CausalSentinel

Protein Dossier — CRISPLD2 (Cysteine-rich secretory protein LCCL domain-containing 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
Lung cancer	-0.261	0.0845	0.00199	Wald ratio	1	cis	NA
Thalamus volume	84.5	31.2	0.00683	Wald ratio	1	cis	NA
Diastolic blood pressure automated reading	-0.027	0.0113	0.0173	Wald ratio	1	cis	NA
Diagnoses - main ICD10: K40 Inguinal hernia	-0.197	0.0831	0.0175	Wald ratio	1	cis	NA
Squamous cell lung cancer	-0.278	0.13	0.032	Wald ratio	1	cis	NA
Hearing difficulty or problems: Yes	-0.0423	0.0199	0.034	Wald ratio	1	cis	NA
Clear cell ovarian cancer	0.384	0.191	0.0438	Wald ratio	1	cis	NA
Coronary heart disease	0.103	0.0518	0.0463	Wald ratio	1	cis	NA
Myocardial infarction	0.115	0.0594	0.0522	Wald ratio	1	cis	NA
Systolic blood pressure automated reading	-0.0218	0.0113	0.0542	Wald ratio	1	cis	NA
Pallidum volume	17.6	9.53	0.0645	Wald ratio	1	cis	NA
Diagnoses - main ICD10: I48 Atrial fibrillation and flutter	-0.255	0.138	0.0653	Wald ratio	1	cis	NA
…and 65 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

111 association rows across 44 traits (98 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
Height	2e-84	rs7204018	24	GCST90245848	no MR -> candidate analysis
Serum levels of protein CRISPLD2	8e-33	rs144759316	2	GCST90089149	no MR -> candidate analysis
creatinine (minimum, inv-norm transformed)	1e-28	rs1874014	2	GCST90475232	no MR -> candidate analysis
creatinine (mean, inv-norm transformed)	7e-27	rs1874014	2	GCST90475229	no MR -> candidate analysis
estimated glomerular filtration rate (eGFR, maximum, inv-nor	4e-26	rs1874014	2	GCST90475280	no MR -> candidate analysis
estimated glomerular filtration rate (eGFR, mean, inv-norm t	4e-26	rs1874014	2	GCST90475282	no MR -> candidate analysis
Seropositivity (peptide co-occurrence module 12: H. pylori,	3e-25	rs1421350113	1	GCST90295934	no MR -> candidate analysis
Cysteine-rich secretory protein LCCL domain-containing 2 lev	2e-23	rs183935383	3	GCST90247162	no MR -> candidate analysis
Inguinal hernia	3e-20	rs4238714	15	GCST90239723	MR: beta=-0.197, p=0.0175 (cis)
Diverticular disease	4e-20	rs17111	3	GCST90301393	MR: beta=-0.129, p=0.287 (cis)
Cysteine-rich secretory protein LCCL domain-containing 2 lev	5e-19	rs12921670	3	GCST90240842	no MR -> candidate analysis
Blood protein levels	2e-18	rs60910901	1	GCST006585	no MR -> candidate analysis
…and 32 more traits (see JSON)

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

Top diseases by Open Targets association (of 209 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
diverticular disease	0.873	—	common-variant locus	MR: beta=-0.129, p=0.287 (cis)
Inguinal hernia	0.816	—	common-variant locus	MR: beta=-0.197, p=0.0175 (cis)
Abnormality of the skeletal system	0.803	—	common-variant locus	no MR -> candidate analysis
Hernia	0.742	—	common-variant locus	MR: beta=-0.197, p=0.0175 (cis)
appendicitis	0.656	—	common-variant locus	MR: beta=-0.18, p=0.368 (cis)
Hernia of the abdominal wall	0.654	—	common-variant locus	no MR -> candidate analysis
vein disorder	0.627	—	common-variant locus	no MR -> candidate analysis
pelvic organ prolapse	0.528	—	common-variant locus	no MR -> candidate analysis
lymphatic system disorder	0.504	—	common-variant locus	no MR -> candidate analysis
coronary artery disorder	0.475	—	common-variant locus	no MR -> candidate analysis
male reproductive organ cancer	0.472	—	common-variant locus	no MR -> candidate analysis
digestive system disorder	0.467	—	common-variant locus	no MR -> candidate analysis
abdominal abscess	0.467	—	common-variant locus	no MR -> candidate analysis
aortic valve stenosis	0.447	—	common-variant locus	no MR -> candidate analysis
abdominal aortic aneurysm	0.431	—	common-variant locus	no MR -> candidate analysis

Of the 15 rows above, 11 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=1.2e-10, LOEUF=0.843 — LoF-tolerant
GWAS Catalog	107 unique SNPs / 220 rows
ClinVar	249 records; 1 pathogenic in sample of 30
PharmGKB/ClinPGx	no annotations

Caveats declared by the tools

• phenome — Top 30 of 209 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 ‘CRISPLD2’.
• clinvar — Pathogenic count is over the 30 record(s) retrieved, NOT over all 249 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 44 traits by best p-value, aggregated from 111 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/Q9H0B8 — 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/ENSG00000103196/associations — Open Targets data release 26.06
• gnomad: https://gnomad.broadinstitute.org/gene/CRISPLD2 — gnomAD constraint via GraphQL API (reference genome GRCh38)
• gwas: https://www.ebi.ac.uk/gwas/genes/CRISPLD2 — GWAS Catalog REST (live; release not exposed by this endpoint)
• clinvar: https://www.ncbi.nlm.nih.gov/clinvar/?term=CRISPLD2%5Bgene%5D — ClinVar build Build260809-1055.1
• gwas_traits: https://www.ebi.ac.uk/gwas/genes/CRISPLD2 — GWAS Catalog search API (live; release not exposed)

Provenance

• Generated: 2026-08-14T02:03:42 · 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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