CausalSentinel

Protein Dossier — ACP2 (Lysosomal acid phosphatase)

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
Systemic lupus erythematosus -0.576 0.178 0.00123 Wald ratio 1 trans NA
Red blood cell count 0.027 0.00838 0.00125 Wald ratio 1 trans NA
Primary sclerosing cholangitis -0.318 0.114 0.00542 Wald ratio 1 trans NA
Diagnoses - main ICD10: R04 Haemorrhage from respiratory passages 0.272 0.101 0.00687 Wald ratio 1 trans NA
Serum cystatin C (eGFRcys) 0.0171 0.00686 0.0124 Wald ratio 1 trans NA
Diagnoses - main ICD10: C50 Malignant neoplasm of breast 0.157 0.063 0.013 Wald ratio 1 trans NA
Nucleus accumbens volume 10.3 4.18 0.0138 Wald ratio 1 trans NA
Mean cell volume -0.234 0.0983 0.0175 Wald ratio 1 trans NA
Subjective well being -0.0267 0.0114 0.0196 Wald ratio 1 trans NA
Underlying (primary) cause of death: ICD10: E85.4 Organ-limited amyloidosis 1.56 0.676 0.0213 Wald ratio 1 trans NA
Non-cancer illness code self-reported: retinal detachment 0.279 0.126 0.0267 Wald ratio 1 trans NA
Alcohol intake frequency 0.0303 0.0139 0.0292 Wald ratio 1 trans NA
…and 101 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

38 association rows across 34 traits (38 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
high density lipoprotein cholesterol (HDLC, mean, inv-norm t 5e-69 rs75393320 1 GCST90479632 no MR -> candidate analysis
high density lipoprotein cholesterol (HDLC, maximum, inv-nor 1e-63 rs75393320 1 GCST90479631 no MR -> candidate analysis
HDL cholesterol 8e-45 rs75393320 1 GCST006611 MR: beta=-0.0244, p=0.182 (trans)
Free Cholesterol to Total Lipids in Large VLDL percentage 4e-38 rs4752973 1 GCST90501163 no MR -> candidate analysis
Metabolic syndrome 5e-34 rs4752973 1 GCST90444487 no MR -> candidate analysis
Triglycerides to Total Lipids in Large VLDL percentage 2e-23 rs4647757 1 GCST90501169 no MR -> candidate analysis
Total cholesterol to total lipids ratio in large HDL 2e-21 rs7109203 1 GCST90301996 no MR -> candidate analysis
HDL cholesterol levels x short total sleep time interaction 2e-21 rs901746 1 GCST009367 no MR -> candidate analysis
Lymphocyte-to-monocyte ratio 3e-20 rs4752973 1 GCST90056181 no MR -> candidate analysis
HDL cholesterol levels x long total sleep time interaction ( 5e-20 rs901746 1 GCST009368 no MR -> candidate analysis
Cholesteryl Esters to Total Lipids in Small LDL percentage 1e-17 rs7129661 1 GCST90501249 no MR -> candidate analysis
CFP protein levels 1e-17 rs4647757 1 GCST90468731 no MR -> candidate analysis
…and 22 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 3146 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
clear cell renal carcinoma 0.378 common-variant locus no MR -> candidate analysis
hypertensive disorder 0.361 common-variant locus no MR -> candidate analysis
kidney failure 0.305 common-variant locus no MR -> candidate analysis
COVID-19 0.283 common-variant locus no MR -> candidate analysis
xeroderma pigmentosum group E 0.278 established (curated) no MR -> candidate analysis
venous thromboembolism 0.265 common-variant locus no MR -> candidate analysis
glaucoma 0.261 common-variant locus MR: beta=-0.0733, p=0.39 (trans)
metabolic syndrome 0.259 common-variant locus no MR -> candidate analysis
health study participation 0.256 common-variant locus no MR -> candidate analysis
Menorrhagia 0.243 common-variant locus no MR -> candidate analysis
physical activity 0.206 common-variant locus no MR -> candidate analysis
hereditary disease 0.195 established (curated) no MR -> candidate analysis
metabolic dysfunction-associated steatotic liver disease 0.156 common-variant locus no MR -> candidate analysis
mathematical ability 0.112 common-variant locus no MR -> candidate analysis
eye injury 0.107 common-variant locus MR: beta=-0.166, p=0.266 (trans)

Of the 15 rows above, 13 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 not available — no ChEMBL target (undrugged)
gnomAD constraint pLI=8.4e-08, LOEUF=0.848 — LoF-tolerant
GWAS Catalog 142 unique SNPs / 349 rows
ClinVar 97 records; 2 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance