CausalSentinel

Protein Dossier — MANSC4 (MANSC domain-containing protein 4)

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
Type 2 diabetes -0.0766 0.0229 8.20e-04 Wald ratio 1 cis NA
Lung adenocarcinoma -0.135 0.0475 0.00458 Wald ratio 1 cis NA
Forced vital capacity (FVC) 0.0103 0.00369 0.00513 Wald ratio 1 cis NA
Age at menopause -0.0785 0.0314 0.0124 Wald ratio 1 cis NA
Systolic blood pressure automated reading -0.0105 0.0046 0.022 Wald ratio 1 cis NA
Hearing difficulty or problems: Yes -0.018 0.0079 0.0227 Wald ratio 1 cis NA
Percent emphysema -0.0506 0.0229 0.0274 Wald ratio 1 cis NA
Pulse rate 0.0173 0.00794 0.0294 Wald ratio 1 cis NA
HbA1C -0.0138 0.00644 0.0318 Wald ratio 1 cis NA
Intracranial volume -7.72e+03 3.66e+03 0.0348 Wald ratio 1 cis NA
2hr glucose -0.0722 0.0345 0.0365 Wald ratio 1 cis NA
Non-cancer illness code self-reported: high cholesterol -0.0261 0.0125 0.0366 Wald ratio 1 cis NA
…and 88 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

14 association rows across 9 traits (14 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
MANSC domain-containing protein 4 levels 1e-569 rs9668702 3 GCST90248401 no MR -> candidate analysis
Blood protein levels 7e-200 rs11049131 1 GCST006585 no MR -> candidate analysis
MANSC domain-containing protein 4 levels (MANSC4.9578.263.3) 7e-117 rs36138811 1 GCST90241876 no MR -> candidate analysis
MANSC4 protein levels 2e-46 rs181298770 3 GCST90469848 no MR -> candidate analysis
Height 2e-37 rs10431270 1 GCST90245848 MR: beta=0.00565, p=0.304 (cis)
IMPG1 protein levels 6e-17 rs12368869 1 GCST90469612 no MR -> candidate analysis
Retinol-binding protein 2 protein levels (SomaScan ID:9578-2 2e-14 rs11049140 1 GCST90442055 no MR -> candidate analysis
Random glucose levels 1e-9 rs11049144 2 GCST90271558 no MR -> candidate analysis
Electrocardiogram morphology (amplitude at temporal datapoin 3e-8 rs11049136 1 GCST010796 no MR -> candidate analysis

4. Phenome map — where this gene is a genetic locus, vs. where MR exists

Top diseases by Open Targets association (of 92 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
type 2 diabetes mellitus 0.655 common-variant locus no MR -> candidate analysis
diabetes mellitus 0.637 common-variant locus no MR -> candidate analysis
osteoarthritis, hip 0.404 common-variant locus no MR -> candidate analysis
diabetic eye disease 0.361 common-variant locus no MR -> candidate analysis
osteoarthritis, knee 0.348 common-variant locus no MR -> candidate analysis
diabetic retinopathy 0.331 common-variant locus no MR -> candidate analysis
alopecia 0.315 common-variant locus no MR -> candidate analysis
diabetic neuropathy 0.249 common-variant locus no MR -> candidate analysis
osteoarthritis 0.248 common-variant locus MR: beta=0.0171, p=0.249 (cis)
musculoskeletal system disorder 0.212 common-variant locus no MR -> candidate analysis
cervical disk degenerative disorder 0.206 common-variant locus no MR -> candidate analysis
total hip arthroplasty 0.183 common-variant locus no MR -> candidate analysis
spinal stenosis 0.183 common-variant locus no MR -> candidate analysis
adverse effect 0.179 common-variant locus no MR -> candidate analysis
response to stimulus 0.179 common-variant locus no MR -> candidate analysis

Of the 15 rows above, 14 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=0.00015, LOEUF=1.6 — LoF-tolerant
GWAS Catalog 102 unique SNPs / 204 rows
ClinVar 80 records; 6 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance