CausalSentinel

Protein Dossier — RCAN1 (Calcipressin-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: R10 Abdominal and pelvic pain -0.154 0.0714 0.0312 Wald ratio 1 trans NA
Diagnoses - main ICD10: I48 Atrial fibrillation and flutter -0.343 0.175 0.0494 Wald ratio 1 trans NA
Non-cancer illness code self-reported: hypertrophic cardiomyopathy (hcm or hocm) 0.876 0.462 0.0581 Wald ratio 1 trans NA
Cancer code self-reported: prostate cancer -0.496 0.263 0.0595 Wald ratio 1 trans NA
Invasive mucinous ovarian cancer 0.454 0.246 0.065 Wald ratio 1 trans NA
Sleep duration 0.0169 0.00984 0.0859 Wald ratio 1 trans NA
ER-positive Breast cancer (Combined Oncoarray; iCOGS; GWAS meta analysis) 0.0811 0.0491 0.0988 Wald ratio 1 trans NA
Diagnoses - main ICD10: C61 Malignant neoplasm of prostate -0.415 0.253 0.101 Wald ratio 1 trans NA
Breast cancer (Combined Oncoarray; iCOGS; GWAS meta analysis) 0.068 0.0417 0.103 Wald ratio 1 trans NA
Non-cancer illness code self-reported: ankylosing spondylitis 0.299 0.184 0.105 Wald ratio 1 trans NA
Non-cancer illness code self-reported: pernicious anaemia 0.287 0.181 0.114 Wald ratio 1 trans NA
Diastolic blood pressure automated reading 0.02 0.0129 0.12 Wald ratio 1 trans NA
…and 58 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

18 association rows across 13 traits (6 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
Calcium levels 1e-14 rs928760 2 GCST90018951 no MR -> candidate analysis
Calcium levels (UKB data field 30680) 1e-11 rs13051296 1 GCST90468065 no MR -> candidate analysis
Rheumatoid arthritis 1e-8 rs79818725 4 GCST90132222 no MR -> candidate analysis
Hypothyroidism 2e-8 rs79125270 1 GCST90627750 no MR -> candidate analysis
Rheumatoid arthritis (ACPA-positive) 3e-8 rs2834512 2 GCST005568 no MR -> candidate analysis
Hippocampal volume 2e-7 rs2284609 1 GCST007009 no MR -> candidate analysis
Cancer 5e-7 rs2834439; rs4817642; rs2834440; rs2834450; rs2834461; rs723548; rs13048252; rs10854373; rs2834475; rs2834478; rs8129326; rs2834485; rs3453; rs2070359; rs2247810; rs4817656; rs11911509; rs2211698; rs7279771; rs727957; rs2834502; rs8131131; rs2834506; rs2834512; rs2284576 1 GCST005275 MR: beta=0.876, p=0.0581 (trans)
Psoriasis 1e-6 rs9305556 1 GCST002874 MR: beta=0.0858, p=0.438 (trans)
Maximum habitual alcohol consumption 1e-6 rs114086924 1 GCST008675 no MR -> candidate analysis
Opioid analgesic dose requirement in cancer pain treatment 5e-6 rs2834573 1 GCST90226002 no MR -> candidate analysis
C reactive protein levels x vegetarianism interaction 5e-6 rs2006998 1 GCST90161180 no MR -> candidate analysis
Epigenetic age acceleration in alcohol use disorder 8e-6 rs1571695 1 GCST008748 no MR -> candidate analysis
…and 1 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 313 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
hypothyroidism 0.414 common-variant locus no MR -> candidate analysis
rheumatoid arthritis 0.372 common-variant locus no MR -> candidate analysis
type 2 diabetes mellitus 0.053 common-variant locus no MR -> candidate analysis
breast cancer 0.07 common-variant locus MR: beta=0.0811, p=0.0988 (trans)
lung cancer 0.025 established (curated) no MR -> candidate analysis
breast carcinoma 0.092 common-variant locus no MR -> candidate analysis
atrial fibrillation 0.104 common-variant locus MR: beta=-0.343, p=0.0494 (trans)

Of the 7 rows above, 5 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=0.061, LOEUF=0.795 — LoF-tolerant
GWAS Catalog 50 unique SNPs / 100 rows
ClinVar 103 records; 13 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance