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Ref Type

Journal Article

PMID

(33619228)

Authors

Calvo JA, Fritchman B, Hernandez D, Persky NS, Johannessen CM, Piccioni F, Kelch BA, Cantor SB

Title

Comprehensive Mutational Analysis of the BRCA1-Associated DNA Helicase and Tumor-Suppressor FANCJ/BACH1/BRIP1.

Journal	Vol	Issue	Date	Pages	Journal Short Title
Molecular cancer research : MCR	19	6	2021 Jun	1015-1025	Mol Cancer Res

URL

Abstract Text

FANCJ (BRIP1/BACH1) is a hereditary breast and ovarian cancer (HBOC) gene encoding a DNA helicase. Similar to HBOC genes, BRCA1 and BRCA2, FANCJ is critical for processing DNA inter-strand crosslinks (ICL) induced by chemotherapeutics, such as cisplatin. Consequently, cells deficient in FANCJ or its catalytic activity are sensitive to ICL-inducing agents. Unfortunately, the majority of FANCJ clinical mutations remain uncharacterized, limiting therapeutic opportunities to effectively use cisplatin to treat tumors with mutated FANCJ. Here, we sought to perform a comprehensive screen to identify FANCJ loss-of-function (LOF) mutations. We developed a FANCJ lentivirus mutation library representing approximately 450 patient-derived FANCJ nonsense and missense mutations to introduce FANCJ mutants into FANCJ knockout (K/O) HeLa cells. We performed a high-throughput screen to identify FANCJ LOF mutants that, as compared with wild-type FANCJ, fail to robustly restore resistance to ICL-inducing agents, cisplatin or mitomycin C (MMC). On the basis of the failure to confer resistance to either cisplatin or MMC, we identified 26 missense and 25 nonsense LOF mutations. Nonsense mutations elucidated a relationship between location of truncation and ICL sensitivity, as the majority of nonsense mutations before amino acid 860 confer ICL sensitivity. Further validation of a subset of LOF mutations confirmed the ability of the screen to identify FANCJ mutations unable to confer ICL resistance. Finally, mapping the location of LOF mutations to a new homology model provides additional functional information. IMPLICATIONS: We identify 51 FANCJ LOF mutations, providing important classification of FANCJ mutations that will afford additional therapeutic strategies for affected patients.

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Showing 1 to 59 of 59 entries

Gene	Variant	Impact	Protein Effect	Variant Description
BRIP1	Q25*	nonsense	loss of function - predicted	BRIP1 Q25* results in a premature truncation of the Brip1 protein at amino acid 25 of 1249 (UniProt.org). Q25* does not confer resistance to interstrand crosslinking agents in a BRIP1-deficient cell line in culture (PMID: 33619228), and therefore, is predicted to lead to a loss of Brip1 protein function.
BRIP1	G49*	nonsense	loss of function - predicted	BRIP1 G49* results in a premature truncation of the Brip1 protein at amino acid 49 of 1249 (UniProt.org). G49* does not confer resistance to interstrand crosslinking agents in a BRIP1-deficient cell line in culture (PMID: 33619228), and therefore, is predicted to lead to a loss of Brip1 protein function.
BRIP1	G49R	missense	loss of function - predicted	BRIP1 G49R lies within the helicase ATP-binding domain of the Brip1 protein (UniProt.org). G49 does not confer resistance to interstrand crosslinking agents in a BRIP1-deficient cell line in culture (PMID: 33619228), and therefore, is predicted to lead to a loss of Brip1 protein function.
BRIP1	G51*	nonsense	loss of function - predicted	BRIP1 G51* results in a premature truncation of the Brip1 protein at amino acid 51 of 1249 (UniProt.org). G51* does not confer resistance to interstrand crosslinking agents in a BRIP1-deficient cell line in culture (PMID: 33619228), and therefore, is predicted to lead to a loss of Brip1 protein function.
BRIP1	K52R	missense	loss of function	BRIP1 K52R lies within the helicase ATP-binding domain of the Brip1 protein (UniProt.org). K52R confers a loss of function to the Brip1 protein as demonstrated by loss of helicase and ATPase activity (PMID: 14983014, PMID: 16116421) and failure to confer resistance to interstrand crosslinking agents in a BRIP1-deficient cell line in culture (PMID: 33619228).
BRIP1	E81*	nonsense	loss of function - predicted	BRIP1 E81* results in a premature truncation of the Brip1 protein at amino acid 81 of 1249 (UniProt.org). E81* does not confer resistance to interstrand crosslinking agents in a BRIP1-deficient cell line in culture (PMID: 33619228), and therefore, is predicted to lead to a loss of Brip1 protein function.
BRIP1	A89V	missense	unknown	BRIP1 A89V lies within the helicase ATP-binding domain of the Brip1 protein (UniProt.org). A89V confers a partial resistance to interstrand crosslinking agents compared to wild-type protein in BRIP1-deficient cells in culture (PMID: 33619228), but has not been fully biochemically characterized and therefore, its effect on Brip1 protein function is unknown.
BRIP1	Q126*	nonsense	loss of function - predicted	BRIP1 Q126* results in a premature truncation of the Brip1 protein at amino acid 126 of 1249 (UniProt.org). Q126* does not confer resistance to interstrand crosslinking agents in a BRIP1-deficient cell line in culture (PMID: 33619228), and therefore, is predicted to lead to a loss of Brip1 protein function.
BRIP1	Y147*	nonsense	loss of function - predicted	BRIP1 Y147* results in a premature truncation of the Brip1 protein at amino acid 147 of 1249 (UniProt.org). Y147* does not confer resistance to interstrand crosslinking agents in a BRIP1-deficient cell line in culture (PMID: 33619228), and therefore, is predicted to lead to a loss of Brip1 protein function.
BRIP1	S189L	missense	loss of function - predicted	BRIP1 S189L lies within the helicase ATP-binding domain of the Brip1 protein (UniProt.org). S189L does not confer resistance to interstrand crosslinking agents in a BRIP1-deficient cell line in culture (PMID: 33619228), and therefore, is predicted to lead to a loss of Brip1 protein function.
BRIP1	G224*	nonsense	loss of function - predicted	BRIP1 G224* results in a premature truncation of the Brip1 protein at amino acid 224 of 1249 (UniProt.org). G224* does not confer resistance to interstrand crosslinking agents in a BRIP1-deficient cell line in culture (PMID: 33619228), and therefore, is predicted to lead to a loss of Brip1 protein function.
BRIP1	Q227*	nonsense	loss of function - predicted	BRIP1 Q227* results in a premature truncation of the Brip1 protein at amino acid 227 of 1249 (UniProt.org). Q227* does not confer resistance to interstrand crosslinking agents in a BRIP1-deficient cell line in culture (PMID: 33619228), and therefore, is predicted to lead to a loss of Brip1 protein function.
BRIP1	T252R	missense	loss of function - predicted	BRIP1 T252R lies within the helicase ATP-binding domain of the Brip1 protein (UniProt.org). T252R does not confer resistance to interstrand crosslinking agents in a BRIP1-deficient cell line in culture (PMID: 33619228), and therefore, is predicted to lead to a loss of Brip1 protein function.
BRIP1	R261*	nonsense	loss of function - predicted	BRIP1 R261* results in a premature truncation of the Brip1 protein at amino acid 261 of 1249 (UniProt.org). R261* does not confer resistance to interstrand crosslinking agents in a BRIP1-deficient cell line in culture (PMID: 33619228), and therefore, is predicted to lead to a loss of Brip1 protein function.
BRIP1	W335L	missense	loss of function - predicted	BRIP1 W335L lies within the helicase ATP-binding domain of the Brip1 protein (UniProt.org). W335L does not confer resistance to interstrand crosslinking agents in a BRIP1-deficient cell line in culture (PMID: 33619228), and therefore, is predicted to lead to a loss of Brip1 protein function.
BRIP1	L340R	missense	loss of function - predicted	BRIP1 L340R lies within the helicase ATP-binding domain of the Brip1 protein (UniProt.org). L340R does not confer resistance to interstrand crosslinking agents in a BRIP1-deficient cell line in culture (PMID: 33619228), and therefore, is predicted to lead to a loss of Brip1 protein function.
BRIP1	V341D	missense	loss of function - predicted	BRIP1 V341D lies within the helicase ATP-binding domain of the Brip1 protein (UniProt.org). V341D does not confer resistance to interstrand crosslinking agents in a BRIP1-deficient cell line in culture (PMID: 33619228), and therefore, is predicted to lead to a loss of Brip1 protein function.
BRIP1	L347P	missense	loss of function - predicted	BRIP1 L347P lies within the helicase ATP-binding domain of the Brip1 protein (UniProt.org). L347P does not confer resistance to interstrand crosslinking agents in a BRIP1-deficient cell line in culture (PMID: 33619228), and therefore, is predicted to lead to a loss of Brip1 protein function.
BRIP1	C350F	missense	loss of function - predicted	BRIP1 C350F lies within the helicase ATP-binding domain of the Brip1 protein (UniProt.org). C350F does not confer resistance to interstrand crosslinking agents in a BRIP1-deficient cell line in culture (PMID: 33619228), and therefore, is predicted to lead to a loss of Brip1 protein function.
BRIP1	P351L	missense	unknown	BRIP1 P351L lies within the helicase ATP-binding domain of the Brip1 protein (UniProt.org). P351L confers a partial resistance to interstrand crosslinking agents compared to wild-type protein in BRIP1-deficient cells in culture (PMID: 33619228), but has not been fully biochemically characterized and therefore, its effect on Brip1 protein function is unknown.
BRIP1	E357*	nonsense	loss of function - predicted	BRIP1 E357* results in a premature truncation of the Brip1 protein at amino acid 357 of 1249 (UniProt.org). E357* confers resistance to interstrand crosslinking agents in BRIP1-null cells in culture (PMID: 33619228), however, due to the effects of other truncation mutations downstream of E357 (PMID: 18628483), is predicted to lead to a loss of Brip1 protein function.
BRIP1	L358P	missense	loss of function - predicted	BRIP1 L358P lies within the helicase ATP-binding domain of the Brip1 protein (UniProt.org). L358P does not confer resistance to interstrand crosslinking agents in a BRIP1-deficient cell line in culture (PMID: 33619228), and therefore, is predicted to lead to a loss of Brip1 protein function.
BRIP1	F366S	missense	loss of function - predicted	BRIP1 F366S lies within the helicase ATP-binding domain of the Brip1 protein (UniProt.org). F366S does not confer resistance to interstrand crosslinking agents in a BRIP1-deficient cell line in culture (PMID: 33619228), and therefore, is predicted to lead to a loss of Brip1 protein function.
BRIP1	E387*	nonsense	loss of function - predicted	BRIP1 E387* results in a premature truncation of the Brip1 protein at amino acid 387 of 1249 (UniProt.org). E387* does not confer resistance to interstrand crosslinking agents in a BRIP1-deficient cell line in culture (PMID: 33619228), and therefore, is predicted to lead to a loss of Brip1 protein function.
BRIP1	D393V	missense	loss of function - predicted	BRIP1 D393V lies within the helicase ATP-binding domain of the Brip1 protein (UniProt.org). D393V does not confer resistance to interstrand crosslinking agents in a BRIP1-deficient cell line in culture (PMID: 33619228), and therefore, is predicted to lead to a loss of Brip1 protein function.
BRIP1	H396D	missense	loss of function	BRIP1 H396D lies within the helicase ATP-binding domain of the Brip1 protein (UniProt.org). H396D demonstrates loss of helicase activity and inefficient DNA binding and ATP hydrolysis compared to wildtype in an in vitro assay (PMID: 29788478) and does not confer resistance to interstrand crosslinking agents in a BRIP1-deficient cell line in culture (PMID: 33619228).
BRIP1	L415P	missense	loss of function - predicted	BRIP1 L415P lies within the helicase ATP-binding domain of the Brip1 protein (UniProt.org). L415P does not confer resistance to interstrand crosslinking agents in a BRIP1-deficient cell line in culture (PMID: 33619228), and therefore, is predicted to lead to a loss of Brip1 protein function.
BRIP1	R439*	nonsense	loss of function - predicted	BRIP1 R439* results in a premature truncation of the Brip1 protein at amino acid 439 of 1249 (UniProt.org). R439* does not confer resistance to interstrand crosslinking agents in a BRIP1-deficient cell line in culture (PMID: 33619228), and therefore, is predicted to lead to a loss of Brip1 protein function.
BRIP1	W448*	nonsense	loss of function - predicted	BRIP1 W448* results in a premature truncation of the Brip1 protein at amino acid 448 of 1249 (UniProt.org). W448* does not confer resistance to interstrand crosslinking agents in a BRIP1-deficient cell line in culture (PMID: 33619228), and therefore, is predicted to lead to a loss of Brip1 protein function.
BRIP1	Y461*	nonsense	loss of function - predicted	BRIP1 Y461* results in a premature truncation of the Brip1 protein at amino acid 461 of 1249 (UniProt.org). Y461* does not confer resistance to interstrand crosslinking agents in a BRIP1-deficient cell line in culture (PMID: 33619228), and therefore, is predicted to lead to a loss of Brip1 protein function.
BRIP1	Q561*	nonsense	loss of function - predicted	BRIP1 Q561* results in a premature truncation of the Brip1 protein at amino acid 561 of 1249 (UniProt.org). Q561* does not confer resistance to interstrand crosslinking agents in a BRIP1-deficient cell line in culture (PMID: 33619228), and therefore, is predicted to lead to a loss of Brip1 protein function.
BRIP1	R581*	nonsense	loss of function - predicted	BRIP1 R581* results in a premature truncation of the Brip1 protein at amino acid 581 of 1249 (UniProt.org). R581* does not confer resistance to interstrand crosslinking agents in a BRIP1-deficient cell line in culture (PMID: 33619228), and therefore, is predicted to lead to a loss of Brip1 protein function.
BRIP1	S614Y	missense	loss of function - predicted	BRIP1 S614Y does not lie within any known functional domains of the Brip1 protein (UniProt.org). S614Y does not confer resistance to interstrand crosslinking agents in a BRIP1-deficient cell line in culture (PMID: 33619228), and therefore, is predicted to lead to a loss of Brip1 protein function.
BRIP1	S618*	nonsense	loss of function - predicted	BRIP1 S618* results in a premature truncation of the Brip1 protein at amino acid 618 of 1249 (UniProt.org). S618* does not confer resistance to interstrand crosslinking agents in a BRIP1-deficient cell line in culture (PMID: 33619228), and therefore, is predicted to lead to a loss of Brip1 protein function.
BRIP1	E626K	missense	loss of function - predicted	BRIP1 E626K does not lie within any known functional domains of the Brip1 protein (UniProt.org). E626K does not confer resistance to interstrand crosslinking agents in a BRIP1-deficient cell line in culture (PMID: 33619228), and therefore, is predicted to lead to a loss of Brip1 protein function.
BRIP1	Q645*	nonsense	loss of function - predicted	BRIP1 Q645* results in a premature truncation of the Brip1 protein at amino acid 645 of 1249 (UniProt.org). Q645* does not confer resistance to interstrand crosslinking agents in a BRIP1-deficient cell line in culture (PMID: 33619228), and therefore, is predicted to lead to a loss of Brip1 protein function.
BRIP1	S653*	nonsense	loss of function - predicted	BRIP1 S653* results in a premature truncation of the Brip1 protein at amino acid 653 of 1249 (UniProt.org). S653* does not confer resistance to interstrand crosslinking agents in a BRIP1-deficient cell line in culture (PMID: 33619228), and therefore, is predicted to lead to a loss of Brip1 protein function.
BRIP1	Q685*	nonsense	loss of function - predicted	BRIP1 Q685* results in a premature truncation of the Brip1 protein at amino acid 685 of 1249 (UniProt.org). Q685* does not confer resistance to interstrand crosslinking agents in a BRIP1-deficient cell line in culture (PMID: 33619228), and therefore, is predicted to lead to a loss of Brip1 protein function.
BRIP1	Q689*	nonsense	loss of function - predicted	BRIP1 Q689* results in a premature truncation of the Brip1 protein at amino acid 689 of 1249 (UniProt.org). Q689* does not confer resistance to interstrand crosslinking agents in a BRIP1-deficient cell line in culture (PMID: 33619228), and therefore, is predicted to lead to a loss of Brip1 protein function.
BRIP1	G690E	missense	loss of function	BRIP1 G690E lies within the helicase domain IV of the Brip1 protein (PMID: 20639400). G690E demonstrates reduced protein stability and fails to rescue mitomycin-induced DNA cross-linking damage in cell culture (PMID: 31822495, PMID: 33619228).
BRIP1	G690R	missense	loss of function - predicted	BRIP1 G690R does not lie within any known functional domains of the Brip1 protein (UniProt.org). G690R does not confer resistance to interstrand crosslinking agents in a BRIP1-deficient cell line in culture (PMID: 33619228), and therefore, is predicted to lead to a loss of Brip1 protein function.
BRIP1	S697F	missense	loss of function - predicted	BRIP1 S697F does not lie within any known functional domains of the Brip1 protein (UniProt.org). S697F does not confer resistance to interstrand crosslinking agents in a BRIP1 deficient cell line in culture (PMID: 33619228), and therefore, is predicted to lead to a loss of Brip1 protein function.
BRIP1	S697P	missense	loss of function - predicted	BRIP1 S697P does not lie within any known functional domains of the Brip1 protein (UniProt.org). S697P does not confer resistance to interstrand crosslinking agents in a BRIP1-deficient cell line in culture (PMID: 33619228), and therefore, is predicted to lead to a loss of Brip1 protein function.
BRIP1	R707C	missense	unknown	BRIP1 R707C does not lie within any known functional domains of the Brip1 protein (UniProt.org). R707C confers a partial resistance to interstrand crosslinking agents in BRIP1-deficient cells in culture (PMID: 33619228), demonstrates inefficient DNA binding, reduced ATP hydrolysis, partially reduced helicase activity, and impaired dimerization, but retains the ability to unwind substrate at a reduced efficiency compared to wild-type protein in an in vitro assay (PMID: 29788478), and therefore, its effect on Brip1 protein function is unknown.
BRIP1	E726*	nonsense	loss of function - predicted	BRIP1 E726* results in a premature truncation of the Brip1 protein at amino acid 726 of 1249 (UniProt.org). E726* does not confer resistance to interstrand crosslinking agents in a BRIP1-deficient cell line in culture (PMID: 33619228), and therefore, is predicted to lead to a loss of Brip1 protein function.
BRIP1	R762P	missense	loss of function - predicted	BRIP1 R762P does not lie within any known functional domains of the Brip1 protein (UniProt.org). R762P does not confer resistance to interstrand crosslinking agents in a BRIP1-deficient cell line in culture (PMID: 33619228), and therefore, is predicted to lead to a loss of Brip1 protein function.
BRIP1	G763C	missense	loss of function - predicted	BRIP1 G763C does not lie within any known functional domains of the Brip1 protein (UniProt.org). G763C does not confer resistance to interstrand crosslinking agents in a BRIP1-deficient cell line in culture (PMID: 33619228), and therefore, is predicted to lead to a loss of Brip1 protein function.
BRIP1	S772*	nonsense	loss of function - predicted	BRIP1 S772* results in a premature truncation of the Brip1 protein at amino acid 772 of 1249 (UniProt.org). S772* does not confer resistance to interstrand crosslinking agents in a BRIP1-deficient cell line in culture (PMID: 33619228), and therefore, is predicted to lead to a loss of Brip1 protein function.
BRIP1	P785L	missense	loss of function - predicted	BRIP1 P785L does not lie within any known functional domains of the Brip1 protein (UniProt.org). P785L does not confer resistance to interstrand crosslinking agents in a BRIP1-deficient cell line in culture (PMID: 33619228), and therefore, is predicted to lead to a loss of Brip1 protein function.
BRIP1	E795*	nonsense	loss of function - predicted	BRIP1 E795* results in a premature truncation of the Brip1 protein at amino acid 795 of 1249 (UniProt.org). E795* demonstrates resistance to interstrand crosslinking agents in a BRIP1-deficient cell line in culture (PMID: 33619228), however, due to the effects of other truncation mutations downstream of E795 (PMID: 18628483), is predicted to lead to a loss of Brip1 protein function.
BRIP1	S805*	nonsense	loss of function - predicted	BRIP1 S805* results in a premature truncation of the Brip1 protein at amino acid 805 of 1249 (UniProt.org). S805* does not confer resistance to interstrand crosslinking agents in a BRIP1-deficient cell line in culture (PMID: 33619228), and therefore, is predicted to lead to a loss of Brip1 protein function.
BRIP1	Q815*	nonsense	loss of function - predicted	BRIP1 Q815* results in a premature truncation of the Brip1 protein at amino acid 815 of 1249 (UniProt.org). Q815* does not confer resistance to interstrand crosslinking agents in a BRIP1-deficient cell line in culture (PMID: 33619228), and therefore, is predicted to lead to a loss of Brip1 protein function.
BRIP1	R831K	missense	loss of function - predicted	BRIP1 R831K does not lie within any known functional domains of the Brip1 protein (UniProt.org). R831K does not confer resistance to interstrand crosslinking agents in a BRIP1-deficient cell line in culture (PMID: 33619228), and therefore, is predicted to lead to a loss of Brip1 protein function.
BRIP1	R836*	nonsense	loss of function - predicted	BRIP1 R836* results in a premature truncation of the Brip1 protein at amino acid 836 of 1249 (UniProt.org). R836* does not confer resistance to interstrand crosslinking agents in a BRIP1-deficient cell line in culture (PMID: 33619228), and therefore, is predicted to lead to a loss of Brip1 protein function.
BRIP1	L860P	missense	loss of function - predicted	BRIP1 L860P does not lie within any known functional domains of the Brip1 protein (UniProt.org). L860P does not confer resistance to interstrand crosslinking agents in a BRIP1-deficient cell line in culture (PMID: 33619228), and therefore, is predicted to lead to a loss of Brip1 protein function.
BRIP1	S960T	missense	unknown	BRIP1 S960T lies within the BRCA1-interacting region of the Brip1 protein (UniProt.org). S960T confers a partial resistance to interstrand crosslinking agents compared to wild-type protein in BRIP1-deficient cells in culture (PMID: 33619228), but has not been fully biochemically characterized and therefore, its effect on Brip1 protein function is unknown.
BRIP1	S990A	missense	loss of function	BRIP1 S990A lies within the BRCA1-interacting region of the Brip1 protein (UniProt.org). S990A maintains the ability to confer resistance to interstrand crosslinking agents in a BRIP1-deficient cell line (PMID: 33619228), but results in a loss of interaction with Brca, and inability to control G2-M checkpoint or rescue senescence in Brip1-deficient cells in culture (PMID: 14576433, PMID: 22137763).
BRIP1	E1145A	missense	unknown	BRIP1 E1145A does not lie within any known functional domains of the Brip1 protein (UniProt.org). E1145A confers a partial resistance to interstrand crosslinking agents compared to wild-type protein in BRIP1-deficient cells in culture (PMID: 33619228), but has not been fully biochemically characterized and therefore, its effect on Brip1 protein function is unknown.
BRIP1	K1146E	missense	unknown	BRIP1 K1146E does not lie within any known functional domains of the Brip1 protein (UniProt.org). K1146E confers a partial resistance to interstrand crosslinking agents compared to wild-type protein in BRIP1-deficient cells in culture (PMID: 33619228), but has not been fully biochemically characterized and therefore, its effect on Brip1 protein function is unknown.

Showing 1 to 59 of 59 entries

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Showing 1 to 54 of 54 entries

Molecular Profile	Indication/Tumor Type	Response Type	Therapy Name	Approval Status	Evidence Type	Efficacy Evidence	References
BRIP1 A349P	Advanced Solid Tumor	sensitive	Cisplatin	Preclinical - Cell culture	Actionable	In a preclinical study, Platinol (cisplatin) treatment inhibited viability of a cell line expressing BRIP1 A349P in culture (PMID: 33619228).	33619228
BRIP1 C350F	Advanced Solid Tumor	sensitive	Cisplatin	Preclinical - Cell culture	Actionable	In a preclinical study, Platinol (cisplatin) treatment inhibited viability of a cell line expressing BRIP1 C350F in culture (PMID: 33619228).	33619228
BRIP1 D393V	Advanced Solid Tumor	sensitive	Cisplatin	Preclinical - Cell culture	Actionable	In a preclinical study, Platinol (cisplatin) treatment inhibited viability of a cell line expressing BRIP1 D393V in culture (PMID: 33619228).	33619228
BRIP1 E357*	Advanced Solid Tumor	resistant	Cisplatin	Preclinical - Cell culture	Actionable	In a preclinical study, Platinol (cisplatin) treatment did not inhibit viability of a cell line expressing BRIP1 E357* in culture (PMID: 33619228).	33619228
BRIP1 E387*	Advanced Solid Tumor	sensitive	Cisplatin	Preclinical - Cell culture	Actionable	In a preclinical study, Platinol (cisplatin) treatment inhibited viability of a cell line expressing BRIP1 E387* in culture (PMID: 33619228).	33619228
BRIP1 E626K	Advanced Solid Tumor	sensitive	Cisplatin	Preclinical - Cell culture	Actionable	In a preclinical study, Platinol (cisplatin) treatment inhibited viability of a cell line expressing BRIP1 E626K in culture (PMID: 33619228).	33619228
BRIP1 E726*	Advanced Solid Tumor	sensitive	Cisplatin	Preclinical - Cell culture	Actionable	In a preclinical study, Platinol (cisplatin) treatment inhibited viability of a cell line expressing BRIP1 E726* in culture (PMID: 33619228).	33619228
BRIP1 E795*	Advanced Solid Tumor	resistant	Cisplatin	Preclinical - Cell culture	Actionable	In a preclinical study, Platinol (cisplatin) treatment did not inhibit viability of a cell line expressing BRIP1 E795* in culture (PMID: 33619228).	33619228
BRIP1 E81*	Advanced Solid Tumor	sensitive	Cisplatin	Preclinical - Cell culture	Actionable	In a preclinical study, Platinol (cisplatin) treatment inhibited viability of a cell line expressing BRIP1 E81* in culture (PMID: 33619228).	33619228
BRIP1 F366S	Advanced Solid Tumor	sensitive	Cisplatin	Preclinical - Cell culture	Actionable	In a preclinical study, Platinol (cisplatin) treatment inhibited viability of a cell line expressing BRIP1 F366S in culture (PMID: 33619228).	33619228
BRIP1 G224*	Advanced Solid Tumor	sensitive	Cisplatin	Preclinical - Cell culture	Actionable	In a preclinical study, Platinol (cisplatin) treatment inhibited viability of a cell line expressing BRIP1 G224* in culture (PMID: 33619228).	33619228
BRIP1 G49*	Advanced Solid Tumor	sensitive	Cisplatin	Preclinical - Cell culture	Actionable	In a preclinical study, Platinol (cisplatin) treatment inhibited viability of a cell line expressing BRIP1 G49* in culture (PMID: 33619228).	33619228
BRIP1 G49R	Advanced Solid Tumor	sensitive	Cisplatin	Preclinical - Cell culture	Actionable	In a preclinical study, Platinol (cisplatin) treatment inhibited viability of a cell line expressing BRIP1 G49R in culture (PMID: 33619228).	33619228
BRIP1 G51*	Advanced Solid Tumor	sensitive	Cisplatin	Preclinical - Cell culture	Actionable	In a preclinical study, Platinol (cisplatin) treatment inhibited viability of a cell line expressing BRIP1 G51* in culture (PMID: 33619228).	33619228
BRIP1 G690E	Advanced Solid Tumor	sensitive	Cisplatin	Preclinical - Cell culture	Actionable	In a preclinical study, Platinol (cisplatin) treatment inhibited viability of a cell line expressing BRIP1 G690E in culture (PMID: 33619228).	33619228
BRIP1 G690R	Advanced Solid Tumor	sensitive	Cisplatin	Preclinical - Cell culture	Actionable	In a preclinical study, Platinol (cisplatin) treatment inhibited viability of a cell line expressing BRIP1 G690R in culture (PMID: 33619228).	33619228
BRIP1 G763C	Advanced Solid Tumor	sensitive	Cisplatin	Preclinical - Cell culture	Actionable	In a preclinical study, Platinol (cisplatin) treatment inhibited viability of a cell line expressing BRIP1 G763C in culture (PMID: 33619228).	33619228
BRIP1 H396D	Advanced Solid Tumor	sensitive	Cisplatin	Preclinical - Cell culture	Actionable	In a preclinical study, Platinol (cisplatin) treatment inhibited viability of a cell line expressing BRIP1 H396D in culture (PMID: 33619228).	33619228
BRIP1 K52R	Advanced Solid Tumor	sensitive	Cisplatin	Preclinical - Cell culture	Actionable	In a preclinical study, Platinol (cisplatin) treatment inhibited viability of a cell line expressing BRIP1 K52R in culture (PMID: 33619228).	33619228
BRIP1 L340R	Advanced Solid Tumor	sensitive	Cisplatin	Preclinical - Cell culture	Actionable	In a preclinical study, Platinol (cisplatin) treatment inhibited viability of a cell line expressing BRIP1 L340R in culture (PMID: 33619228).	33619228
BRIP1 L347P	Advanced Solid Tumor	sensitive	Cisplatin	Preclinical - Cell culture	Actionable	In a preclinical study, Platinol (cisplatin) treatment inhibited viability of a cell line expressing BRIP1 L347P in culture (PMID: 33619228).	33619228
BRIP1 L358P	Advanced Solid Tumor	sensitive	Cisplatin	Preclinical - Cell culture	Actionable	In a preclinical study, Platinol (cisplatin) treatment inhibited viability of a cell line expressing BRIP1 L358P in culture (PMID: 33619228).	33619228
BRIP1 L415P	Advanced Solid Tumor	sensitive	Cisplatin	Preclinical - Cell culture	Actionable	In a preclinical study, Platinol (cisplatin) treatment inhibited viability of a cell line expressing BRIP1 L415P in culture (PMID: 33619228).	33619228
BRIP1 L860P	Advanced Solid Tumor	sensitive	Cisplatin	Preclinical - Cell culture	Actionable	In a preclinical study, Platinol (cisplatin) treatment inhibited viability of a cell line expressing BRIP1 L860P in culture (PMID: 33619228).	33619228
BRIP1 P785L	Advanced Solid Tumor	sensitive	Cisplatin	Preclinical - Cell culture	Actionable	In a preclinical study, Platinol (cisplatin) treatment inhibited viability of a cell line expressing BRIP1 P785L in culture (PMID: 33619228).	33619228
BRIP1 Q126*	Advanced Solid Tumor	sensitive	Cisplatin	Preclinical - Cell culture	Actionable	In a preclinical study, Platinol (cisplatin) treatment inhibited viability of a cell line expressing BRIP1 Q126* in culture (PMID: 33619228).	33619228
BRIP1 Q227*	Advanced Solid Tumor	sensitive	Cisplatin	Preclinical - Cell culture	Actionable	In a preclinical study, Platinol (cisplatin) treatment inhibited viability of a cell line expressing BRIP1 Q227* in culture (PMID: 33619228).	33619228
BRIP1 Q25*	Advanced Solid Tumor	sensitive	Cisplatin	Preclinical - Cell culture	Actionable	In a preclinical study, Platinol (cisplatin) treatment inhibited viability of a cell line expressing BRIP1 Q25* in culture (PMID: 33619228).	33619228
BRIP1 Q561*	Advanced Solid Tumor	sensitive	Cisplatin	Preclinical - Cell culture	Actionable	In a preclinical study, Platinol (cisplatin) treatment inhibited viability of a cell line expressing BRIP1 Q561* in culture (PMID: 33619228).	33619228
BRIP1 Q645*	Advanced Solid Tumor	sensitive	Cisplatin	Preclinical - Cell culture	Actionable	In a preclinical study, Platinol (cisplatin) treatment inhibited viability of a cell line expressing BRIP1 Q645* in culture (PMID: 33619228).	33619228
BRIP1 Q685*	Advanced Solid Tumor	sensitive	Cisplatin	Preclinical - Cell culture	Actionable	In a preclinical study, Platinol (cisplatin) treatment inhibited viability of a cell line expressing BRIP1 Q685* in culture (PMID: 33619228).	33619228
BRIP1 Q689*	Advanced Solid Tumor	sensitive	Cisplatin	Preclinical - Cell culture	Actionable	In a preclinical study, Platinol (cisplatin) treatment inhibited viability of a cell line expressing BRIP1 Q689* in culture (PMID: 33619228).	33619228
BRIP1 Q815*	Advanced Solid Tumor	sensitive	Cisplatin	Preclinical - Cell culture	Actionable	In a preclinical study, Platinol (cisplatin) treatment inhibited viability of a cell line expressing BRIP1 Q815* in culture (PMID: 33619228).	33619228
BRIP1 R261*	Advanced Solid Tumor	sensitive	Cisplatin	Preclinical - Cell culture	Actionable	In a preclinical study, Platinol (cisplatin) treatment inhibited viability of a cell line expressing BRIP1 R261* in culture (PMID: 33619228).	33619228
BRIP1 R439*	Advanced Solid Tumor	sensitive	Cisplatin	Preclinical - Cell culture	Actionable	In a preclinical study, Platinol (cisplatin) treatment inhibited viability of a cell line expressing BRIP1 R439* in culture (PMID: 33619228).	33619228
BRIP1 R581*	Advanced Solid Tumor	sensitive	Cisplatin	Preclinical - Cell culture	Actionable	In a preclinical study, Platinol (cisplatin) treatment inhibited viability of a cell line expressing BRIP1 R581* in culture (PMID: 33619228).	33619228
BRIP1 R762P	Advanced Solid Tumor	sensitive	Cisplatin	Preclinical - Cell culture	Actionable	In a preclinical study, Platinol (cisplatin) treatment inhibited viability of a cell line expressing BRIP1 R762P in culture (PMID: 33619228).	33619228
BRIP1 R831K	Advanced Solid Tumor	sensitive	Cisplatin	Preclinical - Cell culture	Actionable	In a preclinical study, Platinol (cisplatin) treatment inhibited viability of a cell line expressing BRIP1 R831K in culture (PMID: 33619228).	33619228
BRIP1 R836*	Advanced Solid Tumor	sensitive	Cisplatin	Preclinical - Cell culture	Actionable	In a preclinical study, Platinol (cisplatin) treatment inhibited viability of a cell line expressing BRIP1 R836* in culture (PMID: 33619228).	33619228
BRIP1 S189L	Advanced Solid Tumor	sensitive	Cisplatin	Preclinical - Cell culture	Actionable	In a preclinical study, Platinol (cisplatin) treatment inhibited viability of a cell line expressing BRIP1 S189L in culture (PMID: 33619228).	33619228
BRIP1 S614Y	Advanced Solid Tumor	sensitive	Cisplatin	Preclinical - Cell culture	Actionable	In a preclinical study, Platinol (cisplatin) treatment inhibited viability of a cell line expressing BRIP1 S614Y in culture (PMID: 33619228).	33619228
BRIP1 S618*	Advanced Solid Tumor	sensitive	Cisplatin	Preclinical - Cell culture	Actionable	In a preclinical study, Platinol (cisplatin) treatment inhibited viability of a cell line expressing BRIP1 S618* in culture (PMID: 33619228).	33619228
BRIP1 S653*	Advanced Solid Tumor	sensitive	Cisplatin	Preclinical - Cell culture	Actionable	In a preclinical study, Platinol (cisplatin) treatment inhibited viability of a cell line expressing BRIP1 S653* in culture (PMID: 33619228).	33619228
BRIP1 S697F	Advanced Solid Tumor	sensitive	Cisplatin	Preclinical - Cell culture	Actionable	In a preclinical study, Platinol (cisplatin) treatment inhibited viability of a cell line expressing BRIP1 S697F in culture (PMID: 33619228).	33619228
BRIP1 S697P	Advanced Solid Tumor	sensitive	Cisplatin	Preclinical - Cell culture	Actionable	In a preclinical study, Platinol (cisplatin) treatment inhibited viability of a cell line expressing BRIP1 S697P in culture (PMID: 33619228).	33619228
BRIP1 S772*	Advanced Solid Tumor	sensitive	Cisplatin	Preclinical - Cell culture	Actionable	In a preclinical study, Platinol (cisplatin) treatment inhibited viability of a cell line expressing BRIP1 S772* in culture (PMID: 33619228).	33619228
BRIP1 S805*	Advanced Solid Tumor	sensitive	Cisplatin	Preclinical - Cell culture	Actionable	In a preclinical study, Platinol (cisplatin) treatment inhibited viability of a cell line expressing BRIP1 S805* in culture (PMID: 33619228).	33619228
BRIP1 S990A	Advanced Solid Tumor	no benefit	Cisplatin	Preclinical - Cell culture	Actionable	In a preclinical study, Platinol (cisplatin) treatment did not inhibit viability of a cell line expressing BRIP1 S990A in culture (PMID: 33619228).	33619228
BRIP1 T252R	Advanced Solid Tumor	sensitive	Cisplatin	Preclinical - Cell culture	Actionable	In a preclinical study, Platinol (cisplatin) treatment inhibited viability of a cell line expressing BRIP1 T252R in culture (PMID: 33619228).	33619228
BRIP1 V341D	Advanced Solid Tumor	sensitive	Cisplatin	Preclinical - Cell culture	Actionable	In a preclinical study, Platinol (cisplatin) treatment inhibited viability of a cell line expressing BRIP1 V341D in culture (PMID: 33619228).	33619228
BRIP1 W335L	Advanced Solid Tumor	sensitive	Cisplatin	Preclinical - Cell culture	Actionable	In a preclinical study, Platinol (cisplatin) treatment inhibited viability of a cell line expressing BRIP1 W335L in culture (PMID: 33619228).	33619228
BRIP1 W448*	Advanced Solid Tumor	sensitive	Cisplatin	Preclinical - Cell culture	Actionable	In a preclinical study, Platinol (cisplatin) treatment inhibited viability of a cell line expressing BRIP1 W448* in culture (PMID: 33619228).	33619228
BRIP1 Y147*	Advanced Solid Tumor	sensitive	Cisplatin	Preclinical - Cell culture	Actionable	In a preclinical study, Platinol (cisplatin) treatment inhibited viability of a cell line expressing BRIP1 Y147* in culture (PMID: 33619228).	33619228
BRIP1 Y461*	Advanced Solid Tumor	sensitive	Cisplatin	Preclinical - Cell culture	Actionable	In a preclinical study, Platinol (cisplatin) treatment inhibited viability of a cell line expressing BRIP1 Y461* in culture (PMID: 33619228).	33619228

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