CausalSentinel

Protein Dossier — C6orf89 (Bombesin receptor-activated protein C6orf89)

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
Alcohol intake frequency -0.0359 0.0159 0.0238 Wald ratio 1 trans NA
Primary sclerosing cholangitis -0.341 0.155 0.0275 Wald ratio 1 trans NA
Sodium in urine -0.0228 0.0106 0.0306 Wald ratio 1 trans NA
Non-cancer illness code self-reported: sleep apnoea 0.312 0.145 0.032 Wald ratio 1 trans NA
Systolic blood pressure automated reading 0.0222 0.011 0.0436 Wald ratio 1 trans NA
Diagnoses - main ICD10: G47 Sleep disorders 0.227 0.113 0.0455 Wald ratio 1 trans NA
Diagnoses - main ICD10: N92 Excessive frequent and irregular menstruation -0.167 0.0892 0.0611 Wald ratio 1 trans NA
Cancer code self-reported: prostate cancer -0.33 0.182 0.0696 Wald ratio 1 trans NA
Eye problems or disorders: Glaucoma 0.142 0.0782 0.0696 Wald ratio 1 trans NA
Squamous cell lung cancer -0.247 0.136 0.0701 Wald ratio 1 trans NA
Diagnoses - main ICD10: C61 Malignant neoplasm of prostate -0.354 0.197 0.0719 Wald ratio 1 trans NA
Diagnoses - main ICD10: I84 Haemorrhoids 0.106 0.0623 0.0879 Wald ratio 1 trans NA
…and 65 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 13 traits (8 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
PI16 protein levels 3e-58 rs113960910 2 GCST90470229 no MR -> candidate analysis
Serum levels of protein PPIL1 3e-46 rs144656078 1 GCST90090885 no MR -> candidate analysis
Cerebrospinal fluid protein PI16 levels 8e-24 rs12203354 1 GCST90945032 no MR -> candidate analysis
MSMB protein levels 2e-14 rs67854134 1 GCST90469949 no MR -> candidate analysis
Circulating MSMB levels 1e-13 rs6920322 1 GCST90860651 no MR -> candidate analysis
Hypothyroidism 3e-12 rs79809702 1 GCST90627749 no MR -> candidate analysis
Type 2 diabetes 7e-10 rs72846863 2 GCST90492734 MR: beta=-0.11, p=0.486 (trans)
Heel bone mineral density 1e-7 rs9357229 1 GCST007066 no MR -> candidate analysis
Schizophrenia, bipolar disorder or recurrent major depressiv 4e-6 rs1543274 1 GCST012293 no MR -> candidate analysis
Schizophrenia, bipolar disorder or major depressive disorder 4e-6 rs1543274 1 GCST012299 no MR -> candidate analysis
Performance intelligence quotient (cesarean section interact 7e-6 rs4714020 1 GCST007404 no MR -> candidate analysis
Schizophrenia x sex interaction 7e-6 rs1543274 1 GCST012310 no MR -> candidate analysis
…and 1 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 29 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
pontocerebellar hypoplasia, type 14 0.438 established (curated) no MR -> candidate analysis
hemorrhage 0.287 common-variant locus no MR -> candidate analysis
complication 0.287 common-variant locus no MR -> candidate analysis
hereditary disease 0.243 established (curated) no MR -> candidate analysis
diverticular disease 0.055 common-variant locus MR: beta=-0.147, p=0.0954 (trans)
hypothyroidism 0.041 common-variant locus no MR -> candidate analysis
major depressive disorder 0.033 common-variant locus no MR -> candidate analysis

Of the 7 rows above, 6 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=1.2e-07, LOEUF=0.972 — LoF-tolerant
GWAS Catalog 73 unique SNPs / 146 rows
ClinVar 39 records; 4 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance