CausalSentinel

Protein Dossier — ACE (Angiotensin-converting enzyme)

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: hypertension -0.0296 0.00726 4.46e-05 Wald ratio 1 cis NA
Lung adenocarcinoma 0.146 0.0431 6.94e-04 Wald ratio 1 cis NA
Sodium in urine 0.0128 0.00407 0.00167 Wald ratio 1 cis NA
Birth weight -0.0189 0.00617 0.00225 Wald ratio 1 cis NA
Height -0.0146 0.00515 0.00461 Wald ratio 1 cis NA
Alzheimer’s disease -0.0746 0.0266 0.00501 Wald ratio 1 cis NA
Eye problems or disorders: Diabetes related eye disease -0.176 0.0635 0.00557 Wald ratio 1 cis NA
Non-cancer illness code self-reported: arthritis (nos) 0.11 0.0427 0.00983 Wald ratio 1 cis NA
Schizophrenia -0.0453 0.0182 0.0128 Wald ratio 1 cis NA
Non-cancer illness code self-reported: high cholesterol -0.0281 0.0115 0.0144 Wald ratio 1 cis NA
Diagnoses - main ICD10: K60 Fissure and fistula of anal and rectal regions 0.124 0.0542 0.0216 Wald ratio 1 cis NA
Diagnoses - main ICD10: I48 Atrial fibrillation and flutter -0.0964 0.0432 0.0256 Wald ratio 1 cis NA
…and 95 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

80 association rows across 55 traits (75 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
Angiotensin-converting enzyme levels 2e-746 rs4353 3 GCST90246413 no MR -> candidate analysis
Serum levels of protein ACE 2e-257 rs4363 1 GCST90086419 no MR -> candidate analysis
Blood protein levels 9e-136 rs4344 1 GCST006585 no MR -> candidate analysis
Height 6e-121 rs8075924 3 GCST90245848 MR: beta=-0.0146, p=0.00461 (cis)
Metabolite levels (leucylalanine) 1e-70 rs4363 2 GCST90299880 no MR -> candidate analysis
ACE protein levels 3e-53 rs4359 3 GCST90453172 no MR -> candidate analysis
Metabolite levels (serylleucine) 1e-48 rs4363 1 GCST90299888 no MR -> candidate analysis
Serum metabolite levels 2e-41 rs4343 9 GCST012020 no MR -> candidate analysis
Metabolite levels (alpha-glutamylglutamate) 6e-41 rs4363 1 GCST90299528 no MR -> candidate analysis
Aspartylphenylalanine-to-X-14450–phenylalanylleucine ratio 1e-37 rs4343 1 GCST90243899 no MR -> candidate analysis
Cerebrospinal fluid protein ACE levels 5e-37 rs4311 1 GCST90944935 no MR -> candidate analysis
Metabolite levels (aspartylphenylalanine) 2e-29 rs4363 1 GCST90299547 no MR -> candidate analysis
…and 43 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 2523 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
hypertensive disorder 0.806 common-variant locus no MR -> candidate analysis
renal tubular dysgenesis 0.894 established (curated) no MR -> candidate analysis
renal tubular dysgenesis of genetic origin 0.841 established (curated) no MR -> candidate analysis
cardiovascular disorder 0.649 common-variant locus no MR -> candidate analysis
diabetes mellitus 0.55 common-variant locus no MR -> candidate analysis
essential hypertension 0.755 common-variant locus no MR -> candidate analysis
neurodegenerative disease 0.5 common-variant locus no MR -> candidate analysis
type 2 diabetes mellitus 0.706 common-variant locus no MR -> candidate analysis
Alzheimer disease 0.81 common-variant locus no MR -> candidate analysis
congenital anomaly of kidney and urinary tract 0.426 established (curated) no MR -> candidate analysis
dementia 0.691 common-variant locus no MR -> candidate analysis
hereditary disease 0.682 established (curated) no MR -> candidate analysis
schizophrenia 0.614 common-variant locus MR: beta=-0.0453, p=0.0128 (cis)

Of the 13 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 17 known modulators (Angiotensin-converting enzyme)
gnomAD constraint pLI=7.6e-31, LOEUF=0.874 — LoF-tolerant
GWAS Catalog 73 unique SNPs / 146 rows
ClinVar 861 records; 1 pathogenic in sample of 30
PharmGKB/ClinPGx 27 clinical annotations across 31 drugs

Caveats declared by the tools

Sources

Provenance