CausalSentinel

Protein Dossier — MANSC1 (MANSC domain-containing protein 1)

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
Diagnoses - main ICD10: R55 Syncope and collapse 0.213 0.064 8.85e-04 Wald ratio 1 cis NA
Transferrin Saturation 0.0816 0.0312 0.00902 Wald ratio 1 cis NA
Weight 0.0163 0.00656 0.0132 Wald ratio 1 cis NA
Diagnoses - main ICD10: I80 Phlebitis and thrombophlebitis 0.204 0.0896 0.0227 Wald ratio 1 cis NA
Non-cancer illness code self-reported: hyperthyroidism or thyrotoxicosis -0.238 0.111 0.0321 Wald ratio 1 cis NA
Diagnoses - main ICD10: M72 Fibroblastic disorders 0.179 0.0853 0.0359 Wald ratio 1 cis NA
Non-cancer illness code self-reported: arthritis (nos) 0.15 0.0741 0.043 Wald ratio 1 cis NA
Iron 0.0629 0.0312 0.0441 Wald ratio 1 cis NA
Non-cancer illness code self-reported: pulmonary embolism (with or without) dvt 0.142 0.0719 0.0487 Wald ratio 1 cis NA
Non-cancer illness code self-reported: hypothyroidism or myxoedema 0.0607 0.0311 0.0511 Wald ratio 1 cis NA
Non-cancer illness code self-reported: uterine fibroids -0.133 0.0689 0.0541 Wald ratio 1 cis NA
Non-cancer illness code self-reported: hypertension -0.0244 0.013 0.0601 Wald ratio 1 cis NA
…and 93 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

19 association rows across 17 traits (11 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 1 levels 3e-152 rs56829405 1 GCST90248400 no MR -> candidate analysis
Hematological traits (multi-trait analysis) 1e-45 rs7974474 1 GCST90838669 no MR -> candidate analysis
MANSC domain-containing protein 1 levels (MANSC1.9557.5.3) 9e-42 rs2160588 1 GCST90241875 no MR -> candidate analysis
Serum levels of protein MANSC1 1e-37 rs2160588 1 GCST90090750 no MR -> candidate analysis
Blood protein levels 2e-19 rs61922044 1 GCST006585 no MR -> candidate analysis
Cerebrospinal fluid biomarker levels 7e-13 rs3741798 1 GCST004000 no MR -> candidate analysis
MANSC1 protein levels 1e-11 rs3053800 1 GCST90469847 no MR -> candidate analysis
Height 3e-10 rs78807762 1 GCST007841 MR: beta=0.0119, p=0.202 (cis)
Creatinine levels in top 1% of individuals by creatinine lev 2e-9 rs117489454 1 GCST90566751 no MR -> candidate analysis
Femur bone mineral density x serum urate levels interaction 6e-9 rs61922051 1 GCST012490 no MR -> candidate analysis
Height (baseline) 4e-8 rs57725255 1 GCST90565843 no MR -> candidate analysis
Glioblastoma 1e-7 rs184523096 2 GCST90296481 no MR -> candidate analysis
…and 5 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 53 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
hypothyroidism 0.077 common-variant locus MR: beta=0.0607, p=0.0511 (cis)
Alzheimer disease 0.06 common-variant locus no MR -> candidate analysis
atrial fibrillation 0.061 common-variant locus MR: beta=0.0774, p=0.237 (cis)
asthma 0.054 common-variant locus no MR -> candidate analysis
colorectal cancer 0.053 common-variant locus no MR -> candidate analysis
acne 0.048 common-variant locus no MR -> candidate analysis
Cerebral degeneration 0.046 common-variant locus no MR -> candidate analysis
adolescent idiopathic scoliosis 0.043 common-variant locus no MR -> candidate analysis
androgenetic alopecia 0.039 common-variant locus no MR -> candidate analysis

Of the 9 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=5.1e-05, LOEUF=1.46 — LoF-tolerant
GWAS Catalog 58 unique SNPs / 116 rows
ClinVar 128 records; 4 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance