CausalSentinel

Protein Dossier — LRRC4C (Leucine-rich repeat-containing protein 4C)

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
Depressive symptoms 0.0803 0.0292 0.00596 Wald ratio 1 cis NA
Diagnoses - main ICD10: G56 Mononeuropathies of upper limb 0.28 0.102 0.00624 Wald ratio 1 cis NA
Non-cancer illness code self-reported: anxiety or panic attacks 0.272 0.117 0.0207 Wald ratio 1 cis NA
Non-cancer illness code self-reported: hypertension -0.0724 0.0323 0.025 Wald ratio 1 cis NA
Hearing difficulty or problems: Yes 0.0625 0.0286 0.0287 Wald ratio 1 cis NA
Mean platelet volume -0.0175 0.00803 0.0291 Wald ratio 1 cis NA
Myocardial infarction 0.158 0.0784 0.0443 Wald ratio 1 cis NA
HOMA-IR -0.0606 0.0307 0.0481 Wald ratio 1 cis NA
Non-cancer illness code self-reported: osteoporosis -0.457 0.239 0.0558 Wald ratio 1 cis NA
Microalbuminuria -0.285 0.153 0.0633 Wald ratio 1 cis NA
Non-cancer illness code self-reported: hyperthyroidism or thyrotoxicosis 0.286 0.158 0.0705 Wald ratio 1 cis NA
Non-cancer illness code self-reported: enlarged prostate 0.22 0.123 0.0729 Wald ratio 1 cis NA
…and 90 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

168 association rows across 114 traits (101 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
Bone mineral density mean 1e-300 rs148727583 4 GCST90321120 no MR -> candidate analysis
Refractive error 4e-214 rs11602008 7 GCST90841196 no MR -> candidate analysis
Myopia 9e-66 rs11606250 2 GCST003997 no MR -> candidate analysis
Spherical equivalent 9e-51 rs11602008 4 GCST010378 no MR -> candidate analysis
Primary angle-closure glaucoma (MTAG) 1e-50 rs11606250 1 GCST90832185 no MR -> candidate analysis
Myopia (age of diagnosis) 5e-49 rs11602008 1 GCST006290 no MR -> candidate analysis
Spherical equivalent or myopia (age of diagnosis) 2e-44 rs11602008 1 GCST006291 no MR -> candidate analysis
Refractive error (autorefraction measured) 1e-42 rs11602008 1 GCST90244789 no MR -> candidate analysis
Age-related eyesight deterioration (confirmatory factor anal 5e-33 rs11602008 1 GCST90309361 no MR -> candidate analysis
Age started wearing glasses (UKB data field 2217) 6e-31 rs11602008 1 GCST90468156 no MR -> candidate analysis
Smoking initiation 2e-30 rs10837649 9 GCST90243985 no MR -> candidate analysis
Drinks per week 4e-28 rs2956781 4 GCST90243989 no MR -> candidate analysis
…and 102 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 115 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 0.671 common-variant locus no MR -> candidate analysis
smoking initiation 0.652 common-variant locus no MR -> candidate analysis
urolithiasis 0.649 common-variant locus no MR -> candidate analysis
mathematical ability 0.621 common-variant locus no MR -> candidate analysis
placenta praevia 0.615 common-variant locus no MR -> candidate analysis
myopia 0.598 common-variant locus no MR -> candidate analysis
Parkinson disease 0.538 common-variant locus no MR -> candidate analysis
liver disorder 0.537 common-variant locus no MR -> candidate analysis
cervical carcinoma 0.529 common-variant locus no MR -> candidate analysis
Hypermetropia 0.526 common-variant locus no MR -> candidate analysis
refractive error 0.524 common-variant locus no MR -> candidate analysis
gastroduodenitis 0.52 common-variant locus no MR -> candidate analysis
smoking behavior 0.512 common-variant locus no MR -> candidate analysis
systemic lupus erythematosus 0.485 common-variant locus MR: beta=-0.595, p=0.0771 (cis)
autoimmune disorder of musculoskeletal system 0.485 common-variant locus no MR -> candidate analysis

Of the 15 rows above, 14 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=0.313 — LoF-INTOLERANT
GWAS Catalog 122 unique SNPs / 245 rows
ClinVar 93 records; 3 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance