Gene

FBXW7

F-box and WD repeat domain containing 7

Explore in graph →CI-GENE-00001753HGNC:16712 ENSG00000109670 NCBI 55294 CIViC Cancer geneApproved

Curated evidence

Clinical evidence (15)

CIViC items involving this gene, grouped by molecular profile and therapy, with native levels and directions. 50 items per page.

civicCuratedShowing 1–15 of 15 evidence items · levels, directions and significance as curated at the source; each row links to its CIViC record.

Therapy	Cancer	Type	Level	Direction · significance	Rating (1–5)	Status	Evidence	Source
FBXW7 G579W1
Regorafenib Anhydrous	Malignant Colorectal NeoplasmCURATED_BROADER	Predictive	D	Supports Resistance	—

Cohorts

Alteration frequency by cohort (192)

Frequency = cases affected / cases profiled within one cohort. Cohorts are never pooled.

cbioportalObserved192 cohort rows (showing 42, sorted by frequency) · frequency = affected / profiled, as published by each cohort; cohorts are not pooled. Hover a row badge for its release.

Cohort	Mapped cancer	Alteration	Affected (n)	Profiled (n)	Frequency (%)	Rank in cohort	Source
Triple-Negative Breast Cancer (FUSCC, Cell Research 2020) brca_fuscc_2020	Invasive Breast Carcinoma	Ssm

Literature

Linked publications (4)

25 per page, newest first.

pubmedPublishedShowing 1–4 of 4 publications · bibliographic data as recorded by PubMed; abstracts are not reproduced.

Prediction of response to anti-EGFR antibody-based therapies by multigene sequencing in colorectal cancer patients.
· BMC Cancer · 2015 · PMID 26508446 · validated civic_curation pubmed
FBXW7 mutations in patients with advanced cancers: clinical and molecular characteristics and outcomes with mTOR inhibitors.
· PLoS One · 2014 · PMID 24586741 · validated civic_curation pubmed
FBXW7 targets mTOR for degradation and cooperates with PTEN in tumor suppression.
· Science · 2008 · PMID 18787170 · validated civic_curation pubmed
Circadian regulation of mTOR by the ubiquitin pathway in renal cell carcinoma.
· Cancer Res · 2014 · PMID 24253377 · validated civic_curation pubmed

FBXW7 L403FS*341
Regorafenib Anhydrous	Malignant Colorectal NeoplasmCURATED_BROADER	Predictive	D	Supports Resistance	—	submitted	EID4821 In an in vitro study of 16 cancer cell lines, FBXW7 (FBW7) mutant colorectal cancer cell lines (n=8), including SW837 cell line harboring FBW7 L403fs*34 mutation, were associated with resistance to r… (full text at CIViC) PMID 27399335 · Tong et al., 2017 · Open in CIViC	civic

FBXW7 L403FS*341

Regorafenib Anhydrous

Malignant Colorectal NeoplasmCURATED_BROADER

Predictive

Supports Resistance

—

submitted

EID4821

In an in vitro study of 16 cancer cell lines, FBXW7 (FBW7) mutant colorectal cancer cell lines (n=8), including SW837 cell line harboring FBW7 L403fs*34 mutation, were associated with resistance to r… (full text at CIViC)

PMID 27399335 · Tong et al., 2017 · Open in CIViC

civic

FBXW7 Loss-of-function2
Everolimus	Renal Cell CarcinomaCURATED_BROADER	Predictive	E	Supports Sensitivity Response	2	accepted	EID1628 mTOR protein levels were found to underly a circadian 24-hour rhythm regulated by time-dependent Fbxw7-mediated ubiquitination. Survival rates of tumor-bearing mice with everolimus showed time-depende… (full text at CIViC) PMID 24253377 · Okazaki et al., 2014 · Open in CIViC	civic
Sirolimus	Malignant NeoplasmALIAS	Predictive	D	Supports Sensitivity Response	4	accepted	EID1632 FBXW7 was shown to target mTOR for ubiquitination and degradation. A reciprocal relationship between FBXW7 or PTEN loss was identified in breast cancer tumors and cell lines (mutual exclusivity of th… (full text at CIViC) PMID 18787170 · Mao et al., 2008 · Open in CIViC	civic

FBXW7 Loss-of-function2

Everolimus

Renal Cell CarcinomaCURATED_BROADER

Predictive

Supports Sensitivity Response

accepted

EID1628

mTOR protein levels were found to underly a circadian 24-hour rhythm regulated by time-dependent Fbxw7-mediated ubiquitination. Survival rates of tumor-bearing mice with everolimus showed time-depende… (full text at CIViC)

PMID 24253377 · Okazaki et al., 2014 · Open in CIViC

civic

Sirolimus

Malignant NeoplasmALIAS

Predictive

Supports Sensitivity Response

accepted

EID1632

FBXW7 was shown to target mTOR for ubiquitination and degradation. A reciprocal relationship between FBXW7 or PTEN loss was identified in breast cancer tumors and cell lines (mutual exclusivity of th… (full text at CIViC)

PMID 18787170 · Mao et al., 2008 · Open in CIViC

civic

FBXW7 Mutation2
Cetuximab + PanitumumabSubstitutes	Malignant Colorectal NeoplasmCURATED_BROADER	Predictive	B	Supports Resistance	2	accepted	EID718 65 patients were retrospectively analyzed for mutational profiles predictive of response to EGFR-inhibitors (cetuximab or panitumumab). FBXW7 mutation was found to be more prevalent in non-responders … (full text at CIViC) PMID 26508446 · Lupini et al., 2015 · Open in CIViC	civic
MTOR Inhibitor	Malignant NeoplasmALIAS	Predictive	B	Supports Sensitivity Response	2	accepted	EID1631 418 patients with advanced cancer were screened for FBXW7 mutations using a multiplex gene panel. 17 FBXW7 mutations were detected (isolated mutation in 2 patients). Ten patients were treated with an … (full text at CIViC) PMID 24586741 · Jardim et al., 2014 · Open in CIViC	civic

FBXW7 Mutation2

Cetuximab + PanitumumabSubstitutes

Malignant Colorectal NeoplasmCURATED_BROADER

Predictive

Supports Resistance

accepted

EID718

65 patients were retrospectively analyzed for mutational profiles predictive of response to EGFR-inhibitors (cetuximab or panitumumab). FBXW7 mutation was found to be more prevalent in non-responders … (full text at CIViC)

PMID 26508446 · Lupini et al., 2015 · Open in CIViC

civic

MTOR Inhibitor

Malignant NeoplasmALIAS

Predictive

Supports Sensitivity Response

accepted

EID1631

418 patients with advanced cancer were screened for FBXW7 mutations using a multiplex gene panel. 17 FBXW7 mutations were detected (isolated mutation in 2 patients). Ten patients were treated with an … (full text at CIViC)

PMID 24586741 · Jardim et al., 2014 · Open in CIViC

civic

FBXW7 R465C1
(functional)	—UNRESOLVED	Functional	D	Supports Dominant Negative	3	submitted	EID10041 Seven T cell acute lymphoblastic leukemia (T-ALL) cell lines were studied which all constituitively expressed the notch intracellular domain (NICD) but did not contain the expected notch mutations (c-… (full text at CIViC) PMID 17646409 · O'Neil et al., 2007 · Open in CIViC	civic

FBXW7 R465C1

(functional)

—UNRESOLVED

Functional

Supports Dominant Negative

submitted

EID10041

Seven T cell acute lymphoblastic leukemia (T-ALL) cell lines were studied which all constituitively expressed the notch intracellular domain (NICD) but did not contain the expected notch mutations (c-… (full text at CIViC)

PMID 17646409 · O'Neil et al., 2007 · Open in CIViC

civic

FBXW7 R465H2
(predisposing)	T Acute Lymphoblastic LeukemiaCURATED_BROADER	Predisposing	D	Supports Predisposition	4	submitted	EID7174 In mouse models, constitutive NOTCH signaling contributes to the genesis of breast cancer, medulloblastoma, and T cell leukemia, whereas in human cancer its role is best exemplified by T cell acute ly… (full text at CIViC) PMID 17646409 · O'Neil et al., 2007 · Open in CIViC	civic
(functional)	—UNRESOLVED	Functional	E	Supports Loss Of Function	3	rejected	EID7170 T-ALL mutations in FBXW7 are predominantly located at arginine residues R479Q, R505C, and R465H and result in FBXW7 mutants unable to bind to or degrade targets The R465H variant led to low levels of … (full text at CIViC) PMID 27247421 · Yeh et al., 2016 · Open in CIViC	civic

FBXW7 R465H2

(predisposing)

T Acute Lymphoblastic LeukemiaCURATED_BROADER

Predisposing

Supports Predisposition

submitted

EID7174

In mouse models, constitutive NOTCH signaling contributes to the genesis of breast cancer, medulloblastoma, and T cell leukemia, whereas in human cancer its role is best exemplified by T cell acute ly… (full text at CIViC)

PMID 17646409 · O'Neil et al., 2007 · Open in CIViC

civic

(functional)

—UNRESOLVED

Functional

Supports Loss Of Function

rejected

EID7170

T-ALL mutations in FBXW7 are predominantly located at arginine residues R479Q, R505C, and R465H and result in FBXW7 mutants unable to bind to or degrade targets The R465H variant led to low levels of … (full text at CIViC)

PMID 27247421 · Yeh et al., 2016 · Open in CIViC

civic

FBXW7 R479Q1
(functional)	—UNRESOLVED	Functional	D	Supports Dominant Negative	3	submitted	EID10042 Seven T cell acute lymphoblastic leukemia (T-ALL) cell lines were studied which all constituitively expressed the notch intracellular domain (NICD) but did not contain the expected notch mutations (c-… (full text at CIViC) PMID 17646409 · O'Neil et al., 2007 · Open in CIViC	civic

FBXW7 R479Q1

(functional)

—UNRESOLVED

Functional

Supports Dominant Negative

submitted

EID10042

PMID 17646409 · O'Neil et al., 2007 · Open in CIViC

civic

FBXW7 R505C1
Regorafenib Anhydrous	Malignant Colorectal NeoplasmCURATED_BROADER	Predictive	D	Supports Resistance	—	submitted	EID4470 In an in vitro study of 16 cancer cell lines, FBXW7 (FBW7) mutant colorectal cancer cell lines (n=8), including LoVo cell line harboring FBW7 R505C mutation, were associated with resistance to regoraf… (full text at CIViC) PMID 27399335 · Tong et al., 2017 · Open in CIViC	civic

FBXW7 R505C1

Regorafenib Anhydrous

Malignant Colorectal NeoplasmCURATED_BROADER

Predictive

Supports Resistance

—

submitted

EID4470

In an in vitro study of 16 cancer cell lines, FBXW7 (FBW7) mutant colorectal cancer cell lines (n=8), including LoVo cell line harboring FBW7 R505C mutation, were associated with resistance to regoraf… (full text at CIViC)

PMID 27399335 · Tong et al., 2017 · Open in CIViC

civic

FBXW7 R505H1
Regorafenib Anhydrous	Malignant Colorectal NeoplasmCURATED_BROADER	Predictive	D	Supports Resistance	—	submitted	EID4471 In an in vitro study of 16 cancer cell lines, FBXW7 (FBW7) mutant colorectal cancer cell lines (n=8), including LS411N cell line harboring FBW7 R505H mutation, were associated with resistance to regor… (full text at CIViC) PMID 27399335 · Tong et al., 2017 · Open in CIViC	civic

FBXW7 R505H1

Regorafenib Anhydrous

Malignant Colorectal NeoplasmCURATED_BROADER

Predictive

Supports Resistance

—

submitted

EID4471

In an in vitro study of 16 cancer cell lines, FBXW7 (FBW7) mutant colorectal cancer cell lines (n=8), including LS411N cell line harboring FBW7 R505H mutation, were associated with resistance to regor… (full text at CIViC)

PMID 27399335 · Tong et al., 2017 · Open in CIViC

civic

FBXW7 R505L1
(functional)	—UNRESOLVED	Functional	D	Supports Dominant Negative	3	submitted	EID10043 Seven T cell acute lymphoblastic leukemia (T-ALL) cell lines were studied which all constituitively expressed the notch intracellular domain (NICD) but did not contain the expected notch mutations (c-… (full text at CIViC) PMID 17646409 · O'Neil et al., 2007 · Open in CIViC	civic

FBXW7 R505L1

(functional)

—UNRESOLVED

Functional

Supports Dominant Negative

submitted

EID10043

PMID 17646409 · O'Neil et al., 2007 · Open in CIViC

civic

FBXW7 R658Q1
Regorafenib Anhydrous	Malignant Colorectal NeoplasmCURATED_BROADER	Predictive	D	Supports Resistance	—	submitted	EID4823 In an in vitro study of 16 cancer cell lines, FBXW7 (FBW7) mutant colorectal cancer cell lines (n=8), including HCT-8 cell line harboring FBW7 R658Q mutation, were associated with resistance to regora… (full text at CIViC) PMID 27399335 · Tong et al., 2017 · Open in CIViC	civic

FBXW7 R658Q1

Regorafenib Anhydrous

Malignant Colorectal NeoplasmCURATED_BROADER

Predictive

Supports Resistance

—

submitted

EID4823

In an in vitro study of 16 cancer cell lines, FBXW7 (FBW7) mutant colorectal cancer cell lines (n=8), including HCT-8 cell line harboring FBW7 R658Q mutation, were associated with resistance to regora… (full text at CIViC)

PMID 27399335 · Tong et al., 2017 · Open in CIViC

civic

FBXW7 S668FS*391
Regorafenib Anhydrous	Malignant Colorectal NeoplasmCURATED_BROADER	Predictive	D	Supports Resistance	—	submitted	EID4820 In an in vitro study of 16 cancer cell lines, FBXW7 (FBW7) mutant colorectal cancer cell lines (n=8), including SW48 cell line harboring FBW7 S668fs*39 mutation, were associated with resistance to re… (full text at CIViC) PMID 27399335 · Tong et al., 2017 · Open in CIViC	civic

FBXW7 S668FS*391

Regorafenib Anhydrous

Malignant Colorectal NeoplasmCURATED_BROADER

Predictive

Supports Resistance

—

submitted

EID4820

In an in vitro study of 16 cancer cell lines, FBXW7 (FBW7) mutant colorectal cancer cell lines (n=8), including SW48 cell line harboring FBW7 S668fs*39 mutation, were associated with resistance to re… (full text at CIViC)

PMID 27399335 · Tong et al., 2017 · Open in CIViC

civic