CausalSentinel

Protein Dossier — CALCOCO2 (Calcium-binding and coiled-coil domain-containing protein 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
Height 0.0842 0.0216 9.52e-05 Wald ratio 1 cis NA
Systolic blood pressure automated reading -0.0687 0.0183 1.74e-04 Wald ratio 1 cis NA
Weight 0.0484 0.0158 0.00216 Wald ratio 1 cis NA
Forced vital capacity (FVC) 0.0449 0.0146 0.00219 Wald ratio 1 cis NA
Diagnoses - main ICD10: H25 Senile cataract 0.385 0.142 0.00668 Wald ratio 1 cis NA
Potassium in urine 0.0488 0.0181 0.00716 Wald ratio 1 cis NA
Diagnoses - main ICD10: L03 Cellulitis 0.376 0.14 0.00725 Wald ratio 1 cis NA
Non-cancer illness code self-reported: ankylosing spondylitis 0.544 0.207 0.00854 Wald ratio 1 cis NA
Glioma 0.84 0.32 0.00863 Wald ratio 1 cis NA
Ovarian cancer -0.255 0.0994 0.0104 Wald ratio 1 cis NA
Neuroblastoma 0.844 0.339 0.0128 Wald ratio 1 cis NA
Diagnoses - main ICD10: K35 Acute appendicitis 0.429 0.173 0.0132 Wald ratio 1 cis NA
…and 116 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

23 association rows across 20 traits (22 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 7e-95 rs550510 2 GCST90245848 MR: beta=0.0842, p=9.52e-05 (cis)
Calcium-binding and coiled-coil domain-containing protein 2 8e-17 rs550510 2 GCST90246799 no MR -> candidate analysis
Height (baseline) 1e-16 rs78270829 2 GCST90565843 no MR -> candidate analysis
CALCOCO2 protein levels 1e-16 rs606911 1 GCST90468531 no MR -> candidate analysis
Liver enzyme levels (alkaline phosphatase) 2e-14 rs550510 1 GCST90013406 no MR -> candidate analysis
Physical function (baseline) 3e-14 rs78270829 1 GCST90565837 no MR -> candidate analysis
Whole body water mass (UKB data field 23102) 6e-14 rs78270829 1 GCST90468184 no MR -> candidate analysis
Serum levels of protein CALCOCO2 2e-13 rs550510 1 GCST90087053 no MR -> candidate analysis
Body mass index 2e-13 rs534840 1 GCST009871 MR: beta=0.0143, p=0.423 (cis)
Impedance of whole body (UKB data field 23106) 3e-13 rs318102 1 GCST90468173 no MR -> candidate analysis
Basal metabolic rate (UKB data field 23105) 3e-12 rs78270829 1 GCST90468159 no MR -> candidate analysis
Serum alkaline phosphatase levels 3e-11 rs550510 1 GCST90011900 no MR -> candidate analysis
…and 8 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 281 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
Abnormality of the skeletal system 0.622 common-variant locus no MR -> candidate analysis
chronic kidney disease 0.417 common-variant locus MR: beta=-0.195, p=0.0781 (cis)
dementia 0.29 common-variant locus no MR -> candidate analysis
hypothyroidism 0.271 common-variant locus no MR -> candidate analysis
ptosis 0.242 common-variant locus no MR -> candidate analysis
prostate carcinoma 0.2 common-variant locus no MR -> candidate analysis
type 2 diabetes mellitus 0.163 common-variant locus no MR -> candidate analysis
coronary artery disorder 0.13 common-variant locus no MR -> candidate analysis
schizophrenia 0.123 common-variant locus MR: beta=-0.177, p=0.0205 (cis)
metabolic disease 0.102 common-variant locus no MR -> candidate analysis
hyperlipidemia 0.102 common-variant locus no MR -> candidate analysis
kidney failure 0.095 common-variant locus no MR -> candidate analysis
diabetic eye disease 0.094 common-variant locus no MR -> candidate analysis

Of the 13 rows above, 11 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 0 known modulators (Calcium-binding and coiled-coil domain-containing protein 2)
gnomAD constraint pLI=7.4e-10, LOEUF=0.87 — LoF-tolerant
GWAS Catalog 99 unique SNPs / 192 rows
ClinVar 81 records; 0 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance