Protein Dossier — ICOSLG (ICOS ligand)
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 |
| Rheumatoid arthritis |
0.145 |
0.0289 |
5.44e-07 |
Wald ratio |
1 |
cis |
NA |
| Non-cancer illness code self-reported: polio or poliomyelitis |
0.423 |
0.12 |
4.29e-04 |
Wald ratio |
1 |
cis |
NA |
| Diagnoses - main ICD10: R14 Flatulence and related conditions |
0.423 |
0.131 |
0.00123 |
Wald ratio |
1 |
cis |
NA |
| Crohn’s disease |
0.0705 |
0.0241 |
0.00336 |
Wald ratio |
1 |
cis |
NA |
| Thyroid cancer |
-0.393 |
0.153 |
0.0101 |
Wald ratio |
1 |
cis |
NA |
| Non-cancer illness code self-reported: pernicious anaemia |
0.183 |
0.0728 |
0.012 |
Wald ratio |
1 |
cis |
NA |
| Non-cancer illness code self-reported: vitiligo |
0.466 |
0.187 |
0.0125 |
Wald ratio |
1 |
cis |
NA |
| Eczema |
-0.0855 |
0.0343 |
0.0127 |
Wald ratio |
1 |
cis |
NA |
| Non-cancer illness code self-reported: gout |
0.0901 |
0.0362 |
0.0127 |
Wald ratio |
1 |
cis |
NA |
| Non-cancer illness code self-reported: emphysema or chronic bronchitis |
0.0886 |
0.0374 |
0.0178 |
Wald ratio |
1 |
cis |
NA |
| Body mass index (BMI) |
0.0109 |
0.00471 |
0.0205 |
Wald ratio |
1 |
cis |
NA |
| Height |
0.0134 |
0.0059 |
0.0235 |
Wald ratio |
1 |
cis |
NA |
| …and 107 more outcomes (see JSON) |
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2. pQTL instrument availability (Tier-B probe)
| Dataset |
Trait |
Author |
Year |
prot-c-5061_27_3 |
B7-H2 |
Suhre K |
2019 |
3. GWAS Catalog results — traits with signal at this locus
47 association rows across 26 traits (43 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 ICOSLG levels (id: OID00731_OID21351) |
4e-677 |
rs4819388 |
3 |
GCST90860072 |
no MR -> candidate analysis |
| Circulating ICOSLG levels (id: OID00828_OID21351) |
7e-667 |
rs4819388 |
3 |
GCST90860156 |
no MR -> candidate analysis |
| Blood protein levels |
6e-194 |
rs11558819 |
2 |
GCST006585 |
no MR -> candidate analysis |
| ICOS ligand levels (ICOSLG.9303.9.3) |
4e-108 |
rs11558819 |
1 |
GCST90241463 |
no MR -> candidate analysis |
| ICOSLG protein levels |
1e-58 |
rs11558819 |
4 |
GCST90453026 |
no MR -> candidate analysis |
| Eosinophil count |
2e-36 |
rs2847224 |
6 |
GCST90002302 |
no MR -> candidate analysis |
| Eosinophill percentage (UKB data field 30210) |
1e-31 |
rs2847224 |
1 |
GCST90468069 |
no MR -> candidate analysis |
| eosinophil (fraction, mean, inv-norm transformed) |
2e-28 |
rs2847224 |
2 |
GCST90475300 |
no MR -> candidate analysis |
| Eosinophil percentage of white cells |
9e-28 |
rs2847224 |
2 |
GCST90002382 |
no MR -> candidate analysis |
| Eosinophill count (UKB data field 30150) |
6e-26 |
rs2847224 |
1 |
GCST90468068 |
no MR -> candidate analysis |
| eosinophil (fraction, maximum, inv-norm transformed) |
1e-23 |
rs2847224 |
2 |
GCST90475297 |
no MR -> candidate analysis |
| eosinophil (absolute count, mean, inv-norm transformed) |
4e-22 |
rs2847224 |
2 |
GCST90475291 |
no MR -> candidate analysis |
| …and 14 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 333 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 |
| immunodeficiency 119 |
0.547 |
— |
established (curated) |
no MR -> candidate analysis |
| combined immunodeficiency |
0.438 |
— |
established (curated) |
no MR -> candidate analysis |
| rheumatoid arthritis |
0.428 |
— |
common-variant locus |
MR: beta=0.145, p=5.44e-07 (cis) |
| Combined T and B cell immunodeficiency |
0.438 |
— |
established (curated) |
no MR -> candidate analysis |
| hereditary disease |
0.438 |
— |
established (curated) |
no MR -> candidate analysis |
| depressive disorder |
0.315 |
— |
common-variant locus |
no MR -> candidate analysis |
| cardiomyopathy |
0.241 |
— |
common-variant locus |
no MR -> candidate analysis |
| benign urinary system neoplasm |
0.241 |
— |
common-variant locus |
no MR -> candidate analysis |
| type 1 diabetes mellitus |
0.176 |
— |
common-variant locus |
no MR -> candidate analysis |
Of the 9 rows above, 8 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 |
1 known modulators (ICOS ligand) |
| gnomAD constraint |
pLI=NA, LOEUF=NA — Constraint metrics missing; LoF tolerance cannot be judged. |
| GWAS Catalog |
85 unique SNPs / 170 rows |
| ClinVar |
429 records; 3 pathogenic in sample of 30 |
| PharmGKB/ClinPGx |
no annotations |
phenome — Top 30 of 333 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 ‘ICOSLG’ and resolved to ‘ICOS ligand’ — confirm this is the intended target.clinvar — Pathogenic count is over the 30 record(s) retrieved, NOT over all 429 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 26 traits by best p-value, aggregated from 47 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/O75144 — 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/ENSG00000160223/associations — Open Targets data release 26.06chembl: https://www.ebi.ac.uk/chembl/target_report_card/CHEMBL3712949/ — ChEMBL_37 (released 2026-05-01)gnomad: https://gnomad.broadinstitute.org/gene/ICOSLG — gnomAD constraint via GraphQL API (reference genome GRCh38)gwas: https://www.ebi.ac.uk/gwas/genes/ICOSLG — GWAS Catalog REST (live; release not exposed by this endpoint)clinvar: https://www.ncbi.nlm.nih.gov/clinvar/?term=ICOSLG%5Bgene%5D — ClinVar build Build260809-1055.1gwas_traits: https://www.ebi.ac.uk/gwas/genes/ICOSLG — GWAS Catalog search API (live; release not exposed)
Provenance
- Generated: 2026-08-14T03:05:13 · 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