CausalSentinel

Protein Dossier — ECE1 (Endothelin-converting enzyme 1)

MR feasibility tier: B — No published MR estimate in this resource, BUT a pQTL GWAS exists - instruments are derivable, so a two-sample MR could be run. The upstream is waiting.

1. Published MR estimates (retrieved, not computed)

None in the EpiGraphDB pQTL resource. Absence of an estimate is not evidence of no effect.

2. pQTL instrument availability (Tier-B probe)

Dataset Trait Author Year
prot-c-3611_70_4 Endothelin-converting enzyme 1 Suhre K 2019

Instruments exist but no MR estimate is in this resource — a two-sample MR here is un-run work.

3. GWAS Catalog results — traits with signal at this locus

98 association rows across 61 traits (81 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 3e-157 rs212526 7 GCST90245848 no MR -> candidate analysis
ECE1 protein levels 7e-130 rs148461660 2 GCST90469061 no MR -> candidate analysis
Alkaline phosphatase (UKB data field 30610) 3e-112 rs1067237 5 GCST90468060 no MR -> candidate analysis
Circulating ECE1 levels 1e-110 rs148461660 2 GCST90860682 no MR -> candidate analysis
Hematological traits (multi-trait analysis) 1e-48 rs6702331 2 GCST90838669 no MR -> candidate analysis
Serum alkaline phosphatase levels 1e-45 rs6695985 12 GCST90019494 no MR -> candidate analysis
Standing height (UKB data field 50) 1e-36 rs797014597 1 GCST90468178 no MR -> candidate analysis
Height (baseline) 6e-33 rs212515 3 GCST90565843 no MR -> candidate analysis
Appendicular lean mass 4e-29 rs212526 1 GCST90000025 no MR -> candidate analysis
Body shape phenotype PC2 9e-28 rs12743070 1 GCST90832990 no MR -> candidate analysis
Basophil count 2e-23 rs4060971 3 GCST90002292 no MR -> candidate analysis
Calcium levels (UKB data field 30680) 3e-19 rs34693054 1 GCST90468065 no MR -> candidate analysis
…and 49 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 2621 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
Hirschsprung disease 0.72 established (curated) no MR -> candidate analysis
neurodegenerative disease 0.187 common-variant locus no MR -> candidate analysis
liver disorder 0.535 common-variant locus no MR -> candidate analysis
Aganglionic megacolon 0.532 established (curated) no MR -> candidate analysis
stomach disorder 0.484 common-variant locus no MR -> candidate analysis
dementia 0.432 common-variant locus no MR -> candidate analysis
mathematical ability 0.408 common-variant locus no MR -> candidate analysis
Anxiety 0.402 common-variant locus no MR -> candidate analysis
placental abruption 0.315 common-variant locus no MR -> candidate analysis
atrial fibrillation 0.288 common-variant locus no MR -> candidate analysis
hypertensive disorder 0.233 common-variant locus no MR -> candidate analysis
essential hypertension, genetic 0.195 established (curated) no MR -> candidate analysis

Of the 12 rows above, 12 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 1 known modulators (Endothelin-converting enzyme 1)
gnomAD constraint pLI=1, LOEUF=0.471 — LoF-INTOLERANT
GWAS Catalog 91 unique SNPs / 182 rows
ClinVar 197 records; 0 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance