CausalSentinel

Protein Dossier — RAB6B (Ras-related protein Rab-6B)

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
Transferrin 0.214 0.0507 2.44e-05 Wald ratio 1 cis NA
Mean cell haemoglobin -0.172 0.0489 4.40e-04 Wald ratio 1 cis NA
Knee osteoarthritis -0.408 0.139 0.00334 Wald ratio 1 cis NA
Alzheimer’s disease -0.212 0.077 0.00583 Wald ratio 1 cis NA
Non-cancer illness code self-reported: hypopituitarism 0.84 0.32 0.00864 Wald ratio 1 cis NA
Femoral neck bone mineral density 0.0968 0.0372 0.00931 Wald ratio 1 cis NA
Mean cell volume -0.322 0.125 0.0102 Wald ratio 1 cis NA
Schizophrenia -0.133 0.0522 0.0107 Wald ratio 1 cis NA
Heel bone mineral density (BMD) T-score automated 0.0374 0.0157 0.0173 Wald ratio 1 cis NA
Thyroid cancer -1.02 0.432 0.0183 Wald ratio 1 cis NA
Lumbar spine bone mineral density 0.0961 0.0433 0.0265 Wald ratio 1 cis NA
Diagnoses - main ICD10: D12 Benign neoplasm of colon rectum anus and anal canal -0.317 0.144 0.028 Wald ratio 1 cis NA
…and 95 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

21 association rows across 15 traits (14 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
Ras-related protein Rab-6B levels 9e-149 rs10212397 1 GCST90249223 no MR -> candidate analysis
Serum levels of protein RAB6B 4e-31 rs9813363 1 GCST90087852 no MR -> candidate analysis
TF protein levels 2e-27 rs17376530 5 GCST90470841 no MR -> candidate analysis
Iron status biomarkers (total iron binding capacity) 3e-20 rs7637997 1 GCST004571 no MR -> candidate analysis
Iron status biomarkers (transferrin saturation) 3e-20 rs7637997 1 GCST004572 no MR -> candidate analysis
Blood protein levels 1e-17 rs9813363 1 GCST006585 no MR -> candidate analysis
Mean reticulocyte volume 2e-12 rs1525886 1 GCST90002396 no MR -> candidate analysis
Hematological traits (multi-trait analysis) 2e-12 rs940900 1 GCST90838669 no MR -> candidate analysis
Mean corpuscular hemoglobin 9e-11 rs2692685 2 GCST007068 no MR -> candidate analysis
Immune reponse to smallpox (secreted IL-1beta) 7e-8 rs9835973 1 GCST001533 no MR -> candidate analysis
Alkenylphosphatidylethanolamine (P-20:1/20:4) levels 3e-7 rs779501250 1 GCST90024447 no MR -> candidate analysis
5-acetylamino-6-amino-3-methyluracil levels in elite athlete 2e-6 rs2692681 1 GCST90134187 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 80 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
alcohol drinking 0.573 common-variant locus no MR -> candidate analysis
major salivary gland cancer 0.364 common-variant locus no MR -> candidate analysis
bipolar disorder 0.17 common-variant locus MR: beta=-0.23, p=0.062 (cis)
Abnormality of the immune system 0.079 common-variant locus no MR -> candidate analysis
colorectal cancer 0.063 common-variant locus no MR -> candidate analysis
colorectal adenoma 0.063 common-variant locus no MR -> candidate analysis
hypertension, pregnancy-induced 0.035 common-variant locus no MR -> candidate analysis
squamous cell carcinoma 0.031 common-variant locus no MR -> candidate analysis

Of the 8 rows above, 7 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, LOEUF=0.422 — LoF-INTOLERANT
GWAS Catalog 101 unique SNPs / 206 rows
ClinVar 51 records; 2 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance