TCN2 Gene - Transcobalamin 2
Genetic and Functional Insights into Transcobalamin 2 (TCN2)
Gene Information Card
| Symbol | TCN2 |
|---|---|
| Full Name | Transcobalamin 2 |
| Gene Type | Protein coding |
| Chromosomal Location | 22q12.2 |
| NCBI Gene ID | 6948 ncbi.nlm.nih.gov/gene/6948 |
| Ensembl ID | ENSG00000100393 |
| UniProt ID | P20062 |
| OMIM ID | 613441 |
| HGNC ID | 11653 |
| Aliases | TC2, TC-2, transcobalamin II |
Description
The TCN2 gene encodes transcobalamin 2 (TC2), a plasma protein that binds and transports cobalamin (vitamin B12) from the intestine to peripheral tissues. TC2 is essential for cellular uptake of cobalamin via receptor-mediated endocytosis. Mutations in TCN2 cause transcobalamin II deficiency, leading to impaired B12 delivery, resulting in megaloblastic anemia, methylmalonic aciduria, and homocystinuria.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Transcobalamin II deficiency | Loss-of-function mutations in TCN2 impair cobalamin transport, causing intracellular B12 deficiency and accumulation of methylmalonic acid and homocysteine. | ClinVar, OMIM |
| Methylmalonic aciduria due to transcobalamin deficiency | Defective B12 transport leads to reduced adenosylcobalamin, impairing methylmalonyl-CoA mutase activity. | OMIM #613441 |
| Homocystinuria without methylmalonic aciduria | Impaired B12 delivery reduces methionine synthase activity, causing homocysteine accumulation. | OMIM #613441 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 12.3 | Medium |
| Kidney | 8.7 | Medium |
| Small intestine | 6.5 | Medium |
| Bone marrow | 4.2 | Low |
| Placenta | 3.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 10.1 | Hepatocyte cell line |
| Caco-2 | 7.3 | Intestinal epithelial cell line |
| HEK293 | 5.6 | Embryonic kidney cell line |
| K562 | 4.0 | Erythroleukemia cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.580C>T (p.Arg194*) | Nonsense | Rare | Loss of function; truncated protein |
| c.1115G>A (p.Arg372Gln) | Missense | Rare | Impaired cobalamin binding |
| c.1226A>G (p.Tyr409Cys) | Missense | Rare | Reduced secretion and stability |
| c.1A>G (p.Met1Val) | Start loss | Rare | No protein synthesis |
Mutation functional classification
Loss of Function (LOF)
Most TCN2 mutations are loss-of-function, leading to reduced or absent transcobalamin 2 activity, causing impaired cobalamin transport and intracellular B12 deficiency.
Gain of Function (GOF)
No gain-of-function mutations have been reported for TCN2.
Dominant Negative (DN)
No dominant-negative mutations have been described; TCN2 deficiency is autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
| • extracellular region (GO:0005576) | • extracellular space (GO:0005615) |
| • drug binding (GO:0008144) | • L-ascorbic acid binding (GO:0031418) |
| • cobalamin binding (GO:0031769) | • signaling receptor activity (GO:0038023) |
| • hormone binding (GO:0042562) | • ATPase activity (GO:0042623) |
| • intestinal absorption (GO:0050892) | • vitamin transport (GO:0051180) |
| • cobalamin transport (GO:0051181) | • extracellular exosome (GO:0070062) |
Pathways
• Vitamin B12 (cobalamin) transport and metabolism
• Cobalamin (B12) deficiency
• One-carbon metabolism
Protein Summary
Transcobalamin 2 (TC2) is a 427-amino acid glycoprotein synthesized primarily in the liver and secreted into plasma. It binds newly absorbed cobalamin (vitamin B12) with high affinity and delivers it to cells via the transcobalamin receptor (CD320). The protein consists of an N-terminal signal peptide, a cobalamin-binding domain, and a C-terminal region involved in receptor interaction. TC2 is essential for cellular B12 uptake; deficiency leads to severe metabolic and hematologic abnormalities.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| TCN2 Knockout HEK293 Cell Line | EDJ-KQ15666 | Human | 6948 | Details Get a Quote |
| TCN2 Knockout HeLa Cell Line | EDJ-KQ45334 | Human | 6948 | Details Get a Quote |
| TCN2 Knockout A-549 Cell Line | EDJ-KQ46564 | Human | 6948 | Details Get a Quote |
| TCN2 Knockout HCT 116 Cell Line | EDJ-KQ46565 | Human | 6948 | Details Get a Quote |
| TCN2 Knockout THP-1 Cell Line | EDJ-KZ500 | Human | 6948 | Details Get a Quote |
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