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Gene | FANCL |
Variant | R221W |
Impact List | missense |
Protein Effect | loss of function |
Gene Variant Descriptions | FANCL R221W lies within the UBC-RWD region of the Fancl protein (UniProt.org). R221W results in decreased Fancl protein thermal stability, Fancd2 binding and ubiquitination in in vitro assays, and reduced ability to rescue G2 cell cycle arrest in FANCL-null cells in culture (PMID: 32420600). |
Associated Drug Resistance | |
Category Variants Paths |
FANCL mutant FANCL inact mut FANCL R221W |
Transcript | NM_018062.4 |
gDNA | chr2:g.58165754G>A |
cDNA | c.661C>T |
Protein | p.R221W |
Source Database | RefSeq |
Genome Build | GRCh38/hg38 |
Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
---|---|---|---|---|---|
XM_005264395.4 | chr2:g.58165754G>A | c.661C>T | p.R221W | RefSeq | GRCh38/hg38 |
NM_018062.4 | chr2:g.58165754G>A | c.661C>T | p.R221W | RefSeq | GRCh38/hg38 |
NM_018062.3 | chr2:g.58165754G>A | c.661C>T | p.R221W | RefSeq | GRCh38/hg38 |
XM_005264395.5 | chr2:g.58165754G>A | c.661C>T | p.R221W | RefSeq | GRCh38/hg38 |
NM_018062 | chr2:g.58165754G>A | c.661C>T | p.R221W | RefSeq | GRCh38/hg38 |
XM_005264395 | chr2:g.58165754G>A | c.661C>T | p.R221W | RefSeq | GRCh38/hg38 |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
FANCL inact mut | prostate cancer | sensitive | Olaparib | FDA approved - On Companion Diagnostic | Actionable | In a Phase III trial (PROfound) that supported FDA approval, Lynparza (olaparib) treatment significantly improved median imaging-based progression-free survival (5.8 vs 3.5 mo, HR 0.49, p<0.001) compared to control in patients with metastatic castration-resistant prostate cancer who progressed on hormone therapy and harbored deleterious or suspected deleterious mutations in homologous recombination repair genes, including FANCL (PMID: 32343890; NCT02987543). | detail... detail... 32343890 |
FANCL inact mut | prostate cancer | sensitive | Olaparib | Guideline | Actionable | Lynparza (olaparib) is included in guidelines as second-line therapy post androgen receptor-directed therapy for patients with metastatic castration-resistant prostate cancer harboring pathogenic mutations in FANCL (NCCN.org). | detail... |