CausalSentinel

Protein Dossier — ARHGEF10 (Rho guanine nucleotide exchange factor 10)

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
Amyotrophic lateral sclerosis 0.171 0.0761 0.0248 Wald ratio 1 trans NA
Non-cancer illness code self-reported: migraine -0.154 0.069 0.0259 Wald ratio 1 trans NA
Small vessel disease 0.339 0.155 0.0288 Wald ratio 1 trans NA
Diagnoses - main ICD10: R35 Polyuria 0.275 0.126 0.0294 Wald ratio 1 trans NA
Sleep duration 0.0163 0.00795 0.0398 Wald ratio 1 trans NA
Fracture resulting from simple fall 0.0511 0.0255 0.045 Wald ratio 1 trans NA
PGC cross-disorder traits 0.101 0.0517 0.0504 Wald ratio 1 trans NA
Diagnoses - main ICD10: I84 Haemorrhoids 0.114 0.0586 0.0518 Wald ratio 1 trans NA
Sodium in urine 0.0195 0.01 0.0523 Wald ratio 1 trans NA
Alzheimer’s disease 0.135 0.0693 0.0524 Wald ratio 1 trans NA
Diagnoses - main ICD10: K40 Inguinal hernia 0.108 0.0561 0.0535 Wald ratio 1 trans NA
Coronary heart disease 0.0757 0.0397 0.0566 Wald ratio 1 trans NA
…and 81 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

40 association rows across 30 traits (22 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
Rho guanine nucleotide exchange factor 10 levels 4e-37 rs7832438 1 GCST90427632 no MR -> candidate analysis
ARHGEF10 protein levels 2e-36 rs17829719 9 GCST90468357 no MR -> candidate analysis
Localized adiposity (PheCode 278.3) 1e-11 rs535493541 1 GCST90479953 no MR -> candidate analysis
X-11315 levels 9e-11 rs143689932 1 GCST90503991 no MR -> candidate analysis
Gut microbial network clusters (Turquoise (at 3 months) x Ex 5e-9 rs117374333 2 GCST90569282 no MR -> candidate analysis
Gut microbial network clusters (Turquoise (at 3 months) x An 5e-9 rs117374333 2 GCST90569283 no MR -> candidate analysis
Delta-6 desaturase activity response to n3-polyunsaturated f 9e-9 rs2280885 1 GCST005669 no MR -> candidate analysis
Dementia 9e-9 rs7006786 1 GCST90449022 no MR -> candidate analysis
Refractive error 1e-8 rs2280823 1 GCST90841196 no MR -> candidate analysis
Optic disc size 3e-8 rs80218807 1 GCST009462 no MR -> candidate analysis
Total bilirubin levels 3e-8 rs539338508 1 GCST90662900 no MR -> candidate analysis
Gut microbiome abundance (class Clostridium sensu stricto sp 4e-8 rs10441637 1 GCST90569031 no MR -> candidate analysis
…and 18 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 272 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
autosomal dominant slowed nerve conduction velocity 0.585 established (curated) no MR -> candidate analysis
Charcot-Marie-Tooth disease 0.503 established (curated) no MR -> candidate analysis
alcohol drinking 0.457 common-variant locus no MR -> candidate analysis
stroke disorder 0.445 common-variant locus no MR -> candidate analysis
response to polyunsaturated fatty acid supplementation 0.427 common-variant locus no MR -> candidate analysis
atrial septal defect 0.395 common-variant locus no MR -> candidate analysis
dementia 0.395 common-variant locus no MR -> candidate analysis
myeloid leukemia 0.357 common-variant locus no MR -> candidate analysis

Of the 8 rows above, 8 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=1.9e-45, LOEUF=1.09 — LoF-tolerant
GWAS Catalog 66 unique SNPs / 132 rows
ClinVar 1269 records; 0 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance