExWAS burden evidence without curation — a candidate NEW gene-disease relationship; common-variant locus = GWAS signal, classic pQTL-MR territory; multi-layer = burden+GWAS together, an allelic-series candidate (the strongest causal setup). Burden estimand is carrier-vs-noncarrier, not per-SD MR.
| Disease |
genetic assoc. |
burden (ExWAS) |
causal status |
MR status |
| acquired polycythemia vera |
0.784 |
0.758 |
established (curated) |
no MR -> candidate analysis |
| primary myelofibrosis |
0.642 |
0.249 |
established (curated) |
no MR -> candidate analysis |
| ulcerative colitis |
0.818 |
— |
common-variant locus |
no MR -> candidate analysis |
| myeloproliferative disorder |
0.68 |
0.713 |
established (curated) |
no MR -> candidate analysis |
| Crohn disease |
0.807 |
— |
common-variant locus |
no MR -> candidate analysis |
| neoplasm |
0.647 |
0.76 |
established (curated) |
MR: beta=0.166, p=0.134 (trans) |
| Splenomegaly |
0.79 |
0.865 |
established (curated) |
no MR -> candidate analysis |
| acute myeloid leukemia |
0.743 |
— |
established (curated) |
no MR -> candidate analysis |
| cancer |
0.654 |
— |
common-variant locus |
MR: beta=-0.448, p=4.65e-04 (trans) |
| essential thrombocythemia |
0.377 |
— |
established (curated) |
no MR -> candidate analysis |
| thrombocythemia 3 |
0.826 |
— |
established (curated) |
no MR -> candidate analysis |
| hematologic disorder |
0.81 |
0.824 |
multi-layer: burden+GWAS (allelic-series candidate) |
no MR -> candidate analysis |
| ankylosing spondylitis |
0.492 |
— |
common-variant locus |
MR: beta=-0.465, p=0.207 (trans) |
| hemorrhagic disease |
0.751 |
0.76 |
multi-layer: burden+GWAS (allelic-series candidate) |
no MR -> candidate analysis |
| Hepatomegaly |
0.707 |
0.753 |
multi-layer: burden+GWAS (allelic-series candidate) |
no MR -> candidate analysis |
Of the 15 rows above, 12 have no MR estimate in this resource. Across all retrieved diseases for this gene: 1 exploratory rare-variant signal(s), 3 multi-layer (allelic-series candidate) pair(s). Final triage still belongs to a statistical geneticist.
5. Downstream annotation (druggability & safety preview)
| Layer |
Result |
| ChEMBL druggability |
20 known modulators (Tyrosine-protein kinase JAK2) |
| gnomAD constraint |
pLI=1.2e-16, LOEUF=0.739 — LoF-tolerant |
| GWAS Catalog |
103 unique SNPs / 217 rows |
| ClinVar |
796 records; 7 pathogenic in sample of 30 |
| PharmGKB/ClinPGx |
no annotations |
phenome — Top 30 of 1636 associated diseases by overall score. genetic_association aggregates GWAS common-variant AND rare-variant evidence. These are ASSOCIATIONS (loci), not causal claims.chembl — ChEMBL target matched by text search on ‘JAK2’ and resolved to ‘Tyrosine-protein kinase JAK2’ — confirm this is the intended target.clinvar — Pathogenic count is over the 30 record(s) retrieved, NOT over all 796 ClinVar records for this gene; it is a sample, not a rate.pharmgkb — No PharmGKB/ClinPGx clinical annotations (gene may not be a pharmacogene).gwas_traits — Top 20 of 160 traits by best p-value, aggregated from 346 association rows. These are GWAS ASSOCIATIONS (loci), not causal claims; mapped genes at a locus are not necessarily the effector gene.
Sources
uniprot: https://www.uniprot.org/uniprotkb/O60674 — UniProt release 2026_02 (10-June-2026)mr_outcomes: https://epigraphdb.org/pqtl/ — EpiGraphDB pQTL MR (Zheng et al., Nat Genet 2020) — pre-computed two-sample MR; retrieved, not computed by this agent; EpiGraphDB build 1.0, pQTL dataset v3.0phenome: https://platform.opentargets.org/target/ENSG00000096968/associations — Open Targets data release 26.06chembl: https://www.ebi.ac.uk/chembl/target_report_card/CHEMBL2971/ — ChEMBL_37 (released 2026-05-01)gnomad: https://gnomad.broadinstitute.org/gene/JAK2 — gnomAD constraint via GraphQL API (reference genome GRCh38)gwas: https://www.ebi.ac.uk/gwas/genes/JAK2 — GWAS Catalog REST (live; release not exposed by this endpoint)clinvar: https://www.ncbi.nlm.nih.gov/clinvar/?term=JAK2%5Bgene%5D — ClinVar build Build260809-1055.1gwas_traits: https://www.ebi.ac.uk/gwas/genes/JAK2 — GWAS Catalog search API (live; release not exposed)
Provenance
- Generated: 2026-08-14T03:20:07 · Tier: A
- Fully mechanical: every cell above is rendered from tool return values. No language model wrote any part of this dossier.
- MR estimates, where present, are retrieved from published work (EpiGraphDB pQTL, Zheng et al. Nat Genet 2020); nothing is computed here.
- Tool errors this run: none