CausalSentinel

Protein Dossier — CREB3L4 (Cyclic AMP-responsive element-binding protein 3-like protein 4)

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
Schizophrenia 0.158 0.0426 2.11e-04 Wald ratio 1 cis NA
Putamen volume -76.6 23.5 0.00112 Wald ratio 1 cis NA
Primary sclerosing cholangitis 0.362 0.117 0.00203 Wald ratio 1 cis NA
Neuroblastoma -0.513 0.169 0.00238 Wald ratio 1 cis NA
Hippocampus volume -55.1 18.4 0.00271 Wald ratio 1 cis NA
Diagnoses - main ICD10: K44 Diaphragmatic hernia -0.248 0.0978 0.0113 Wald ratio 1 cis NA
Fasting glucose 0.0313 0.0125 0.0124 Wald ratio 1 cis NA
Happiness -0.0292 0.0117 0.0125 Wald ratio 1 cis NA
Eye problems or disorders: Diabetes related eye disease 0.24 0.096 0.0125 Wald ratio 1 cis NA
Neo-openness to experience 0.715 0.287 0.0128 Wald ratio 1 cis NA
Non-cancer illness code self-reported: asthma 0.0581 0.0249 0.0198 Wald ratio 1 cis NA
Myocardial infarction 0.0931 0.0415 0.0248 Wald ratio 1 cis NA
…and 111 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

14 association rows across 12 traits (12 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
Cyclic AMP-responsive element-binding protein 3-like protein 2e-123 rs11288257 1 GCST90247145 no MR -> candidate analysis
Serum levels of protein CREB3L4 1e-51 rs11264736 1 GCST90086676 no MR -> candidate analysis
Prostate cancer 2e-38 rs11264734 3 GCST90274713 MR: beta=0.102, p=0.309 (cis)
Cyclic AMP-responsive element-binding protein 3-like protein 7e-25 rs4845586 1 GCST90240818 no MR -> candidate analysis
wg lh intensity-contrast precuneus 9e-15 rs4845586 1 GCST90003816 no MR -> candidate analysis
wg lh intensity-contrast superiorparietal 4e-13 rs6661009 1 GCST90003820 no MR -> candidate analysis
Irritable bowel syndrome (MTAG) 1e-11 rs6671362 1 GCST90824080 no MR -> candidate analysis
wg lh intensity-contrast inferiorparietal 4e-11 rs4845586 1 GCST90003799 no MR -> candidate analysis
Brain shape (segment 15) 4e-9 rs6666703 1 GCST90012894 no MR -> candidate analysis
Cortical thickness (MOSTest) 4e-8 rs6666703 1 GCST010700 no MR -> candidate analysis
Lentiform nucleus volume 4e-6 rs11264736 1 GCST001640 no MR -> candidate analysis
Itch intensity from mosquito bite adjusted by bite size 9e-6 rs78314980 1 GCST004865 no MR -> candidate analysis

4. Phenome map — where this gene is a genetic locus, vs. where MR exists

Top diseases by Open Targets association (of 209 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
placental retention 0.336 common-variant locus no MR -> candidate analysis
prostate carcinoma 0.244 common-variant locus no MR -> candidate analysis
prostate cancer 0.171 common-variant locus MR: beta=0.102, p=0.309 (cis)
cervical carcinoma 0.131 common-variant locus no MR -> candidate analysis
hypertensive disorder 0.119 common-variant locus no MR -> candidate analysis
schizophrenia 0.113 common-variant locus MR: beta=0.158, p=2.11e-04 (cis)

Of the 6 rows above, 4 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=5.9e-08, LOEUF=1.04 — LoF-tolerant
GWAS Catalog 60 unique SNPs / 119 rows
ClinVar 94 records; 2 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance