CausalSentinel

Protein Dossier — ATF6 (Cyclic AMP-dependent transcription factor ATF-6 alpha)

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
Eczema 0.252 0.0924 0.00641 Wald ratio 1 trans NA
Clear cell ovarian cancer 0.409 0.17 0.016 Wald ratio 1 trans NA
Neuroticism 0.0317 0.0132 0.0164 Wald ratio 1 trans NA
Invasive mucinous ovarian cancer 0.405 0.17 0.0173 Wald ratio 1 trans NA
Diagnoses - main ICD10: G56 Mononeuropathies of upper limb 0.136 0.061 0.0254 Wald ratio 1 trans NA
Depressive symptoms 0.0343 0.0158 0.0303 Wald ratio 1 trans NA
Diagnoses - main ICD10: G47 Sleep disorders 0.193 0.0996 0.0528 Wald ratio 1 trans NA
Non-cancer illness code self-reported: sleep apnoea 0.249 0.131 0.0582 Wald ratio 1 trans NA
Diagnoses - main ICD10: K20 Oesophagitis 0.149 0.0803 0.0638 Wald ratio 1 trans NA
Endometrioid ovarian cancer 0.223 0.127 0.0786 Wald ratio 1 trans NA
Myocardial infarction 0.102 0.0589 0.0847 Wald ratio 1 trans NA
Diagnoses - main ICD10: K35 Acute appendicitis 0.189 0.11 0.0869 Wald ratio 1 trans NA
…and 61 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

91 association rows across 37 traits (79 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
Circulating FCRLB levels 4e-272 rs181939013 2 GCST90860085 no MR -> candidate analysis
FCGR3B protein levels 5e-215 rs78349639 10 GCST90469202 no MR -> candidate analysis
Circulating FCGR3B levels 7e-201 rs188703531 1 GCST90860423 no MR -> candidate analysis
FCGR2A protein levels 1e-186 rs9787369 4 GCST90469200 no MR -> candidate analysis
Hematological traits (multi-trait analysis) 2e-120 rs10918341 2 GCST90838667 no MR -> candidate analysis
FCRLB protein levels 6e-87 rs11585262 15 GCST90469210 no MR -> candidate analysis
Non-albumin protein levels 1e-85 rs9787369 8 GCST90019515 no MR -> candidate analysis
White blood cell count (neutrophil) 5e-83 rs10918341 2 GCST90026508 no MR -> candidate analysis
White blood cell count 2e-61 rs2340727 4 GCST008049 no MR -> candidate analysis
Total protein levels (UKB data field 30860) 2e-60 rs71634909 5 GCST90468105 no MR -> candidate analysis
Serum total protein levels 6e-54 rs9787369 6 GCST90019522 no MR -> candidate analysis
Hematology traits 2e-23 rs2340727 1 GCST001779 no MR -> candidate analysis
…and 25 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 978 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
achromatopsia 0.845 established (curated) no MR -> candidate analysis
Retinal dystrophy 0.774 established (curated) no MR -> candidate analysis
Sensorineural hearing impairment 0.684 established (curated) no MR -> candidate analysis
Cone rod dystrophy 0.608 established (curated) no MR -> candidate analysis
cone-rod dystrophy 0.608 established (curated) no MR -> candidate analysis
Rod-cone dystrophy 0.608 established (curated) no MR -> candidate analysis
alcohol drinking 0.438 common-variant locus no MR -> candidate analysis
Macular dystrophy 0.426 established (curated) no MR -> candidate analysis
adolescent idiopathic scoliosis 0.359 common-variant locus no MR -> candidate analysis
neutropenia 0.329 common-variant locus no MR -> candidate analysis
Decreased total leukocyte count 0.324 common-variant locus no MR -> candidate analysis
hereditary disease 0.318 established (curated) no MR -> candidate analysis
cystic kidney disease 0.171 common-variant locus no MR -> candidate analysis

Of the 13 rows above, 13 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 0 known modulators (Cyclic AMP-dependent transcription factor ATF-6 alpha)
gnomAD constraint pLI=4e-11, LOEUF=0.797 — LoF-tolerant
GWAS Catalog 162 unique SNPs / 417 rows
ClinVar 542 records; 4 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance