CausalSentinel

Protein Dossier — CRYZ (Zeta-crystallin)

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
Non-cancer illness code self-reported: muscle or soft tissue injuries 0.0989 0.0322 0.00211 Wald ratio 1 cis NA
Subjective well being -0.0119 0.00426 0.00511 Wald ratio 1 cis NA
Non-cancer illness code self-reported: gout 0.0624 0.0237 0.00838 Wald ratio 1 cis NA
Ischemic stroke 0.0505 0.0195 0.00961 Wald ratio 1 cis NA
Body fat 0.0165 0.00638 0.00969 Wald ratio 1 cis NA
Ferritin 0.0285 0.0116 0.0138 Wald ratio 1 cis NA
Diagnoses - main ICD10: S66 Injury of muscle and tendon at wrist and hand level 0.158 0.0645 0.0142 Wald ratio 1 cis NA
Invasive mucinous ovarian cancer 0.115 0.0475 0.0155 Wald ratio 1 cis NA
Eye problems or disorders: Diabetes related eye disease -0.0985 0.0425 0.0203 Wald ratio 1 cis NA
Lung adenocarcinoma 0.088 0.0383 0.0214 Wald ratio 1 cis NA
Lung cancer 0.0532 0.0235 0.0239 Wald ratio 1 cis NA
Non-cancer illness code self-reported: kidney stone or ureter stone or bladder stone -0.0825 0.0369 0.0253 Wald ratio 1 cis NA
…and 113 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

8 association rows across 6 traits (7 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
Blood protein levels 3e-292 rs3819946 1 GCST006585 no MR -> candidate analysis
Estimated bone mineral density 6e-10 rs277402 1 GCST90726625 no MR -> candidate analysis
Protein quantitative trait loci (liver) 1e-9 rs61790703 2 GCST011427 no MR -> candidate analysis
Heel bone mineral density 2e-9 rs277402 1 GCST006433 no MR -> candidate analysis
Neurofibrillary tangles (SNP x SNP interaction) 3e-9 rs7512474 x rs12668317 2 GCST010343 no MR -> candidate analysis
Gut microbiota (bacterial taxa, hurdle binary method) 8e-6 rs150733404 1 GCST010396 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 98 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
response to paracetamol 0.444 common-variant locus no MR -> candidate analysis
ovarian neoplasm 0.422 common-variant locus no MR -> candidate analysis
amyotrophic lateral sclerosis 0.353 common-variant locus no MR -> candidate analysis
adolescent idiopathic scoliosis 0.337 common-variant locus no MR -> candidate analysis
kidney cancer 0.136 common-variant locus no MR -> candidate analysis
Wheezing 0.09 common-variant locus no MR -> candidate analysis
jaw disease 0.053 common-variant locus no MR -> candidate analysis
skin aging 0.052 common-variant locus no MR -> candidate analysis
Cerebral degeneration 0.033 common-variant locus no MR -> candidate analysis
health study participation 0.031 common-variant locus no MR -> candidate analysis

Of the 10 rows above, 10 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 0 known modulators (Quinone oxidoreductase)
gnomAD constraint pLI=8.3e-13, LOEUF=1.36 — LoF-tolerant
GWAS Catalog 26 unique SNPs / 51 rows
ClinVar 99 records; 3 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance