CausalSentinel

Protein Dossier — LAMC2 (Laminin subunit gamma-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
Diastolic blood pressure automated reading 0.0153 0.00446 6.17e-04 Wald ratio 1 cis NA
Pulse rate 0.0244 0.00771 0.00158 Wald ratio 1 cis NA
Height -0.0162 0.00569 0.00427 Wald ratio 1 cis NA
Parkinson’s disease 0.201 0.0732 0.0059 Wald ratio 1 cis NA
Subjective well being -0.0179 0.0065 0.00596 Wald ratio 1 cis NA
Age at menopause 0.0812 0.0325 0.0124 Wald ratio 1 cis NA
Diagnoses - main ICD10: D12 Benign neoplasm of colon rectum anus and anal canal -0.102 0.0408 0.0124 Wald ratio 1 cis NA
Forced expiratory volume in 1-second (FEV1) 0.00891 0.00377 0.0181 Wald ratio 1 cis NA
ER-positive Breast cancer (Combined Oncoarray; iCOGS; GWAS meta analysis) -0.032 0.0138 0.0205 Wald ratio 1 cis NA
Serum creatinine (eGFRcrea) -0.00374 0.00162 0.0214 Wald ratio 1 cis NA
Coronary heart disease 0.038 0.0166 0.0222 Wald ratio 1 cis NA
Urate 0.0244 0.0107 0.023 Wald ratio 1 cis NA
…and 97 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

48 association rows across 37 traits (40 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
Laminin subunit gamma-2 levels 3e-849 rs2276543 3 GCST90427862 no MR -> candidate analysis
Serum levels of protein LAMC2 2e-235 rs2276543 2 GCST90090762 no MR -> candidate analysis
Laminin subunit gamma-2 levels (LAMC2.9580.5.3) 4e-133 rs2276543 2 GCST90241739 no MR -> candidate analysis
Blood protein levels 2e-81 rs2276543 1 GCST006585 no MR -> candidate analysis
Morning person 1e-19 rs183708046 1 GCST007565 no MR -> candidate analysis
Circulating LAMA4 levels 8e-16 rs75394497 1 GCST90860668 no MR -> candidate analysis
Vitamin K-dependent protein C protein levels (SomaScan ID:95 6e-13 rs2276543 1 GCST90438417 no MR -> candidate analysis
Circulating GAL levels 6e-13 rs3120034 1 GCST90860395 no MR -> candidate analysis
NPL protein levels 7e-13 rs2276543 1 GCST90470072 no MR -> candidate analysis
GAL protein levels 7e-13 rs6703054 1 GCST90469300 no MR -> candidate analysis
acne vulgaris 4e-12 rs513398 3 GCST90092000 no MR -> candidate analysis
Acne (severe) 4e-12 rs10911268 1 GCST007234 no MR -> candidate analysis
…and 25 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 1114 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
Junctional epidermolysis bullosa, Herlitz type 0.839 established (curated) no MR -> candidate analysis
junctional epidermolysis bullosa Herlitz type 0.839 established (curated) no MR -> candidate analysis
epidermolysis bullosa, junctional 3B, severe 0.903 established (curated) no MR -> candidate analysis
epidermolysis bullosa, junctional 3A, intermediate 0.896 established (curated) no MR -> candidate analysis
junctional epidermolysis bullosa 0.911 established (curated) no MR -> candidate analysis
junctional epidermolysis bullosa, non-Herlitz type 0.823 established (curated) no MR -> candidate analysis
Generalized junctional epidermolysis bullosa, non-Herlitz type 0.608 established (curated) no MR -> candidate analysis
atrial fibrillation 0.704 common-variant locus no MR -> candidate analysis
acne 0.629 common-variant locus no MR -> candidate analysis
generalized junctional epidermolysis bullosa non-Herlitz type 0.608 established (curated) no MR -> candidate analysis
Abnormality of the skin 0.438 established (curated) no MR -> candidate analysis
colonic neoplasm 0.421 common-variant locus no MR -> candidate analysis
benign neoplasm of rectum 0.425 common-variant locus MR: beta=-0.102, p=0.0124 (cis)
alcohol drinking 0.414 common-variant locus no MR -> candidate analysis
prostate carcinoma 0.403 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 1 known modulators (Laminin)
gnomAD constraint pLI=2.6e-22, LOEUF=0.819 — LoF-tolerant
GWAS Catalog 77 unique SNPs / 151 rows
ClinVar 1357 records; 3 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance