CausalSentinel

Protein Dossier — DSC2 (Desmocollin-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
Diagnoses - main ICD10: K43 Ventral hernia 0.377 0.142 0.00779 Wald ratio 1 cis NA
Fractured bone site(s): Wrist 0.205 0.0788 0.0094 Wald ratio 1 cis NA
Diagnoses - main ICD10: L03 Cellulitis 0.288 0.114 0.0117 Wald ratio 1 cis NA
Fractured or broken bones in last 5 years 0.0901 0.0384 0.0191 Wald ratio 1 cis NA
Cancer code self-reported: basal cell carcinoma 0.247 0.111 0.0265 Wald ratio 1 cis NA
Diagnoses - main ICD10: G56 Mononeuropathies of upper limb 0.176 0.0866 0.0415 Wald ratio 1 cis NA
Diagnoses - main ICD10: N81 Female genital prolapse 0.187 0.0943 0.0478 Wald ratio 1 cis NA
Non-cancer illness code self-reported: asthma 0.0685 0.0352 0.052 Wald ratio 1 cis NA
Non-cancer illness code self-reported: ankylosing spondylitis 0.341 0.189 0.071 Wald ratio 1 cis NA
Percent emphysema -0.0875 0.0491 0.0746 Wald ratio 1 cis NA
Fasting insulin 0.0973 0.0556 0.0801 Wald ratio 1 cis NA
Ovarian cancer 0.129 0.0743 0.0822 Wald ratio 1 cis NA
…and 57 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

9 association rows across 5 traits (8 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
DSC2 protein levels 4e-265 rs71175758 3 GCST90469040 no MR -> candidate analysis
Circulating DSC2 levels 2e-116 rs10084050 1 GCST90860596 no MR -> candidate analysis
Desmocollin-2 levels 2e-36 rs1790683 3 GCST90422097 no MR -> candidate analysis
Desmocollin-2 levels (DSC2.13126.52.3) 2e-13 rs1789063 1 GCST90240894 no MR -> candidate analysis
Bronchopulmonary dysplasia 7e-6 rs1126214 1 GCST002104 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 950 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
Arrhythmogenic right ventricular dysplasia 0.762 established (curated) no MR -> candidate analysis
familial isolated arrhythmogenic right ventricular dysplasia 0.943 established (curated) no MR -> candidate analysis
arrhythmogenic right ventricular cardiomyopathy 0.836 established (curated) no MR -> candidate analysis
Abnormality of the cardiovascular system 0.924 established (curated) no MR -> candidate analysis
atrial fibrillation 0.667 common-variant locus no MR -> candidate analysis
cardiomyopathy 0.63 established (curated) no MR -> candidate analysis
familial isolated arrhythmogenic ventricular dysplasia, right dominant form 0.608 established (curated) no MR -> candidate analysis
familial isolated arrhythmogenic ventricular dysplasia, biventricular form 0.608 established (curated) no MR -> candidate analysis
familial isolated arrhythmogenic ventricular dysplasia, left dominant form 0.608 established (curated) no MR -> candidate analysis
dilated cardiomyopathy 1A 0.486 established (curated) no MR -> candidate analysis
arrhythmogenic right ventricular dysplasia 1 0.486 established (curated) no MR -> candidate analysis
dilated cardiomyopathy 0.285 established (curated) no MR -> candidate analysis
Prolonged QT interval 0.263 established (curated) no MR -> candidate analysis
cardiac arrhythmia 0.243 established (curated) no MR -> candidate analysis
familial hypertrophic cardiomyopathy 0.243 established (curated) no MR -> candidate analysis

Of the 15 rows above, 15 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=3.4e-09, LOEUF=0.735 — LoF-tolerant
GWAS Catalog 29 unique SNPs / 58 rows
ClinVar 2161 records; 8 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance