CausalSentinel

Protein Dossier — NAGPA (N-acetylglucosamine-1-phosphodiester alpha-N-acetylglucosaminidase)

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
Hearing difficulty or problems: Yes -0.037 0.0135 0.00621 Wald ratio 1 cis NA
Potassium in urine -0.0168 0.00765 0.0281 Wald ratio 1 cis NA
Creatinine (enzymatic) in urine -0.015 0.00722 0.0377 Wald ratio 1 cis NA
Diagnoses - main ICD10: D12 Benign neoplasm of colon rectum anus and anal canal 0.116 0.0569 0.0413 Wald ratio 1 cis NA
Diagnoses - main ICD10: R35 Polyuria 0.202 0.0998 0.0434 Wald ratio 1 cis NA
Diagnoses - main ICD10: N20 Calculus of kidney and ureter 0.156 0.0774 0.0444 Wald ratio 1 cis NA
Depressive symptoms -0.0287 0.0144 0.0455 Wald ratio 1 cis NA
Diagnoses - main ICD10: N40 Hyperplasia of prostate 0.137 0.0688 0.0473 Wald ratio 1 cis NA
Diagnoses - main ICD10: R07 Pain in throat and chest -0.0675 0.036 0.061 Wald ratio 1 cis NA
Non-cancer illness code self-reported: hayfever or allergic rhinitis -0.0609 0.033 0.0651 Wald ratio 1 cis NA
Hirschsprung’s disease 0.563 0.32 0.0779 Wald ratio 1 cis NA
Neuroticism -0.0168 0.00957 0.0801 Wald ratio 1 cis NA
…and 69 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

26 association rows across 21 traits (23 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
NAGPA protein levels 4e-104 rs76557209 4 GCST90469996 no MR -> candidate analysis
N-acetylglucosamine-1-phosphodiester alpha-N-acetylglucosami 1e-74 rs12599777 2 GCST90248588 no MR -> candidate analysis
CPVL protein levels 6e-66 rs1045693 1 GCST90468848 no MR -> candidate analysis
Serum levels of protein NAGPA 7e-50 rs12599777 2 GCST90086611 no MR -> candidate analysis
N-acetylglucosamine-6-sulfatase (analyte X3616.3) levels 1e-46 rs12448709 1 GCST90425832 no MR -> candidate analysis
N-acetylglucosamine-1-phosphodiester alpha-N-acetylglucosami 1e-39 rs12599777 1 GCST90242004 no MR -> candidate analysis
Serum levels of protein HPSE 2e-37 rs1045693 1 GCST90089086 no MR -> candidate analysis
Cerebrospinal fluid protein NAGPA levels 5e-35 rs2340713 1 GCST90944447 no MR -> candidate analysis
TPP1 protein levels 2e-33 rs15951 1 GCST90470946 no MR -> candidate analysis
Circulating TPP1 levels 2e-31 rs15951 1 GCST90860671 no MR -> candidate analysis
Procollagen-lysine,2-oxoglutarate 5-dioxygenase 2 levels 8e-27 rs12448709 1 GCST90426832 no MR -> candidate analysis
Blood protein levels 2e-18 rs12599777 1 GCST006585 no MR -> candidate analysis
…and 9 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 64 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
Kawasaki disease 0.505 common-variant locus no MR -> candidate analysis
vasculitis 0.505 common-variant locus no MR -> candidate analysis
stuttering, familial persistent, 2 0.228 established (curated) no MR -> candidate analysis
chronic laryngitis 0.095 common-variant locus no MR -> candidate analysis
alcohol drinking 0.083 common-variant locus no MR -> candidate analysis
acute tonsillitis 0.054 common-variant locus no MR -> candidate analysis
pathological myopia 0.042 common-variant locus no MR -> candidate analysis
Peyronie disease 0.037 common-variant locus no MR -> candidate analysis
secondary malignant neoplasm 0.034 common-variant locus no MR -> candidate analysis
liver disorder 0.034 common-variant locus no MR -> candidate analysis
rhabdomyolysis 0.034 common-variant locus no MR -> candidate analysis
smoking initiation 0.032 common-variant locus no MR -> candidate analysis
systemic inflammatory response syndrome 0.031 common-variant locus no MR -> candidate analysis

Of the 13 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 0 known modulators (N-acetylglucosamine-1-phosphodiester alpha-N-acetylglucosaminidase)
gnomAD constraint pLI=4.9e-22, LOEUF=1.44 — LoF-tolerant
GWAS Catalog 71 unique SNPs / 142 rows
ClinVar 201 records; 1 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance