CausalSentinel

Protein Dossier — TCN1 (Transcobalamin-1)

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
Hearing difficulty or problems: Yes	0.0364	0.0146	0.0125	Wald ratio	1	cis	NA
Non-cancer illness code self-reported: osteoporosis	0.149	0.0608	0.0145	Wald ratio	1	cis	NA
Sodium in urine	0.0176	0.00861	0.0405	Wald ratio	1	cis	NA
Non-cancer illness code self-reported: uterine fibroids	-0.167	0.0842	0.048	Wald ratio	1	cis	NA
Non-cancer illness code self-reported: osteoarthritis	0.0531	0.0278	0.056	Wald ratio	1	cis	NA
Non-cancer illness code self-reported: diverticular disease or diverticulitis	-0.186	0.101	0.0657	Wald ratio	1	cis	NA
High grade serous ovarian cancer	0.105	0.0602	0.0813	Wald ratio	1	cis	NA
Non-cancer illness code self-reported: pernicious anaemia	-0.526	0.304	0.0837	Wald ratio	1	cis	NA
Diagnoses - main ICD10: M72 Fibroblastic disorders	-0.28	0.163	0.0855	Wald ratio	1	cis	NA
Diagnoses - main ICD10: R14 Flatulence and related conditions	0.428	0.257	0.0951	Wald ratio	1	cis	NA
Diagnoses - main ICD10: R11 Nausea and vomiting	0.191	0.117	0.103	Wald ratio	1	cis	NA
Diagnoses - main ICD10: M17 Gonarthrosis [arthrosis of knee]	-0.109	0.0708	0.122	Wald ratio	1	cis	NA
…and 49 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

33 association rows across 16 traits (32 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
Vitamin B-complex deficiencies (PheCode 261.2)	1e-140	rs503644	4	GCST90479910	no MR -> candidate analysis
TCN1 protein levels	6e-137	rs186499460	3	GCST90470819	no MR -> candidate analysis
Transcobalamin-1 levels	3e-125	rs34324219	3	GCST90249967	no MR -> candidate analysis
Vitamin B12 levels	1e-111	rs34324219	3	GCST90277442	no MR -> candidate analysis
Other vitamin B12 deficiency anemia (PheCode 281.12)	1e-72	rs503644	3	GCST90479962	no MR -> candidate analysis
Megaloblastic anemia (PheCode 281.1)	3e-63	rs34324219	2	GCST90475774	no MR -> candidate analysis
Other deficiency anemia (PheCode 281)	1e-53	rs34324219	2	GCST90475772	no MR -> candidate analysis
Serum levels of protein TCN1	4e-47	rs34324219	1	GCST90086628	no MR -> candidate analysis
Transcobalamin-1 level in Chronic kidney disease with hypert	2e-36	rs11822978	1	GCST90233141	no MR -> candidate analysis
Transcobalamin-1 level in Chronic kidney disease with hypert	5e-31	rs11822978	1	GCST90235293	no MR -> candidate analysis
Transcobalamin-1 levels (TCN1.11232.46.3)	5e-30	rs34528912	2	GCST90243040	no MR -> candidate analysis
Vitamin deficiency (PheCode 261)	7e-22	rs34324219	3	GCST90475700	no MR -> candidate analysis
…and 4 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 231 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
vitamin B deficiency	0.899	—	common-variant locus	no MR -> candidate analysis
vitamin B12 deficiency	0.885	—	common-variant locus	no MR -> candidate analysis
megaloblastic anemia	0.87	—	common-variant locus	no MR -> candidate analysis
deficiency anemia	0.87	—	common-variant locus	no MR -> candidate analysis
transcobalamin I deficiency	0.868	—	established (curated)	no MR -> candidate analysis
vitamin deficiency disorder	0.852	—	common-variant locus	no MR -> candidate analysis
pernicious anemia	0.794	—	common-variant locus	no MR -> candidate analysis
nutritional deficiency disease	0.588	—	common-variant locus	no MR -> candidate analysis
celiac disease	0.389	—	common-variant locus	no MR -> candidate analysis
uveitis	0.363	—	common-variant locus	no MR -> candidate analysis
tuberculosis	0.049	—	common-variant locus	no MR -> candidate analysis

Of the 11 rows above, 11 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=9.8e-17, LOEUF=1.29 — LoF-tolerant
GWAS Catalog	37 unique SNPs / 74 rows
ClinVar	195 records; 4 pathogenic in sample of 30
PharmGKB/ClinPGx	no annotations

Caveats declared by the tools

• phenome — Top 30 of 231 associated diseases by overall score. genetic_association aggregates GWAS common-variant AND rare-variant evidence. These are ASSOCIATIONS (loci), not causal claims.
• chembl — No ChEMBL target for ‘TCN1’.
• clinvar — Pathogenic count is over the 30 record(s) retrieved, NOT over all 195 ClinVar records for this gene; it is a sample, not a rate.
• pharmgkb — No PharmGKB/ClinPGx clinical annotations (gene may not be a pharmacogene).
• gwas_traits — Top 16 of 16 traits by best p-value, aggregated from 33 association rows. These are GWAS ASSOCIATIONS (loci), not causal claims; mapped genes at a locus are not necessarily the effector gene.

Sources

• uniprot: https://www.uniprot.org/uniprotkb/P20061 — UniProt release 2026_02 (10-June-2026)
• mr_outcomes: https://epigraphdb.org/pqtl/ — EpiGraphDB pQTL MR (Zheng et al., Nat Genet 2020) — pre-computed two-sample MR; retrieved, not computed by this agent; EpiGraphDB build 1.0, pQTL dataset v3.0
• phenome: https://platform.opentargets.org/target/ENSG00000134827/associations — Open Targets data release 26.06
• gnomad: https://gnomad.broadinstitute.org/gene/TCN1 — gnomAD constraint via GraphQL API (reference genome GRCh38)
• gwas: https://www.ebi.ac.uk/gwas/genes/TCN1 — GWAS Catalog REST (live; release not exposed by this endpoint)
• clinvar: https://www.ncbi.nlm.nih.gov/clinvar/?term=TCN1%5Bgene%5D — ClinVar build Build260809-1055.1
• gwas_traits: https://www.ebi.ac.uk/gwas/genes/TCN1 — GWAS Catalog search API (live; release not exposed)

Provenance

• Generated: 2026-08-14T05:17:54 · Tier: A
• Fully mechanical: every cell above is rendered from tool return values. No language model wrote any part of this dossier.
• MR estimates, where present, are retrieved from published work (EpiGraphDB pQTL, Zheng et al. Nat Genet 2020); nothing is computed here.
• Tool errors this run: none

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