CausalSentinel

Protein Dossier — MGP (Matrix Gla protein)

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
Heel bone mineral density (BMD) T-score automated 0.0545 0.0121 6.42e-06 Wald ratio 1 cis NA
Fractured or broken bones in last 5 years -0.147 0.0338 1.29e-05 Wald ratio 1 cis NA
Height 0.0351 0.0113 0.00194 Wald ratio 1 cis NA
Mean cell haemoglobin 0.105 0.0374 0.00498 Wald ratio 1 cis NA
Non-cancer illness code self-reported: psoriasis 0.2 0.0724 0.00565 Wald ratio 1 cis NA
Weight 0.022 0.00825 0.00752 Wald ratio 1 cis NA
Fractured bone site(s): Ankle -0.278 0.107 0.00913 Wald ratio 1 cis NA
Diagnoses - main ICD10: H25 Senile cataract 0.214 0.0867 0.0138 Wald ratio 1 cis NA
Fractured bone site(s): Wrist -0.199 0.082 0.0153 Wald ratio 1 cis NA
Lumbar spine bone mineral density 0.0822 0.034 0.0157 Wald ratio 1 cis NA
Mean cell volume 0.223 0.0955 0.0193 Wald ratio 1 cis NA
Sleep duration 0.017 0.00729 0.0195 Wald ratio 1 cis NA
…and 90 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

3 association rows across 3 traits (3 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
Hand grip strength left (UKB data field 46) 3e-30 rs1800801 1 GCST90468168 no MR -> candidate analysis
Erosive hand osteoarthritis 4e-13 rs1800801 1 GCST90271957 no MR -> candidate analysis
Estimated glomerular filtration rate (creatinine) 2e-9 rs11393307 1 GCST90100220 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 1118 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
Keutel syndrome 0.794 established (curated) no MR -> candidate analysis
spondyloepiphyseal dysplasia 0.195 established (curated) no MR -> candidate analysis
osteoarthritis, hand 0.581 common-variant locus no MR -> candidate analysis
osteoarthritis, knee 0.568 common-variant locus no MR -> candidate analysis
osteoarthritis, hip 0.542 common-variant locus no MR -> candidate analysis
total joint arthroplasty 0.487 common-variant locus no MR -> candidate analysis
hereditary disease 0.265 established (curated) no MR -> candidate analysis
polyarticular arthritis 0.262 common-variant locus no MR -> candidate analysis
Short distal phalanx of finger 0.195 established (curated) no MR -> candidate analysis
Short palm 0.195 established (curated) no MR -> candidate analysis
Platyspondyly 0.195 established (curated) no MR -> candidate analysis
Short stature 0.195 established (curated) 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=6.5e-05, LOEUF=1.42 — LoF-tolerant
GWAS Catalog 39 unique SNPs / 78 rows
ClinVar 179 records; 4 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance