CausalSentinel

Protein Dossier — ISLR2 (Immunoglobulin superfamily containing leucine-rich repeat protein 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
LDL cholesterol	-0.184	0.0282	7.03e-11	Wald ratio	1	trans	0.988
Total cholesterol	-0.115	0.027	2.27e-05	Wald ratio	1	trans	NA
Triglycerides	-0.0999	0.0259	1.16e-04	Wald ratio	1	trans	NA
Diagnoses - main ICD10: L03 Cellulitis	0.00251	0.000842	0.00289	Inverse variance weighted	2	cis	NA
Diagnoses - main ICD10: L03 Cellulitis	0.00251	0.000842	0.00289	Inverse variance weighted	2	trans	NA
Depressive symptoms	-0.0473	0.0168	0.00488	Inverse variance weighted	2	cis	NA
Depressive symptoms	-0.0473	0.0168	0.00488	Inverse variance weighted	2	trans	NA
Chronic kidney disease	0.158	0.059	0.0073	Inverse variance weighted	2	cis	NA
Chronic kidney disease	0.158	0.059	0.0073	Inverse variance weighted	2	trans	NA
Diagnoses - main ICD10: H25 Senile cataract	0.002	0.000824	0.0149	Inverse variance weighted	2	cis	NA
Diagnoses - main ICD10: H25 Senile cataract	0.002	0.000824	0.0149	Inverse variance weighted	2	trans	NA
HDL cholesterol	0.0642	0.0267	0.016	Wald ratio	1	trans	NA
…and 153 more outcomes (see JSON)

2. pQTL instrument availability (Tier-B probe)

No prot-* pQTL GWAS dataset found for this protein (matched by UniProt accession and symbol).

3. GWAS Catalog results — traits with signal at this locus

1 association rows across 1 traits (1 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
Standing height (UKB data field 50)	3e-12	rs112473448	1	GCST90468178	no MR -> candidate analysis

4. Phenome map — where this gene is a genetic locus, vs. where MR exists

Top diseases by Open Targets association (of 110 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
undetermined early-onset epileptic encephalopathy	0.438	—	established (curated)	no MR -> candidate analysis
developmental and epileptic encephalopathy, 33	0.438	—	established (curated)	no MR -> candidate analysis
aortic disorder	0.419	—	common-variant locus	no MR -> candidate analysis
Dermatochalasis	0.318	—	common-variant locus	no MR -> candidate analysis
skin aging	0.245	—	common-variant locus	no MR -> candidate analysis
COVID-19	0.206	—	common-variant locus	no MR -> candidate analysis
Abnormality of the skeletal system	0.164	—	common-variant locus	no MR -> candidate analysis
osteoarthritis	0.102	—	common-variant locus	no MR -> candidate analysis

Of the 8 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	not available — no ChEMBL target (undrugged)
gnomAD constraint	pLI=0.0005, LOEUF=0.954 — LoF-tolerant
GWAS Catalog	55 unique SNPs / 110 rows
ClinVar	133 records; 2 pathogenic in sample of 30
PharmGKB/ClinPGx	no annotations

Caveats declared by the tools

• phenome — Top 30 of 110 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 ‘ISLR2’.
• clinvar — Pathogenic count is over the 30 record(s) retrieved, NOT over all 133 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 1 of 1 traits by best p-value, aggregated from 1 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/Q6UXK2 — 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 v3.0
• phenome: https://platform.opentargets.org/target/ENSG00000167178/associations — Open Targets data release 26.06
• gnomad: https://gnomad.broadinstitute.org/gene/ISLR2 — gnomAD constraint via GraphQL API (reference genome GRCh38)
• gwas: https://www.ebi.ac.uk/gwas/genes/ISLR2 — GWAS Catalog REST (live; release not exposed by this endpoint)
• clinvar: https://www.ncbi.nlm.nih.gov/clinvar/?term=ISLR2%5Bgene%5D — ClinVar build Build260809-1055.1
• gwas_traits: https://www.ebi.ac.uk/gwas/genes/ISLR2 — GWAS Catalog search API (live; release not exposed)

Provenance

• Generated: 2026-08-14T03:18:22 · 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

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