CausalSentinel

Protein Dossier — SCP2D1 (SCP2 sterol-binding domain-containing 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
Cancer code self-reported: basal cell carcinoma 0.088 0.0291 0.00251 Wald ratio 1 trans NA
Non-cancer illness code self-reported: bone disorder 0.155 0.0558 0.0054 Wald ratio 1 trans NA
Diagnoses - main ICD10: J33 Nasal polyp -0.142 0.0511 0.00554 Wald ratio 1 trans NA
Diagnoses - main ICD10: M17 Gonarthrosis [arthrosis of knee] -0.0622 0.0233 0.00768 Wald ratio 1 trans NA
Diagnoses - main ICD10: K35 Acute appendicitis -0.118 0.0493 0.017 Wald ratio 1 trans NA
Birth weight -0.0113 0.00485 0.0201 Wald ratio 1 trans NA
Diagnoses - main ICD10: M23 Internal derangement of knee -0.0467 0.0215 0.0296 Wald ratio 1 trans NA
Ischemic stroke 0.0552 0.0255 0.0303 Wald ratio 1 trans NA
Ferritin 0.0248 0.0135 0.0661 Wald ratio 1 trans NA
Diagnoses - main ICD10: K57 Diverticular disease of intestine 0.0378 0.0206 0.0671 Wald ratio 1 trans NA
Diagnoses - main ICD10: K80 Cholelithiasis 0.0373 0.0204 0.0677 Wald ratio 1 trans NA
Diastolic blood pressure automated reading 0.00559 0.00312 0.073 Wald ratio 1 trans NA
…and 87 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

49 association rows across 25 traits (25 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 1e-56 rs6132147 3 GCST90245848 MR: beta=0.00679, p=0.203 (trans)
Pulse pressure 4e-18 rs17812022 2 GCST90310296 no MR -> candidate analysis
Systolic blood pressure 2e-13 rs17812022 2 GCST90310294 MR: beta=0.00349, p=0.263 (trans)
Hip circumference adjusted for BMI 7e-13 rs2876517 6 GCST90020028 no MR -> candidate analysis
Systolic blood pressure (MTAG) 9e-11 rs17812022 1 GCST90449056 no MR -> candidate analysis
Hip index 1e-10 rs375702194 4 GCST90020026 no MR -> candidate analysis
Sleep (1/3-day periodicity) 3e-9 rs149624949 1 GCST012033 no MR -> candidate analysis
Body size or adipose distribution (multivariate analysis) 9e-9 rs6136595 1 GCST90624105 no MR -> candidate analysis
Gut microbiome abundance (class Clostridium sensu stricto sp 2e-8 rs34392806 1 GCST90569029 no MR -> candidate analysis
C-reactive protein (red blood cell fatty acid level interact 3e-8 rs3762220 1 GCST004815 no MR -> candidate analysis
DNA methylation variation (age effect) 4e-8 rs117183447 1 GCST006660 no MR -> candidate analysis
Bioavailable testosterone levels 4e-8 rs143240517 1 GCST90027085 no MR -> candidate analysis
…and 13 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 22 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
liver disorder 0.265 common-variant locus no MR -> candidate analysis
pneumonitis 0.258 common-variant locus no MR -> candidate analysis
alcohol drinking 0.191 common-variant locus no MR -> candidate analysis
rectosigmoid junction neoplasm 0.191 common-variant locus no MR -> candidate analysis
urolithiasis 0.191 common-variant locus no MR -> candidate analysis
Abnormal central motor function 0.163 0.163 exploratory rare-variant signal no MR -> candidate analysis
smoking initiation 0.059 common-variant locus no MR -> candidate analysis
chronic hepatitis 0.057 common-variant locus no MR -> candidate analysis
hemorrhage 0.052 common-variant locus no MR -> candidate analysis
gastric ulcer 0.052 common-variant locus no MR -> candidate analysis
diverticular disease 0.03 common-variant locus MR: beta=0.0378, p=0.0671 (trans)
intestinal disorder 0.03 common-variant locus no MR -> candidate analysis

Of the 12 rows above, 11 have no MR estimate in this resource. Across all retrieved diseases for this gene: 1 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=0.0021, LOEUF=1.57 — LoF-tolerant
GWAS Catalog 18 unique SNPs / 36 rows
ClinVar 51 records; 4 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance