CausalSentinel

Protein Dossier — CD59 (CD59 glycoprotein)

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
Pulse rate -0.0422 0.0133 0.00157 Wald ratio 1 cis NA
Systolic blood pressure automated reading -0.0226 0.00775 0.00347 Wald ratio 1 cis NA
Diagnoses - main ICD10: K20 Oesophagitis 0.179 0.0642 0.00524 Wald ratio 1 cis NA
Birth weight -0.0304 0.0119 0.0105 Wald ratio 1 cis NA
Pancreatic cancer -0.385 0.151 0.0107 Wald ratio 1 cis NA
Diagnoses - main ICD10: G47 Sleep disorders 0.196 0.0818 0.0167 Wald ratio 1 cis NA
Diastolic blood pressure automated reading -0.0179 0.00775 0.0213 Wald ratio 1 cis NA
Body mass index (BMI) 0.0168 0.00757 0.0266 Wald ratio 1 cis NA
Thyroid cancer 0.719 0.33 0.0293 Wald ratio 1 cis NA
Diagnoses - main ICD10: M17 Gonarthrosis [arthrosis of knee] 0.107 0.0491 0.0296 Wald ratio 1 cis NA
Large vessel disease -0.231 0.11 0.0348 Wald ratio 1 cis NA
Forearm bone mineral density 0.104 0.0498 0.0374 Wald ratio 1 cis NA
…and 96 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

21 association rows across 15 traits (19 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
Circulating CD59 levels 7e-293 rs2273121 3 GCST90860447 no MR -> candidate analysis
CD59 protein levels 5e-288 rs704701 2 GCST90468639 no MR -> candidate analysis
CD59 glycoprotein levels (CD59.11514.196.3) 5e-41 rs2273121 1 GCST90240644 no MR -> candidate analysis
CD59 glycoprotein levels 5e-31 rs704701 2 GCST90246945 no MR -> candidate analysis
Serum levels of protein CD59 3e-30 rs831636 1 GCST90086775 no MR -> candidate analysis
Morning person 1e-27 rs11032362 2 GCST007565 no MR -> candidate analysis
Chronotype 1e-27 rs11032362 1 GCST007576 no MR -> candidate analysis
Morningness 3e-17 rs11032362 1 GCST007983 no MR -> candidate analysis
Blood protein levels 1e-14 rs831636 1 GCST006585 no MR -> candidate analysis
Fresh fruit consumption 3e-11 rs11032362 1 GCST90132979 no MR -> candidate analysis
Calcium (mean, inv-norm transformed) 4e-11 rs1718066 1 GCST90479530 no MR -> candidate analysis
Fruit consumption 1e-10 rs11032362 1 GCST010136 no MR -> candidate analysis
…and 3 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 1099 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
primary CD59 deficiency 0.769 established (curated) no MR -> candidate analysis
hereditary disease 0.294 established (curated) no MR -> candidate analysis

Of the 2 rows above, 2 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 (CD59 glycoprotein)
gnomAD constraint pLI=0.29, LOEUF=1.1 — LoF-tolerant
GWAS Catalog 25 unique SNPs / 50 rows
ClinVar 149 records; 8 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance