CausalSentinel

Protein Dossier — CD3E (T-cell surface glycoprotein CD3 epsilon chain)

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
Non-cancer illness code self-reported: high cholesterol 0.062 0.0239 0.00945 Wald ratio 1 trans NA
Clear cell ovarian cancer 0.332 0.159 0.0376 Wald ratio 1 trans NA
Non-cancer illness code self-reported: hypopituitarism 0.616 0.307 0.0452 Wald ratio 1 trans NA
Forced vital capacity (FVC) -0.0152 0.00771 0.0487 Wald ratio 1 trans NA
Diagnoses - main ICD10: J33 Nasal polyp 0.216 0.112 0.0523 Wald ratio 1 trans NA
Diagnoses - main ICD10: M17 Gonarthrosis [arthrosis of knee] 0.116 0.0605 0.0542 Wald ratio 1 trans NA
Diagnoses - main ICD10: H25 Senile cataract -0.279 0.145 0.0546 Wald ratio 1 trans NA
Non-cancer illness code self-reported: kidney stone or ureter stone or bladder stone 0.168 0.0906 0.0638 Wald ratio 1 trans NA
Non-cancer illness code self-reported: polio or poliomyelitis 0.444 0.248 0.0732 Wald ratio 1 trans NA
Creatinine (enzymatic) in urine 0.0158 0.00899 0.0782 Wald ratio 1 trans NA
Cigarettes smoked per day 0.591 0.339 0.081 Wald ratio 1 trans NA
Diagnoses - main ICD10: M23 Internal derangement of knee 0.0984 0.0575 0.0869 Wald ratio 1 trans NA
…and 82 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

24 association rows across 15 traits (15 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
TREH protein levels 2e-58 rs565299958 3 GCST90470959 no MR -> candidate analysis
Red blood cell count 8e-14 rs12798851 6 GCST90662905 no MR -> candidate analysis
Red blood cell erythrocyte count (UKB data field 30010) 6e-13 rs12798851 1 GCST90468098 no MR -> candidate analysis
Serum urate levels 4e-12 rs12798851 2 GCST90455669 no MR -> candidate analysis
Height (baseline) 1e-9 rs141752759 1 GCST90565843 no MR -> candidate analysis
Serum uric acid levels 3e-9 rs12798851 1 GCST90018977 no MR -> candidate analysis
Pulse pressure 3e-8 rs117204111 1 GCST007096 no MR -> candidate analysis
Crohn’s disease 5e-8 rs141340254 2 GCST90446792 no MR -> candidate analysis
Lung cancer in ever smokers 4e-7 rs61677309 1 GCST004749 no MR -> candidate analysis
Pain 7e-7 rs17122021 1 GCST000326 MR: beta=0.0381, p=0.384 (trans)
Parental extreme longevity (95 years and older) 1e-6 rs11216843 1 GCST003395 no MR -> candidate analysis
High-sensitivity C-reactive protein (log-transformed) x plas 1e-6 rs12577841 1 GCST90566442 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 403 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
immunodeficiency 18 0.915 established (curated) no MR -> candidate analysis
T-B+ severe combined immunodeficiency due to CD3delta/CD3epsilon/CD3zeta 0.608 established (curated) no MR -> candidate analysis
severe combined immunodeficiency 0.509 established (curated) no MR -> candidate analysis

Of the 3 rows above, 3 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 7 known modulators (T-cell surface glycoprotein CD3 epsilon chain)
gnomAD constraint pLI=0.048, LOEUF=0.701 — LoF-tolerant
GWAS Catalog 59 unique SNPs / 118 rows
ClinVar 338 records; 3 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance