CausalSentinel

Protein Dossier — SLC5A8 (Sodium-coupled monocarboxylate transporter 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
Triglycerides -0.252 0.014 7.71e-73 Wald ratio 1 trans 0.998
HDL cholesterol 0.236 0.0143 5.55e-61 Wald ratio 1 trans 0.998
LDL cholesterol -0.21 0.0154 2.73e-42 Wald ratio 1 trans 4.21e-13
Total cholesterol -0.16 0.015 1.46e-26 Wald ratio 1 trans 6.56e-14
Non-cancer illness code self-reported: high cholesterol -0.316 0.0396 1.39e-15 Wald ratio 1 trans 2e-13
Non-cancer illness code self-reported: gastro-oesophageal reflux (gord) or gastric reflux 0.145 0.0445 0.00113 Wald ratio 1 trans NA
Diagnoses - main ICD10: M72 Fibroblastic disorders 0.32 0.107 0.00266 Wald ratio 1 trans NA
Celiac disease 0.232 0.08 0.00373 Wald ratio 1 trans NA
Mean cell volume -0.284 0.105 0.00699 Wald ratio 1 trans NA
Clear cell ovarian cancer 0.453 0.171 0.00794 Wald ratio 1 trans NA
Alzheimer’s disease -0.176 0.0669 0.00851 Wald ratio 1 trans NA
Non-cancer illness code self-reported: vaginal prolapse or uterine prolapse 0.281 0.111 0.0109 Wald ratio 1 trans NA
…and 105 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 15 traits (7 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
Educational attainment 2e-12 rs7397905 1 GCST90105038 no MR -> candidate analysis
Neurofibrillary tangles (SNP x SNP interaction) 5e-10 rs11787434 x rs2712622 1 GCST010343 no MR -> candidate analysis
Stem Cell Growth Factor-beta levels 4e-9 rs56086228 1 GCST90428433 no MR -> candidate analysis
A body shape index 1e-8 rs7296340 1 GCST90020024 no MR -> candidate analysis
Waist-hip index 4e-8 rs7296340 1 GCST90020027 no MR -> candidate analysis
Triglycerides in LDL meal response (OrNLSr) 4e-8 rs2037053 1 GCST90091794 no MR -> candidate analysis
Triglycerides levels in medium LDL meal response (OrNLSr) 4e-8 rs2037053 1 GCST90091795 no MR -> candidate analysis
SSRI response to psychomotor-insight syndromal factor measur 6e-7 rs824315 1 GCST90270299 no MR -> candidate analysis
Granulocyte-colony stimulating factor levels 1e-6 rs143158039 1 GCST004458 no MR -> candidate analysis
Shingles 4e-6 rs721633 1 GCST005001 no MR -> candidate analysis
Serum barium levels 4e-6 rs58616750 1 GCST90100519 no MR -> candidate analysis
Colorectal cancer x total fish intake interaction 4e-6 rs823559 1 GCST90502813 no MR -> candidate analysis
…and 3 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 155 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
pneumothorax 0.512 common-variant locus MR: beta=0.473, p=0.217 (trans)
pleural empyema 0.512 common-variant locus no MR -> candidate analysis
urinary tract obstruction 0.512 common-variant locus no MR -> candidate analysis
cartilage disease 0.505 common-variant locus no MR -> candidate analysis
stroke disorder 0.482 common-variant locus no MR -> candidate analysis
alcohol drinking 0.482 common-variant locus no MR -> candidate analysis
corneal ulcer 0.48 common-variant locus no MR -> candidate analysis
medical procedure 0.095 common-variant locus no MR -> candidate analysis
complication 0.095 common-variant locus no MR -> candidate analysis
trauma complication 0.095 common-variant locus no MR -> candidate analysis
lacrimal apparatus disorder 0.074 common-variant locus no MR -> candidate analysis
secondary malignant neoplasm 0.044 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=9.3e-15, LOEUF=0.958 — LoF-tolerant
GWAS Catalog 25 unique SNPs / 44 rows
ClinVar 122 records; 1 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance