CausalSentinel

Protein Dossier — REG4 (Regenerating islet-derived 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
Diagnoses - main ICD10: I30 Acute pericarditis 1.02 0.256 6.44e-05 Wald ratio 1 cis NA
Diagnoses - main ICD10: K60 Fissure and fistula of anal and rectal regions 0.335 0.124 0.00715 Wald ratio 1 cis NA
Lumbar spine bone mineral density -0.122 0.0512 0.0169 Wald ratio 1 cis NA
Eczema -0.276 0.125 0.0275 Wald ratio 1 cis NA
Diagnoses - main ICD10: N92 Excessive frequent and irregular menstruation 0.146 0.0698 0.0366 Wald ratio 1 cis NA
Non-cancer illness code self-reported: polio or poliomyelitis 0.544 0.281 0.0528 Wald ratio 1 cis NA
Diagnoses - main ICD10: L03 Cellulitis -0.367 0.194 0.0584 Wald ratio 1 cis NA
Non-cancer illness code self-reported: hayfever or allergic rhinitis 0.082 0.0438 0.0613 Wald ratio 1 cis NA
Hearing difficulty or problems: Yes 0.0352 0.0192 0.0665 Wald ratio 1 cis NA
ER-positive Breast cancer (Combined Oncoarray; iCOGS; GWAS meta analysis) 0.086 0.0477 0.0715 Wald ratio 1 cis NA
Diagnoses - main ICD10: D25 Leiomyoma of uterus -0.226 0.13 0.0832 Wald ratio 1 cis NA
Diastolic blood pressure automated reading -0.0204 0.0118 0.0836 Wald ratio 1 cis NA
…and 43 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

32 association rows across 20 traits (28 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
Circulating REG4 levels 1e-181 rs79795228 3 GCST90860391 no MR -> candidate analysis
REG4 protein levels 4e-163 rs79795228 2 GCST90470451 no MR -> candidate analysis
X-18922 levels 7e-51 rs1163548 3 GCST90245656 no MR -> candidate analysis
Regenerating islet-derived protein 4 levels 3e-38 rs58163904 3 GCST90421303 no MR -> candidate analysis
Acetone levels 1e-24 rs2582783 3 GCST90501095 no MR -> candidate analysis
Serum uric acid levels 9e-24 rs150147865 2 GCST90018977 no MR -> candidate analysis
Urate levels (UKB data field 30880) 3e-18 rs150147865 1 GCST90468107 no MR -> candidate analysis
DNA methylation-estimated granulocyte proportions 2e-16 rs4659238 1 GCST90014293 no MR -> candidate analysis
Regenerating islet-derived protein 4 levels (REG4.11102.22.3 1e-15 rs79795228 2 GCST90242614 no MR -> candidate analysis
X-21736 levels 1e-13 rs1163548 2 GCST90245691 no MR -> candidate analysis
ACP6 protein levels 6e-13 rs34595089 1 GCST90468204 no MR -> candidate analysis
Plasma X-18922 levels in chronic kidney disease 8e-12 rs12132674 1 GCST90266465 no MR -> candidate analysis
…and 8 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 194 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
cutaneous lupus erythematosus 0.457 common-variant locus no MR -> candidate analysis
pneumonia 0.395 common-variant locus no MR -> candidate analysis
fungal lung infectious disease 0.395 common-variant locus no MR -> candidate analysis

Of the 3 rows above, 3 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=9.7e-05, LOEUF=1.09 — LoF-tolerant
GWAS Catalog 78 unique SNPs / 156 rows
ClinVar 56 records; 1 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance