CausalSentinel

Protein Dossier — PCBD1 (Pterin-4-alpha-carbinolamine dehydratase)

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
Lung adenocarcinoma 0.496 0.158 0.00165 Wald ratio 1 cis NA
Diagnoses - main ICD10: R14 Flatulence and related conditions 0.935 0.3 0.00182 Wald ratio 1 cis NA
PGC cross-disorder traits 0.255 0.0842 0.00248 Wald ratio 1 cis NA
Non-cancer illness code self-reported: depression -0.252 0.0885 0.00439 Wald ratio 1 cis NA
Major depressive disorder 0.372 0.149 0.0126 Wald ratio 1 cis NA
Cancer code self-reported: small intestine or small bowel cancer 0.882 0.38 0.0204 Wald ratio 1 cis NA
Eye problems or disorders: Glaucoma -0.668 0.301 0.0265 Wald ratio 1 cis NA
Non-cancer illness code self-reported: pernicious anaemia 0.44 0.207 0.0334 Wald ratio 1 cis NA
Lung cancer 0.229 0.11 0.0371 Wald ratio 1 cis NA
Fasting insulin -0.0428 0.0217 0.0482 Wald ratio 1 cis NA
Knee and hip osteoarthritis 0.282 0.144 0.05 Wald ratio 1 cis NA
Non-cancer illness code self-reported: hypothyroidism or myxoedema 0.127 0.065 0.0509 Wald ratio 1 cis NA
…and 81 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

3 association rows across 2 traits (3 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
Immature fraction of reticulocytes 3e-10 rs10999573 1 GCST004628 no MR -> candidate analysis
Type 2 diabetes 4e-10 rs827237 2 GCST010555 MR: beta=0.269, p=0.109 (cis)

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

Top diseases by Open Targets association (of 404 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
Hyperphenylalaninemia 0.907 established (curated) no MR -> candidate analysis
pterin-4 alpha-carbinolamine dehydratase 1 deficiency 0.849 established (curated) no MR -> candidate analysis
Dehydratase deficiency 0.608 established (curated) no MR -> candidate analysis
type 2 diabetes mellitus 0.742 common-variant locus no MR -> candidate analysis
diabetes mellitus 0.546 common-variant locus no MR -> candidate analysis
neuroendocrine neoplasm 0.388 common-variant locus no MR -> candidate analysis
ovarian neoplasm 0.388 common-variant locus no MR -> candidate analysis
placenta praevia 0.378 common-variant locus no MR -> candidate analysis
amyotrophic lateral sclerosis 0.36 common-variant locus no MR -> candidate analysis
digestive system disorder 0.348 common-variant locus no MR -> candidate analysis
alcohol drinking 0.32 common-variant locus no MR -> candidate analysis
frozen shoulder 0.306 common-variant locus no MR -> candidate analysis
urolithiasis 0.306 common-variant locus no MR -> candidate analysis
hereditary disease 0.285 established (curated) no MR -> candidate analysis

Of the 14 rows above, 14 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=3e-07, LOEUF=1.93 — LoF-tolerant
GWAS Catalog 38 unique SNPs / 76 rows
ClinVar 155 records; 7 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance