CausalSentinel

Protein Dossier — RFESD (Rieske domain-containing 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
Diagnoses - main ICD10: D25 Leiomyoma of uterus 0.196 0.0738 0.00786 Wald ratio 1 cis NA
Cancer code self-reported: basal cell carcinoma 0.216 0.0858 0.0118 Wald ratio 1 cis NA
Diagnoses - main ICD10: K29 Gastritis and duodenitis 0.117 0.0585 0.0454 Wald ratio 1 cis NA
Non-cancer illness code self-reported: enlarged prostate 0.147 0.0752 0.0511 Wald ratio 1 cis NA
Myocardial infarction 0.086 0.0446 0.0539 Wald ratio 1 cis NA
High grade serous ovarian cancer -0.135 0.071 0.057 Wald ratio 1 cis NA
Happiness -0.0234 0.0125 0.061 Wald ratio 1 cis NA
Body mass index (BMI) -0.0187 0.0101 0.0646 Wald ratio 1 cis NA
Diagnoses - main ICD10: K44 Diaphragmatic hernia 0.13 0.0715 0.069 Wald ratio 1 cis NA
Eye problems or disorders: Glaucoma 0.126 0.0748 0.0917 Wald ratio 1 cis NA
Diagnoses - main ICD10: M23 Internal derangement of knee -0.132 0.0782 0.0918 Wald ratio 1 cis NA
Diagnoses - main ICD10: N20 Calculus of kidney and ureter 0.173 0.103 0.0922 Wald ratio 1 cis NA
…and 57 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

5 association rows across 5 traits (2 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
Rieske domain-containing protein levels (RFESD.13603.7.3) 2e-25 rs77881626 1 GCST90242681 no MR -> candidate analysis
Alanine aminotransferase level after methotrexate initiation 3e-8 rs72783407 1 GCST90244104 no MR -> candidate analysis
Pharmacokinetics of antiepileptic drugs in severe mental dis 2e-7 rs17790731 1 GCST002887 no MR -> candidate analysis
Familial squamous cell lung carcinoma 6e-6 rs115593965 1 GCST006088 no MR -> candidate analysis
Ischemic stroke (cardioembolic) 7e-6 rs72781498 1 GCST90020242 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 12 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
vitiligo 0.46 common-variant locus MR: beta=0.504, p=0.28 (cis)
alcohol drinking 0.249 common-variant locus no MR -> candidate analysis
seasonal allergic rhinitis 0.249 common-variant locus no MR -> candidate analysis
placental abruption 0.042 common-variant locus no MR -> candidate analysis
infectious disease 0.036 common-variant locus no MR -> candidate analysis

Of the 5 rows above, 4 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=0.00028, LOEUF=0.997 — LoF-tolerant
GWAS Catalog 17 unique SNPs / 33 rows
ClinVar 59 records; 3 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance