LIG4 Gene: DNA Ligase 4
Essential for DNA double-strand break repair via non-homologous end joining
Gene Information Card
| Symbol | LIG4 |
|---|---|
| Full Name | DNA ligase 4 |
| Gene Type | protein-coding |
| Chromosomal Location | 13q33.3 |
| NCBI Gene ID | 3981 ncbi.nlm.nih.gov/gene/3981 |
| Ensembl ID | ENSG00000174405 |
| UniProt ID | P49917 |
| OMIM ID | 601837 |
| HGNC ID | 6601 |
| Aliases | LIG4S, DNA ligase IV, DNLL, LIG4 |
Description
The LIG4 gene encodes DNA ligase 4, a critical enzyme in the non-homologous end joining (NHEJ) pathway for repairing DNA double-strand breaks. It catalyzes the final ligation step during V(D)J recombination and repair of radiation-induced breaks. Mutations in LIG4 cause LIG4 syndrome, characterized by immunodeficiency, developmental delay, and increased cancer risk.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| LIG4 syndrome | Loss-of-function mutations impair NHEJ, leading to defective V(D)J recombination and DNA repair | OMIM #606593 |
| Severe combined immunodeficiency (SCID) | Defective NHEJ blocks lymphocyte development | ClinVar, PMID: 11526498 |
| Acute lymphoblastic leukemia (ALL) | Somatic mutations and reduced LIG4 activity linked to genomic instability | COSMIC, PMID: 23334667 |
| Breast cancer | LIG4 polymorphisms associated with increased risk | NCBI Gene, PMID: 19127258 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Bone marrow | 12.5 | Medium |
| Lymph node | 10.2 | Medium |
| Spleen | 9.8 | Medium |
| Testis | 8.1 | Low |
| Brain | 4.3 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 15.0 | High expression |
| K562 | 12.3 | Leukemia cell line |
| HeLa | 10.5 | Cervical cancer cell line |
| MCF7 | 8.9 | Breast cancer cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| R278H | Missense | Rare | Reduced ligase activity, associated with LIG4 syndrome |
| R580X | Nonsense | Rare | Truncated protein, loss of function |
| T9I | Missense | Rare | Impaired interaction with XRCC4 |
| K469E | Missense | Rare | Reduced adenylation activity |
Mutation functional classification
Loss of Function (LOF)
Most LIG4 mutations are loss-of-function, impairing DNA ligation and NHEJ, leading to immunodeficiency and radiosensitivity.
Gain of Function (GOF)
No known gain-of-function mutations reported.
Dominant Negative (DN)
Some missense mutations may exert dominant-negative effects by interfering with the XRCC4-LIG4 complex.
View complete mutation data：
Gene Ontology (GO)
| • DNA ligase activity (GO:0003909) | • DNA binding (GO:0003677) |
| • ATP binding (GO:0005524) | • DNA repair (GO:0006281) |
| • Non-homologous end joining (GO:0006303) | • V(D)J recombination (GO:0033151) |
Pathways
• Non-homologous end joining (NHEJ) - Reactome R-HSA-5693571
• DNA double-strand break repair - KEGG hsa03450
• V(D)J recombination - KEGG hsa04659
Protein Summary
DNA ligase 4 (UniProt P49917) is a 911-amino acid nuclear protein that forms a complex with XRCC4 and XLF to catalyze the ATP-dependent ligation of DNA double-strand breaks during NHEJ. It contains an N-terminal DNA-binding domain, a central adenylation domain, and a C-terminal BRCT domain. The protein is essential for V(D)J recombination and cellular resistance to ionizing radiation.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| LIG4 Knockout HEK293 Cell Line | EDJ-KQ5127 | Human | 3981 | Details Get a Quote |
| LIG4 Knockout A-549 Cell Line | EDJ-KQ28087 | Human | 3981 | Details Get a Quote |
| LIG4 Knockout HCT 116 Cell Line | EDJ-KQ28088 | Human | 3981 | Details Get a Quote |
| LIG4 Knockout HeLa Cell Line | EDJ-KQ28089 | Human | 3981 | Details Get a Quote |
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