CausalSentinel

Protein Dossier — PKDCC (Extracellular tyrosine-protein kinase PKDCC)

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
Heel bone mineral density (BMD) T-score automated 0.197 0.0158 1.82e-35 Wald ratio 1 cis NA
Femoral neck bone mineral density 0.169 0.0373 5.87e-06 Wald ratio 1 cis NA
Forearm bone mineral density 0.242 0.0771 0.00169 Wald ratio 1 cis NA
Fasting insulin -0.0407 0.0148 0.00609 Wald ratio 1 cis NA
Non-cancer illness code self-reported: sleep apnoea 0.364 0.158 0.0215 Wald ratio 1 cis NA
Lung cancer -0.193 0.0853 0.0236 Wald ratio 1 cis NA
Height 0.0314 0.014 0.0249 Wald ratio 1 cis NA
Diastolic blood pressure automated reading -0.0269 0.0125 0.0319 Wald ratio 1 cis NA
Diagnoses - main ICD10: M23 Internal derangement of knee -0.22 0.104 0.0345 Wald ratio 1 cis NA
Gallbladder cancer 2.69 1.29 0.0367 Wald ratio 1 cis NA
Diagnoses - main ICD10: J33 Nasal polyp 0.281 0.137 0.0409 Wald ratio 1 cis NA
Diagnoses - main ICD10: R35 Polyuria 0.301 0.149 0.0431 Wald ratio 1 cis NA
…and 114 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

222 association rows across 81 traits (207 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
Estimated bone mineral density 2e-120 rs11887431 2 GCST90726625 no MR -> candidate analysis
Heel bone mineral density 1e-117 rs35657711 14 GCST007066 MR: beta=0.197, p=1.82e-35 (cis)
Vertex-wise sulcal depth 1e-92 rs2424 2 GCST90095129 no MR -> candidate analysis
Height 2e-54 rs12479347 6 GCST90245848 MR: beta=0.0314, p=0.0249 (cis)
CCL18/RARRES2 protein level ratio 3e-42 rs7570219 1 GCST90313690 no MR -> candidate analysis
Circulating CCL18 levels 2e-40 rs6715862 2 GCST90860473 no MR -> candidate analysis
Vertex-wise cortical surface area 4e-40 rs2424 1 GCST90095130 no MR -> candidate analysis
CCL18 protein levels 1e-38 rs6715862 1 GCST90468570 no MR -> candidate analysis
Serum levels of protein PKDCC 1e-37 rs34372645 2 GCST90090255 no MR -> candidate analysis
Vertex-wise cortical thickness 2e-32 rs12623480 1 GCST90095131 no MR -> candidate analysis
Hematological traits (multi-trait analysis) 5e-28 rs182284067 1 GCST90838669 no MR -> candidate analysis
Brain shape (segment 1) 3e-27 rs12623480 1 GCST90012880 no MR -> candidate analysis
…and 69 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 2745 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
rhizomelic limb shortening with dysmorphic features 0.813 established (curated) no MR -> candidate analysis
hair color 0.748 common-variant locus no MR -> candidate analysis
hereditary disease 0.744 established (curated) no MR -> candidate analysis
Abnormality of the skeletal system 0.572 established (curated) no MR -> candidate analysis
Hallux valgus 0.505 common-variant locus no MR -> candidate analysis
cleft lip 0.459 common-variant locus no MR -> candidate analysis
amyotrophic lateral sclerosis 0.454 common-variant locus MR: beta=-0.0805, p=0.366 (cis)
cleft palate 0.408 common-variant locus no MR -> candidate analysis
hypospadias 0.432 common-variant locus no MR -> candidate analysis
mathematical ability 0.372 common-variant locus no MR -> candidate analysis
smoking initiation 0.366 common-variant locus no MR -> candidate analysis
exostosis 0.354 common-variant locus no MR -> candidate analysis
ventricular fibrillation 0.354 common-variant locus no MR -> candidate analysis
Hypocalcemia 0.349 common-variant locus no MR -> candidate analysis
diverticular disease 0.346 common-variant locus MR: beta=0.122, p=0.238 (cis)

Of the 15 rows above, 13 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=5.1e-10, LOEUF=1.04 — LoF-tolerant
GWAS Catalog 149 unique SNPs / 355 rows
ClinVar 308 records; 1 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance