OncoSignal
Live from Open Targets Platform, fetched 2026-11-12 01:43 UTC. Every row links to its source record.

LIG4 DNA ligase 4

ENSG00000174405 · protein coding · Open Targets profile

DNA ligase involved in DNA non-homologous end joining (NHEJ); required for double-strand break (DSB) repair and V(D)J recombination (PubMed:12517771, PubMed:17290226, PubMed:23523427, PubMed:29980672, PubMed:33586762, PubMed:8798671, PubMed:9242410, PubMed:9809069). Catalyzes the NHEJ ligation step of the broken DNA during DSB repair by resealing the DNA breaks after the gap filling is completed (PubMed:12517771, PubMed:17290226, PubMed:9242410, PubMed:9809069). Joins single-strand breaks in a double-stranded polydeoxynucleotide in an ATP-dependent reaction (PubMed:12517771, PubMed:17290226, PubMed:9242410, PubMed:9809069). LIG4 is mechanistically flexible: it can ligate nicks as well as compatible DNA overhangs alone, while in the presence of XRCC4, it can ligate ends with 2-nucleotides (nt) microhomology and 1-nt gaps (PubMed:17290226). Forms a subcomplex with XRCC4; the LIG4-XRCC4 subcomplex is responsible for the NHEJ ligation step and XRCC4 enhances the joining activity of LIG4 (PubMed:9242410, PubMed:9809069). Binding of the LIG4-XRCC4 complex to DNA ends is dependent on the assembly of the DNA-dependent protein kinase complex DNA-PK to these DNA ends (PubMed:10854421). LIG4 regulates nuclear localization of XRCC4 (PubMed:24984242). {ECO:0000269|PubMed:10854421, ECO:0000269|PubMed:12517771, ECO:0000269|PubMed:17290226, ECO:0000269|PubMed:23523427, ECO:0000269|PubMed:24984242, ECO:0000269|PubMed:29980672, ECO:0000269|PubMed:33586762, ECO:0000269|PubMed:8798671, ECO:0000269|PubMed:9242410, ECO:0000269|PubMed:9809069}.

In 3 of 15 cancers, the evidence for LIG4 comes mainly from inherited variants

Each row is a cancer, strongest overall evidence first. The two dots show how strong the inherited (germline) and tumour-mutation (somatic) evidence is; the line between them is the gap.

Inherited (germline) variantsMutations in tumours (somatic)
00.250.50.751DNA ligase IV deficiencyDNA ligase IV deficiencyDNA ligase IV deficiency: germline 0.90plasma cell myelomaplasma cell myelomaplasma cell myeloma: germline 0.90lymphomalymphomaacute lymphoblastic leukemiaacute lymphoblastic leukemiathyroid gland papillary carcinomathyroid gland papillary carcinomathyroid gland papillary carcinoma: germline 0.44colorectal carcinomacolorectal carcinomacentral nervous system cancercentral nervous system cancergliomagliomaglioblastomaglioblastomamelanomamelanomatriple-negative breast carcinomatriple-negative breast carcinomaneuroblastomaneuroblastomaautoimmune lymphoproliferative syndromeautoimmune lymphoproliferative syndromeacute erythroblastic leukemiaacute erythroblastic leukemiaX-linked lymphoproliferative syndromeX-linked lymphoproliferative syndrome

Scores run from 0 (no evidence) to 1 (strongest). A missing dot at 0 means Open Targets holds no evidence of that kind. Source: Open Targets Platform, fetched live.

Tractability

Small molecule
Structure with Ligand
PROTAC
Database Ubiquitination, Half-life Data, Small Molecule Binder

gnomAD loss of function constraint: o/e 0.6833299994468689 (upper bound 1.086400032043457). Low values mean loss of function is poorly tolerated, a safety flag for inhibition.

Who runs trials of these drugs

No named investigators on registry trials of LIG4's approved or late-stage drugs in the last three years.

No terminated, withdrawn or suspended trials of LIG4's drugs are registered

All 0 drugs and clinical candidates as a table

Each drug, stage and indication links to its Open Targets record, where the trials and approvals behind it are listed. Salt forms (for example a mesylate) are listed as Open Targets records them, as separate entries.

DrugTypeHighest stageIndicationsSource records
No drugs or clinical candidates recorded.