CausalSentinel

Protein Dossier — LRRN1 (Leucine-rich repeat and calponin homology domain-containing protein 4)

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 expiratory volume in 1-second (FEV1) 0.0367 0.00891 3.85e-05 Wald ratio 1 cis NA
Weight 0.0247 0.00909 0.00654 Wald ratio 1 cis NA
Bipolar disorder 0.267 0.0988 0.00678 Wald ratio 1 cis NA
Forced vital capacity (FVC) 0.0225 0.00845 0.00786 Wald ratio 1 cis NA
Non-cancer illness code self-reported: bone disorder 0.4 0.151 0.00813 Wald ratio 1 cis NA
Thyroid cancer -0.86 0.36 0.017 Wald ratio 1 cis NA
Rheumatoid arthritis -0.159 0.0695 0.0218 Wald ratio 1 cis NA
Non-cancer illness code self-reported: vaginal prolapse or uterine prolapse 0.25 0.11 0.0231 Wald ratio 1 cis NA
Type 2 diabetes -0.198 0.0885 0.0251 Wald ratio 1 cis NA
Diagnoses - main ICD10: M17 Gonarthrosis [arthrosis of knee] -0.203 0.0918 0.0267 Wald ratio 1 cis NA
Glioma 0.378 0.18 0.0357 Wald ratio 1 cis NA
Internalizing problems -0.204 0.098 0.0376 Wald ratio 1 cis NA
…and 86 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

15 association rows across 8 traits (12 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 LRRN1 levels 2e-55 rs543062071 2 GCST90860552 no MR -> candidate analysis
LRRN1 protein levels 3e-55 rs7648844 7 GCST90469806 no MR -> candidate analysis
Gut microbial network clusters (SkyBlue (at 3 months) x Any 8e-9 rs17037086 1 GCST90569272 no MR -> candidate analysis
Adventurousness 1e-8 rs6807234 1 GCST007324 no MR -> candidate analysis
Gut microbial network clusters (Salmon (at 1 year) x Any Bre 1e-8 rs62247368 1 GCST90569461 no MR -> candidate analysis
beta-nerve growth factor levels 7e-6 rs66515854 1 GCST004421 no MR -> candidate analysis
5-bromotryptophan levels in elite athletes 7e-6 rs17037518 1 GCST90133535 no MR -> candidate analysis
Waist circumference adjusted for body mass index 8e-6 rs767244068 1 GCST008161 no MR -> candidate analysis

4. Phenome map — where this gene is a genetic locus, vs. where MR exists

Top diseases by Open Targets association (of 135 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
alcohol drinking 0.682 common-variant locus no MR -> candidate analysis
placenta praevia 0.623 common-variant locus no MR -> candidate analysis
mathematical ability 0.57 common-variant locus no MR -> candidate analysis
tooth disorder 0.523 common-variant locus no MR -> candidate analysis
risk-taking behaviour 0.516 common-variant locus no MR -> candidate analysis
smoking initiation 0.512 common-variant locus no MR -> candidate analysis
methicillin-resistant staphylococcus aureus infectious disease 0.51 common-variant locus no MR -> candidate analysis
response to antihypertensive drug 0.419 common-variant locus no MR -> candidate analysis
intervertebral disk degenerative disorder 0.408 common-variant locus no MR -> candidate analysis
substance abuse 0.408 common-variant locus no MR -> candidate analysis
attention deficit-hyperactivity disorder 0.408 common-variant locus no MR -> candidate analysis
mental disorder 0.404 common-variant locus no MR -> candidate analysis
hemorrhage 0.396 common-variant locus no MR -> candidate analysis
complication 0.396 common-variant locus no MR -> candidate analysis
type 2 diabetes mellitus 0.394 common-variant locus no MR -> candidate analysis

Of the 15 rows above, 15 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=0.99, LOEUF=0.478 — LoF-INTOLERANT
GWAS Catalog 74 unique SNPs / 148 rows
ClinVar 206 records; 3 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance