CausalSentinel

Protein Dossier — ALPP (Alkaline phosphatase, placental type)

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
Diagnoses - main ICD10: N20 Calculus of kidney and ureter -0.357 0.14 0.0106 Wald ratio 1 cis NA
Diagnoses - main ICD10: I48 Atrial fibrillation and flutter 0.165 0.0647 0.0108 Wald ratio 1 cis NA
Diagnoses - main ICD10: K44 Diaphragmatic hernia -0.192 0.0784 0.0142 Wald ratio 1 cis NA
Diagnoses - main ICD10: H25 Senile cataract 0.177 0.0771 0.0214 Wald ratio 1 cis NA
Alcohol intake frequency 0.0271 0.0119 0.022 Wald ratio 1 cis NA
Forearm bone mineral density -0.114 0.0514 0.0261 Wald ratio 1 cis NA
Non-cancer illness code self-reported: osteoporosis -0.17 0.0768 0.0271 Wald ratio 1 cis NA
Hirschsprung’s disease -0.902 0.414 0.0293 Wald ratio 1 cis NA
Intracranial volume -1.42e+04 6.63e+03 0.0318 Wald ratio 1 cis NA
Non-cancer illness code self-reported: hayfever or allergic rhinitis 0.062 0.031 0.0458 Wald ratio 1 cis NA
Non-cancer illness code self-reported: osteoarthritis 0.0501 0.0255 0.0497 Wald ratio 1 cis NA
Forced vital capacity (FVC) -0.0125 0.00658 0.0573 Wald ratio 1 cis NA
…and 51 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

5 association rows across 3 traits (5 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
Alkaline phosphatase, placental type levels 1e-68 rs2853378 1 GCST90246488 no MR -> candidate analysis
ALPP protein levels 9e-16 rs201578205 3 GCST90468286 no MR -> candidate analysis
Refractive error 2e-10 rs1130335 1 GCST90104407 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 397 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
ovarian disorder 0.412 common-variant locus no MR -> candidate analysis
fallopian tube disorder 0.412 common-variant locus no MR -> candidate analysis
alcohol drinking 0.204 common-variant locus no MR -> candidate analysis
male reproductive organ cancer 0.183 common-variant locus no MR -> candidate analysis
transient ischemic attack 0.146 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 (Alkaline phosphatase, placental type)
gnomAD constraint pLI=7.9e-11, LOEUF=1 — LoF-tolerant
GWAS Catalog 103 unique SNPs / 212 rows
ClinVar 185 records; 2 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance