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Gene | RAD54L |
Variant | K189A |
Impact List | missense |
Protein Effect | loss of function |
Gene Variant Descriptions | RAD54L K189A lies within the helicase ATP-binding domain of the Rad54l protein (UniProt.org). K189A confers a loss of function to the Rad54l protein as demonstrated by impaired D-loop formation in an vitro assay (PMID: 17417655), increased sensitivity to DNA damage induction, and decreased displacement of Rad51 from DNA in cultured cells (PMID: 21357745). |
Associated Drug Resistance | |
Category Variants Paths |
RAD54L mutant RAD54L inact mut RAD54L K189A |
Transcript | NM_001142548.2 |
gDNA | chr1:g.46260814_46260815delAAinsGC |
cDNA | c.565_566delAAinsGC |
Protein | p.K189A |
Source Database | RefSeq |
Genome Build | GRCh38/hg38 |
Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
---|---|---|---|---|---|
NM_001142548 | chr1:g.46260814_46260815delAAinsGC | c.565_566delAAinsGC | p.K189A | RefSeq | GRCh38/hg38 |
NM_003579.4 | chr1:g.46260814_46260815delAAinsGC | c.565_566delAAinsGC | p.K189A | RefSeq | GRCh38/hg38 |
NM_003579.3 | chr1:g.46260814_46260815delAAinsGC | c.565_566delAAinsGC | p.K189A | RefSeq | GRCh38/hg38 |
NM_001142548.1 | chr1:g.46260814_46260815delAAinsGC | c.565_566delAAinsGC | p.K189A | RefSeq | GRCh38/hg38 |
NM_001142548.2 | chr1:g.46260814_46260815delAAinsGC | c.565_566delAAinsGC | p.K189A | RefSeq | GRCh38/hg38 |
NM_003579 | chr1:g.46260814_46260815delAAinsGC | c.565_566delAAinsGC | p.K189A | RefSeq | GRCh38/hg38 |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
RAD54L 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 RAD54L (NCCN.org). | detail... |
RAD54L inact mut | prostate cancer | sensitive | Olaparib | FDA approved - On Companion Diagnostic | Actionable | In a Phase III trial (PROfound) that supported FDA approval, Lynparza (olaparib) improved median imaging-based progression-free survival (5.8 vs 3.5 mo, HR 0.49, p<0.001) compared to control in metastatic castration-resistant prostate cancer patients harboring deleterious or suspected deleterious mutations in homologous recombination repair genes who progressed on hormone therapy, HR for progression or death was 0.33 in RAD54L-mutant patients (PMID: 32343890; NCT02987543). | detail... detail... 32343890 |