CausalSentinel

Protein Dossier — MAN1C1 (Mannosyl-oligosaccharide 1,2-alpha-mannosidase IC)

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
ER-negative Breast cancer (Combined Oncoarray; iCOGS; GWAS meta analysis) 0.241 0.0721 8.18e-04 Wald ratio 1 cis NA
Non-cancer illness code self-reported: diverticular disease or diverticulitis 0.302 0.0986 0.00219 Wald ratio 1 cis NA
Non-cancer illness code self-reported: emphysema or chronic bronchitis 0.254 0.0946 0.00736 Wald ratio 1 cis NA
Happiness 0.0439 0.0173 0.011 Wald ratio 1 cis NA
Diagnoses - main ICD10: C50 Malignant neoplasm of breast -0.432 0.174 0.0131 Wald ratio 1 cis NA
Diagnoses - main ICD10: I48 Atrial fibrillation and flutter 0.254 0.104 0.0142 Wald ratio 1 cis NA
Ovarian cancer -0.196 0.082 0.0168 Wald ratio 1 cis NA
Non-cancer illness code self-reported: migraine -0.203 0.0999 0.0421 Wald ratio 1 cis NA
Depressive symptoms 0.0465 0.0233 0.0455 Wald ratio 1 cis NA
Diagnoses - main ICD10: M17 Gonarthrosis [arthrosis of knee] -0.261 0.133 0.05 Wald ratio 1 cis NA
Breast cancer (Combined Oncoarray; iCOGS; GWAS meta analysis) 0.0767 0.0395 0.0522 Wald ratio 1 cis NA
Amyotrophic lateral sclerosis -0.196 0.104 0.0597 Wald ratio 1 cis NA
…and 69 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

28 association rows across 23 traits (23 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
Mannosyl-oligosaccharide 1,2-alpha-mannosidase IC levels 7e-78 rs2072748 3 GCST90248374 no MR -> candidate analysis
Height 5e-63 rs807250 2 GCST90245848 no MR -> candidate analysis
Circulating ASAH2 levels 2e-51 rs11247595 1 GCST90859724 no MR -> candidate analysis
ASAH2 protein levels 6e-46 rs12032634 1 GCST90468374 no MR -> candidate analysis
Serum levels of protein MAN1C1 4e-21 rs12032634 1 GCST90087434 no MR -> candidate analysis
ICAM4 protein levels 1e-20 rs181721303 2 GCST90469501 no MR -> candidate analysis
EXTL1 protein levels 1e-20 rs1971442 2 GCST90469161 no MR -> candidate analysis
Circulating IL1RL2 levels 6e-19 rs11247595 1 GCST90859762 no MR -> candidate analysis
Hematological traits (multi-trait analysis) 1e-18 rs2982315 1 GCST90838669 no MR -> candidate analysis
EGFL7 protein levels 8e-18 rs78945826 1 GCST90469083 no MR -> candidate analysis
Blood protein levels 9e-14 rs3767879 1 GCST006585 no MR -> candidate analysis
Circulating IL18R1 levels 9e-14 rs11247595 1 GCST90859873 no MR -> candidate analysis
…and 11 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 86 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
placenta praevia 0.404 common-variant locus no MR -> candidate analysis
influenza A (H1N1) 0.396 common-variant locus no MR -> candidate analysis
diabetes mellitus 0.362 common-variant locus no MR -> candidate analysis
type 2 diabetes mellitus 0.362 common-variant locus no MR -> candidate analysis
Hypercholesterolemia 0.308 common-variant locus no MR -> candidate analysis
Crohn disease 0.066 common-variant locus no MR -> candidate analysis
preeclampsia 0.04 common-variant locus no MR -> candidate analysis

Of the 7 rows above, 7 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=1.3e-11, LOEUF=0.869 — LoF-tolerant
GWAS Catalog 84 unique SNPs / 168 rows
ClinVar 123 records; 0 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance