CausalSentinel

Protein Dossier — AMBP (Protein AMBP)

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
Forced vital capacity (FVC) -0.0717 0.0181 7.18e-05 Wald ratio 1 trans NA
Forced expiratory volume in 1-second (FEV1) -0.0667 0.019 4.62e-04 Wald ratio 1 trans NA
Height -0.0855 0.0265 0.00126 Wald ratio 1 trans NA
Total cholesterol 0.136 0.0444 0.00223 Wald ratio 1 trans NA
Diagnoses - main ICD10: G47 Sleep disorders 0.531 0.175 0.00241 Wald ratio 1 trans NA
LDL cholesterol 0.131 0.0453 0.00389 Wald ratio 1 trans NA
Diagnoses - main ICD10: S66 Injury of muscle and tendon at wrist and hand level 0.775 0.278 0.00535 Wald ratio 1 trans NA
Ovarian cancer 0.317 0.119 0.00786 Wald ratio 1 trans NA
High grade serous ovarian cancer 0.368 0.142 0.0095 Wald ratio 1 trans NA
Sleep duration 0.0444 0.0172 0.00968 Wald ratio 1 trans NA
Non-cancer illness code self-reported: hayfever or allergic rhinitis 0.193 0.0751 0.0102 Wald ratio 1 trans NA
Femoral neck bone mineral density -0.178 0.0696 0.0106 Wald ratio 1 trans NA
…and 98 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

32 association rows across 25 traits (27 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
Circulating AMBP levels 1e-257 rs147941577 4 GCST90859790 no MR -> candidate analysis
AMBP protein levels 1e-200 rs147941577 3 GCST90468288 no MR -> candidate analysis
Hepatocyte nuclear factor 4-alpha levels 5e-153 rs141738059 1 GCST90247907 no MR -> candidate analysis
Sulfatase-modifying factor 1 levels 3e-69 rs141738059 1 GCST90249730 no MR -> candidate analysis
Tissue factor levels 2e-31 rs141738059 2 GCST90249810 no MR -> candidate analysis
Signaling lymphocytic activation molecule levels 1e-29 rs141738059 1 GCST90249563 no MR -> candidate analysis
Malignant T-cell-amplified sequence 1 levels 4e-29 rs141738059 1 GCST90248530 no MR -> candidate analysis
Calcipressin-1 levels 2e-27 rs141738059 1 GCST90246924 no MR -> candidate analysis
Alpha-1-microglobulin levels 5e-25 rs10817564 1 GCST90246393 no MR -> candidate analysis
Protein AMBP levels 3e-24 rs147941577 1 GCST90179222 no MR -> candidate analysis
Hepatocyte nuclear factor 4-alpha levels (HNF4A.10041.3.3) 1e-20 rs141738059 1 GCST90241401 no MR -> candidate analysis
Protein kinase C gamma type levels 4e-19 rs141738059 1 GCST90249013 no MR -> candidate analysis
…and 13 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 315 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
osteoarthritis 0.097 common-variant locus MR: beta=-0.62, p=0.0157 (trans)
osteoarthritis, knee 0.092 common-variant locus MR: beta=-0.349, p=0.0864 (trans)
arthropathy 0.087 common-variant locus no MR -> candidate analysis
Knee pain 0.08 common-variant locus no MR -> candidate analysis
osteoarthritis, hip 0.079 common-variant locus MR: beta=-0.62, p=0.0157 (trans)
placental retention 0.073 common-variant locus no MR -> candidate analysis
ovarian neoplasm 0.065 common-variant locus no MR -> candidate analysis
acute pancreatitis 0.063 common-variant locus no MR -> candidate analysis
response to clozapine 0.06 common-variant locus no MR -> candidate analysis
diabetes mellitus 0.051 common-variant locus no MR -> candidate analysis
type 2 diabetes mellitus 0.051 common-variant locus no MR -> candidate analysis
medical procedure 0.056 common-variant locus no MR -> candidate analysis
androgenetic alopecia 0.057 common-variant locus no MR -> candidate analysis
breast carcinoma 0.043 common-variant locus no MR -> candidate analysis
total knee arthroplasty 0.053 common-variant locus no MR -> candidate analysis

Of the 15 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 not available — no ChEMBL target (undrugged)
gnomAD constraint pLI=9.6e-11, LOEUF=1.05 — LoF-tolerant
GWAS Catalog 78 unique SNPs / 155 rows
ClinVar 120 records; 1 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance