CausalSentinel

Protein Dossier — CGREF1 (Cell growth regulator with EF hand domain protein 1)

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
Eye problems or disorders: Glaucoma 0.257 0.0665 1.14e-04 Wald ratio 1 trans NA
Eye problems or disorders: Injury or trauma resulting in loss of vision 0.355 0.0947 1.80e-04 Wald ratio 1 trans NA
Diagnoses - main ICD10: K60 Fissure and fistula of anal and rectal regions 0.386 0.104 2.10e-04 Wald ratio 1 trans NA
Squamous cell lung cancer -0.437 0.125 4.65e-04 Wald ratio 1 trans NA
Forced vital capacity (FVC) 0.0263 0.00838 0.00172 Wald ratio 1 trans NA
Packed cell volume -0.288 0.109 0.00814 Wald ratio 1 trans NA
Haemoglobin concentration -0.0948 0.036 0.00848 Wald ratio 1 trans NA
Height 0.0373 0.0153 0.015 Wald ratio 1 trans NA
Percent emphysema -0.094 0.0406 0.0205 Wald ratio 1 trans NA
Forced expiratory volume in 1-second (FEV1) 0.0203 0.00884 0.0218 Wald ratio 1 trans NA
Non-cancer illness code self-reported: diverticular disease or diverticulitis -0.302 0.133 0.0236 Wald ratio 1 trans NA
Serum creatinine (eGFRcrea) 0.00911 0.00414 0.0278 Wald ratio 1 trans NA
…and 84 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

142 association rows across 37 traits (137 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
CGREF1 protein levels 4e-71 rs61750982 5 GCST90468735 no MR -> candidate analysis
Low-density lipoprotein levels (MTAG) 3e-31 rs75388820 1 GCST90179148 no MR -> candidate analysis
Monounsaturated fatty acid levels 4e-30 rs7573066 11 GCST90502030 no MR -> candidate analysis
Omega-6 fatty acids to total fatty acids percentage 3e-28 rs7573066 12 GCST90502121 no MR -> candidate analysis
Saturated fatty acids levels 2e-27 rs7588926 16 GCST90502186 no MR -> candidate analysis
Total fatty acid levels 6e-26 rs7588926 13 GCST90502212 no MR -> candidate analysis
Polyunsaturated fatty acids to monounsaturated fatty acids r 9e-26 rs7573066 11 GCST90502147 no MR -> candidate analysis
Monounsaturated fatty acids to total fatty acids percentage 1e-25 rs7573066 10 GCST90502043 no MR -> candidate analysis
Cerebrospinal fluid protein CGREF1 levels 4e-25 rs75388820 1 GCST90944186 no MR -> candidate analysis
Triglyceride levels 5e-22 rs116170113 2 GCST90019523 no MR -> candidate analysis
Polyunsaturated fatty acids to total fatty acids percentage 1e-21 rs7588926 8 GCST90502173 no MR -> candidate analysis
Polyunsaturated fatty acids to saturated fatty acids ratio 1e-18 rs7588926 6 GCST90502160 no MR -> candidate analysis
…and 25 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 88 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
risk-taking behaviour 0.564 common-variant locus no MR -> candidate analysis
musculoskeletal system disorder 0.444 common-variant locus no MR -> candidate analysis
attention deficit-hyperactivity disorder 0.434 common-variant locus no MR -> candidate analysis
osteoarthritis, hip 0.409 common-variant locus no MR -> candidate analysis
osteoarthritis, knee 0.409 common-variant locus no MR -> candidate analysis
Limb pain 0.401 common-variant locus no MR -> candidate analysis
Abdominal pain 0.326 common-variant locus MR: beta=-0.0585, p=0.265 (trans)
Headache 0.326 common-variant locus no MR -> candidate analysis
essential fructosuria 0.313 established (curated) no MR -> candidate analysis
mathematical ability 0.292 common-variant locus no MR -> candidate analysis
anxiety disorder 0.25 common-variant locus no MR -> candidate analysis
smoking cessation 0.245 common-variant locus no MR -> candidate analysis
endometriosis 0.129 common-variant locus no MR -> candidate analysis
metabolic dysfunction-associated steatotic liver disease 0.058 common-variant locus no MR -> candidate analysis
arthropathy 0.058 common-variant locus no MR -> candidate analysis

Of the 15 rows above, 14 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=6.4e-06, LOEUF=1.4 — LoF-tolerant
GWAS Catalog 102 unique SNPs / 210 rows
ClinVar 130 records; 1 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance