CausalSentinel

Protein Dossier — MANEA (Glycoprotein endo-alpha-1,2-mannosidase)

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
Height -0.0125 0.00309 5.38e-05 Wald ratio 1 cis NA
Sodium in urine -0.00925 0.00253 2.61e-04 Wald ratio 1 cis NA
Serum creatinine (eGFRcrea) 0.00309 0.000952 0.00115 Wald ratio 1 cis NA
Diagnoses - main ICD10: I48 Atrial fibrillation and flutter -0.0739 0.0263 0.0049 Wald ratio 1 cis NA
Pancreatic cancer -0.135 0.0521 0.00941 Wald ratio 1 cis NA
Thalamus volume -17.4 6.71 0.00956 Wald ratio 1 cis NA
Diagnoses - main ICD10: M54 Dorsalgia -0.0539 0.0211 0.0107 Wald ratio 1 cis NA
Mean cell haemoglobin concentration -0.00928 0.00375 0.0133 Wald ratio 1 cis NA
HDL cholesterol 0.0125 0.00529 0.0178 Wald ratio 1 cis NA
Myocardial infarction -0.0255 0.0113 0.0235 Wald ratio 1 cis NA
Birth weight 0.00886 0.00398 0.0262 Wald ratio 1 cis NA
Femoral neck bone mineral density -0.0192 0.00865 0.0263 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

74 association rows across 62 traits (52 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
Glycoprotein endo-alpha-1,2-mannosidase levels 2e-1586 rs35772543 4 GCST90247717 no MR -> candidate analysis
Blood protein levels 8e-531 rs4413619 1 GCST006585 no MR -> candidate analysis
Glycoprotein endo-alpha-1,2-mannosidase levels (MANEA.8014.3 2e-518 rs80268500 3 GCST90241298 no MR -> candidate analysis
Serum levels of protein MANEA 2e-65 rs72928283 1 GCST90089986 no MR -> candidate analysis
Height 4e-43 rs13205436 2 GCST90245848 MR: beta=-0.0125, p=5.38e-05 (cis)
Circulating IL1RL2 levels 5e-37 rs13203302 1 GCST90859762 no MR -> candidate analysis
IL1RL2 protein levels 1e-34 rs13203302 1 GCST90469575 no MR -> candidate analysis
Glycoprotein endo-alpha-1,2-mannosidase level in Chronic kid 9e-24 rs4388292 1 GCST90238767 no MR -> candidate analysis
CTRC protein levels 2e-22 rs201630890 3 GCST90468906 no MR -> candidate analysis
MSR1 protein levels 4e-21 rs117820411 1 GCST90469950 no MR -> candidate analysis
Integrin a11b1 protein levels (SomaScan ID:8014-359) 2e-19 rs117820411 1 GCST90441133 no MR -> candidate analysis
CD300C protein levels 2e-17 rs13206900 1 GCST90468620 no MR -> candidate analysis
…and 50 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 118 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
preeclampsia 0.545 common-variant locus no MR -> candidate analysis
placental abruption 0.489 common-variant locus no MR -> candidate analysis
alcohol drinking 0.479 common-variant locus no MR -> candidate analysis
urolithiasis 0.479 common-variant locus no MR -> candidate analysis
Splenomegaly 0.418 common-variant locus no MR -> candidate analysis
disease of peritoneum 0.417 common-variant locus no MR -> candidate analysis
Abnormality of the gastrointestinal tract 0.417 common-variant locus no MR -> candidate analysis
chronic venous hypertension 0.393 common-variant locus no MR -> candidate analysis
complex regional pain syndrome 0.393 common-variant locus no MR -> candidate analysis
placenta praevia 0.361 common-variant locus no MR -> candidate analysis
obesity disorder 0.287 common-variant locus no MR -> candidate analysis
arthropathy 0.275 common-variant locus no MR -> candidate analysis
insomnia 0.261 common-variant locus no MR -> candidate analysis
dyshidrosis 0.206 common-variant locus no MR -> candidate analysis
schizophrenia 0.06 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=2.3e-06, LOEUF=0.949 — LoF-tolerant
GWAS Catalog 50 unique SNPs / 82 rows
ClinVar 99 records; 0 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance