transcobalamin I deficiency
disease diseaseOn this page
Also known as Haptocorrin deficiencyTCI deficiencytranscobalamin 1 deficiencytranscobalamin-1 deficiency
Summary
transcobalamin I deficiency (MONDO:0008659) is a disease with 1 cohort gene.
At a glance
- Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
- Cohort genes: 1
- ClinVar variants: 123
Clinical features
Epidemiology
Prevalence records
1 prevalence record(s), Orphanet:
| Type | Class | Value | Geography | Validation |
|---|---|---|---|---|
| Point prevalence | <1 / 1 000 000 | Worldwide | Validated |
Identifiers
Disease identifiers
| Field | Value |
|---|---|
| Canonical name | transcobalamin I deficiency |
| Mondo ID | MONDO:0008659 |
| MeSH | C562798 |
| OMIM | 193090 |
| Orphanet | 2967 |
| SNOMED CT | 237933007 |
| UMLS | C0342700 |
| MedGen | 90993 |
| GARD | 0004522 |
| Is cancer (heuristic) | no |
Also known as: Haptocorrin deficiency · TCI deficiency · transcobalamin 1 deficiency · transcobalamin I deficiency · transcobalamin-1 deficiency
Data availability: 123 ClinVar variants · 1 GenCC gene-disease record.
Disease family
Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › inborn errors of metabolism › inborn vitamin metabolic disorder › inborn disorder of cobalamin metabolism and transport › transcobalamin I deficiency
Related subtypes (8): hereditary intrinsic factor deficiency, Imerslund-Grasbeck syndrome, transcobalamin II deficiency, methylmalonic acidemia due to transcobalamin receptor defect, methylmalonic aciduria and homocystinuria, vitamin B12-responsive methylmalonic acidemia, homocystinuria without methylmalonic aciduria, methylmalonic aciduria and/or homocystinuria, cblD type
Genetics & variants
GWAS landscape
No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.
Variant details and genetic-evidence tiers
ClinVar germline variants
123 retrieved; paginated sample, class counts are floors:
57 likely benign, 47 uncertain significance, 7 pathogenic, 6 benign, 4 conflicting classifications of pathogenicity, 2 benign/likely benign
| ClinVar | Variant (HGVS) | Gene | Classification | Review |
|---|---|---|---|---|
| 1459208 | NM_001062.4(TCN1):c.69C>A (p.Cys23Ter) | TCN1 | Pathogenic | criteria provided, single submitter |
| 2745906 | NM_001062.4(TCN1):c.82del (p.Glu27_Val28insTer) | TCN1 | Pathogenic | criteria provided, single submitter |
| 2918494 | NM_001062.4(TCN1):c.524_530del (p.Lys175fs) | TCN1 | Pathogenic | criteria provided, single submitter |
| 3665609 | NM_001062.4(TCN1):c.217C>T (p.Gln73Ter) | TCN1 | Pathogenic | criteria provided, single submitter |
| 4742884 | NM_001062.4(TCN1):c.455del (p.Leu152fs) | TCN1 | Pathogenic | criteria provided, single submitter |
| 4762049 | NM_001062.4(TCN1):c.229C>T (p.Gln77Ter) | TCN1 | Pathogenic | criteria provided, single submitter |
| 568555 | NM_001062.4(TCN1):c.26del (p.Leu9fs) | TCN1 | Pathogenic | criteria provided, single submitter |
| 2278839 | NM_001062.4(TCN1):c.173T>C (p.Val58Ala) | TCN1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 779598 | NM_001062.4(TCN1):c.1000A>G (p.Ile334Val) | TCN1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 780975 | NM_001062.4(TCN1):c.172del (p.Val58fs) | TCN1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 800251 | NM_001062.4(TCN1):c.343G>A (p.Asp115Asn) | TCN1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1005971 | NM_001062.4(TCN1):c.358G>A (p.Asp120Asn) | TCN1 | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 1011214 | NM_001062.4(TCN1):c.1151C>T (p.Pro384Leu) | TCN1 | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 1018822 | NM_001062.4(TCN1):c.556+5G>A | TCN1 | Uncertain significance | criteria provided, single submitter |
| 1019642 | NC_000011.9:g.(?59628980)(59629175_?)dup | TCN1 | Uncertain significance | criteria provided, single submitter |
| 1025075 | NM_001062.4(TCN1):c.727A>C (p.Ser243Arg) | TCN1 | Uncertain significance | criteria provided, single submitter |
| 1035343 | NM_001062.4(TCN1):c.140A>G (p.Asn47Ser) | TCN1 | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 1036789 | NM_001062.4(TCN1):c.344A>T (p.Asp115Val) | TCN1 | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 1043075 | NM_001062.4(TCN1):c.497T>C (p.Val166Ala) | TCN1 | Uncertain significance | criteria provided, single submitter |
| 1057314 | NM_001062.4(TCN1):c.505C>T (p.His169Tyr) | TCN1 | Uncertain significance | criteria provided, single submitter |
| 1346260 | NM_001062.4(TCN1):c.623A>G (p.Lys208Arg) | TCN1 | Uncertain significance | criteria provided, single submitter |
| 1385555 | NM_001062.4(TCN1):c.322G>A (p.Ala108Thr) | TCN1 | Uncertain significance | criteria provided, single submitter |
| 1386775 | NM_001062.4(TCN1):c.542G>A (p.Ser181Asn) | TCN1 | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 1387853 | NM_001062.4(TCN1):c.557A>C (p.Asp186Ala) | TCN1 | Uncertain significance | criteria provided, single submitter |
| 1406523 | NM_001062.4(TCN1):c.597G>T (p.Lys199Asn) | TCN1 | Uncertain significance | criteria provided, single submitter |
| 1424205 | NM_001062.4(TCN1):c.112C>A (p.Pro38Thr) | TCN1 | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 1432371 | NM_001062.4(TCN1):c.473A>G (p.Asn158Ser) | TCN1 | Uncertain significance | criteria provided, single submitter |
| 1511533 | NM_001062.4(TCN1):c.730A>G (p.Thr244Ala) | TCN1 | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 1525440 | NM_001062.4(TCN1):c.214A>T (p.Met72Leu) | TCN1 | Uncertain significance | criteria provided, single submitter |
| 1715456 | NM_001062.4(TCN1):c.128T>C (p.Met43Thr) | TCN1 | Uncertain significance | criteria provided, single submitter |
Genes & proteins
Mendelian disease overlap and somatic drivers
GenCC: 1 · Orphanet: 0 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0
GenCC gene–disease validity (cohort genes)
the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.
| Gene | Classification | Inheritance | Disease | Records |
|---|---|---|---|---|
| TCN1 | Moderate | Autosomal recessive | transcobalamin I deficiency |
Cohort genes → proteins
1 cohort genes, 1 distinct canonical proteins.
Evidence partition
| Subset | Genes |
|---|---|
| multi_evidence | 1 |
Cohort genes (full)
| Symbol | HGNC | Ensembl | UniProt | Name | Evidence |
|---|---|---|---|---|---|
| TCN1 | HGNC:11652 | ENSG00000134827 | P20061 | Transcobalamin-1 | gencc,clinvar |
Cohort function summary
Lead sentence per gene, UniProt-curated.
| Symbol | Protein name | Function (lead sentence) |
|---|---|---|
| TCN1 | Transcobalamin-1 | Binds vitamin B12 with femtomolar affinity and protects it from the acidic environment of the stomach. |
Protein-family classification
Druggable: 0 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.0
Family distribution
Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.
| Family | Genes | Fold | FDR |
|---|---|---|---|
| Other/Unknown | 1 | 1.8× | 0.558 |
Per-gene assignment
| Symbol | Family | Druggable? | EC | InterPro (top 3) |
|---|---|---|---|---|
| TCN1 | Other/Unknown | no | Cbl-bd_prot, Transcobalamin-like_C, Cobalamin_Transport |
Expression context
Cohort genes with no expression data: 0.
1 cohort gene are a single-cell marker in ≥1 SCXA experiment.
Breadth distribution (Bgee present_calls)
| Bucket | Genes |
|---|---|
| narrow (1-5 tissues) | 0 |
| moderate (6-20) | 0 |
| broad (>20) | 1 |
| unknown | 0 |
Top tissues across cohort
| Tissue | Cohort genes |
|---|---|
| olfactory segment of nasal mucosa | 1 |
| pancreatic ductal cell | 1 |
| trachea | 1 |
Per-gene tissue summary (top 30)
| Symbol | Bgee breadth | FANTOM5 breadth | SCXA | Top tissues |
|---|---|---|---|---|
| TCN1 | 187 | tissue_specific | marker | pancreatic ductal cell, olfactory segment of nasal mucosa, trachea |
Protein interactions among cohort
Intra-cohort edges: 0.
Hub genes (top 10 by interactor count)
| Symbol | Interactor count |
|---|---|
| TCN1 | 845 |
Structural data
PDB: 1 · AlphaFold-only: 0 · No structure: 0
Cohort genes with PDB structures (top 30)
| Symbol | UniProt | PDB entries |
|---|---|---|
| TCN1 | P20061 | 2 |
Function
Pathway analysis
Distinct Reactome pathways touched by cohort: 9. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).
Pathways by enrichment
Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.
| Pathway | Cohort genes | Fold | FDR | Sample cohort genes |
|---|---|---|---|---|
| Transport of RCbl within the body | 1 | 1427.5× | 0.004 | TCN1 |
| Uptake of dietary cobalamins into enterocytes | 1 | 1142.0× | 0.004 | TCN1 |
| Cobalamin (Cbl, vitamin B12) transport and metabolism | 1 | 634.4× | 0.005 | TCN1 |
| Metabolism of water-soluble vitamins and cofactors | 1 | 181.3× | 0.012 | TCN1 |
| Metabolism of vitamins and cofactors | 1 | 116.5× | 0.015 | TCN1 |
| Innate Immune System | 1 | 25.5× | 0.056 | TCN1 |
| Neutrophil degranulation | 1 | 23.1× | 0.056 | TCN1 |
| Immune System | 1 | 13.0× | 0.086 | TCN1 |
| Metabolism | 1 | 11.6× | 0.086 | TCN1 |
GO biological processes by enrichment
Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.
| GO term | Cohort genes | Fold | FDR | Sample cohort genes |
|---|---|---|---|---|
| cobalt ion transport | 1 | 2407.4× | 5e-04 | TCN1 |
| cobalamin transport | 1 | 1872.4× | 5e-04 | TCN1 |
Therapeutics
Drug target analysis
Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1
Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).
Top cohort targets by molecule count
| Symbol | Molecules | Max phase |
|---|---|---|
| TCN1 | 0 | 0 |
Bioactivity and enzyme data
Enzyme cohort genes (≥1 EC): 0.
Pharmacogenomics
Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.
No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).
Chemical tractability of cohort targets
0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.
Druggability pyramid
Cohort genes binned by druggability tier (high → low):
| Tier | Definition | Genes | Symbols |
|---|---|---|---|
| A | Approved (phase 4 drug) | 0 | |
| B | Phased (≥1) drug, not yet approved | 0 | |
| C | Druggable family + PDB, no drug | 0 | |
| D | Druggable family + AlphaFold only, no drug | 0 | |
| E | Difficult family or no structure, no drug | 1 | TCN1 |
Undrugged target profiles
1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).
| Symbol | ChEMBL assays | Drugged partners (top 3) |
|---|---|---|
| TCN1 | 0 | — |
Clinical trials & evidence
Clinical trials
Clinical trials: 0.
Related Atlas pages
- Cohort genes: TCN1