CausalSentinel

Protein Dossier — SCUBE1 (Signal peptide, CUB and EGF-like 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
Urate -0.0926 0.0296 0.00178 Wald ratio 1 cis NA
Non-cancer illness code self-reported: joint disorder 0.379 0.131 0.00374 Wald ratio 1 cis NA
Pancreatic cancer -0.709 0.26 0.00643 Wald ratio 1 cis NA
Height 0.037 0.0159 0.02 Wald ratio 1 cis NA
Body mass index (BMI) -0.0285 0.0128 0.026 Wald ratio 1 cis NA
Invasive mucinous ovarian cancer 0.456 0.206 0.027 Wald ratio 1 cis NA
Neo-conscientiousness -0.874 0.409 0.0324 Wald ratio 1 cis NA
Diagnoses - main ICD10: H25 Senile cataract 0.246 0.116 0.0339 Wald ratio 1 cis NA
Non-cancer illness code self-reported: psoriasis -0.373 0.182 0.0407 Wald ratio 1 cis NA
Weight -0.0229 0.0113 0.043 Wald ratio 1 cis NA
Diagnoses - main ICD10: G47 Sleep disorders 0.261 0.131 0.0472 Wald ratio 1 cis NA
Pallidum volume -19.9 10.2 0.0516 Wald ratio 1 cis NA
…and 97 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

59 association rows across 44 traits (39 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 3e-67 rs139027 9 GCST90245848 MR: beta=0.037, p=0.02 (cis)
Signal peptide, CUB and EGF-like domain-containing protein 1 7e-42 rs5759269 4 GCST90427586 no MR -> candidate analysis
DNAJB1 protein levels 8e-33 rs9612021 1 GCST90469012 no MR -> candidate analysis
Serum levels of protein SCUBE1 1e-22 rs2859441 1 GCST90090430 no MR -> candidate analysis
Circulating DNAJB1 levels 3e-21 rs138969 1 GCST90860533 no MR -> candidate analysis
Vertex-wise sulcal depth 3e-16 rs2015868 1 GCST90095129 no MR -> candidate analysis
Cortical surface area 1e-15 rs5996329 1 GCST90091060 no MR -> candidate analysis
Standing height (UKB data field 50) 3e-14 rs139030 1 GCST90468178 no MR -> candidate analysis
Blood protein levels 4e-14 rs2744874 1 GCST006585 no MR -> candidate analysis
Mean platelet thrombocyte volume (UKB data field 30100) 5e-14 rs113166111 1 GCST90468087 no MR -> candidate analysis
Vertex-wise cortical surface area 4e-13 rs5996329 1 GCST90095130 no MR -> candidate analysis
GLIPR1 protein levels 1e-12 rs374680689 1 GCST90469357 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 637 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
self-injurious ideation 0.4 common-variant locus no MR -> candidate analysis
diabetic ketoacidosis 0.382 common-variant locus no MR -> candidate analysis
corneal degeneration 0.366 common-variant locus no MR -> candidate analysis
kidney transplant 0.314 common-variant locus no MR -> candidate analysis
mucositis 0.297 common-variant locus no MR -> candidate analysis
stomatitis 0.297 common-variant locus no MR -> candidate analysis
prostate carcinoma 0.259 common-variant locus no MR -> candidate analysis

Of the 7 rows above, 7 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=1.7e-05, LOEUF=0.589 — LoF-tolerant
GWAS Catalog 100 unique SNPs / 200 rows
ClinVar 244 records; 0 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance