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Gene | FANCA |
Variant | E1239_R1243del |
Impact List | deletion |
Protein Effect | loss of function |
Gene Variant Descriptions | FANCA E1239_R1243del results in the deletion of five amino acids in the Fanca protein from amino acids 1239 to 1243 (UniProt.org). E1239_R1243del confers a loss of function to the Fanca protein as demonstrated by decreased Fanca phosphorylation, reduced interaction with Fancc and Fancf, failure to restore Fancd2 monoubiquitination, and inability to complement cellular sensitivity to mitomycin C in culture (PMID: 12444097). |
Associated Drug Resistance | |
Category Variants Paths |
FANCA mutant FANCA inact mut FANCA E1239_R1243del |
Transcript | NM_000135.4 |
gDNA | chr16:g.89742841_89742855del15 |
cDNA | c.3715_3729del15 |
Protein | p.E1239_R1243delEENIR |
Source Database | RefSeq |
Genome Build | GRCh38/hg38 |
Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
---|---|---|---|---|---|
XM_005256294.4 | chr16:g.89742841_89742855del15 | c.3715_3729del15 | p.E1239_R1243delEENIR | RefSeq | GRCh38/hg38 |
XM_017023044.2 | chr16:g.89740070_89740084del15 | c.3715_3729del15 | p.P1239_H1243delPKAFH | RefSeq | GRCh38/hg38 |
NM_001286167 | chr16:g.89742841_89742855del15 | c.3715_3729del15 | p.E1239_R1243delEENIR | RefSeq | GRCh38/hg38 |
NM_000135.3 | chr16:g.89742841_89742855del15 | c.3715_3729del15 | p.E1239_R1243delEENIR | RefSeq | GRCh38/hg38 |
NM_000135.4 | chr16:g.89742841_89742855del15 | c.3715_3729del15 | p.E1239_R1243delEENIR | RefSeq | GRCh38/hg38 |
NM_000135 | chr16:g.89742841_89742855del15 | c.3715_3729del15 | p.E1239_R1243delEENIR | RefSeq | GRCh38/hg38 |
NM_001286167.2 | chr16:g.89742841_89742855del15 | c.3715_3729del15 | p.E1239_R1243delEENIR | RefSeq | GRCh38/hg38 |
NM_001286167.3 | chr16:g.89742841_89742855del15 | c.3715_3729del15 | p.E1239_R1243delEENIR | RefSeq | GRCh38/hg38 |
XM_005256294 | chr16:g.89742841_89742855del15 | c.3715_3729del15 | p.E1239_R1243delEENIR | RefSeq | GRCh38/hg38 |
XM_017023044 | chr16:g.89740070_89740084del15 | c.3715_3729del15 | p.P1239_H1243delPKAFH | RefSeq | GRCh38/hg38 |
XM_011522945.2 | chr16:g.89740070_89740084del15 | c.3715_3729del15 | p.P1239_H1243delPKAFH | RefSeq | GRCh38/hg38 |
XM_011522945 | chr16:g.89740070_89740084del15 | c.3715_3729del15 | p.P1239_H1243delPKAFH | RefSeq | GRCh38/hg38 |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
FANCA inact mut | prostate cancer | predicted - sensitive | Abiraterone + Niraparib + Prednisone | Phase III | Actionable | In a Phase III trial (MAGNITUDE), Zejula (niraparib) in combination with Zytiga (abiraterone) and Adasone (prednisone) (AAP) improved radiographic progression-free survival (HR 0.59) compared to placebo and AAP in patients with metastatic castration-resistant prostate cancer harboring inactivating mutations in the homologous recombination repair (HRR)-Fanconi pathway genes including BRIP1, FANCA, and PALB2 (J Clin Oncol 40, no. 16_suppl (June 01, 2022) 5020; NCT03748641). | detail... |
FANCA inact mut | prostate cancer | sensitive | Enzalutamide + Talazoparib | FDA approved | Actionable | In a Phase III trial (TALAPRO-2) that supported FDA approval, Talzenna (talazoparib) plus Xtandi (enzalutamide) improved median radiographic progression-free survival compared to enzalutamide plus placebo (27.9 vs 16.4 mo, HR 0.46, p=0.0003) in patients with metastatic castration-resistant prostate cancer harboring deficient homologous recombination repair genes including FANCA, with an HR of 0.66 (p=0.12) in patients with non-BRCA mutations treated with Talzenna (talazoparib) (PMID: 37285865; NCT03395197). | detail... 37285865 |
FANCA inact mut | prostate cancer | sensitive | Enzalutamide + Talazoparib | Guideline | Actionable | Talzenna (talazoparib) plus Xtandi (enzalutamide) is included in guidelines as systemic therapy for patients with metastatic castration-resistant prostate cancer harboring a pathogenic germline or somatic FANCA mutation who have not been treated in the setting of castration-resistant prostate cancer (NCCN.org). | detail... |
FANCA inact mut | prostate cancer | predicted - sensitive | Rucaparib | Case Reports/Case Series | Actionable | In a Phase II trial, 1 of 4 patients with metastatic castrate-resistant prostate cancer harboring deleterious FANCA alterations demonstrated a PSA response and complete radiographic response after treatment with Rubraca (rucaparib), which were ongoing at the time of visit cutoff (PMID: 32086346; NCT02952534). | 32086346 |