Protein Dossier — TYK2 (Non-receptor tyrosine-protein kinase TYK2)
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 |
| Myocardial infarction |
-0.154 |
0.044 |
4.76e-04 |
Wald ratio |
1 |
trans |
NA |
| Coronary heart disease |
-0.133 |
0.0399 |
8.64e-04 |
Wald ratio |
1 |
trans |
NA |
| Amyotrophic lateral sclerosis |
-0.235 |
0.0722 |
0.00113 |
Wald ratio |
1 |
trans |
NA |
| Eczema |
0.212 |
0.0705 |
0.00266 |
Wald ratio |
1 |
trans |
NA |
| Years of schooling |
-0.0471 |
0.0157 |
0.0027 |
Wald ratio |
1 |
trans |
NA |
| Diagnoses - main ICD10: N92 Excessive frequent and irregular menstruation |
0.166 |
0.056 |
0.00297 |
Wald ratio |
1 |
trans |
NA |
| Chronic kidney disease |
0.173 |
0.0627 |
0.00596 |
Wald ratio |
1 |
trans |
NA |
| Forced vital capacity (FVC) |
-0.0211 |
0.00776 |
0.00649 |
Wald ratio |
1 |
trans |
NA |
| LDL cholesterol |
-0.0592 |
0.022 |
0.00701 |
Wald ratio |
1 |
trans |
NA |
| Sodium in urine |
0.0235 |
0.00931 |
0.0115 |
Wald ratio |
1 |
trans |
NA |
| Heel bone mineral density (BMD) T-score automated |
0.03 |
0.0122 |
0.0143 |
Wald ratio |
1 |
trans |
NA |
| Non-cancer illness code self-reported: deep venous thrombosis (dvt) |
-0.2 |
0.0826 |
0.0153 |
Wald ratio |
1 |
trans |
NA |
| …and 99 more outcomes (see JSON) |
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2. pQTL instrument availability (Tier-B probe)
| Dataset |
Trait |
Author |
Year |
prot-c-5260_80_3 |
TYK2 |
Suhre K |
2019 |
3. GWAS Catalog results — traits with signal at this locus
237 association rows across 118 traits (222 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 |
| IFNAR1 protein levels |
2e-83 |
rs12720356 |
3 |
GCST90469512 |
no MR -> candidate analysis |
| Height |
4e-59 |
rs6511696 |
3 |
GCST90245848 |
MR: beta=-0.0129, p=0.302 (trans) |
| Circulating ICAM3 levels |
3e-56 |
rs4611572 |
3 |
GCST90860465 |
no MR -> candidate analysis |
| Platelet count |
3e-47 |
rs34536443 |
6 |
GCST90662907 |
no MR -> candidate analysis |
| Low density lipoprotein cholesterol levels |
3e-45 |
rs12720359 |
2 |
GCST90239655 |
no MR -> candidate analysis |
| BST2 protein levels |
1e-40 |
rs12720356 |
2 |
GCST90468475 |
no MR -> candidate analysis |
| Platelet crit (UKB data field 30090) |
7e-39 |
rs34536443 |
1 |
GCST90468096 |
no MR -> candidate analysis |
| Total cholesterol levels |
2e-38 |
rs12720359 |
2 |
GCST90239673 |
no MR -> candidate analysis |
| IL12RB1 protein levels |
4e-38 |
rs34536443 |
2 |
GCST90469550 |
no MR -> candidate analysis |
| Non-HDL cholesterol levels |
4e-37 |
rs12720359 |
2 |
GCST90239667 |
no MR -> candidate analysis |
| Circulating IL12RB1 levels (id: OID00835_OID20486) |
8e-37 |
rs34536443 |
2 |
GCST90860161 |
no MR -> candidate analysis |
| Circulating IL12RB1 levels (id: OID01019_OID20486) |
1e-36 |
rs34536443 |
2 |
GCST90860245 |
no MR -> candidate analysis |
| …and 106 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 948 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 |
| rheumatoid arthritis |
0.931 |
— |
common-variant locus |
no MR -> candidate analysis |
| immunodeficiency 35 |
0.864 |
— |
established (curated) |
no MR -> candidate analysis |
| psoriasis |
0.93 |
— |
common-variant locus |
MR: beta=0.093, p=0.256 (trans) |
| psoriasis vulgaris |
0.874 |
— |
common-variant locus |
no MR -> candidate analysis |
| Crohn disease |
0.801 |
— |
common-variant locus |
no MR -> candidate analysis |
| psoriatic arthritis |
0.692 |
— |
common-variant locus |
no MR -> candidate analysis |
| COVID-19 |
0.914 |
— |
common-variant locus |
no MR -> candidate analysis |
| systemic lupus erythematosus |
0.878 |
— |
common-variant locus |
no MR -> candidate analysis |
| ulcerative colitis |
0.052 |
— |
common-variant locus |
no MR -> candidate analysis |
| Autosomal recessive hyper-IgE syndrome due to TYK2 deficiency |
0.608 |
— |
established (curated) |
no MR -> candidate analysis |
| hypothyroidism |
0.913 |
— |
common-variant locus |
MR: beta=-0.0401, p=0.361 (trans) |
| type 1 diabetes mellitus |
0.858 |
— |
common-variant locus |
no MR -> candidate analysis |
| autoimmune disease |
0.864 |
— |
common-variant locus |
no MR -> candidate analysis |
| sarcoidosis |
0.827 |
— |
common-variant locus |
no MR -> candidate analysis |
| skin disorder |
0.846 |
— |
common-variant locus |
no MR -> candidate analysis |
Of the 15 rows above, 13 have no MR estimate in this resource. Across all retrieved diseases for this gene: 0 exploratory rare-variant signal(s), 0 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 |
8 known modulators (Non-receptor tyrosine-protein kinase TYK2) |
| gnomAD constraint |
pLI=2.8e-07, LOEUF=0.611 — LoF-tolerant |
| GWAS Catalog |
158 unique SNPs / 394 rows |
| ClinVar |
1152 records; 3 pathogenic in sample of 30 |
| PharmGKB/ClinPGx |
no annotations |
phenome — Top 30 of 948 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 ‘TYK2’ and resolved to ‘Non-receptor tyrosine-protein kinase TYK2’ — confirm this is the intended target.clinvar — Pathogenic count is over the 30 record(s) retrieved, NOT over all 1152 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 118 traits by best p-value, aggregated from 237 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/P29597 — 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/ENSG00000105397/associations — Open Targets data release 26.06chembl: https://www.ebi.ac.uk/chembl/target_report_card/CHEMBL3553/ — ChEMBL_37 (released 2026-05-01)gnomad: https://gnomad.broadinstitute.org/gene/TYK2 — gnomAD constraint via GraphQL API (reference genome GRCh38)gwas: https://www.ebi.ac.uk/gwas/genes/TYK2 — GWAS Catalog REST (live; release not exposed by this endpoint)clinvar: https://www.ncbi.nlm.nih.gov/clinvar/?term=TYK2%5Bgene%5D — ClinVar build Build260809-1055.1gwas_traits: https://www.ebi.ac.uk/gwas/genes/TYK2 — GWAS Catalog search API (live; release not exposed)
Provenance
- Generated: 2026-08-14T05:31:00 · 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