CausalSentinel

Protein Dossier — LMAN2L (VIP36-like protein)

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
Bipolar disorder -0.499 0.0989 4.57e-07 Wald ratio 1 cis NA
Non-cancer illness code self-reported: hypertrophic cardiomyopathy (hcm or hocm) 1.07 0.254 2.60e-05 Wald ratio 1 cis NA
Schizophrenia -0.173 0.043 5.66e-05 Wald ratio 1 cis NA
Systemic lupus erythematosus -0.75 0.189 6.94e-05 Wald ratio 1 cis NA
Diastolic blood pressure automated reading 0.0364 0.00999 2.70e-04 Wald ratio 1 cis NA
PGC cross-disorder traits -0.164 0.0491 8.55e-04 Wald ratio 1 cis NA
Non-cancer illness code self-reported: high cholesterol 0.0805 0.0244 9.53e-04 Wald ratio 1 cis NA
HbA1C 0.0426 0.0137 0.00186 Wald ratio 1 cis NA
Juvenile idiopathic arthritis 0.656 0.216 0.00241 Wald ratio 1 cis NA
Diagnoses - main ICD10: G56 Mononeuropathies of upper limb 0.183 0.0621 0.00325 Wald ratio 1 cis NA
Red blood cell count 0.0274 0.00989 0.00562 Wald ratio 1 cis NA
Paget’s disease -0.645 0.242 0.00755 Wald ratio 1 cis NA
…and 107 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

31 association rows across 18 traits (27 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
Calcium levels 3e-51 rs72941253 1 GCST90018951 no MR -> candidate analysis
Height 3e-45 rs6746896 5 GCST90245848 MR: beta=-0.0186, p=0.126 (cis)
magnesium (Mg, mean, inv-norm transformed) 1e-25 rs968470 1 GCST90479679 no MR -> candidate analysis
VIP36-like protein levels (LMAN2L.8013.9.3) 4e-24 rs2271893 1 GCST90243343 no MR -> candidate analysis
VIP36-like protein levels 2e-23 rs2271893 2 GCST90427209 no MR -> candidate analysis
Serum levels of protein LMAN2L 9e-22 rs72809827 1 GCST90089985 no MR -> candidate analysis
magnesium (Mg, minimum, inv-norm transformed) 2e-20 rs968470 1 GCST90479680 no MR -> candidate analysis
magnesium (Mg, maximum, inv-norm transformed) 4e-15 rs968470 1 GCST90479678 no MR -> candidate analysis
Aspartate aminotransferase levels 4e-13 rs968470 1 GCST90662897 no MR -> candidate analysis
Blood protein levels 2e-12 rs2271893 1 GCST006585 no MR -> candidate analysis
Forced expiratory volume (baseline) 4e-11 rs189255944 1 GCST90565844 no MR -> candidate analysis
Bipolar disorder 5e-11 rs4619651 6 GCST012465 MR: beta=-0.499, p=4.57e-07 (cis)
…and 6 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 74 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
autosomal recessive non-syndromic intellectual disability 0.695 established (curated) no MR -> candidate analysis
bipolar disorder 0.841 common-variant locus MR: beta=-0.499, p=4.57e-07 (cis)
intellectual disability, autosomal dominant 52 0.608 established (curated) no MR -> candidate analysis
intellectual developmental disorder, autosomal dominant 69 0.547 established (curated) no MR -> candidate analysis
schizophrenia 0.508 common-variant locus MR: beta=-0.173, p=5.66e-05 (cis)
major depressive disorder 0.508 common-variant locus MR: beta=-0.0656, p=0.445 (cis)
attention deficit-hyperactivity disorder 0.508 common-variant locus no MR -> candidate analysis
autism spectrum disorder 0.508 common-variant locus no MR -> candidate analysis
anorexia nervosa 0.508 common-variant locus MR: beta=-0.186, p=0.106 (cis)
obsessive-compulsive disorder 0.508 common-variant locus no MR -> candidate analysis
Tourette syndrome 0.508 common-variant locus no MR -> candidate analysis
bipolar I disorder 0.504 common-variant locus no MR -> candidate analysis
placental abruption 0.455 common-variant locus no MR -> candidate analysis
neurodevelopmental disorder 0.195 established (curated) no MR -> candidate analysis
hyperphosphatasia-intellectual disability syndrome 0.195 established (curated) no MR -> candidate analysis

Of the 15 rows above, 11 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=2.1e-07, LOEUF=0.918 — LoF-tolerant
GWAS Catalog 33 unique SNPs / 66 rows
ClinVar 151 records; 3 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance