Alt. symbols: LIG4S

Approved name: DNA ligase 4
Alt. names: ligase IV, DNA, ATP-dependent | polydeoxyribonucleotide synthase [ATP] 4, polynucleotide ligase, sealase, DNA repair enzyme, DNA joinase

Location: 13q33.3: 108207439 - 108218368 (-)
Gene type: protein_coding, 19 transcripts.

Scores: LoFtool: 0.531000 | pLI: 0.00210124 | LOEUF: 0.802

HGNC: 6601

NCBI: 3981, RefSeq: NG_007396.1

Ensembl: ENSG00000174405.15

LRG_79 | Status: public

OMIM: 601837

Expression | ProteinAtlas

The LIG4 gene encode the protein DNA ligase IV. DNA ligases are enzymes that play a crucial role in DNA repair processes, specifically in the joining or "ligation" of DNA strands. DNA ligase IV is involved in a specific type of DNA repair known as non-homologous end joining (NHEJ). NHEJ is a mechanism that repairs DNA double-strand breaks (DSBs), which are severe types of DNA damage that can occur due to various factors such as radiation, chemicals, or errors during DNA replication. DNA ligase IV acts as a key component of the NHEJ pathway by catalyzing the final step of DSB repair, which is the ligation of the broken DNA ends. More specifically, it catalyzes the formation of a phosphodiester bond between the DNA ends, effectively sealing the break and restoring the integrity of the DNA molecule. This process is essential for maintaining genomic stability and preventing the accumulation of mutations that can lead to genetic disorders or cancer. At the cellular level, DNA ligase IV is primarily expressed in dividing cells, where DNA replication and repair activities are more active. It is particularly important during embryonic development and in rapidly proliferating tissues such as the bone marrow, where it is involved in the generation and maintenance of immune cells.

Biallelic loss-of-function (both truncating and missense) mutations in LIG4 were first reported to cause disease in 2001 by O'Driscoll et al. The condition was termed LIG4 syndrome, and patients present with a combination of immunodeficiency, unusual facial features, microcephaly and developmental and growth delay. As in the Nijmegen breakage syndrome, patient cells showed pronounced radiosensitivity due to impaired DNA double-strand break rejoining; however, they showed normal cell cycle checkp oint responses. More recently (in 2023), 2 specific monoallelic loss-of-function variants (p.R580Q, p.A842D) were reported to cause a new condition characterized by autoimmunity and immunodeficiency in 4 patients from 3 unrelated families (PMID: 37004747). [Load More]