CausalSentinel

Protein Dossier — TCN2 (Transcobalamin-2)

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
Height 0.0152 0.00414 2.46e-04 Wald ratio 1 cis NA
Age at menarche 0.0262 0.00815 0.0013 Wald ratio 1 cis NA
Non-cancer illness code self-reported: deep venous thrombosis (dvt) 0.0672 0.0221 0.00234 Wald ratio 1 cis NA
Non-cancer illness code self-reported: depression 0.0377 0.0132 0.00434 Wald ratio 1 cis NA
Diagnoses - main ICD10: N81 Female genital prolapse 0.0716 0.0259 0.00575 Wald ratio 1 cis NA
Primary sclerosing cholangitis -0.109 0.0414 0.00861 Wald ratio 1 cis NA
Urinary albumin-to-creatinine ratio -0.0221 0.00856 0.00986 Wald ratio 1 cis NA
Ferritin 0.0333 0.013 0.0104 Wald ratio 1 cis NA
Urate -0.0193 0.00773 0.0124 Wald ratio 1 cis NA
Forced expiratory volume in 1-second (FEV1) 0.0069 0.00288 0.0167 Wald ratio 1 cis NA
Neuroticism -0.00966 0.00414 0.0196 Wald ratio 1 cis NA
PGC cross-disorder traits -0.0381 0.0168 0.0238 Wald ratio 1 cis NA
…and 105 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

46 association rows across 30 traits (43 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
Transcobalamin-2 levels 2e-4615 rs5753236 3 GCST90249968 no MR -> candidate analysis
Circulating TCN2 levels 8e-1779 rs740234 3 GCST90860457 no MR -> candidate analysis
Holo-Transcobalamin-2 levels 5e-547 rs1801198 2 GCST90247921 no MR -> candidate analysis
Transcobalamin-2 levels (TCN2.5584.21.3) 4e-256 rs4820885 4 GCST90243041 no MR -> candidate analysis
Serum levels of protein TCN2 5e-214 rs5753236 3 GCST90089075 no MR -> candidate analysis
Cerebrospinal fluid protein TCN2 levels 1e-122 rs9621047 1 GCST90945052 no MR -> candidate analysis
Blood protein levels 1e-120 rs4820023 1 GCST006585 no MR -> candidate analysis
Vascular endothelial growth factor receptor 1 protein levels 7e-61 rs4820885 1 GCST90443210 no MR -> candidate analysis
Vitamin B12 levels 5e-49 rs1131603 2 GCST90277442 no MR -> candidate analysis
Vitamin B-complex deficiencies (PheCode 261.2) 6e-46 rs1131603 2 GCST90479910 no MR -> candidate analysis
F8WE86 protein level (protein group normalized intensity) 2e-27 rs4820023 1 GCST90570768 no MR -> candidate analysis
Other vitamin B12 deficiency anemia (PheCode 281.12) 5e-25 rs1131603 2 GCST90479962 no MR -> candidate analysis
…and 18 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 274 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
transcobalamin II deficiency 0.905 established (curated) no MR -> candidate analysis
Transcobalamin deficiency 0.875 established (curated) no MR -> candidate analysis
Pancytopenia 0.547 established (curated) no MR -> candidate analysis
vitamin B12 deficiency 0.793 common-variant locus no MR -> candidate analysis
megaloblastic anemia 0.793 common-variant locus no MR -> candidate analysis
vitamin B deficiency 0.76 common-variant locus no MR -> candidate analysis
hereditary disease 0.682 established (curated) no MR -> candidate analysis
deficiency anemia 0.668 common-variant locus no MR -> candidate analysis
vitamin deficiency disorder 0.662 common-variant locus no MR -> candidate analysis
transcobalamin I deficiency 0.608 established (curated) no MR -> candidate analysis
Alzheimer disease 0.517 common-variant locus no MR -> candidate analysis
Nephroblastoma 0.445 common-variant locus no MR -> candidate analysis
atrial fibrillation 0.3 common-variant locus MR: beta=0.0549, p=0.066 (cis)
aortic stenosis 0.18 common-variant locus no MR -> candidate analysis
placenta praevia 0.153 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=1.3e-08, LOEUF=0.931 — LoF-tolerant
GWAS Catalog 84 unique SNPs / 168 rows
ClinVar 832 records; 6 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance