CausalSentinel

Protein Dossier — CRISP2 (Cysteine-rich secretory 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
Underlying (primary) cause of death: ICD10: E85.4 Organ-limited amyloidosis 1.34 0.272 9.33e-07 Wald ratio 1 cis NA
Diastolic blood pressure automated reading -0.0114 0.00433 0.00848 Wald ratio 1 cis NA
Squamous cell lung cancer -0.114 0.0452 0.0113 Wald ratio 1 cis NA
Lung cancer -0.0746 0.0301 0.0131 Wald ratio 1 cis NA
Non-cancer illness code self-reported: pulmonary embolism (with or without) dvt -0.118 0.0529 0.0257 Wald ratio 1 cis NA
Hip osteoarthritis -0.102 0.0463 0.0271 Wald ratio 1 cis NA
Diagnoses - main ICD10: C50 Malignant neoplasm of breast 0.0663 0.0309 0.032 Wald ratio 1 cis NA
Diagnoses - main ICD10: K29 Gastritis and duodenitis 0.0552 0.0259 0.033 Wald ratio 1 cis NA
Alzheimer’s disease -0.0529 0.0272 0.0521 Wald ratio 1 cis NA
Eye problems or disorders: Glaucoma 0.0634 0.0331 0.0557 Wald ratio 1 cis NA
Eye problems or disorders: Injury or trauma resulting in loss of vision 0.0906 0.0505 0.0725 Wald ratio 1 cis NA
Anorexia nervosa 0.0888 0.0497 0.0741 Wald ratio 1 cis NA
…and 75 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

26 association rows across 18 traits (23 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 CRISP2 levels 8e-1000 rs113140471 3 GCST90860530 no MR -> candidate analysis
Cysteine-rich secretory protein 2 levels 2e-246 rs112840264 2 GCST90247160 no MR -> candidate analysis
CRISP3 protein levels 2e-216 rs765003308 5 GCST90468866 no MR -> candidate analysis
Cysteine-rich secretory protein 2 levels (CRISP2.9282.12.3) 2e-82 rs36069724 1 GCST90240840 no MR -> candidate analysis
Cerebrospinal fluid protein CRISP2 levels 6e-44 rs112840264 1 GCST90943230 no MR -> candidate analysis
Mean spheric corpuscular volume 4e-28 rs188522023 1 GCST90002397 no MR -> candidate analysis
Cysteine-rich secretory protein 2 level in Chronic kidney di 3e-17 rs360541 1 GCST90239289 no MR -> candidate analysis
CRISP2 protein levels 3e-15 rs143650014 1 GCST90468865 no MR -> candidate analysis
Mean corpuscular hemoglobin concentration 1e-14 rs188522023 2 GCST90002391 no MR -> candidate analysis
Reticulocyte fraction of red cells 4e-13 rs188522023 1 GCST90002406 no MR -> candidate analysis
Reticulocyte count 5e-13 rs188522023 1 GCST90002405 no MR -> candidate analysis
Mean reticulocyte volume 4e-12 rs188522023 1 GCST90002396 no MR -> candidate analysis
…and 6 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 118 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
Aganglionic megacolon 0.195 established (curated) no MR -> candidate analysis
carotid artery disorder 0.145 common-variant locus no MR -> candidate analysis

Of the 2 rows above, 2 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=8.5e-10, LOEUF=1.25 — LoF-tolerant
GWAS Catalog 50 unique SNPs / 96 rows
ClinVar 54 records; 1 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance