OncoSignal
Live from Open Targets Platform, fetched 2026-11-12 01:57 UTC. Every row links to its source record.

WRN WRN RecQ like helicase

ENSG00000165392 · protein coding · Open Targets profile

Multifunctional enzyme that has magnesium and ATP-dependent 3'-5' DNA-helicase activity on partially duplex substrates (PubMed:9224595, PubMed:9288107, PubMed:9611231). Also has 3'->5' exonuclease activity towards double-stranded (ds)DNA with a 5'-overhang (PubMed:11863428). Has no nuclease activity towards single-stranded (ss)DNA or blunt-ended dsDNA (PubMed:11863428). Helicase activity is most efficient with (d)ATP, but (d)CTP will substitute with reduced efficiency; strand displacement is enhanced by single-strand binding- protein (heterotrimeric replication protein A complex, RPA1, RPA2, RPA3) (PubMed:9611231). Binds preferentially to DNA substrates containing alternate secondary structures, such as replication forks and Holliday junctions. May play an important role in the dissociation of joint DNA molecules that can arise as products of homologous recombination, at stalled replication forks or during DNA repair. Alleviates stalling of DNA polymerases at the site of DNA lesions. Plays a role in the formation of DNA replication focal centers; stably associates with foci elements generating binding sites for RP-A (By similarity). Plays a role in double-strand break repair after gamma- irradiation (PubMed:9224595, PubMed:9288107, PubMed:9611231). Unwinds some G-quadruplex DNA (d(CGG)n tracts); unwinding seems to occur in both 5'-3' and 3'-5' direction and requires a short single-stranded tail (PubMed:10212265). d(CGG)n tracts have a propensity to assemble into tetraplex structures; other G-rich substrates from a telomeric or IgG switch sequence are not unwound (PubMed:10212265). Depletion leads to chromosomal breaks and genome instability (PubMed:33199508). {ECO:0000250|UniProtKB:O09053, ECO:0000269|PubMed:10212265, ECO:0000269|PubMed:11863428, ECO:0000269|PubMed:17563354, ECO:0000269|PubMed:18596042, ECO:0000269|PubMed:19283071, ECO:0000269|PubMed:19652551, ECO:0000269|PubMed:21639834, ECO:0000269|PubMed:27063109, ECO:0000269|PubMed:33199508, ECO:0000269|PubMed:9224595, ECO:0000269|PubMed:9288107, ECO:0000269|PubMed:9611231}.

In 12 of 15 cancers, the evidence for WRN comes mainly from mutations found in tumours

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)
00.250.50.751melanomamelanomamelanoma: somatic 0.46thyroid gland carcinomathyroid gland carcinomathyroid gland carcinoma: somatic 0.46gastric carcinomagastric carcinomagastric carcinoma: somatic 0.61ovarian cancerovarian cancerovarian cancer: germline 0.62prostate carcinomaprostate carcinomaprostate carcinoma: somatic 0.61lung carcinomalung carcinomalung carcinoma: somatic 0.61thyroid cancerthyroid cancercolorectal adenocarcinomacolorectal adenocarcinomacolorectal adenocarcinoma: somatic 0.61sarcomasarcomaesophageal adenocarcinomaesophageal adenocarcinomaesophageal adenocarcinoma: somatic 0.61skin carcinomaskin carcinomaskin carcinoma: somatic 0.61lymphoid neoplasmlymphoid neoplasmlymphoid neoplasm: somatic 0.61bile duct carcinomabile duct carcinomabile duct carcinoma: somatic 0.61breast ductal adenocarcinomabreast ductal adenocarcinomabreast ductal adenocarcinoma: somatic 0.61carcinoma of liver and intrahepatic bil…carcinoma of liver and intrahepatic biliary tractcarcinoma of liver and intrahepatic biliary tract: somatic 0.61

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, High-Quality Ligand
PROTAC
UniProt Ubiquitination, Database Ubiquitination, Half-life Data, Small Molecule Binder

gnomAD loss of function constraint: o/e 0.8245499730110168 (upper bound 0.9446300268173218). 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 WRN's approved or late-stage drugs in the last three years.

No terminated, withdrawn or suspended trials of WRN'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.