CausalSentinel

Protein Dossier — ARHGAP1 (Rho GTPase-activating 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
Systolic blood pressure automated reading 0.048 0.0151 0.00149 Wald ratio 1 cis NA
Diagnoses - main ICD10: C50 Malignant neoplasm of breast -0.57 0.215 0.00819 Wald ratio 1 cis NA
Diastolic blood pressure automated reading 0.0388 0.0151 0.0102 Wald ratio 1 cis NA
Pulse rate 0.0616 0.0262 0.0187 Wald ratio 1 cis NA
Diagnoses - main ICD10: N92 Excessive frequent and irregular menstruation -0.331 0.147 0.024 Wald ratio 1 cis NA
Alcohol intake frequency -0.0439 0.0218 0.0438 Wald ratio 1 cis NA
Diagnoses - main ICD10: K40 Inguinal hernia -0.212 0.113 0.0614 Wald ratio 1 cis NA
Cancer code self-reported: basal cell carcinoma 0.211 0.127 0.096 Wald ratio 1 cis NA
Non-cancer illness code self-reported: gastro-oesophageal reflux (gord) or gastric reflux 0.107 0.0641 0.096 Wald ratio 1 cis NA
Fractured bone site(s): Arm 0.202 0.123 0.102 Wald ratio 1 cis NA
Non-cancer illness code self-reported: emphysema or chronic bronchitis -0.275 0.174 0.114 Wald ratio 1 cis NA
Diagnoses - main ICD10: H25 Senile cataract -0.429 0.284 0.131 Wald ratio 1 cis NA
…and 64 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

39 association rows across 34 traits (37 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
Monounsaturated fatty acids to total fatty acids percentage 1e-27 rs4603265 4 GCST90501219 no MR -> candidate analysis
Hypertrophic cardiomyopathy 2e-24 rs187474069 1 GCST90018861 MR: beta=0.8, p=0.299 (cis)
Serum levels of protein ARHGAP1 1e-20 rs144801476 1 GCST90086893 no MR -> candidate analysis
Heel bone mineral density 4e-20 rs764166931 1 GCST006433 no MR -> candidate analysis
Femoral neck bone mineral density 5e-18 rs7932354 1 GCST007691 no MR -> candidate analysis
Metabolic syndrome 5e-18 rs4603265 1 GCST90859207 no MR -> candidate analysis
Triglyceride percentage of total lipids in intermediate-dens 2e-17 rs4603265 1 GCST90454489 no MR -> candidate analysis
Triglyceride to phosphoglyceride ratio 4e-16 rs4603265 1 GCST90454483 no MR -> candidate analysis
GLIPR1 protein levels 2e-15 rs184204306 1 GCST90469357 no MR -> candidate analysis
Triacylglycerol 36:0(FA12:0) (Model 1) 7e-15 rs142892685 1 GCST90830355 no MR -> candidate analysis
Metabolic syndrome cluster 1 (non-descriptive endotype) 3e-14 rs4603265 1 GCST90859208 no MR -> candidate analysis
Pulmonary embolism 5e-14 rs141481090 1 GCST90468148 no MR -> candidate analysis
…and 22 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 488 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
heart disorder 0.527 common-variant locus no MR -> candidate analysis
pulmonary embolism 0.482 common-variant locus no MR -> candidate analysis
hypertrophic cardiomyopathy 0.48 common-variant locus MR: beta=0.8, p=0.299 (cis)
cardiomyopathy 0.431 common-variant locus MR: beta=0.8, p=0.299 (cis)
Pulmonary Infarction 0.418 common-variant locus no MR -> candidate analysis
deep vein thrombosis 0.411 common-variant locus no MR -> candidate analysis
schizophrenia 0.246 common-variant locus no MR -> candidate analysis
Familial exudative vitreoretinopathy 0.228 established (curated) no MR -> candidate analysis
heart failure 0.21 common-variant locus no MR -> candidate analysis
aneurysm 0.131 common-variant locus no MR -> candidate analysis
hypertensive disorder 0.101 common-variant locus no MR -> candidate analysis
venous thromboembolism 0.099 common-variant locus no MR -> candidate analysis
essential hypertension 0.085 common-variant locus no MR -> candidate analysis

Of the 13 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=0.055, LOEUF=0.625 — LoF-tolerant
GWAS Catalog 89 unique SNPs / 178 rows
ClinVar 102 records; 1 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance