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Gene Symbol FBXW7
Synonyms AGO | CDC4 | FBW6 | FBW7 | FBX30 | FBXO30 | FBXW6 | hAgo | hCdc4 | SEL-10 | SEL10
Gene Description FBXW7, F-box/WD repeat-containing protein 7, is part of the SCF E3 ubiquitin-protein ligase complex, which plays a role in the degradation of proteins involved in cell division and cell growth (PMID: 17909001, PMID: 22673505). FBXW7 mutations have been associated with cholangiocarcinoma and acute lymphocytic leukemia (PMID: 17909001) and have been identified in many other cancers, including colorectal (PMID: 28424412), endometrial, and stomach cancer (PMID: 17909001).

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Variant Impact Protein Effect Variant Description Associated with drug Resistance
A481V missense unknown FBXW7 A481V lies within WD repeat 3 of the Fbxw7 protein (UniProt.org). A481V has not been characterized in the scientific literature and therefore, its effect on Fbxw7 protein function is unknown (PubMed, May 2020).
A503T missense unknown FBXW7 A503T lies within WD repeat 4 of the Fbxw7 protein (UniProt.org). A503T has been identified in sequencing studies (PMID: 25148578), but has not been biochemically characterized and therefore, its effect on Fbxw7 protein function is unknown (PubMed, Jun 2020).
A503V missense unknown FBXW7 A503V lies within WD repeat 4 of the Fbxw7 protein (UniProt.org). A503V results in aberrant cellular localization of Fbxw7 (PMID: 30510140) and decreases binding to large T antigen (PMID: 32427880), but demonstrates Notch1 intracellular domain binding similar to wild-type Fbxw7 in culture (PMID: 30510140), and therefore, its effect on Fbxw7 protein function is unknown.
C386W missense unknown FBXW7 C386W lies within WD repeat 1 of the Fbxw7 protein (UniProt.org). C386W has been identified in sequencing studies (PMID: 17457043), but has not been biochemically characterized and therefore, its effect on Fbxw7 protein function is unknown (PubMed, May 2020).
C453fs frameshift loss of function - predicted FBXW7 C453fs results in a change in the amino acid sequence of the Fbxw7 protein beginning at aa 453 of 707, likely resulting in premature truncation of the functional protein (UniProt.org). C453fs has not been characterized however, based on the effects of other truncation mutations downstream of C453 (PMID: 24838835), is predicted to lead to a loss of Fbxw7 protein function.
D135Y missense unknown FBXW7 D135Y does not lie within any known functional domains of the Fbxw7 protein (UniProt.org). D135Y has not been characterized in the scientific literature and therefore, its effect on Fbxw7 protein function is unknown (PubMed, May 2020).
D362* nonsense loss of function - predicted FBXW7 D362* results in a premature truncation of the Fbxw7 protein at amino acid 362 of 707 (UniProt.org). D362* has not been characterized however, due to the effects of other truncation mutations downstream of D362 (PMID: 30510140), D362* is predicted to lead to a loss of Fbxw7 protein function.
D440N missense unknown FBXW7 D440N lies within WD repeat 2 of the Fbxw7 protein (UniProt.org). D440N has been identified in sequencing studies (PMID: 17909001), but has not been biochemically characterized and therefore, its effect on Fbxw7 protein function is unknown (PubMed, Jun 2020).
D480N missense loss of function - predicted FBXW7 D480N lies within WD repeat 3 of the Fbxw7 protein (UniProt.org). D480N results in aberrant subnuclear localization and decreased Notch1 intracellular domain binding in culture (PMID: 30510140), and therefore, is predicted to lead to a loss of Fbxw7 protein function.
D480Y missense unknown FBXW7 D480Y lies within WD repeat 3 of the Fbxw7 protein (UniProt.org). D480Y has been identified in sequencing studies (PMID: 18948947), but has not been biochemically characterized and therefore, its effect on Fbxw7 protein function is unknown (PubMed, May 2020).
D520N missense unknown FBXW7 D520N lies within WD repeat 4 of the Fbxw7 protein (UniProt.org). D520N has been identified in sequencing studies (PMID: 22810696, PMID: 24121792), but has not been biochemically characterized and therefore, its effect on Fbxw7 protein function is unknown (PubMed, May 2020).
D550Mfs*6 frameshift unknown FBXW7 D550Mfs*6 indicates a shift in the reading frame starting at amino acid 550 and terminating 6 residues downstream causing a premature truncation of the 707 amino acid Fbxw7 protein (UniProt.org). D550Mfs*6 has been identified in sequencing studies (PMID: 26960398), but has not been biochemically characterized and therefore, its effect on Fbxw7 protein function is unknown (PubMed, Apr 2020).
D560G missense unknown FBXW7 D560G lies within WD repeat 5 of the Fbxw7 protein (UniProt.org). D560G has been identified in sequencing studies (PMID: 22895193), but has not been biochemically characterized and therefore, its effect on Fbxw7 protein function is unknown (PubMed, May 2020).
D600H missense unknown FBXW7 D600H lies within WD repeat 6 of the Fbxw7 protein (UniProt.org). D600H has not been characterized in the scientific literature and therefore, its effect on Fbxw7 protein function is unknown (PubMed, May 2020).
D600Y missense unknown FBXW7 D600Y lies within WD repeat 6 of the Fbxw7 protein (UniProt.org). D600Y has been identified in sequencing studies (PMID: 30224629, PMID: 22895193), but has not been biochemically characterized and therefore, its effect on Fbxw7 protein function is unknown (PubMed, Jun 2020).
del deletion loss of function FBXW7 del indicates a deletion of the FBXW7 gene.
E113D missense unknown FBXW7 E113D does not lie within any known functional domains of the Fbxw7 protein (UniProt.org). E113D has been identified in sequencing studies (PMID: 26182302, PMID: 30959466), but has not been biochemically characterized and therefore, its effect on Fbxw7 protein function is unknown (PubMed, May 2020).
E117del deletion unknown FBXW7 E117del results in the deletion of an amino acid in the Fbxw7 protein at amino acid 117 (UniProt.org). E117del has been identified in sequencing studies (PMID: 24909261, PMID: 27284958), but has not been biochemically characterized and therefore, its effect on Fbxw7 protein function is unknown (PubMed, May 2020).
E192A missense unknown FBXW7 E192A does not lie within any known functional domains of the Fbxw7 protein (UniProt.org). E192A has been identified in sequencing studies (PMID: 24586741, PMID: 26328274), but has not been biochemically characterized and therefore, its effect on Fbxw7 protein function is unknown (PubMed, May 2020).
E248D missense unknown FBXW7 E248D does not lie within any known functional domains of the Fbxw7 protein (UniProt.org). E248D has not been characterized and therefore, its effect on Fbxw7 protein function is unknown (PubMed, May 2020).
E287V missense unknown FBXW7 E287V lies within the F-box domain of the Fbxw7 protein (UniProt.org). E287V has been identified in sequencing studies (PMID: 22810696, PMID: 28924241), but has not been biochemically characterized and therefore, its effect on Fbxw7 protein function is unknown (PubMed, May 2020).
E369* nonsense loss of function - predicted FBXW7 E369* results in a premature truncation of the Fbxw7 protein at amino acid 369 of 707 (UniProt.org). Due to the loss of all WD repeat domains (UniProt.org), R369* is predicted to result in a loss of function.
G16delinsVR indel no effect - predicted FBXW7 G16delinsVR results in a deletion of glycine (G) at amino acid 16 in the Fbxw7 protein, combined with the insertion of a valine (V) and an arginine (R) at the same site (UniProt.org). G16delinsVR results in similar nuclear localization patterns and Notch1 intracellular domain binding to wild-type Fbxw7 in culture (PMID: 30510140), and therefore, is predicted to have no effect on Fbxw7 protein function.
G397D missense unknown FBXW7 G397D lies within WD repeat 1 of the Fbxw7 protein (UniProt.org). G397D has been identified in the scientific literature (PMID: 14999283), but has not been biochemically characterized and therefore, its effect on Fbxw7 protein function is unknown (PubMed, May 2020).
G411S missense unknown FBXW7 G411S lies within WD repeat 1 of the Fbxw7 protein (UniProt.org). G411S has not been characterized in the scientific literature and therefore, its effect on Fbxw7 protein function is unknown (PubMed, May 2020).
G422C missense unknown FBXW7 G422C lies within WD repeat 2 of the Fbxw7 protein (UniProt.org). G422C has not been characterized in the scientific literature and therefore, its effect on Fbxw7 protein function is unknown (PubMed, May 2020).
G423* nonsense loss of function - predicted FBXW7 G423* results in a premature truncation of the Fbxw7 protein at amino acid 423 of 707 within the WD repeat domain (UniProt.org). G423* has not been characterized, however due to the loss of the WD repeat domain (UniProt.org), G423* is predicted to lead to a loss of Fbxw7 function.
G423R missense unknown FBXW7 G423R lies within WD repeat 2 of the Fbxw7 protein (UniProt.org). G423R does not enhance xenograft tumor growth in animal models compared to controls (PMID: 24838835), however, it has not been biochemically characterized and therefore, its effect on Fbxw7 protein function is unknown.
G423V missense loss of function FBXW7 G423V lies within WD repeat 2 of the Fbxw7 protein (UniProt.org). G423V confers a loss of function to the Fbxw7 protein, as demonstrated by aberrant subnuclear localization and the absence of Notch1 intracellular domain binding in culture, and elevated expression levels and stability of Notch1 intracellular domain in a patient sample (PMID: 30510140).
G437E missense unknown FBXW7 G437E lies within WD repeat 2 of the Fbxw7 protein (UniProt.org). G437E has been identified in the scientific literature (PMID: 27879972), but has not been biochemically characterized and therefore, its effect on Fbxw7 protein function is unknown (PubMed, May 2020).
G437R missense unknown FBXW7 G437R lies within WD repeat 2 of the Fbxw7 protein (UniProt.org). G437R has been identified in sequencing studies (PMID: 22810696), but has not been biochemically characterized and therefore, its effect on Fbxw7 protein function is unknown (PubMed, May 2020).
G437V missense unknown FBXW7 G437V lies within WD repeat 2 of the Fbxw7 protein (UniProt.org). G437V has been identified in sequencing studies (PMID: 29316426, PMID: 28940304, PMID: 23263491), but has not been biochemically characterized and therefore, its effect on Fbxw7 protein function is unknown (PubMed, Jun 2020).
G477S missense unknown FBXW7 G477S lies within WD repeat 3 of the Fbxw7 protein (UniProt.org). G477S has been identified in the scientific literature (PMID: 19109228), but has not been biochemically characterized and therefore, its effect on Fbxw7 protein function is unknown (PubMed, May 2020).
G499Vfs*25 frameshift loss of function - predicted FBXW7 G499Vfs*25 indicates a shift in the reading frame starting at amino acid 499 and terminating 25 residues downstream causing a premature truncation of the 707 amino acid Fbxw7 protein (UniProt.org). Due to the loss of several WD domains (UniProt.org), G499Vfs*25 is predicted to lead to a loss of Fbxw7 protein function.
G517E missense unknown FBXW7 G517E lies within WD repeat 4 of the Fbxw7 protein (UniProt.org). G517E has been identified in the scientific literature (PMID: 27399335), but has not been biochemically characterized and therefore, its effect on Fbxw7 protein function is unknown (PubMed, May 2020).
G579W missense unknown FBXW7 G579W does not lie within any known functional domains of the Fbxw7 protein (UniProt.org). G579W has been identified in the scientific literature (PMID: 24755471, PMID: 27399335), but has not been biochemically characterized and therefore, its effect on Fbxw7 protein function is unknown (PubMed, May 2020).
G597E missense unknown FBXW7 G597E lies within WD repeat 6 of the Fbxw7 protein (UniProt.org). G597E has been identified in sequencing studies (PMID: 23415222), but has not been biochemically characterized and therefore, its effect on Fbxw7 protein function is unknown (PubMed, May 2020).
G667fs frameshift unknown FBXW7 G667fs results in a change in the amino acid sequence of the Fbxw7 protein beginning at aa 667 of 707, likely resulting in premature truncation of the functional protein (UniProt.org). G667fs has been identified in the scientific literature (PMID: 25562415), but has not been biochemically characterized and therefore, its effect on Fbxw7 protein function is unknown (PubMed, May 2020).
G670fs frameshift unknown FBXW7 G670fs results in a change in the amino acid sequence of the Fbxw7 protein beginning at aa 670 of 707, likely resulting in premature truncation of the functional protein (UniProt.org). G670fs has been identified in sequencing studies (PMID: 26076459), but has not been biochemically characterized and therefore, its effect on Fbxw7 protein function is unknown (PubMed, May 2020).
H379R missense unknown FBXW7 H379R lies within WD repeat 1 of the Fbxw7 protein (UniProt.org). H379R has been identified in sequencing studies (PMID: 22980976), but has not been biochemically characterized and therefore, its effect on Fbxw7 protein function is unknown (PubMed, May 2020).
H382N missense unknown FBXW7 H382N lies within WD repeat 1 of the Fbxw7 protein (UniProt.org). H382N has been identified in sequencing studies (PMID: 26010451), but has not been biochemically characterized and therefore, its effect on Fbxw7 protein function is unknown (PubMed, May 2020).
H420Y missense unknown FBXW7 H420Y lies within the WD repeat 2 of the Fbxw7 protein (UniProt.org). H420Y is predicted to affect substrate targeting of the Fbxw7 protein based on structural modeling (PMID: 18485478), but has not been biochemically characterized and therefore, its effect on Fbxw7 protein function is unknown (PubMed, May 2020).
H460R missense loss of function - predicted FBXW7 H460R lies within the WD repeat domain of the Fbxw7 protein (UniProt.org). H460R is predicted to confer a loss of function to the Fbxw7 protein, as demonstrated by overexpression of the Fbxw7 ubiquitination target protein, Ccne1 (PMID: 14507635).
H460Y missense unknown FBXW7 H460Y lies within WD repeat 3 of the Fbxw7 protein (UniProt.org). H460Y has been identified in sequencing studies (PMID: 29029407), but has not been biochemically characterized and therefore, its effect on Fbxw7 protein function is unknown (PubMed, May 2020).
H470P missense unknown FBXW7 H470P lies within WD repeat 3 of the Fbxw7 protein (UniProt.org). H470P has been identified in the scientific literature (PMID: 18485478), but has not been biochemically characterized and therefore, its effect on Fbxw7 protein function is unknown (PubMed, May 2020).
H500D missense unknown FBXW7 H500D lies within WD repeat 4 of the Fbxw7 protein (UniProt.org). H500D has not been characterized in the scientific literature and therefore, its effect on Fbxw7 protein function is unknown (PubMed, May 2020).
H500R missense unknown FBXW7 H500R lies within WD repeat 4 of the Fbxw7 protein (UniProt.org). H500R has been identified in sequencing studies (PMID: 22842228), but has not been biochemically characterized and therefore, its effect on Fbxw7 protein function is unknown (PubMed, May 2020).
H500Y missense unknown FBXW7 H500Y lies within WD repeat 4 of the Fbxw7 protein (UniProt.org). H500Y has been identified in sequencing studies (PMID: 30578357), but has not been biochemically characterized and therefore, its effect on Fbxw7 protein function is unknown (PubMed, May 2020).
I347M missense unknown FBXW7 I347M does not lie within any known functional domains of the Fbxw7 protein (UniProt.org). I347M is predicted to have activity similar to wild-type Fbxw7 based on comparison and correlation analysis of induced gene expression signatures (PMID: 27147599), but has not been biochemically characterized and therefore, its effect on Fbxw7 protein function is unknown.
I435fs frameshift loss of function - predicted FBXW7 I435fs results in a change in the amino acid sequence of the Fbxw7 protein beginning at aa 435 of 707, likely resulting in premature truncation of the functional protein (UniProt.org). Due to a loss of a majority of the WD repeat domains (UniProt.org), I435fs is predicted to lead to a loss of Fbxw7 protein function.
I563T missense unknown FBXW7 I563T lies within WD repeat 5 of the Fbxw7 protein (UniProt.org). I563T has been identified in sequencing studies (PMID: 18772397), but has not been biochemically characterized and therefore, its effect on Fbxw7 protein function is unknown (PubMed, May 2020).
inact mut unknown loss of function FBXW7 inact mut indicates that this variant results in a loss of function of the Fbxw7 protein. However, the specific amino acid change has not been identified.
K11R missense loss of function - predicted FBXW7 K11R does not lie within any known functional domains of the Fbxw7 protein (UniProt.org). K11R is predicted to confer a loss of function to the Fbxw7 protein, as demonstrated by disruption of the NSL1 function of the Fbxw7 protein in cell culture (PMID: 20815813).
K167T missense unknown FBXW7 K167T does not lie within any known functional domains of the Fbxw7 protein (UniProt.org). K167T has not been characterized and therefore, its effect on Fbxw7 protein function is unknown (PubMed, May 2020).
K239Q missense unknown FBXW7 K239Q does not lie within any known functional domains of the Fbxw7 protein (UniProt.org). K239Q has not been characterized and therefore, its effect on Fbxw7 protein function is unknown (PubMed, May 2020).
K299fs frameshift loss of function - predicted FBXW7 K299fs results in a change in the amino acid sequence of the Fbxw7 protein beginning at aa 299 of 707, likely resulting in premature truncation of the functional protein (UniProt.org). Due to the loss of the WD repeat domains (UniProt.org), K299fs is predicted to lead to a loss of Fbxw7 protein function.
K404E missense unknown FBXW7 K404E lies within WD repeat 1 of the Fbxw7 protein (UniProt.org). K404E has not been characterized in the scientific literature and therefore, its effect on Fbxw7 protein function is unknown (PubMed, May 2020).
K444fs frameshift loss of function - predicted FBXW7 K444fs results in a change in the amino acid sequence of the Fbxw7 protein beginning at aa 444 of 707, likely resulting in premature truncation of the functional protein (UniProt.org). Due to a loss of a majority of the WD repeat domains (UniProt.org), K444fs is predicted to lead to a loss of Fbxw7 protein function.
L301P missense unknown FBXW7 L301P lies within the F-box domain of the Fbxw7 protein (UniProt.org). L301P has been identified in sequencing studies (PMID: 29604063), but has not been biochemically characterized and therefore, its effect on Fbxw7 protein function is unknown (PubMed, Apr 2020).
L320I missense unknown FBXW7 L320I lies within the F-box domain of the Fbxw7 protein (UniProt.org). L320I has not been characterized in the scientific literature and therefore, its effect on Fbxw7 protein function is unknown (PubMed, May 2020).
L443H missense unknown FBXW7 L443H lies within WD repeat 2 of the Fbxw7 protein (UniProt.org). L443H results in increased migration and invasion, but has no effect on cell proliferation and variable effect on colony formation in culture (PMID: 31161818), and therefore, its effect on Fbxw7 protein is unknown.
loss unknown loss of function FBXW7 loss indicates loss of the Fbxw7 gene, mRNA, and protein.
mutant unknown unknown FBXW7 mutant indicates an unspecified mutation in the FBXW7 gene.
P247T missense unknown FBXW7 P247T does not lie within any known functional domains of the Fbxw7 protein (UniProt.org). P247T has not been characterized and therefore, its effect on Fbxw7 protein function is unknown (PubMed, May 2020).
P285H missense unknown FBXW7 P285H lies within the F-box domain of the Fbxw7 protein (UniProt.org). P285H has not been characterized in the scientific literature and therefore, its effect on Fbxw7 protein function is unknown (PubMed, May 2020).
P298L missense unknown FBXW7 P298L lies within the F-box domain of the Fbxw7 protein (UniProt.org). P298L has not been characterized in the scientific literature and therefore, its effect on Fbxw7 protein function is unknown (PubMed, May 2020).
Q127* nonsense loss of function - predicted FBXW7 Q127* results in a premature truncation of the Fbxw7 protein at amino acid 127 of 707 (UniProt.org). Due to the loss of all known functional domains (UniProt.org), Q127* is predicted to result in a loss of function.
Q275* nonsense loss of function - predicted FBXW7 Q275* results in a premature truncation of the Fbxw7 protein at amino acid 275 of 707 (UniProt.org). Due to the loss of all known functional domains (UniProt.org), FBXW7 Q275* is predicted to lead to a loss of Fbxw7 function.
Q306* nonsense loss of function - predicted FBXW7 Q306* results in a premature truncation of the Fbxw7 protein at amino acid 306 of 707 (UniProt.org). Due to the loss of the WD repeat domain, Q306* is predicted to lead to a loss of Fbxw7 protein function (UniProt.org).
Q47* nonsense loss of function - predicted FBXW7 Q47* results in a premature truncation of the Fbxw7 protein at amino acid 47 of 707 (UniProt.org). Due to the loss of all known functional domains, Q47* is predicted to lead to a loss of Fbxw7 protein function (UniProt.org).
Q631* nonsense unknown FBXW7 Q631* results in a premature truncation of the Fbxw7 protein at amino acid 631 of 707 (UniProt.org). Q631* has been identified in sequencing studies (PMID: 24390348), but has not been characterized and therefore, its effect on Fbxw7 protein function is unknown (PubMed, May 2020).
R14Q missense unknown FBXW7 R14Q does not lie within any known functional domains of the Fbxw7 protein (UniProt.org). R14Q has been identified in sequencing studies (PMID: 22810696, PMID: 27149842), but has not been biochemically characterized and therefore, its effect on Fbxw7 protein function is unknown (PubMed, May 2020).
R179C missense unknown FBXW7 R179C does not lie within any known functional domains of the Fbxw7 protein (UniProt.org). R179C has been identified in sequencing studies (PMID: 30239046, PMID: 27714650), but has not been biochemically characterized and therefore, its effect on Fbxw7 protein function is unknown (PubMed, May 2020).
R179H missense unknown FBXW7 R179H does not lie within any known functional domains of the Fbxw7 protein (UniProt.org). R179H has been identified in sequencing studies (PMID: 22810696), but has not been biochemically characterized and therefore, its effect on Fbxw7 protein function is unknown (PubMed, May 2020).
R222* nonsense loss of function - predicted FBXW7 R222* results in a premature truncation of the Fbxw7 protein at amino acid 222 of 707 (UniProt.org). Due to the loss of all known functional domains (UniProt.org), R222* is predicted to result in a loss of function.
R224* nonsense loss of function - predicted FBXW7 R224* results in a premature truncation of the Fbxw7 protein at amino acid 224 of 707 (UniProt.org). Due to the loss of all functional domains (UniProt.org), R224* is predicted to lead to a loss of Fbxw7 protein function.
R224Q missense unknown FBXW7 R224Q does not lie within any known functional domains of the Fbxw7 protein (UniProt.org). R224Q has been identified in sequencing studies (PMID: 22895193), but has not been biochemically characterized and therefore, its effect on Fbxw7 protein function is unknown (PubMed, May 2020).
R278* nonsense loss of function - predicted FBXW7 R278* results in a premature truncation of the Fbxw7 protein at amino acid 278 of 707 (UniProt.org). Due to the loss of all known functional domains (UniProt.org), R278* is predicted to result in a loss of function.
R367* nonsense loss of function - predicted FBXW7 R367* results in a premature truncation of the Fbxw7 protein at amino acid 367 of 707 (UniProt.org). Due to the loss of the WD repeat domain, R367* is predicted to lead to a loss of Fbxw7 protein function (UniProt.org).
R393* nonsense loss of function - predicted FBXW7 R393* results in a premature truncation of the Fbxw7 protein at amino acid 393 of 707 (UniProt.org). Due to the disruption of the WD repeat domain, R393* is predicted to lead to a loss of Fbxw7 protein function (UniProt.org).
R441W missense unknown FBXW7 R441W lies within WD repeat 2 of the Fbxw7 protein (UniProt.org). R441W has been identified in sequencing studies (PMID: 28581676, PMID: 28249663), but has not been biochemically characterized and therefore, its effect on Fbxw7 protein function is unknown (PubMed, May 2020).
R465C missense loss of function FBXW7 R465C lies within WD repeat 3 of the Fbxw7 protein (UniProt.org). R465C confers a loss of Fbxw7 protein function as demonstrated by a loss of Fbxw7-substrate interaction and impaired substrate degradation by Fbxw7, resulting in sustained Notch1 intracellular domain and Myc expression (PMID: 17646409), impaired degradation of Klf5 (PMID: 28963353), aberrant subnuclear localization relative to wild-type Fbxw7 in culture (PMID: 30510140), and reduced suppression of migration, invasion, and colony formation in culture (PMID: 31161818).
R465H missense loss of function FBXW7 R465H (corresponds to R385H in isoform 2) lies within the WD repeat 3 of the Fbxw7 protein (UniProt.org). R465H confers a loss of FBXW7-substrate interaction and impairs substrate degradation by FBXW7, resulting in sustained NICD and MYC expression (PMID: 17646409) and also has impaired degradation of Klf5 (PMID: 28963353).
R465L missense loss of function FBXW7 R465L lies within the WD repeat domain 3 of the Fbxw7 protein (UniProt.org). R465L confers a loss of FBXW7-substrate interaction and impairs substrate degradation by FBXW7, resulting in activation of a Notch-driven reporter (PMID: 19340001).
R465P missense loss of function - predicted FBXW7 R465P lies within the WD repeat domain of the Fbxw7 protein (UniProt.org). R465P has not been characterized, however other R465 hotspots inactivate Fbxw7, therefore, R465P is predicted to lead to a loss of function (PMID: 17646409, PMID: 17909001, PMID: 19340001).
R465Y missense loss of function - predicted FBXW7 R465Y lies within the WD repeat domain of the Fbxw7 protein (UniProt.org). R465Y has not been characterized however other R465 hotspots inactivate Fbxw7 therefore, R465Y is predicted to lead to a loss of function (PMID: 17646409, PMID: 17909001, PMID: 19340001).
R473fs frameshift loss of function - predicted FBXW7 R473fs results in a change in the amino acid sequence of the Fbxw7 protein beginning at aa 473 of 707, likely resulting in a premature truncation of the functional protein (UniProt.org). Due to the loss of the majority of the WD repeat domains (UniProt.org), R473fs is predicted to lead to a loss of Fbxw7 protein function.
R479* nonsense loss of function - predicted FBXW7 R479* results in a premature truncation of the Fbxw7 protein at amino acid 479 of 707 (UniProt.org). Due to the disruption of the WD repeat domain, R479* is predicted to lead to a loss of Fbxw7 protein function (UniProt.org).
R479G missense loss of function - predicted FBXW7 R479G lies within the WD repeat domain of the Fbxw7 protein (UniProt.org). R479G has not been characterized, however other R479 hotspot mutations inactivate Fbxw7 therefore, R479G is predicted to lead to a loss of function (PMID: 17646409, PMID: 17575125, PMID: 22608923).
R479H missense loss of function FBXW7 R479H lies within the WD repeat domain of the Fbxw7 protein (UniProt.org). R479H confers a loss of FBXW7-substrate interaction and impairs substrate degradation by FBXW7, resulting in activation of a Notch-driven reporter (PMID: 17575125).
R479L missense loss of function FBXW7 R479L lies within the WD repeat domain of the Fbxw7 protein (UniProt.org). R479L confers a loss of function to the Fbxw7 protein as demonstrated by increased ubiquitination and decreased stability of the Fbxw7 protein (PMID: 22608923).
R479P missense loss of function - predicted FBXW7 R479P lies within the WD repeat domain of the Fbxw7 protein (UniProt.org). R479P has not been biochemically characterized, however, results in increased proliferation, migration, invasion, and colony formation in culture (PMID: 31161818), and therefore, is predicted to lead to a loss of Fbxw7 protein function.
R479Q missense loss of function FBXW7 R479Q lies within WD repeat 3 of the Fbxw7 protein (UniProt.org). R479Q confers a loss of FBXW7-substrate interation and impairs substrate degradation by FBXW7, resulting in sustained Notch1 intracellular domain and Myc expression (PMID: 17646409, PMID: 25450649), and aberrant subcellular nuclear localization and loss of Notch1 intracellular domain binding in culture (PMID: 30510140).
R479S missense unknown FBXW7 R479S lies within WD repeat 3 of the Fbxw7 protein (UniProt.org). R479S has been identified in sequencing studies (PMID: 23165447), but has not been biochemically characterized and therefore, its effect on Fbxw7 protein function is unknown (PubMed, May 2020).
R505C missense loss of function FBXW7 R505C lies within WD repeat 4 of the Fbxw7 protein (UniProt.org). R505C confers a loss of FBXW7-substrate interaction and impairs substrate degradation by FBXW7, resulting in sustained Notch intracellular domain and Myc expression (PMID: 17646409), demonstrates aberrant subnuclear localization (PMID: 30510140), and has impaired degradation of Klf5 (PMID: 28963353).
R505G missense loss of function - predicted FBXW7 R505G lies within WD repeat 4 of the Fbxw7 protein (UniProt.org). R505G has not been biochemically characterized, however, results in increased proliferation, migration, invasion, and colony formation in culture (PMID: 31161818), and therefore, is predicted to lead to a loss of Fbxw7 protein function.
R505H missense unknown FBXW7 R505H lies within WD repeat 4 of the Fbxw7 protein (UniProt.org). R505H has been identified in sequencing studies (PMID: 25617745, PMID: 28671688, PMID: 30615206), but has not been biochemically characterized and therefore, its effect on Fbxw7 protein function is unknown (PubMed, May 2020).
R505L missense loss of function FBXW7 R505L lies within the WD repeat 4 of the Fbxw7 protein (UniProt.org). R505L confers a loss of function on Fbxw7, as demonstrated by activation of the NOTCH pathway in cultured cells (PMID: 17646409) and the inability to bind substrates (PMID: 28522751).
R505S missense unknown FBXW7 R505S lies within WD repeat 4 of the Fbxw7 protein (UniProt.org). R505S has been identified in sequencing studies (PMID: 27101000, PMID: 25670083, PMID: 29097733), but has not been biochemically characterized and therefore, its effect on Fbxw7 protein function is unknown (PubMed, Aug 2020).
R543fs frameshift unknown FBXW7 R543fs results in a change in the amino acid sequence of the Fbxw7 protein beginning at aa 543 of 707, likely resulting in premature truncation of the functional protein (UniProt.org). R543fs has not been characterized in the scientific literature and therefore, its effect on Fbxw7 protein function is unknown (PubMed, May 2020).
R658* nonsense unknown FBXW7 R658* results in a premature truncation of the Fbxw7 protein at amino acid 658 of 707 (UniProt.org). R658* is associated with decreased Fbxw7 protein level in cell culture, but does not result in increased tumorigenesis compared to wild-type Fbxw7 in mouse models (PMID: 24838835), and therefore its effect on Fbxw7 protein function is unknown.
R658Q missense unknown FBXW7 R658Q lies within WD repeat 7 of the Fbxw7 protein (UniProt.org). R658Q is predicted to have activity similar to wild-type Fbxw7 based on comparison and correlation analysis of induced gene expression signatures (PMID: 27147599), but has not been biochemically characterized and therefore, its effect on Fbxw7 protein function is unknown (PubMed, Jun 2020).
R689Q missense unknown FBXW7 R689Q does not lie within any known functional domains of the Fbxw7 protein (UniProt.org). R689Q is predicted to have activity similar to wild-type Fbxw7 based on comparison and correlation analysis of induced gene expression signatures (PMID: 27147599), but has not been biochemically characterized and therefore, its effect on Fbxw7 protein function is unknown (PubMed, Jul 2020).
R689W missense unknown FBXW7 R689W does not lie within any known functional domains of the Fbxw7 protein (UniProt.org). R689W has been identified in the scientific literature (PMID: 30510140, PMID: 19245433), but has not been biochemically characterized and therefore, its effect on Fbxw7 protein function is unknown (PubMed, May 2020).
S227A missense loss of function FBXW7 S227A lies within a phosphorylation site in the Fbxw7 protein (PMID: 21147854). S227A confers a loss of function to the Fbxw7 protein as demonstrated by the inability of S227A to induce apoptosis (PMID: 21620836), and reduced degradation of c-Myc and Notch1 intracellular domain relative to wild-type Fbxw7 in culture due to the loss of phosphorylation by Sgk1 (PMID: 21147854).
S282* nonsense loss of function - predicted FBXW7 S282* results in a premature truncation of the Fbxw7 protein at amino acid 282 of 707 (UniProt.org). Due to the loss of all known functional domains (UniProt.org), S282* is predicted to result in a loss of function.
S396fs frameshift loss of function - predicted FBXW7 S396fs results in a change in the amino acid sequence of the Fbxw7 protein beginning at aa 396 of 707, likely resulting in premature truncation of the functional protein (UniProt.org). S396fs results in increased expression and activity of Myc, Hif1a, and Notch1 compared to wild-type Fbxw7 in cell culture (PMID: 30510140), and therefore, is predicted to result in a loss of Fbxw7 protein function.
S396N missense unknown FBXW7 S396N lies within WD repeat 1 of the Fbxw7 protein (UniProt.org). S396N has been identified in sequencing studies (PMID: 28292439), but has not been biochemically characterized and therefore, its effect on Fbxw7 protein function is unknown (PubMed, May 2020).
S398F missense unknown FBXW7 S398F lies within WD repeat 1 of the Fbxw7 protein (UniProt.org). S398F has been identified in sequencing studies (PMID: 29996881), but has not been biochemically characterized and therefore, its effect on Fbxw7 protein function is unknown (PubMed, May 2020).
S426L missense unknown FBXW7 S426L lies within WD repeat 2 of the Fbxw7 protein (UniProt.org). S426L has not been characterized and therefore, its effect on Fbxw7 protein is unknown (PubMed, May 2020.
S462Y missense unknown FBXW7 S462Y lies within WD repeat 3 of the Fbxw7 protein (UniProt.org). S462Y is predicted to have activity similar to wild-type Fbxw7 based on comparison and correlation analysis of induced gene expression signatures (PMID: 27147599), but has not been biochemically characterized and therefore, its effect on Fbxw7 protein function is unknown (PubMed, Jun 2020).
S476I missense unknown FBXW7 S476I lies within WD repeat 3 of the Fbxw7 protein (UniProt.org). S476I has not been characterized and therefore, its effect on Fbxw7 protein function is unknown (PubMed, May 2020).
S476R missense unknown FBXW7 S476R lies within WD repeat 3 of the Fbxw7 protein (UniProt.org). S476R has not been characterized and therefore, its effect on Fbxw7 protein function is unknown (PubMed, May 2020).
S516N missense unknown FBXW7 S516N lies within WD repeat 4 of the Fbxw7 protein (UniProt.org). S516N hasbeen identified in sequencing studies (PMID: 29106415), but has not been biochemically characterized and therefore, its effect on Fbxw7 protein function is unknown (PubMed, May 2020).
S516R missense unknown FBXW7 S516R lies within WD repeat 4 of the Fbxw7 protein (UniProt.org). S516R has not been characterized in the scientific literature and therefore, its effect on Fbxw7 protein function is unknown (PubMed, May 2020).
S546L missense unknown FBXW7 S546L lies within WD repeat 5 of the Fbxw7 protein (UniProt.org). S546L has been identified in sequencing studies (PMID: 26000489), but has not been biochemically characterized and therefore, its effect on Fbxw7 protein function is unknown (PubMed, May 2020).
S558F missense unknown FBXW7 S558F lies within WD repeat 5 of the Fbxw7 protein (UniProt.org). S558F has been identified in sequencing studies (PMID: 28256603), but has not been biochemically characterized and therefore, its effect on Fbxw7 protein function is unknown (PubMed, May 2020).
S562L missense unknown FBXW7 S562L lies within WD repeat 5 of the Fbxw7 protein (UniProt.org). S562L demonstrates tumor growth similar to wild-type Fbxw7 in a mouse model (PMID: 24838835), but has not been biochemically characterized and therefore, its effect on Fbxw7 protein function is unknown.
S582L missense unknown FBXW7 S582L lies within WD repeat 6 of the Fbxw7 protein (UniProt.org). S582L has been identified in the scientific literature (PMID: 25450649, PMID: 28120820, PMID: 28424412), but has not been biochemically characterized and therefore, its effect on Fbxw7 protein function is unknown (PubMed, May 2020).
S601F missense unknown FBXW7 S601F lies within WD repeat 6 of the Fbxw7 protein (UniProt.org). S601F has been identified in sequencing studies (PMID: 22622578), but has not been biochemically characterized and therefore, its effect on Fbxw7 protein function is unknown (PubMed, May 2020).
S668fs frameshift unknown FBXW7 S668fs results in a change in the amino acid sequence of the Fbxw7 protein beginning at aa 668 of 707, likely resulting in premature truncation of the functional protein (UniProt.org). S668fs has been identified in sequencing studies (PMID: 26373574, PMID: 30412912, PMID: 30239046), but has not been biochemically characterized and therefore, its effect on Fbxw7 protein function is unknown (PubMed, May 2020).
S86L missense unknown FBXW7 S86L does not lie within any known functional domains of the Fbxw7 protein (UniProt.org). S86L has been identified in sequencing studies (PMID: 30503610, PMID: 31401123, PMID: 30239046), but has not been biochemically characterized and therefore, its effect on Fbxw7 protein function is unknown (PubMed, Aug 2020).
T144R missense unknown FBXW7 T144R does not lie within any known functional domains of the Fbxw7 protein (UniProt.org). T144R has been identified in sequencing studies (PMID: 29338072), but has not been biochemically characterized and therefore, its effect on Fbxw7 protein function is unknown (PubMed, May 2020).
T15_G16insP insertion loss of function FBXW7 T15_G16insP results in the insertion of a proline (P) in the Fbxw7 protein between amino acids 15 and 16 (UniProt.org). T15_G16insP results in decreased binding of Fbxw7 to cyclinE1 and aberrant Fbxw7 localization in cell culture (PMID: 17909001).
T15_G16insTP insertion unknown FBXW7 T15_G16insTP results in the insertion of two amino acids in the Fbxw7 protein between amino acids 15 and 16 (UniProt.org). T15_G16insTP has not been characterized in the scientific literature and therefore, its effect on Fbxw7 protein function is unknown (PubMed, May 2020).
T165fs frameshift loss of function - predicted FBXW7 T165fs results in a change in the amino acid sequence of the Fbxw7 protein beginning at aa 165 of 707, likely resulting in premature truncation of the functional protein (UniProt.org). Due to the loss of multiple functional domains, T165fs is predicted to lead to a loss of Fbxw7 protein function (UniProt.org).
V154I missense no effect - predicted FBXW7 V154I does not lie within any known functional domains of the Fbxw7 protein (UniProt.org). V154I results in nuclear and subnuclear localization and Notch1 intracellular domain binding similar to wild-type Fbxw7 in culture (PMID: 30510140), and therefore, is predicted to have no effect on Fbxw7 protein function.
V265I missense unknown FBXW7 V265I does not lie within any known functional domains of the Fbxw7 protein (UniProt.org). V265I has been identified in sequencing studies (PMID: 21282377), but has not been biochemically characterized and therefore, its effect on Fbxw7 protein function is unknown (PubMed, May 2020).
V418M missense no effect - predicted FBXW7 V418M lies within WD repeat 1 of the Fbxw7 protein (UniProt.org). V418M results in Cyclin E, Notch1 intracellular domain, and Myc protein expression, and Fbxw7 half-life similar to wild-type in culture (PMID: 30556601), and therefore, is predicted to have no effect on Fbxw7 protein function.
V464E missense unknown FBXW7 V464E lies within WD repeat 3 of the Fbxw7 protein (UniProt.org). V464E results in the loss of gene expression signature correlation with Myc downregulation compared to wild-type Fbxw7 in culture (PMID: 29195078), but has not been biochemically characterized and therefore, its effect on Fbxw7 is unknown.
V464M missense unknown FBXW7 V464M lies within WD repeat 3 of the Fbxw7 protein (UniProt.org). V464M has been identified in sequencing studies (PMID: 28424412), but has not been biochemically characterized and therefore, its effect on Fbxw7 protein function is unknown (PubMed, May 2020).
V504I missense unknown FBXW7 V504I lies within WD repeat 4 of the Fbxw7 protein (UniProt.org). V504I has been identified in sequencing studies (PMID: 17909001), but has not been biochemically characterized and therefore, its effect on Fbxw7 protein function is unknown (PubMed, May 2020).
V514F missense loss of function - predicted FBXW7 V514F lies within WD repeat 4 of the Fbxw7 protein (UniProt.org). V514F results in aberrant subnuclear localization and decreased Notch1 intracellular domain binding in culture (PMID: 30510140), and therefore, is predicted to lead to a loss of Fbxw7 protein function.
W237* nonsense loss of function - predicted FBXW7 W237* results in a premature truncation of the Fbxw7 protein at amino acid 237 of 707 (UniProt.org). Due to the loss of the WD repeat domain, W237* is predicted to lead to a loss of Fbxw7 protein function (UniProt.org).
W244* nonsense loss of function - predicted FBXW7 W244* results in a premature truncation of the Fbxw7 protein at amino acid 244 of 707 (UniProt.org). Due to the loss of all known functional domains (UniProt.org), W244* is predicted to result in a loss of function.
W425C missense loss of function FBXW7 W425C lies within WD repeat 2 of the Fbxw7 protein (UniProt.org). W425C confers a loss of function to the Fbxw7 protein, as demonstrated by aberrant subnuclear localization and the absence of Notch1 intracellular domain binding in culture (PMID: 30510140).
W446C missense unknown FBXW7 W446C lies within WD repeat 2 of the Fbxw7 protein (UniProt.org). W446C has been identified in sequencing studies (PMID: 28120820, PMID: 23103869), but has not been biochemically characterized and therefore, its effect on Fbxw7 protein function is unknown (PubMed, Jun 2020).
W486* nonsense loss of function - predicted FBXW7 W486* results in a premature truncation of the Fbxw7 protein at amino acid 486 of 707 (Uniprot.org). W486* is predicted to confer a loss of function to the Fbxw7, as demonstrated by increased tumorigenesis in cultured cells (PMID: 24838835).
W526L missense unknown FBXW7 W526L lies within WD repeat 4 of the Fbxw7 protein (UniProt.org). W526L has not been characterized in the scientific literature and therefore, its effect on Fbxw7 protein function is unknown (PubMed, May 2020).
W526R missense unknown FBXW7 W526R lies within WD repeat 4 of the Fbxw7 protein (UniProt.org). W526R has not been characterized and therefore, its effect on Fbxw7 protein function is unknown (PubMed, May 2020).
W606* nonsense unknown FBXW7 W606* results in a premature truncation of the Fbxw7 protein at amino acid 606 of 707 (UniProt.org). W606* has been identified in the scientific literature (PMID: 27870570), but has not been biochemically characterized and therefore, its effect on Fbxw7 protein function is unknown (PubMed, Mar 2020).
wild-type none no effect Wild-type FBXW7 indicates that no mutation has been detected within the FBXW7 gene.
Y519C missense unknown FBXW7 Y519C lies within WD repeat 4 of the Fbxw7 protein (UniProt.org). Y519C has been identified in sequencing studies (PMID: 31328403), but has not been biochemically characterized and therefore, its effect on Fbxw7 protein function is unknown (PubMed, Apr 2020).
Y545C missense loss of function - predicted FBXW7 Y545C lies within WD repeat 5 of the Fbxw7 protein (UniProt.org). Y545C results in aberrant subnuclear localization and decreased Notch1 intracellular domain binding in culture (PMID: 30510140), and therefore, is predicted to lead to a loss of Fbxw7 protein function.