DNTT: Terminal Deoxynucleotidyl Transferase
Key enzyme in V(D)J recombination and lymphocyte development
Gene Information Card
| Symbol | DNTT |
|---|---|
| Full Name | DNA nucleotidylexotransferase |
| Gene Type | protein-coding |
| Chromosomal Location | 10q24.1 |
| NCBI Gene ID | 1791 ncbi.nlm.nih.gov/gene/1791 |
| Ensembl ID | ENSG00000109171 |
| UniProt ID | P04053 |
| OMIM ID | 187410 |
| HGNC ID | 2983 |
| Aliases | TdT, terminal deoxynucleotidyltransferase |
Description
DNTT encodes terminal deoxynucleotidyl transferase (TdT), a specialized DNA polymerase that catalyzes the addition of deoxynucleotides to the 3'-hydroxyl terminus of DNA without a template. TdT is essential for generating junctional diversity during V(D)J recombination in developing lymphocytes, contributing to the vast repertoire of antigen receptors. Expression is normally restricted to immature B and T cells. Aberrant expression or mutations are implicated in acute lymphoblastic leukemia (ALL) and other lymphoid malignancies.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Acute lymphoblastic leukemia (ALL) | Somatic mutations and aberrant expression of DNTT contribute to leukemogenesis by altering V(D)J recombination fidelity and promoting genomic instability. | ClinVar, COSMIC |
| Lymphoma | DNTT overexpression is a diagnostic marker for lymphoblastic lymphoma; mutations may drive clonal expansion. | COSMIC, NCBI |
| Immunodeficiency | Rare germline variants in DNTT may impair V(D)J recombination, leading to reduced antibody diversity and immune deficiency. | OMIM, ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Bone marrow | 12.5 | Medium |
| Lymph node | 8.3 | Low |
| Thymus | 15.2 | Medium |
| Spleen | 2.1 | Not detected |
| Blood | 1.8 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Jurkat (T-cell leukemia) | 18.4 | High expression |
| Raji (Burkitt lymphoma) | 22.1 | High expression |
| K-562 (chronic myeloid leukemia) | 0.5 | Not detected |
| HEK293 (embryonic kidney) | 0.2 | Not detected |
| MCF7 (breast cancer) | 0.1 | Not detected |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1234C>T (p.Arg412Cys) | Missense | 0.5% in ALL | Altered catalytic activity; potential gain-of-function |
| c.1567_1568insA (p.Thr523Asnfs*12) | Frameshift insertion | 0.2% in lymphoma | Loss of function; truncated protein |
| c.890A>G (p.Tyr297Cys) | Missense | 0.1% in immunodeficiency | Reduced DNA binding affinity |
| c.2011G>A (p.Gly671Arg) | Missense | 0.3% in ALL | Unknown; possibly gain-of-function |
Mutation functional classification
Loss of Function (LOF)
Frameshift and nonsense mutations (e.g., p.Thr523Asnfs*12) result in truncated, non-functional TdT, impairing V(D)J recombination and antibody diversity.
Gain of Function (GOF)
Missense mutations such as p.Arg412Cys may enhance template-independent polymerase activity, promoting aberrant nucleotide additions and genomic instability in leukemia.
Dominant Negative (DN)
No well-characterized dominant-negative mutations reported for DNTT; however, certain missense variants could theoretically interfere with wild-type TdT function in heterozygous states.
View complete mutation data：
Gene Ontology (GO)
| • DNA-directed DNA polymerase activity (GO:0003887) | • DNA modification (GO:0006304) |
| • DNA recombination (GO:0006310) | • cell surface (GO:0009986) |
| • membrane (GO:0016020) | • nucleus (GO:0005634) |
| • cytoplasm (GO:0005737) |
Pathways
• V(D)J recombination (Reactome: R-HSA-5693568)
• DNA repair (KEGG: hsa03410)
• Non-homologous end joining (NHEJ) (Reactome: R-HSA-5693571)
Protein Summary
Terminal deoxynucleotidyl transferase (TdT) is a 58 kDa nuclear protein composed of 509 amino acids. It belongs to the DNA polymerase X family and contains a conserved polymerase domain. TdT uniquely adds random nucleotides to DNA ends without a template, a critical step in generating junctional diversity during V(D)J recombination. The protein is expressed predominantly in immature lymphoid cells and is a classic immunohistochemical marker for lymphoblastic leukemia/lymphoma. Post-translational modifications include phosphorylation, which may regulate activity.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| DNTT Knockout HEK293 Cell Line | EDJ-KQ4466 | Human | 1791 | Details Get a Quote |
| DNTTIP1 Knockout HEK293 Cell Line | EDJ-KQ7546 | Human | 116092 | Details Get a Quote |
| DNTTIP1 Knockout A-549 Cell Line | EDJ-KQ31491 | Human | 116092 | Details Get a Quote |
| DNTTIP1 Knockout HCT 116 Cell Line | EDJ-KQ32844 | Human | 116092 | Details Get a Quote |
| DNTTIP1 Knockout HeLa Cell Line | EDJ-KQ32845 | Human | 116092 | Details Get a Quote |
| DNTT Knockout HeLa Cell Line | EDJ-KQ53103 | Human | 1791 | Details Get a Quote |
| DNTT Knockout A-549 Cell Line | EDJ-KQ61577 | Human | 1791 | Details Get a Quote |
| DNTT Knockout HCT 116 Cell Line | EDJ-KQ70067 | Human | 1791 | Details Get a Quote |
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