Protein Dossier — THBS2 (Thrombospondin-2)
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 |
| Diagnoses - main ICD10: D25 Leiomyoma of uterus |
0.127 |
0.0392 |
0.00118 |
Wald ratio |
1 |
cis |
NA |
| Cough on most days |
-0.0743 |
0.0277 |
0.00739 |
Wald ratio |
1 |
cis |
NA |
| Non-cancer illness code self-reported: deep venous thrombosis (dvt) |
-0.0971 |
0.0394 |
0.0136 |
Wald ratio |
1 |
cis |
NA |
| Cancer code self-reported: small intestine or small bowel cancer |
0.402 |
0.164 |
0.0142 |
Wald ratio |
1 |
cis |
NA |
| Systolic blood pressure automated reading |
0.0125 |
0.00514 |
0.0153 |
Wald ratio |
1 |
cis |
NA |
| Forced vital capacity (FVC) |
-0.00971 |
0.00412 |
0.0186 |
Wald ratio |
1 |
cis |
NA |
| Diagnoses - main ICD10: M17 Gonarthrosis [arthrosis of knee] |
-0.0899 |
0.0397 |
0.0236 |
Wald ratio |
1 |
cis |
NA |
| Diastolic blood pressure automated reading |
-0.0108 |
0.00514 |
0.035 |
Wald ratio |
1 |
cis |
NA |
| Non-cancer illness code self-reported: depression |
0.0417 |
0.0199 |
0.0362 |
Wald ratio |
1 |
cis |
NA |
| Diagnoses - main ICD10: M54 Dorsalgia |
0.0752 |
0.0363 |
0.0383 |
Wald ratio |
1 |
cis |
NA |
| Forced expiratory volume in 1-second (FEV1) |
-0.00864 |
0.00435 |
0.047 |
Wald ratio |
1 |
cis |
NA |
| Diagnoses - main ICD10: I48 Atrial fibrillation and flutter |
-0.0997 |
0.0528 |
0.059 |
Wald ratio |
1 |
cis |
NA |
| …and 63 more outcomes (see JSON) |
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2. pQTL instrument availability (Tier-B probe)
| Dataset |
Trait |
Author |
Year |
prot-c-3339_33_1 |
TSP2 |
Suhre K |
2019 |
3. GWAS Catalog results — traits with signal at this locus
93 association rows across 42 traits (84 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 |
| Circulating THBS2 levels |
8e-1272 |
rs73043837 |
7 |
GCST90859788 |
no MR -> candidate analysis |
| Thrombospondin-2 levels |
4e-299 |
rs74507247 |
8 |
GCST90249995 |
no MR -> candidate analysis |
| THBS2 protein levels |
4e-209 |
rs7756742 |
6 |
GCST90470854 |
no MR -> candidate analysis |
| Thrombospondin-2 levels (THBS2.3339.33.1) |
7e-99 |
rs73043857 |
2 |
GCST90243011 |
no MR -> candidate analysis |
| Height |
7e-88 |
rs12665286 |
7 |
GCST90245848 |
no MR -> candidate analysis |
| Serum levels of protein THBS2 |
8e-85 |
rs73041845 |
1 |
GCST90088324 |
no MR -> candidate analysis |
| Blood protein levels |
7e-54 |
rs73041845 |
1 |
GCST006585 |
no MR -> candidate analysis |
| Pulse pressure |
7e-45 |
rs1322639 |
14 |
GCST90310296 |
no MR -> candidate analysis |
| Thrombospondin-2 (analyte X3339.33) levels |
4e-30 |
rs7341189 |
1 |
GCST90425705 |
no MR -> candidate analysis |
| systolic blood pressure (SBP, mean, inv-normal transformed) |
1e-28 |
rs1322639 |
2 |
GCST90476403 |
no MR -> candidate analysis |
| diastolic blood pressure (DBP, mean, inv-normal transformed) |
3e-24 |
rs1322639 |
1 |
GCST90479581 |
no MR -> candidate analysis |
| Diastolic blood pressure |
3e-18 |
rs1322639 |
7 |
GCST90310295 |
MR: beta=-0.0108, p=0.035 (cis) |
| …and 30 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 917 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 |
| Abnormality of the skeletal system |
0.877 |
— |
common-variant locus |
no MR -> candidate analysis |
| Hernia |
0.734 |
— |
common-variant locus |
MR: beta=-0.0456, p=0.281 (cis) |
| Ehlers-Danlos syndrome |
0.608 |
— |
established (curated) |
no MR -> candidate analysis |
| Ehlers-Danlos syndrome, classic-like, 3 |
0.596 |
— |
established (curated) |
no MR -> candidate analysis |
| anorectal malformation |
0.577 |
— |
common-variant locus |
no MR -> candidate analysis |
| Varicose veins |
0.555 |
— |
common-variant locus |
no MR -> candidate analysis |
| placental retention |
0.533 |
— |
common-variant locus |
no MR -> candidate analysis |
| aneurysm |
0.515 |
— |
common-variant locus |
no MR -> candidate analysis |
| aortic aneurysm |
0.512 |
— |
common-variant locus |
no MR -> candidate analysis |
| hemorrhoid |
0.505 |
— |
common-variant locus |
no MR -> candidate analysis |
| chronic primary adrenal insufficiency |
0.492 |
— |
common-variant locus |
no MR -> candidate analysis |
| hypopituitarism |
0.492 |
— |
common-variant locus |
no MR -> candidate analysis |
| familial glucocorticoid deficiency |
0.492 |
— |
common-variant locus |
no MR -> candidate analysis |
| Peyronie disease |
0.487 |
— |
common-variant locus |
no MR -> candidate analysis |
| Inguinal hernia |
0.453 |
— |
common-variant locus |
no MR -> candidate analysis |
Of the 15 rows above, 14 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 |
not available — no ChEMBL target (undrugged) |
| gnomAD constraint |
pLI=1, LOEUF=0.443 — LoF-INTOLERANT |
| GWAS Catalog |
66 unique SNPs / 132 rows |
| ClinVar |
324 records; 6 pathogenic in sample of 30 |
| PharmGKB/ClinPGx |
no annotations |
phenome — Top 30 of 917 associated diseases by overall score. genetic_association aggregates GWAS common-variant AND rare-variant evidence. These are ASSOCIATIONS (loci), not causal claims.chembl — No ChEMBL target for ‘THBS2’.clinvar — Pathogenic count is over the 30 record(s) retrieved, NOT over all 324 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 42 traits by best p-value, aggregated from 93 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/P35442 — 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/ENSG00000186340/associations — Open Targets data release 26.06gnomad: https://gnomad.broadinstitute.org/gene/THBS2 — gnomAD constraint via GraphQL API (reference genome GRCh38)gwas: https://www.ebi.ac.uk/gwas/genes/THBS2 — GWAS Catalog REST (live; release not exposed by this endpoint)clinvar: https://www.ncbi.nlm.nih.gov/clinvar/?term=THBS2%5Bgene%5D — ClinVar build Build260809-1055.1gwas_traits: https://www.ebi.ac.uk/gwas/genes/THBS2 — GWAS Catalog search API (live; release not exposed)
Provenance
- Generated: 2026-08-14T05:20:33 · 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