CausalSentinel

Protein Dossier — CYB5D2 (Neuferricin)

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
ER-negative Breast cancer (Combined Oncoarray; iCOGS; GWAS meta analysis) 0.262 0.0667 8.66e-05 Wald ratio 1 cis NA
Diagnoses - main ICD10: N40 Hyperplasia of prostate 0.391 0.109 3.24e-04 Wald ratio 1 cis NA
Weight -0.0416 0.0134 0.00196 Wald ratio 1 cis NA
Creatinine (enzymatic) in urine -0.0382 0.0145 0.00867 Wald ratio 1 cis NA
HbA1C 0.0494 0.019 0.00932 Wald ratio 1 cis NA
Lumbar spine bone mineral density -0.126 0.0499 0.0115 Wald ratio 1 cis NA
Femoral neck bone mineral density -0.101 0.0431 0.0194 Wald ratio 1 cis NA
Breast cancer (Combined Oncoarray; iCOGS; GWAS meta analysis) 0.0787 0.0374 0.0356 Wald ratio 1 cis NA
Non-cancer illness code self-reported: osteoarthritis -0.118 0.0575 0.0394 Wald ratio 1 cis NA
Diagnoses - main ICD10: R55 Syncope and collapse 0.26 0.127 0.0403 Wald ratio 1 cis NA
Body mass index (BMI) -0.031 0.0152 0.0412 Wald ratio 1 cis NA
Non-cancer illness code self-reported: hayfever or allergic rhinitis -0.146 0.0728 0.0451 Wald ratio 1 cis NA
…and 93 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

17 association rows across 14 traits (15 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
Neuferricin levels 7e-156 rs118123280 3 GCST90248654 no MR -> candidate analysis
Protein disulfide-isomerase A4 (analyte X7146.5) levels 5e-27 rs117969979 1 GCST90426941 no MR -> candidate analysis
Protein disulfide-isomerase A4 levels 1e-21 rs118123280 1 GCST90248918 no MR -> candidate analysis
Serum levels of protein CYB5D2 3e-21 rs77246175 1 GCST90086501 no MR -> candidate analysis
Hemoglobin A1c (HbA1c, maximum, inv-norm transformed) 1e-15 rs12940450 1 GCST90479500 no MR -> candidate analysis
Protein disulfide-isomerase A4 (analyte X7146.16) levels 8e-15 rs118123280 1 GCST90426940 no MR -> candidate analysis
Blood protein levels 2e-13 rs77246175 1 GCST006585 no MR -> candidate analysis
Diastolic blood pressure 3e-11 rs12943517 1 GCST007268 no MR -> candidate analysis
Hematocrit 6e-11 rs8078296 1 GCST90002308 no MR -> candidate analysis
Medication use (agents acting on the renin-angiotensin syste 9e-10 rs12940450 1 GCST90018988 no MR -> candidate analysis
Total cholesterol levels 6e-9 rs2278524 1 GCST90662895 no MR -> candidate analysis
Height 8e-9 rs7219437 1 GCST90018959 MR: beta=-0.0251, p=0.125 (cis)
…and 2 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 63 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
type 2 diabetes mellitus 0.118 common-variant locus no MR -> candidate analysis
diabetes mellitus 0.109 common-variant locus no MR -> candidate analysis
Pancreatic pseudocyst 0.088 common-variant locus no MR -> candidate analysis
hypertensive disorder 0.08 common-variant locus no MR -> candidate analysis
atrial fibrillation 0.066 common-variant locus MR: beta=-0.226, p=0.23 (cis)
Increased blood pressure 0.066 common-variant locus no MR -> candidate analysis
diabetic neuropathy 0.066 common-variant locus no MR -> candidate analysis
essential hypertension 0.055 common-variant locus no MR -> candidate analysis
Abnormality of refraction 0.053 common-variant locus no MR -> candidate analysis
cardiovascular disorder 0.053 common-variant locus no MR -> candidate analysis
upper respiratory tract disorder 0.049 common-variant locus no MR -> candidate analysis
diabetic retinopathy 0.048 common-variant locus no MR -> candidate analysis
anorexia nervosa 0.043 common-variant locus no MR -> candidate analysis
metabolic syndrome 0.04 common-variant locus no MR -> candidate analysis
obesity disorder 0.031 common-variant locus no MR -> candidate analysis

Of the 15 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=1.2e-08, LOEUF=1.43 — LoF-tolerant
GWAS Catalog 62 unique SNPs / 120 rows
ClinVar 116 records; 1 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance