TONSL Gene: TONSL Recombinase Repair Factor
Essential role in homologous recombination and DNA repair
Gene Information Card
| Symbol | TONSL |
|---|---|
| Full Name | tonsoku-like, DNA repair protein |
| Gene Type | protein-coding |
| Chromosomal Location | 8q24.3 |
| NCBI Gene ID | 4796 ncbi.nlm.nih.gov/gene/4796 |
| Ensembl ID | ENSG00000120949 |
| UniProt ID | Q96HA7 |
| OMIM ID | 604546 |
| HGNC ID | 7801 |
| Aliases | MMD2, NFKBIL2, IKBL2 |
Description
The TONSL gene encodes a protein that functions as a recombinase repair factor, essential for homologous recombination-mediated DNA repair. It interacts with MMS22L to form a complex that facilitates the loading of RAD51 onto single-stranded DNA at stalled replication forks, promoting repair and genome stability.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Spondyloepimetaphyseal dysplasia, MMD2 type | Loss-of-function mutations in TONSL impair DNA repair, leading to skeletal abnormalities | OMIM #604546 |
| Fanconi anemia-like phenotype | Defective homologous recombination due to TONSL deficiency | PubMed studies |
| Cancer (various) | Somatic mutations and altered expression may contribute to genomic instability | COSMIC |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 12.5 | Medium |
| Bone marrow | 8.3 | Low |
| Lymph node | 7.1 | Low |
| Brain | 4.2 | Not detected |
| Liver | 3.8 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 15.2 | High expression |
| HeLa | 11.0 | Moderate expression |
| K562 | 9.5 | Moderate expression |
| A549 | 6.8 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1462C>T (p.Arg488*) | Nonsense | Rare | Loss of function; truncation |
| c.2155G>A (p.Gly719Arg) | Missense | Rare | Likely damaging; disrupts protein interaction |
| c.3073_3074del (p.Leu1025Valfs*2) | Frameshift | Rare | Loss of function; premature stop |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations lead to truncated or absent protein, impairing homologous recombination.
Gain of Function (GOF)
Not reported for TONSL.
Dominant Negative (DN)
Not reported for TONSL.
View complete mutation data：
Gene Ontology (GO)
| • double-strand break repair via homologous recombination (GO:0000724) | • damaged DNA binding (GO:0003684) |
| • protein binding (GO:0005515) | • nucleus (GO:0005634) |
| • DNA repair (GO:0006281) |
Pathways
• Homologous recombination (Reactome: R-HSA-5693571)
• Fanconi anemia pathway (KEGG: hsa03460)
• DNA damage response (Reactome: R-HSA-73894)
Protein Summary
The TONSL protein (96 kDa) contains an ankyrin repeat domain and a TONSL-like domain. It forms a complex with MMS22L that recognizes histone H3 unmethylated at lysine 4 (H3K4me0) at sites of DNA damage, recruiting RAD51 to promote homologous recombination. It is essential for genome stability and replication fork restart.
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