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Gene | RAD51D |
Variant | K91fs |
Impact List | frameshift |
Protein Effect | loss of function |
Gene Variant Descriptions | RAD51D K91fs results in a change in the amino acid sequence of the Rad51d protein beginning at aa 91 of 328, likely resulting in premature truncation of the functional protein (UniProt.org). K91fs results in decreased Rad51d protein stability, impaired DNA homologous recombination activity and DNA damage response, and increased sensitivity to PARP inhibitors in culture (PMID: 33151324). |
Associated Drug Resistance | |
Category Variants Paths |
RAD51D mutant RAD51D inact mut RAD51D K91fs |
Transcript | NM_002878.4 |
gDNA | chr17:g.(35107440_35107441) |
cDNA | c.(271_270) |
Protein | p.K91fs |
Source Database | RefSeq |
Genome Build | GRCh38/hg38 |
Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
---|---|---|---|---|---|
NM_002878.3 | chr17:g.(35107440_35107441) | c.(271_270) | p.K91fs | RefSeq | GRCh38/hg38 |
NM_002878.4 | chr17:g.(35107440_35107441) | c.(271_270) | p.K91fs | RefSeq | GRCh38/hg38 |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
RAD51D 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 RAD51D (PMID: 32343890; NCT02987543). | detail... detail... 32343890 |
RAD51D 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 RAD51D (NCCN.org). | detail... |