CausalSentinel

Protein Dossier — PGM1 (Phosphoglucomutase-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
Cancer code self-reported: prostate cancer 0.299 0.0874 6.17e-04 Wald ratio 1 cis NA
Non-cancer illness code self-reported: hiatus hernia 0.181 0.0548 9.58e-04 Wald ratio 1 cis NA
Non-cancer illness code self-reported: joint disorder 0.326 0.107 0.00219 Wald ratio 1 cis NA
Diagnoses - main ICD10: C61 Malignant neoplasm of prostate 0.282 0.0933 0.00248 Wald ratio 1 cis NA
Years of schooling -0.0418 0.0139 0.0027 Wald ratio 1 cis NA
Diagnoses - main ICD10: S76 Injury of muscle and tendon at hip and thigh level 0.673 0.262 0.0103 Wald ratio 1 cis NA
Rheumatoid arthritis -0.216 0.0857 0.0118 Wald ratio 1 cis NA
Happiness 0.0273 0.0124 0.0271 Wald ratio 1 cis NA
Height -0.0268 0.0129 0.0374 Wald ratio 1 cis NA
Cancer code self-reported: basal cell carcinoma -0.264 0.139 0.0574 Wald ratio 1 cis NA
HbA1C -0.0254 0.0146 0.0822 Wald ratio 1 cis NA
Paget’s disease -0.454 0.262 0.0829 Wald ratio 1 cis NA
…and 86 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

59 association rows across 37 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
Bone mineral density mean 1e-300 rs115515529 1 GCST90321120 no MR -> candidate analysis
Vertex-wise sulcal depth 3e-39 rs12723887 1 GCST90095129 no MR -> candidate analysis
Phosphoglucomutase-1 levels 4e-33 rs2269247 3 GCST90248981 no MR -> candidate analysis
Vertex-wise cortical surface area 2e-24 rs1627221 1 GCST90095130 no MR -> candidate analysis
Type 2 diabetes 1e-23 rs2269247 8 GCST90492734 MR: beta=0.106, p=0.363 (cis)
Phosphoglucomutase-1 levels (PGM1.9173.21.3) 3e-23 rs1126728 2 GCST90242254 no MR -> candidate analysis
Unsupervised deep imaging phenotypes (UDIP-FA) 6e-21 rs2787681 1 GCST90860937 no MR -> candidate analysis
Vertex-wise cortical thickness 7e-21 rs1701531 1 GCST90095131 no MR -> candidate analysis
Free Cholesterol to Cholesteryl Esters in Small HDL ratio 9e-20 rs115229534 1 GCST90827928 no MR -> candidate analysis
ROR1 protein levels 1e-19 rs1506402 1 GCST90470492 no MR -> candidate analysis
Cortical surface area 1e-17 rs1628254 2 GCST90091060 no MR -> candidate analysis
Cortical thickness 1e-17 rs1701531 1 GCST90091061 no MR -> candidate analysis
…and 25 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 289 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
PGM1-congenital disorder of glycosylation 0.926 established (curated) no MR -> candidate analysis
hereditary disease 0.816 established (curated) no MR -> candidate analysis
type 2 diabetes mellitus 0.809 common-variant locus no MR -> candidate analysis
congenital disorder of glycosylation 0.438 established (curated) no MR -> candidate analysis
type 1 diabetes mellitus 0.663 common-variant locus no MR -> candidate analysis
adverse effect 0.407 common-variant locus no MR -> candidate analysis
alcohol drinking 0.407 common-variant locus no MR -> candidate analysis
liver disorder 0.379 common-variant locus no MR -> candidate analysis
eye color 0.108 common-variant locus no MR -> candidate analysis
severe acute respiratory syndrome 0.103 common-variant locus no MR -> candidate analysis
COVID-19 0.103 common-variant locus no MR -> candidate analysis
arthropathy 0.066 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=4.4e-17, LOEUF=1.18 — LoF-tolerant
GWAS Catalog 57 unique SNPs / 98 rows
ClinVar 568 records; 4 pathogenic in sample of 30
PharmGKB/ClinPGx 1 clinical annotations across 1 drugs

Caveats declared by the tools

Sources

Provenance