CausalSentinel

Protein Dossier — MAN1A2 (Mannosyl-oligosaccharide 1,2-alpha-mannosidase IB)

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
Clear cell ovarian cancer -0.671 0.201 8.25e-04 Wald ratio 1 cis NA
Non-cancer illness code self-reported: depression 0.135 0.0438 0.00207 Wald ratio 1 cis NA
Diagnoses - main ICD10: H25 Senile cataract 0.303 0.103 0.00332 Wald ratio 1 cis NA
Sleep duration 0.0262 0.00947 0.00572 Wald ratio 1 cis NA
Non-cancer illness code self-reported: pulmonary embolism (with or without) dvt 0.281 0.103 0.00617 Wald ratio 1 cis NA
Schizophrenia 0.141 0.0533 0.00801 Wald ratio 1 cis NA
Non-cancer illness code self-reported: osteoarthritis 0.0961 0.0369 0.00919 Wald ratio 1 cis NA
Happiness -0.0345 0.0151 0.0218 Wald ratio 1 cis NA
Non-cancer illness code self-reported: hypothyroidism or myxoedema -0.143 0.0625 0.0219 Wald ratio 1 cis NA
Vascular or heart problems diagnosed by doctor: Angina 0.132 0.0599 0.0279 Wald ratio 1 cis NA
Non-cancer illness code self-reported: uterine fibroids -0.27 0.131 0.0391 Wald ratio 1 cis NA
Neuroticism -0.0381 0.019 0.0455 Wald ratio 1 cis NA
…and 67 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

53 association rows across 36 traits (48 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 IB levels 4e-110 rs35505705 5 GCST90248373 no MR -> candidate analysis
CD101 protein levels 8e-60 rs181883268 1 GCST90468596 no MR -> candidate analysis
Smoking initiation 1e-29 rs3820500 2 GCST90243985 no MR -> candidate analysis
Serum levels of protein MAN1A2 4e-24 rs111711406 2 GCST90090492 no MR -> candidate analysis
Circulating AGER levels 9e-23 rs7517996 2 GCST90859774 no MR -> candidate analysis
White blood cell count 2e-22 rs34368125 2 GCST90026503 no MR -> candidate analysis
Mannosyl-oligosaccharide 1,2-alpha-mannosidase IB levels (MA 1e-20 rs35505705 1 GCST90241874 no MR -> candidate analysis
Circulating GPC1 levels 8e-19 rs2359248 2 GCST90860018 no MR -> candidate analysis
TFF1/TFF2 protein level ratio 1e-17 rs58694069 1 GCST90315914 no MR -> candidate analysis
Educational attainment 1e-16 rs73002120 2 GCST90105038 no MR -> candidate analysis
Circulating BCAN levels 1e-16 rs6667019 2 GCST90859689 no MR -> candidate analysis
GPC1 protein levels 3e-16 rs4460623 1 GCST90469386 no MR -> candidate analysis
…and 24 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 292 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
insomnia 0.535 common-variant locus no MR -> candidate analysis
smoking initiation 0.534 common-variant locus no MR -> candidate analysis
injury 0.482 common-variant locus no MR -> candidate analysis
chronic primary adrenal insufficiency 0.466 common-variant locus no MR -> candidate analysis
familial glucocorticoid deficiency 0.466 common-variant locus no MR -> candidate analysis
skin disorder 0.456 common-variant locus no MR -> candidate analysis
type 2 diabetes mellitus 0.449 common-variant locus no MR -> candidate analysis
diabetic ketoacidosis 0.443 common-variant locus no MR -> candidate analysis
diabetes mellitus 0.432 common-variant locus no MR -> candidate analysis
alcohol drinking 0.356 common-variant locus no MR -> candidate analysis
mathematical ability 0.331 common-variant locus no MR -> candidate analysis
obstructive sleep apnea syndrome 0.299 common-variant locus no MR -> candidate analysis

Of the 12 rows above, 12 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=0.99, LOEUF=0.476 — LoF-INTOLERANT
GWAS Catalog 109 unique SNPs / 260 rows
ClinVar 73 records; 1 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance