CausalSentinel

Protein Dossier — STIM1 (Stromal interaction molecule 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: R04 Haemorrhage from respiratory passages 0.368 0.13 0.00462 Wald ratio 1 trans NA
Primary sclerosing cholangitis -0.432 0.161 0.00718 Wald ratio 1 trans NA
Diagnoses - main ICD10: C50 Malignant neoplasm of breast 0.213 0.0843 0.0115 Wald ratio 1 trans NA
Non-cancer illness code self-reported: enlarged prostate 0.223 0.0914 0.0145 Wald ratio 1 trans NA
Non-cancer illness code self-reported: pernicious anaemia 0.371 0.174 0.0332 Wald ratio 1 trans NA
Non-cancer illness code self-reported: vitiligo 0.85 0.413 0.0396 Wald ratio 1 trans NA
Alcohol intake frequency 0.04 0.0196 0.0411 Wald ratio 1 trans NA
Non-cancer illness code self-reported: osteoporosis 0.182 0.0894 0.0422 Wald ratio 1 trans NA
Serum cystatin C (eGFRcys) 0.0214 0.0107 0.0455 Wald ratio 1 trans NA
Subjective well being -0.0321 0.0161 0.0455 Wald ratio 1 trans NA
Thalamus volume 84.5 43.4 0.0513 Wald ratio 1 trans NA
Diagnoses - main ICD10: N20 Calculus of kidney and ureter 0.231 0.128 0.0705 Wald ratio 1 trans NA
…and 78 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

55 association rows across 35 traits (51 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
Bone mineral density mean 1e-300 rs184778371 3 GCST90321120 no MR -> candidate analysis
Hematological traits (multi-trait analysis) 7e-48 rs7932404 2 GCST90838669 no MR -> candidate analysis
Mean platelet volume 9e-43 rs11030122 4 GCST90002346 no MR -> candidate analysis
Mean platelet thrombocyte volume (UKB data field 30100) 1e-40 rs4414209 1 GCST90468087 no MR -> candidate analysis
mean platelet volume (MPV, mean, inv-norm transformed) 5e-29 rs113746149 2 GCST90475520 no MR -> candidate analysis
mean platelet volume (MPV, maximum, inv-norm transformed) 1e-27 rs113746149 2 GCST90475517 no MR -> candidate analysis
Stromal interaction molecule 1 levels 6e-20 rs11030122 1 GCST90249678 no MR -> candidate analysis
Atrial fibrillation 3e-19 rs7126252 4 GCST90624411 MR: beta=-0.138, p=0.35 (trans)
Platelet distribution width (UKB data field 30110) 4e-19 rs11030122 1 GCST90468097 no MR -> candidate analysis
Mitochondrial DNA copy number 6e-16 rs139115730 1 GCST90026371 no MR -> candidate analysis
GLIPR1 protein levels 4e-14 rs189094988 1 GCST90469357 no MR -> candidate analysis
Platelet distribution width 5e-14 rs11030122 2 GCST90002401 no MR -> candidate analysis
…and 23 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 2594 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
myopathy, tubular aggregate, 1 0.921 established (curated) no MR -> candidate analysis
combined immunodeficiency due to STIM1 deficiency 0.827 established (curated) no MR -> candidate analysis
Stormorken syndrome 0.876 established (curated) no MR -> candidate analysis
tubular aggregate myopathy 0.843 established (curated) no MR -> candidate analysis
Stormorken-Sjaastad-Langslet syndrome 0.608 established (curated) no MR -> candidate analysis
combined immunodeficiency due to CRAC channel dysfunction 0.608 established (curated) no MR -> candidate analysis
atrial fibrillation 0.674 common-variant locus MR: beta=-0.138, p=0.35 (trans)
familial hemolytic anemia 0.598 common-variant locus no MR -> candidate analysis
inherited hemoglobinopathy 0.593 common-variant locus no MR -> candidate analysis
atrial flutter 0.485 common-variant locus MR: beta=-0.138, p=0.35 (trans)
myopathy, autophagic vacuolar, infantile-onset 0.438 established (curated) no MR -> candidate analysis
non-autoimmune hemolytic anemia 0.43 common-variant locus no MR -> candidate analysis
sickle cell disease and related diseases 0.43 common-variant locus no MR -> candidate analysis
alcohol drinking 0.427 common-variant locus no MR -> candidate analysis
urolithiasis 0.414 common-variant locus no MR -> candidate analysis

Of the 15 rows above, 13 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 0 known modulators (ORAI1/STIM1)
gnomAD constraint pLI=1, LOEUF=0.467 — LoF-INTOLERANT
GWAS Catalog 73 unique SNPs / 146 rows
ClinVar 955 records; 0 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance