CausalSentinel

Protein Dossier — NPTX1 (Neuronal pentraxin-1)

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
Body mass index (BMI) -0.0368 0.00814 6.10e-06 Wald ratio 1 cis NA
Weight -0.0319 0.00719 9.33e-06 Wald ratio 1 cis NA
Cancer code self-reported: small intestine or small bowel cancer 0.681 0.205 8.85e-04 Wald ratio 1 cis NA
Diagnoses - main ICD10: I84 Haemorrhoids -0.187 0.0634 0.00314 Wald ratio 1 cis NA
Serum creatinine (eGFRcrea) 0.00895 0.00311 0.00404 Wald ratio 1 cis NA
Non-cancer illness code self-reported: joint disorder 0.232 0.0953 0.0149 Wald ratio 1 cis NA
Non-cancer illness code self-reported: hypertension -0.0347 0.0144 0.0158 Wald ratio 1 cis NA
Systolic blood pressure automated reading -0.02 0.00833 0.0167 Wald ratio 1 cis NA
Neuroticism 0.0272 0.0117 0.0196 Wald ratio 1 cis NA
Diagnoses - main ICD10: R07 Pain in throat and chest -0.0928 0.0399 0.0202 Wald ratio 1 cis NA
Diagnoses - main ICD10: N40 Hyperplasia of prostate -0.256 0.111 0.0212 Wald ratio 1 cis NA
Diagnoses - main ICD10: R10 Abdominal and pelvic pain 0.0828 0.0363 0.0224 Wald ratio 1 cis NA
…and 104 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

36 association rows across 22 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
Cerebrospinal fluid protein KIAA0232 levels 3e-309 rs144443274 1 GCST90940117 no MR -> candidate analysis
NPTX1 protein levels 2e-112 rs28670551 5 GCST90470078 no MR -> candidate analysis
Cerebrospinal fluid protein NPTX1 levels 8e-69 rs144443274 1 GCST90944838 no MR -> candidate analysis
Neuronal pentraxin-1 levels 2e-38 rs144443274 1 GCST90248720 no MR -> candidate analysis
SGSH protein levels 1e-32 rs12949110 2 GCST90470615 no MR -> candidate analysis
Blood protein levels 2e-18 rs62067239 1 GCST006585 no MR -> candidate analysis
Body mass index 2e-17 rs144443274 6 GCST90301650 MR: beta=-0.0368, p=6.10e-06 (cis)
Moyamoya disease 8e-17 rs28670551 4 GCST90310003 no MR -> candidate analysis
Personality traits or cognitive traits (multivariate analysi 2e-14 rs144443274 1 GCST90270074 no MR -> candidate analysis
BMI and adiposity (confirmatory factor analysis Factor 7) 2e-12 rs144443274 1 GCST90309342 no MR -> candidate analysis
Leg fat percentage left (UKB data field 23115) 3e-12 rs144443274 1 GCST90468174 no MR -> candidate analysis
Thalamus volume 1e-10 rs12600720 1 GCST009669 no MR -> candidate analysis
…and 10 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 177 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
spinocerebellar ataxia 50 0.806 established (curated) no MR -> candidate analysis
Irritability 0.755 common-variant locus no MR -> candidate analysis
hereditary disease 0.559 established (curated) no MR -> candidate analysis
morbid obesity 0.464 common-variant locus no MR -> candidate analysis
arthropathy 0.19 common-variant locus no MR -> candidate analysis
injury 0.189 common-variant locus no MR -> candidate analysis
Abnormality of the skeletal system 0.169 common-variant locus no MR -> candidate analysis
Moyamoya disease 0.094 common-variant locus no MR -> candidate analysis
smoking initiation 0.088 common-variant locus no MR -> candidate analysis
type 2 diabetes mellitus 0.088 common-variant locus no MR -> candidate analysis
Blindness 0.065 common-variant locus no MR -> candidate analysis
metabolic syndrome 0.048 common-variant locus no MR -> candidate analysis

Of the 12 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=0.98, LOEUF=0.503 — LoF-INTOLERANT
GWAS Catalog 51 unique SNPs / 101 rows
ClinVar 92 records; 1 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance