Protein Dossier — LGMN (Legumain)
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 vital capacity (FVC) |
0.0421 |
0.0121 |
5.13e-04 |
Wald ratio |
1 |
cis |
NA |
| Forced expiratory volume in 1-second (FEV1) |
0.0437 |
0.0128 |
6.40e-04 |
Wald ratio |
1 |
cis |
NA |
| Non-cancer illness code self-reported: retinal detachment |
0.459 |
0.168 |
0.00649 |
Wald ratio |
1 |
cis |
NA |
| Fractured or broken bones in last 5 years |
0.104 |
0.0416 |
0.0121 |
Wald ratio |
1 |
cis |
NA |
| Birth weight |
0.053 |
0.0243 |
0.0289 |
Wald ratio |
1 |
cis |
NA |
| Non-cancer illness code self-reported: high cholesterol |
-0.0915 |
0.0439 |
0.0372 |
Wald ratio |
1 |
cis |
NA |
| Breast cancer (Combined Oncoarray; iCOGS; GWAS meta analysis) |
0.0858 |
0.0425 |
0.0436 |
Wald ratio |
1 |
cis |
NA |
| ER-positive Breast cancer (Combined Oncoarray; iCOGS; GWAS meta analysis) |
0.101 |
0.0507 |
0.0463 |
Wald ratio |
1 |
cis |
NA |
| Diagnoses - main ICD10: M54 Dorsalgia |
-0.325 |
0.164 |
0.0477 |
Wald ratio |
1 |
cis |
NA |
| Squamous cell lung cancer |
-0.32 |
0.165 |
0.0528 |
Wald ratio |
1 |
cis |
NA |
| Sodium in urine |
-0.0267 |
0.0145 |
0.0662 |
Wald ratio |
1 |
cis |
NA |
| Weight |
0.0236 |
0.013 |
0.0709 |
Wald ratio |
1 |
cis |
NA |
| …and 64 more outcomes (see JSON) |
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2. pQTL instrument availability (Tier-B probe)
| Dataset |
Trait |
Author |
Year |
prot-c-3622_33_4 |
LGMN |
Suhre K |
2019 |
3. GWAS Catalog results — traits with signal at this locus
55 association rows across 36 traits (53 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 LGMN levels |
2e-298 |
rs148659834 |
7 |
GCST90860643 |
no MR -> candidate analysis |
| LGMN protein levels |
2e-298 |
rs148659834 |
6 |
GCST90469766 |
no MR -> candidate analysis |
| LGMN/TIMP1 protein level ratio |
1e-278 |
rs117845934 |
1 |
GCST90315325 |
no MR -> candidate analysis |
| CD164/LGMN protein level ratio |
3e-262 |
rs117845934 |
1 |
GCST90313741 |
no MR -> candidate analysis |
| LGMN/SPINT2 protein level ratio |
3e-119 |
rs17128502 |
1 |
GCST90315324 |
no MR -> candidate analysis |
| TMEM106A protein levels |
3e-97 |
rs72701845 |
3 |
GCST90470886 |
no MR -> candidate analysis |
| Legumain levels |
1e-43 |
rs7157038 |
4 |
GCST90248281 |
no MR -> candidate analysis |
| Transmembrane protein 106A levels |
5e-38 |
rs72701845 |
3 |
GCST90249752 |
no MR -> candidate analysis |
| ASAH1 protein levels |
5e-33 |
rs72701845 |
1 |
GCST90468373 |
no MR -> candidate analysis |
| Beta-mannosidase levels |
3e-31 |
rs35792499 |
2 |
GCST90246709 |
no MR -> candidate analysis |
| CD164 protein levels |
6e-27 |
rs72701845 |
1 |
GCST90468602 |
no MR -> candidate analysis |
| Legumain (analyte X3622.33) levels |
4e-22 |
rs4904977 |
1 |
GCST90425835 |
no MR -> candidate analysis |
| …and 24 more traits (see JSON) |
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|
4. Phenome map — where this gene is a genetic locus, vs. where MR exists
Top diseases by Open Targets association (of 1008 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 |
| crush injury |
0.49 |
— |
common-variant locus |
no MR -> candidate analysis |
| Alzheimer disease |
0.419 |
— |
common-variant locus |
no MR -> candidate analysis |
| post term pregnancy |
0.419 |
— |
common-variant locus |
no MR -> candidate analysis |
| rosacea |
0.419 |
— |
common-variant locus |
no MR -> candidate analysis |
| pathological myopia |
0.182 |
— |
established (curated) |
no MR -> candidate analysis |
| myopia |
0.182 |
— |
established (curated) |
no MR -> candidate analysis |
Of the 6 rows above, 6 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 |
0 known modulators (Legumain) |
| gnomAD constraint |
pLI=7.1e-08, LOEUF=0.836 — LoF-tolerant |
| GWAS Catalog |
114 unique SNPs / 196 rows |
| ClinVar |
135 records; 0 pathogenic in sample of 30 |
| PharmGKB/ClinPGx |
no annotations |
phenome — Top 30 of 1008 associated diseases by overall score. genetic_association aggregates GWAS common-variant AND rare-variant evidence. These are ASSOCIATIONS (loci), not causal claims.chembl — ChEMBL target matched by text search on ‘LGMN’ and resolved to ‘Legumain’ — confirm this is the intended target.clinvar — Pathogenic count is over the 30 record(s) retrieved, NOT over all 135 ClinVar records for this gene; it is a sample, not a rate.pharmgkb — No PharmGKB/ClinPGx clinical annotations (gene may not be a pharmacogene).gwas_traits — Top 20 of 36 traits by best p-value, aggregated from 55 association rows. These are GWAS ASSOCIATIONS (loci), not causal claims; mapped genes at a locus are not necessarily the effector gene.
Sources
uniprot: https://www.uniprot.org/uniprotkb/Q99538 — UniProt release 2026_02 (10-June-2026)mr_outcomes: https://epigraphdb.org/pqtl/ — EpiGraphDB pQTL MR (Zheng et al., Nat Genet 2020) — pre-computed two-sample MR; retrieved, not computed by this agent; EpiGraphDB build 1.0, pQTL dataset v3.0phenome: https://platform.opentargets.org/target/ENSG00000100600/associations — Open Targets data release 26.06chembl: https://www.ebi.ac.uk/chembl/target_report_card/CHEMBL4244/ — ChEMBL_37 (released 2026-05-01)gnomad: https://gnomad.broadinstitute.org/gene/LGMN — gnomAD constraint via GraphQL API (reference genome GRCh38)gwas: https://www.ebi.ac.uk/gwas/genes/LGMN — GWAS Catalog REST (live; release not exposed by this endpoint)clinvar: https://www.ncbi.nlm.nih.gov/clinvar/?term=LGMN%5Bgene%5D — ClinVar build Build260809-1055.1gwas_traits: https://www.ebi.ac.uk/gwas/genes/LGMN — GWAS Catalog search API (live; release not exposed)
Provenance
- Generated: 2026-08-14T03:31:56 · Tier: A
- Fully mechanical: every cell above is rendered from tool return values. No language model wrote any part of this dossier.
- MR estimates, where present, are retrieved from published work (EpiGraphDB pQTL, Zheng et al. Nat Genet 2020); nothing is computed here.
- Tool errors this run: none