CausalSentinel

Protein Dossier — AMY2B (Alpha-amylase 2B)

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
Eczema 0.148 0.0586 0.0114 Wald ratio 1 cis NA
Diagnoses - main ICD10: K40 Inguinal hernia 0.099 0.0404 0.0142 Wald ratio 1 cis NA
Diagnoses - main ICD10: I30 Acute pericarditis 0.593 0.247 0.0161 Wald ratio 1 cis NA
Neo-openness to experience 0.56 0.242 0.0207 Wald ratio 1 cis NA
Birth length -0.0693 0.0303 0.022 Wald ratio 1 cis NA
Non-cancer illness code self-reported: muscle or soft tissue injuries 0.166 0.0733 0.0231 Wald ratio 1 cis NA
Non-cancer illness code self-reported: pneumothorax 0.475 0.237 0.0453 Wald ratio 1 cis NA
Packed cell volume -0.133 0.0665 0.0455 Wald ratio 1 cis NA
Non-cancer illness code self-reported: hypertrophic cardiomyopathy (hcm or hocm) 0.613 0.308 0.0467 Wald ratio 1 cis NA
Diagnoses - main ICD10: M17 Gonarthrosis [arthrosis of knee] 0.0947 0.0478 0.0476 Wald ratio 1 cis NA
Schizophrenia -0.067 0.0339 0.0485 Wald ratio 1 cis NA
Weight 0.0124 0.00643 0.0543 Wald ratio 1 cis NA
…and 89 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

33 association rows across 14 traits (30 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
AMY1A or AMY1B or AMY1C protein levels 4e-264 rs113630435 5 GCST90468297 no MR -> candidate analysis
Alpha-amylase 1 levels 9e-166 rs78811372 5 GCST90246401 no MR -> candidate analysis
AMY2A protein levels 2e-151 rs150391908 5 GCST90468298 no MR -> candidate analysis
AMY2B protein levels 7e-134 rs150391908 4 GCST90468299 no MR -> candidate analysis
Alpha-amylase 2B levels 2e-51 rs79456674 3 GCST90246402 no MR -> candidate analysis
Blood protein levels 3e-36 rs17014913 1 GCST006585 no MR -> candidate analysis
Serum levels of protein AMY2B 8e-36 rs77729677 1 GCST90086269 no MR -> candidate analysis
Serum levels of protein AMY1A 4e-32 rs114922930 2 GCST90089921 no MR -> candidate analysis
CST5 protein levels 2e-19 rs113630435 1 GCST90468895 no MR -> candidate analysis
Circulating CST5 levels 2e-15 rs79456674 1 GCST90859850 no MR -> candidate analysis
Alpha-amylase 1 levels (AMY1A.7918.114.3) 4e-15 rs114922930 1 GCST90240245 no MR -> candidate analysis
Amylase levels 2e-8 rs60560048 1 GCST90429173 no MR -> candidate analysis
…and 2 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 83 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
dentures 0.182 common-variant locus no MR -> candidate analysis
osteoarthritis 0.081 common-variant locus MR: beta=-0.0906, p=0.254 (cis)
vertebral joint disorder 0.078 common-variant locus no MR -> candidate analysis
intelligence 0.065 common-variant locus no MR -> candidate analysis
Sensorineural hearing impairment 0.059 common-variant locus no MR -> candidate analysis
hearing loss disorder 0.059 common-variant locus no MR -> candidate analysis
chronic atrophic gastritis 0.055 common-variant locus no MR -> candidate analysis
polycythemia 0.044 common-variant locus no MR -> candidate analysis
hyperaldosteronism 0.042 common-variant locus no MR -> candidate analysis
lagophthalmos 0.041 common-variant locus no MR -> candidate analysis
placenta praevia 0.038 common-variant locus no MR -> candidate analysis
oropharynx cancer 0.034 common-variant locus no MR -> candidate analysis
osteoarthritis, hip 0.033 common-variant locus MR: beta=-0.0683, p=0.276 (cis)

Of the 13 rows above, 11 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=4e-23, LOEUF=1.31 — LoF-tolerant
GWAS Catalog 37 unique SNPs / 73 rows
ClinVar 156 records; 0 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance