CausalSentinel

Protein Dossier — RARRES1 (Retinoic acid receptor responder protein 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
Diagnoses - main ICD10: K43 Ventral hernia 0.106 0.0338 0.00167 Wald ratio 1 cis NA
Height -0.00973 0.00314 0.00197 Wald ratio 1 cis NA
Diagnoses - main ICD10: R10 Abdominal and pelvic pain 0.0281 0.0118 0.017 Wald ratio 1 cis NA
Diagnoses - main ICD10: J33 Nasal polyp 0.0801 0.0336 0.0172 Wald ratio 1 cis NA
Sodium in urine 0.00562 0.00247 0.0226 Wald ratio 1 cis NA
Squamous cell lung cancer 0.0668 0.0313 0.033 Wald ratio 1 cis NA
Ovarian cancer -0.0289 0.0139 0.0375 Wald ratio 1 cis NA
Diagnoses - main ICD10: D12 Benign neoplasm of colon rectum anus and anal canal -0.0443 0.0221 0.0451 Wald ratio 1 cis NA
Depressive symptoms 0.00748 0.00374 0.0455 Wald ratio 1 cis NA
Diagnoses - main ICD10: K57 Diverticular disease of intestine 0.0334 0.0171 0.0501 Wald ratio 1 cis NA
ER-negative Breast cancer (Combined Oncoarray; iCOGS; GWAS meta analysis) -0.0235 0.012 0.0511 Wald ratio 1 cis NA
Putamen volume 11.8 6.06 0.0516 Wald ratio 1 cis NA
…and 101 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

15 association rows across 10 traits (13 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 RARRES1 levels 6e-1014 rs6441224 2 GCST90860306 no MR -> candidate analysis
Retinoic acid receptor responder protein 1 levels (RARRES1.8 7e-514 rs112493023 3 GCST90242640 no MR -> candidate analysis
Blood protein levels 5e-481 rs73030851 1 GCST006585 no MR -> candidate analysis
Retinoic acid receptor responder protein 1 levels 2e-333 rs17699997 2 GCST90249381 no MR -> candidate analysis
Circulating LXN levels 6e-97 rs1548013 1 GCST90859687 no MR -> candidate analysis
RARRES1 protein levels 5e-30 rs74516361 2 GCST90470427 no MR -> candidate analysis
Mouth ulcers 4e-11 rs73156502 1 GCST007839 no MR -> candidate analysis
Systolic blood pressure 2e-9 rs9849301 1 GCST007267 MR: beta=-0.00199, p=0.438 (cis)
C.albicans induced TNF-a level 5e-7 rs16829318 1 GCST90308659 no MR -> candidate analysis
Diisocyanate-induced asthma 2e-6 rs190141647 1 GCST002875 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 192 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
premature birth 0.566 common-variant locus no MR -> candidate analysis
placental retention 0.46 common-variant locus no MR -> candidate analysis
placental abruption 0.421 common-variant locus no MR -> candidate analysis
pathological myopia 0.421 common-variant locus no MR -> candidate analysis
Oral ulcer 0.393 common-variant locus no MR -> candidate analysis
cervical carcinoma 0.356 common-variant locus no MR -> candidate analysis
congestive heart failure 0.112 common-variant locus no MR -> candidate analysis
neuroblastoma 0.097 common-variant locus no MR -> candidate analysis
chronic obstructive pulmonary disease 0.088 common-variant locus no MR -> candidate analysis
major depressive disorder 0.078 common-variant locus no MR -> candidate analysis
bipolar disorder 0.053 common-variant locus MR: beta=0.0383, p=0.419 (cis)
handedness 0.049 common-variant locus no MR -> candidate analysis

Of the 12 rows above, 11 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=3.1e-13, LOEUF=1.48 — LoF-tolerant
GWAS Catalog 48 unique SNPs / 96 rows
ClinVar 104 records; 2 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance