CausalSentinel

Protein Dossier — NLGN2 (Neuroligin-2)

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: R14 Flatulence and related conditions 1.08 0.285 1.44e-04 Wald ratio 1 cis NA
Alcohol intake frequency 0.0882 0.0271 0.00115 Wald ratio 1 cis NA
Glioma -0.934 0.302 0.00202 Wald ratio 1 cis NA
Years of schooling -0.0714 0.0238 0.0027 Wald ratio 1 cis NA
Anorexia nervosa -0.659 0.223 0.00308 Wald ratio 1 cis NA
Height -0.0516 0.021 0.0142 Wald ratio 1 cis NA
Non-cancer illness code self-reported: enlarged prostate 0.284 0.12 0.0181 Wald ratio 1 cis NA
Diagnoses - main ICD10: R10 Abdominal and pelvic pain 0.176 0.0749 0.0187 Wald ratio 1 cis NA
Lung cancer -0.284 0.134 0.034 Wald ratio 1 cis NA
HbA1C -0.0528 0.025 0.0348 Wald ratio 1 cis NA
Diagnoses - main ICD10: K57 Diverticular disease of intestine 0.218 0.105 0.0383 Wald ratio 1 cis NA
Sleep duration 0.0291 0.0143 0.0422 Wald ratio 1 cis NA
…and 95 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

22 association rows across 13 traits (22 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
Sex hormone-binding globulin levels 1e-307 rs35386490 5 GCST90019518 no MR -> candidate analysis
Testosterone levels 7e-52 rs35386490 2 GCST90019520 no MR -> candidate analysis
Neuroligin-2 levels 2e-26 rs114576150 1 GCST90248690 no MR -> candidate analysis
SHBG protein levels 3e-26 rs3174744 1 GCST90470622 no MR -> candidate analysis
Uterine fibroids 2e-20 rs72842813 3 GCST90461958 no MR -> candidate analysis
Serum alkaline phosphatase levels 6e-20 rs35386490 1 GCST90019494 no MR -> candidate analysis
Mean platelet thrombocyte volume (UKB data field 30100) 2e-15 rs2241233 1 GCST90468087 no MR -> candidate analysis
Serum levels of protein NLGN2 3e-14 rs114576150 1 GCST90090815 no MR -> candidate analysis
Body fat percentage (adjusted for testosterone and SHBG) 1e-13 rs11078674 3 GCST90432180 no MR -> candidate analysis
Height (standard GWA) 4e-12 rs78355381 1 GCST90267284 no MR -> candidate analysis
Smoking cessation 3e-10 rs9900691 1 GCST90243988 no MR -> candidate analysis
Height (baseline) 2e-9 rs72842813 1 GCST90565843 no MR -> candidate analysis
…and 1 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 119 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
seasonal allergic rhinitis 0.215 common-variant locus no MR -> candidate analysis
alcohol drinking 0.215 common-variant locus no MR -> candidate analysis
autism 0.195 established (curated) MR: beta=0.178, p=0.364 (cis)
nervous system benign neoplasm 0.183 common-variant locus no MR -> candidate analysis
duodenal ulcer 0.148 common-variant locus no MR -> candidate analysis
smoking cessation 0.106 common-variant locus no MR -> candidate analysis

Of the 6 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 not available — no ChEMBL target (undrugged)
gnomAD constraint pLI=1, LOEUF=0.374 — LoF-INTOLERANT
GWAS Catalog 148 unique SNPs / 348 rows
ClinVar 303 records; 1 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance