CausalSentinel

Protein Dossier — REG3G (Regenerating islet-derived protein 3-gamma)

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: N81 Female genital prolapse 0.164 0.0436 1.73e-04 Wald ratio 1 cis NA
Paget’s disease -0.572 0.198 0.00394 Wald ratio 1 cis NA
Diagnoses - main ICD10: N20 Calculus of kidney and ureter -0.197 0.0899 0.0284 Wald ratio 1 cis NA
Hearing difficulty or problems: Yes -0.0228 0.0108 0.0352 Wald ratio 1 cis NA
Diagnoses - main ICD10: K43 Ventral hernia -0.254 0.121 0.0357 Wald ratio 1 cis NA
Rheumatoid arthritis -0.0805 0.0403 0.0457 Wald ratio 1 cis NA
HbA1C -0.0191 0.00986 0.0527 Wald ratio 1 cis NA
Non-cancer illness code self-reported: joint disorder -0.22 0.113 0.0527 Wald ratio 1 cis NA
Mean cell haemoglobin 0.0604 0.0314 0.0547 Wald ratio 1 cis NA
Forced expiratory volume in 1-second (FEV1) -0.0102 0.00531 0.0557 Wald ratio 1 cis NA
Transferrin Saturation -0.0561 0.03 0.0615 Wald ratio 1 cis NA
Lumbar spine bone mineral density 0.0398 0.0218 0.0677 Wald ratio 1 cis NA
…and 98 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

28 association rows across 18 traits (23 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
REG3G protein levels 1e-292 rs2861742 5 GCST90470450 no MR -> candidate analysis
Regenerating islet-derived protein 3-gamma levels 1e-251 rs2861742 4 GCST90249276 no MR -> candidate analysis
Serum levels of protein REG3G 1e-117 rs439914 2 GCST90090648 no MR -> candidate analysis
Blood protein levels 9e-63 rs429694 2 GCST006585 no MR -> candidate analysis
Regenerating islet-derived protein 3-gamma level in Chronic 2e-41 rs77167115 1 GCST90234394 no MR -> candidate analysis
REG1B protein levels 6e-23 rs34977007 2 GCST90470448 no MR -> candidate analysis
Bone mineral density mean 9e-19 rs72814698 1 GCST90321120 no MR -> candidate analysis
Serum levels of protein REG1A 2e-16 rs17753345 1 GCST90087370 no MR -> candidate analysis
Lithostathine-1-alpha levels 1e-13 rs6710164 1 GCST90161283 no MR -> candidate analysis
Alzheimer’s disease or family history of Alzheimer’s disease 2e-12 rs1439643019 1 GCST90624094 no MR -> candidate analysis
REG1A protein levels 2e-11 rs189958205 1 GCST90470447 no MR -> candidate analysis
Musculoskeletal symptoms referable to limbs (PheCode 771) 2e-11 rs371737875 1 GCST90480576 no MR -> candidate analysis
…and 6 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 269 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
Anisometropia 0.448 common-variant locus no MR -> candidate analysis
alcohol drinking 0.435 common-variant locus no MR -> candidate analysis
smoking initiation 0.4 common-variant locus no MR -> candidate analysis
Alzheimer disease 0.388 common-variant locus no MR -> candidate analysis
osteoarthritis, hand 0.386 common-variant locus no MR -> candidate analysis
musculoskeletal system disorder 0.36 common-variant locus no MR -> candidate analysis
osteoarthritis 0.357 common-variant locus MR: beta=-0.0838, p=0.241 (cis)
attention deficit-hyperactivity disorder 0.357 common-variant locus no MR -> candidate analysis
substance abuse 0.357 common-variant locus no MR -> candidate analysis
bile duct disorder 0.354 common-variant locus no MR -> candidate analysis
stroke disorder 0.346 common-variant locus no MR -> candidate analysis
cervical carcinoma 0.346 common-variant locus no MR -> candidate analysis
femoral neck fracture 0.346 common-variant locus no MR -> candidate analysis
hidradenitis 0.346 common-variant locus no MR -> candidate analysis
ovarian dysfunction 0.342 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=9e-07, LOEUF=1.34 — LoF-tolerant
GWAS Catalog 42 unique SNPs / 83 rows
ClinVar 65 records; 0 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance