CausalSentinel

Protein Dossier — ECH1 (Delta(3,5)-Delta(2,4)-dienoyl-CoA isomerase, mitochondrial)

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: kidney stone or ureter stone or bladder stone 0.199 0.0686 0.00368 Wald ratio 1 cis NA
Diagnoses - main ICD10: N40 Hyperplasia of prostate -0.298 0.105 0.00444 Wald ratio 1 cis NA
Type 2 diabetes -0.295 0.11 0.00766 Wald ratio 1 cis NA
Non-cancer illness code self-reported: uterine fibroids -0.17 0.071 0.0167 Wald ratio 1 cis NA
Diagnoses - main ICD10: I80 Phlebitis and thrombophlebitis -0.342 0.156 0.029 Wald ratio 1 cis NA
Diagnoses - main ICD10: L03 Cellulitis 0.151 0.0709 0.0333 Wald ratio 1 cis NA
Potassium in urine -0.0158 0.00748 0.0347 Wald ratio 1 cis NA
Non-cancer illness code self-reported: hiatus hernia -0.113 0.0543 0.0382 Wald ratio 1 cis NA
Diagnoses - main ICD10: M17 Gonarthrosis [arthrosis of knee] 0.0981 0.0482 0.042 Wald ratio 1 cis NA
Diagnoses - main ICD10: I30 Acute pericarditis 0.512 0.275 0.0631 Wald ratio 1 cis NA
Cancer code self-reported: prostate cancer -0.191 0.106 0.0715 Wald ratio 1 cis NA
Amygdala volume -13.3 7.64 0.0823 Wald ratio 1 cis NA
…and 59 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

10 association rows across 9 traits (9 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
Delta(3,5)-Delta(2,4)-dienoyl-CoA isomerase, mitochondrial l 1e-282 rs2229259 1 GCST90247247 no MR -> candidate analysis
LGALS4 protein levels 5e-48 rs28496951 2 GCST90469762 no MR -> candidate analysis
Serum levels of protein ECH1 6e-42 rs2229259 1 GCST90087134 no MR -> candidate analysis
Blood protein levels 2e-33 rs4802890 1 GCST006585 no MR -> candidate analysis
Enoyl-CoA delta isomerase 2, mitochondrial levels 4e-22 rs4802890 1 GCST90247387 no MR -> candidate analysis
Circulating LGALS4 levels 4e-17 rs10426289 1 GCST90859971 no MR -> candidate analysis
platelet count (mean, inv-norm transformed) 9e-15 rs11671711 1 GCST90480651 no MR -> candidate analysis
Diffuse plaques (SNP x SNP interaction) 3e-9 rs11671711 x rs8122161 1 GCST010341 no MR -> candidate analysis
TNFB levels 4e-6 rs2287953 1 GCST90503395 no MR -> candidate analysis

4. Phenome map — where this gene is a genetic locus, vs. where MR exists

Top diseases by Open Targets association (of 103 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
alcohol drinking 0.326 common-variant locus no MR -> candidate analysis
urolithiasis 0.326 common-variant locus no MR -> candidate analysis
decubitus ulcer 0.182 common-variant locus no MR -> candidate analysis
dementia 0.163 common-variant locus no MR -> candidate analysis
neurodegenerative disease 0.131 common-variant locus no MR -> candidate analysis

Of the 5 rows above, 5 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 (Delta(3,5)-Delta(2,4)-dienoyl-CoA isomerase, mitochondrial)
gnomAD constraint pLI=4.9e-09, LOEUF=1.1 — LoF-tolerant
GWAS Catalog 61 unique SNPs / 122 rows
ClinVar 87 records; 1 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance