Gene Detail

Gene Symbol CBL
Synonyms C-CBL | CBL2 | FRA11B | NSLL | RNF55
Gene Description CBL, Cbl proto-oncogene, E3 ubiquitin protein ligase, is an E3 ubiquitin-protein ligase involved in cell signaling and ubiquitination of tyrosine kinases (PMID: 23085373). Loss of function mutations in CBL result in increased tyrosine kinase signaling and oncogenic transformation, which may be responsive to FLT3 inhibitors (PMID: 23085373, PMID: 22990016).
Entrez Id 867
Chromosome 11
Map Location 11q23.3
Canonical Transcript NM_005188

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Variant Impact Protein Effect Variant Description Associated with drug Resistance
Q249E missense gain of function - predicted CBL Q249E lies within the Cbl-PTB domain of the Cbl protein (UniProt.org). Q249E is predicted to confer a loss of function to the Cbl protein, as demonstrated by increased Cbl activity as compared to wild-type (PMID: 26676746).
P546L missense unknown CBL P546L does not lie within any known functional domains of the Cbl protein (UniProt.org). P546L has not been characterized in the scientific literature and therefore, its effect on Cbl protein function is unknown (PubMed, Jan 2018).
C401R missense unknown CBL C401R lies within the RING-type zinc finger domain of the Cbl protein (UniProt.org). C401R has not been biochemically characterized, but is predicted to disrupt Cbl stability by computer modeling (PMID: 26676746).
G868E missense unknown CBL G868E lies within the UBA domain of the Cbl protein (UniProt.org). G868E has not been characterized in the scientific literature and therefore, its effect on Cbl protein function is unknown (PubMed, Jan 2018).
P417H missense unknown CBL P417H lies within the RING-type zinc finger region of the Cbl protein (UniProt.org). P417H has been identified in sequencing studies (PMID: 23010802), but has not been biochemically characterized and therefore, its effect on Cbl protein function is unknown (PubMed, Jan 2018).
G397V missense unknown CBL G397V lies within the RING-type zinc finger domain of the Cbl protein (UniProt.org). G397V has been identified in sequencing studies (PMID: 23010802), but has not been biochemically characterized and therefore, its effect on Cbl protein function is unknown (PubMed, Jan 2018).
Y368_K382del deletion unknown CBL Y368_K382del results in the deletion of fifteen amino acids in the linker region of the Cbl protein from amino acids 368 to 382 (UniProt.org). Y368_K382del has not been characterized in the scientific literature and therefore, its effect on Cbl protein function is unknown (PubMed, Jun 2018).
C401Y missense unknown CBL C401Y lies within the RING-type zinc finger domain of the Cbl protein (UniProt.org). C401Y has not been biochemically characterized, but is predicted to disrupt Cbl stability by computer modeling (PMID: 26676746).
Y455_D456del deletion unknown CBL Y455_D456del results in the deletion of two amino acids of the Cbl protein from amino acids 455 to 456 (UniProt.org). Y455_D456del has not been characterized in the scientific literature and therefore, its effect on Cbl protein function is unknown (PubMed, Jan 2018).
G375P missense loss of function - predicted CBL G375P lies within a linker region of the Cbl protein (UniProt.org). G375P is predicted to confer a loss of function to the Cbl protein, as demonstrated by reduced Cbl activity (PMID: 26676746).
V391I missense loss of function CBL V391I lies within the RING finger domain of the Cbl protein (PMID: 20126411). V391I is predicted to result in a loss of function by interfering with the E3 ubiquitin ligase activity of Cbl and displays reduced ubiquitination towards a Cbl target, Egfr (PMID: 20126411, PMID: 26676746).
F622C missense unknown CBL F622C does not lie within any known functional domains of the Cbl protein (UniProt.org). F622C has not been characterized in the scientific literature and therefore, its effect on Cbl protein function is unknown (PubMed, Jan 2018).
H398Y missense loss of function CBL H398Y lies with the RING-type zinc finger domain of the Cbl protein (UniProt.org). H398Y results in a loss of ubiquitin ligase activity and is transforming in culture (PMID: 19387008).
C404Y missense unknown CBL C404Y lies within the RING-type zinc finger domain of the Cbl protein (UniProt.org). C404Y has not been biochemically characterized, but is predicted to disrupt Cbl stability by computer modeling (PMID: 26676746).
P433Q missense unknown CBL P433Q does not lie within any known functional domains of the Cbl protein (UniProt.org). P433Q has not been characterized in the scientific literature and therefore, its effect on Cbl protein function is unknown (PubMed, Jan 2018).
Q367P missense loss of function CBL Q367P lies within the linker domain of the Cbl protein (PMID: 19620960). Q367P results in decreased Cbl ubiquitinating activity and increased AKT activation, is transforming in cell culture, and leads to increased tumor growth in mouse models (PMID: 19620960).
R830K missense unknown CBL R830K lies within the CD2AP-interacting region of the Cbl protein (UniProt.org). R830K has been identified in sequencing studies (PMID: 20126411), but has not been biochemically characterized and therefore, its effect on Cbl protein function is unknown (PubMed, Jan 2018).
Y371H missense loss of function CBL Y371H lies within the linker region of the Cbl protein (PMID: 20622007). Y371H results in a loss of Cbl ubiquitin ligase activity, leading to activation of FLT3, AKT, and STAT5, and transformation of cultured cells when co-expressed with FLT3 or KIT (PMID: 23696637, PMID: 20622007).
E276K missense unknown CBL E276K lies within the Cbl-PTB domain of the Cbl protein (UniProt.org). E276K has not been characterized in the scientific literature and therefore, its effect on Cbl protein function is unknown (PubMed, Jan 2018).
F418V missense unknown CBL F418V lies within the RING-type zinc finger domain of the Cbl protein (UniProt.org). F418V has been identified in sequencing studies (PMID: 19620960), but has not been biochemically characterized and therefore, its effect on Cbl protein function is unknown (PubMed, Jan 2018).
L281H missense unknown CBL L281H lies within the Cbl-PTB domain of the Cbl protein (UniProt.org). L281H has been identified in sequencing studies (PMID: 22495314), but has not been biochemically characterized and therefore, its effect on Cbl protein function is unknown (PubMed, Jan 2018).
P417A missense loss of function CBL P417A lies within the RING-finger domain of the Cbl protein (PMID: 20501843). P417A results in decreased Cbl ubiquitin ligase activity, increased cell survival, and is transforming in cell culture (PMID: 19387008).
E894* nonsense unknown CBL E894* results in a premature truncation of the Cbl protein at amino acid 894 of 906 (UniProt.org). E894* has not been characterized in the scientific literature and therefore, its effect on Cbl protein function is unknown (PubMed, Jan 2018).
Q367K missense loss of function CBL Q367K lies within the linker region of the Cbl protein (UniProt.org). Q367K results in a loss of Cbl E3 ubiquitin ligase activity, is transforming in cell culture, and promotes tumor formation in animal models (PMID: 19620960).
C401F missense unknown CBL C401F lies within the RING-type zinc finger domain of the Cbl protein (UniProt.org). C401F has not been biochemically characterized, but is predicted to disrupt Cbl stability by computer modeling (PMID: 26676746).
D501H missense unknown CBL D501H does not lie within any known functional domains of the Cbl protein (UniProt.org). D501H has not been characterized in the scientific literature and therefore, its effect on Cbl protein function is unknown (PubMed, Jan 2018).
L620F missense unknown CBL L620F lies within a proline-rich region of the Cbl protein (UniProt.org). L620F has been identified in the scientific literature (PMID: 20126411), but has not been biochemically characterized and therefore, its effect on Cbl protein function is unknown (PubMed, Jan 2018).
H661P missense unknown CBL H661P lies within the CD2AP-interacting region of the Cbl protein (UniProt.org). H661P has not been characterized in the scientific literature and therefore, its effect on Cbl protein function is unknown (PubMed, Jan 2018).
Q882H missense unknown CBL Q882H lies within the UBA domain of the Cbl protein (UniProt.org). Q882H has not been characterized in the scientific literature and therefore, its effect on Cbl protein function is unknown (PubMed, Jan 2018).
L399V missense loss of function - predicted CBL L399V lies within the RING-type zinc finger domain of the Cbl protein (UniProt.org). L399V is predicted to confer a loss of function to the Cbl protein, as demonstrated by reduced Cbl activity in cell culture (PMID: 26676746).
dec exp none no effect CBL dec exp indicates decreased expression of the Cbl protein. However, the mechanism causing the decreased expression is unspecified.
del deletion loss of function CBL del indicates a deletion of the CBL gene.
M374V missense no effect - predicted CBL M374V lies within the RING-type zinc finger domain of the Cbl protein (UniProt.org). M374V demonstrates activity comparable to wild-type Cbl in cell culture (PMID: 26676746) and therefore, is predicted to have no effect on Cbl protein functio.
R822G missense unknown CBL R822G lies within the CD2AP-interacting region of the Cbl protein (UniProt.org). R822G has not been characterized in the scientific literature and therefore, its effect on Cbl protein function is unknown (PubMed, Jan 2018).
Y368C missense loss of function CBL Y368C lies within the linker region of the Cbl protein (UniProt.org). Y368C results in a loss of Cbl E3 ubiquitin ligase activity, is transforming in cell culture, and promotes tumor formation in animal models (PMID: 19620960).
Y371S missense loss of function CBL Y371S lies within the linker domain of the Cbl protein (PMID: 19620960). Y371S results in decreased Cbl ubiquitinating activity and increased AKT activation, is transforming in cell culture, and leads to increased tumor growth in mouse models (PMID: 19620960).
R709Q missense unknown CBL R709Q lies within the CD2AP-interacting region of the Cbl protein (UniProt.org). R709Q has been identified in sequencing studies (PMID: 27449473), but has not been biochemically characterized and therefore, its effect on Cbl protein function is unknown (PubMed, Jun 2018).
Y371D missense loss of function - predicted CBL Y371D lies within the linker region of the Cbl protein (UniProt.org). Y371D disrupts Cbl conformation in in vitro assays, and is transforming in cell culture (PMID: 27609087).
E366K missense unknown CBL E366K lies within the linker region of the Cbl protein (UniProt.org). E366K has been identified in sequencing studies (PMID: 20678218), but has not been biochemically characterized and therefore, its effect on Cbl protein function is unknown (PubMed, Jan 2018).
C419R missense unknown CBL C419R lies within the RING-type zinc finger domain of the Cbl protein (UniProt.org). C419R has not been biochemically characterized, but is predicted to disrupt Cbl stability by computer modeling (PMID: 26676746).
R788Q missense unknown CBL R788Q lies within the CD2AP-interacting region of the Cbl protein (UniProt.org). R788Q has not been characterized in the scientific literature and therefore, its effect on Cbl protein function is unknown (PubMed, Jan 2018).
S253F missense unknown CBL S253F lies within the Cbl-PTB domain of the Cbl protein (UniProt.org). S253F has not been characterized in the scientific literature and therefore, its effect on Cbl protein function is unknown (PubMed, Jan 2018).
V478L missense unknown CBL V478L does not lie within any known functional domains of the Cbl protein (UniProt.org). V478L has not been characterized in the scientific literature and therefore, its effect on Cbl protein function is unknown (PubMed, Jun 2018).  
E886* nonsense unknown CBL E886* results in a premature truncation of the Cbl protein at amino acid 886 of 906 (UniProt.org). E886* has not been characterized in the scientific literature and therefore, its effect on Cbl protein function is unknown (PubMed, Jan 2018).
C381A missense loss of function - predicted CBL C381A lies within the RING-type zinc finger domain of the Cbl protein (UniProt.org). C381A is predicted to confer a loss of function to the Cbl protein, as demonstrated by lack of Cbl activity in cell culture (PMID: 26676746).
A850V missense unknown CBL A850V lies within the CD2AP-interacting region of the Cbl protein (UniProt.org). A850V has not been characterized in the scientific literature and therefore, its effect on Cbl protein function is unknown (PubMed, Jun 2018).
C416R missense unknown CBL C416R lies within the RING-type zinc finger domain of the Cbl protein (UniProt.org). C416R has not been biochemically characterized, but is predicted to disrupt Cbl stability by computer modeling (PMID: 26676746).
W408L missense unknown CBL W408L lies within the RING-type zinc finger domain of the Cbl protein (UniProt.org). W408L has not been biochemically characterized, but is predicted to disrupt Cbl stability by computer modeling (PMID: 26676746).
R96S missense unknown CBL R96S lies within the Cbl-PTB domain of the Cbl protein (UniProt.org). R96S has not been characterized in the scientific literature and therefore, its effect on Cbl protein function is unknown (PubMed, Jan 2018).
E815D missense unknown CBL E815D lies within the CD2AP-interacting region of the Cbl protein (UniProt.org). E815D has not been characterized in the scientific literature and therefore, its effect on Cbl protein function is unknown (PubMed, Jan 2018).
C384W missense unknown CBL C384W lies within the RING-type zinc finger domain of the Cbl protein (UniProt.org). C384W has not been characterized in the scientific literature and therefore, its effect on Cbl protein function is unknown (PubMed, Jan 2018).
Q365_E366insSK insertion loss of function CBL Q365_E366insSK lies within the linker region of the Cbl protein (UniProt.org). Q365_E366insSK results in a loss of E3-ligase activity, leading to activation of FLT3, and is transforming when expressed with FLT3 or KIT (PMID: 20622007).
C416S missense unknown CBL C416S lies within the RING-type zinc finger domain of the Cbl protein (UniProt.org). C416S has been identified in sequencing studies (PMID: 22071139), but has not been biochemically characterized and therefore, its effect on Cbl protein function is unknown (PubMed, Jan 2018).
M400R missense unknown CBL M400R lies within the RING-type zinc finger domain of the Cbl protein (UniProt.org). M400R has not been biochemically characterized, but is predicted to disrupt Cbl stability by computer modeling (PMID: 26676746).
A757T missense unknown CBL A757T lies within the CD2AP-interacting region of the Cbl protein (UniProt.org). A757T has been identified in sequencing studies (PMID: 24728327), but has not been biochemically characterized and therefore, its effect on Cbl protein function is unknown (PubMed, Jun 2018).
C416W missense unknown CBL C416W lies within the RING-type zinc finger domain of the Cbl protein (UniProt.org). C416W has not been biochemically characterized, but is predicted to disrupt Cbl stability by computer modeling (PMID: 26676746).
K382E missense loss of function - predicted CBL K382E lies within the RING-type zinc finger domain of the Cbl protein (UniProt.org). K382E is predicted to confer a loss of function to the Cbl protein, as demonstrated by lack of Cbl activity in cell culture (PMID: 26676746).
R343* nonsense unknown CBL R343* results in a premature truncation of the Cbl protein at amino acid 343 of 906 (UniProt.org). R343* has been identified in sequencing studies (PMID: 24030381), but has not been biochemically characterized and therefore, its effect on Cbl protein function is unknown (PubMed, Jun 2018).
R149Q missense unknown CBL R149Q lies within the Cbl-PTB domain of the Cbl protein (UniProt.org). R149Q has been identified in sequencing studies (PMID: 24755471), but has not been biochemically characterized and therefore, its effect on Cbl protein function is unknown (PubMed, Jan 2018).
R420L missense unknown CBL R420L lies within the RING-type zinc finger domain of the Cbl protein (UniProt.org). R420L has not been biochemically characterized, but is predicted to disrupt Cbl stability by computer modeling (PMID: 26676746).
A678D missense unknown CBL A678D lies within the CD2AP-interacting region of the Cbl protein (UniProt.org). A678D has not been characterized in the scientific literature and therefore, its effect on Cbl protein function is unknown (PubMed, Jun 2018).
E369_Y371del deletion unknown CBL E369_Y371del results in the deletion of three amino acids in the linker region of the Cbl protein from amino acids 369 to 371 (UniProt.org). E369_Y371del has not been characterized in the scientific literature and therefore, its effect on Cbl protein function is unknown (PubMed, Jun 2018).
G868V missense unknown CBL G868V lies within the UBA domain of the Cbl protein (UniProt.org). G868V has not been characterized in the scientific literature and therefore, its effect on Cbl protein function is unknown (PubMed, Jan 2018).
G413R missense unknown CBL G413R lies within the RING-type zinc finger domain of the Cbl protein (UniProt.org). C413R has not been biochemically characterized, but is predicted to disrupt Cbl stability by computer modeling (PMID: 26676746).
H398P missense unknown CBL H398P lies within the RING-type zinc finger domain of the Cbl protein (UniProt.org). H398P has not been biochemically characterized, but is predicted to disrupt Cbl stability by computer modeling (PMID: 26676746).
C381R missense loss of function - predicted CBL C381R lies within the RING-type zinc finger domain of the Cbl protein (UniProt.org). C381R is predicted to disupt Cbl stability in computer models (PMID: 26676746), and results in activation of ELK and c-Jun and decreased Notch1 signaling in cell culture (PMID: 22591685).
E143D missense unknown CBL E143D lies within the Cbl-PTB domain of the Cbl protein (UniProt.org). E143D has not been characterized in the scientific literature and therefore, its effect on Cbl protein function is unknown (PubMed, Jan 2018).
inact mut unknown loss of function CBL inact mut indicates that this variant results in a loss of function of the Cbl protein. However, the specific amino acid change has not been identified.
H398R missense unknown CBL H398R lies within the RING-type zinc finger domain of the Cbl protein (UniProt.org). H398R has not been biochemically characterized, but is predicted to disrupt Cbl stability by computer modeling (PMID: 26676746).
Q867* nonsense unknown CBL Q867* results in a premature truncation of the Cbl protein at amino acid 867 of 906 (UniProt.org). Q867* has not been characterized in the scientific literature and therefore, its effect on Cbl protein function is unknown (PubMed, Jan 2018).
K322T missense unknown CBL K322T lies within the Cbl-PTB domain of the Cbl protein (UniProt.org). K322T has not been characterized in the scientific literature and therefore, its effect on Cbl protein function is unknown (PubMed, Jan 2018).
T426A missense unknown CBL T426A lies within the RING-type zinc finger domain of the Cbl protein (UniProt.org). T426A has not been characterized in the scientific literature and therefore, its effect on Cbl protein function is unknown (PubMed, Jan 2018).
S80N missense unknown CBL S80N lies within the Cbl-PTB domain of the Cbl protein (UniProt.org). S80N in combination with H94Y displayed activity comparable to wild-type Cbl in culture (PMID: 26676746), however, has not been individually characterized and therefore, its effect on Cbl protein function is unknown.
F418I missense unknown CBL F418I lies within the RING-type zinc finger domain of the Cbl protein (UniProt.org). F418I has been identified in sequencing studies (PMID: 24618614), but has not been biochemically characterized and therefore, its effect on Cbl protein function is unknown (PubMed, Jan 2018).
A877V missense unknown CBL A877V lies within the UBA domain of the Cbl protein (UniProt.org). A877V has not been characterized in the scientific literature and therefore, its effect on Cbl protein function is unknown (PubMed, Jun 2018).
G415S missense unknown CBL G415S lies within the RING-type zinc finger domain of the Cbl protein (UniProt.org). G415S has not been biochemically characterized, but is predicted to disrupt Cbl stability by computer modeling (PMID: 26676746).
S217Y missense unknown CBL S217Y lies within the Cbl-PTB domain of the Cbl protein (UniProt.org). S217Y has not been characterized in the scientific literature and therefore, its effect on Cbl protein function is unknown (PubMed, Jan 2018).
Q367R missense unknown CBL Q367R lies within the linker region of the Cbl protein (UniProt.org). Q367R has been identified in sequencing studies (PMID: 24896186), but has not been biochemically characterized and therefore, its effect on Cbl protein function is unknown (PubMed, Jan 2018).
C384G missense loss of function CBL C384G lies within the linker region of the Cbl protein (UniProt.org). C384G results in a loss of Cbl E3 ubiquitin ligase activity, is transforming in cell culture, and promotes tumor formation in animal models (PMID: 19620960).
L405R missense unknown CBL L405R lies within the RING-type zinc finger domain of the Cbl protein (UniProt.org). L405R has not been characterized in the scientific literature and therefore, its effect on Cbl protein function is unknown (PubMed, Jan 2018).
mutant unknown unknown CBL mutant indicates an unspecified mutation in the CBL gene.
P201S missense unknown CBL P201S lies within the Cbl-PTB domain of the Cbl protein (UniProt.org). P201S has not been characterized in the scientific literature and therefore, its effect on Cbl protein function is unknown (PubMed, Jan 2018).
P532S missense unknown CBL P532S does not lie within any known functional domains of the Cbl protein (UniProt.org). P532S has not been characterized in the scientific literature and therefore, its effect on Cbl protein function is unknown (PubMed, Jan 2018).
K477M missense unknown CBL K477M does not lie within any known functional domains of the Cbl protein (UniProt.org). K477M has been identified in sequencing studies (PMID: 22980975), but has not been biochemically characterized and therefore, its effect on Cbl protein function is unknown (PubMed, Jan 2018).
I98T missense unknown CBL I98T lies within the Cbl-PTB domain of the Cbl protein (UniProt.org). I98T has not been biochemically characterized, but is predicted to disrupt Cbl stability by computer modeling (PMID: 26676746).
S403F missense unknown CBL S403F lies within the RING-type zinc finger domain of the Cbl protein (UniProt.org). S403F has been identified in sequencing studies (PMID: 24755471), but has not been biochemically characterized and therefore, its effect on Cbl protein function is unknown (PubMed, Jan 2018).
C396R missense loss of function - predicted CBL C396R lies within the RING-type zinc finger domain of the Cbl protein (UniProt.org). C396R is predicted to confer a loss of function to the Cbl protein, as demonstrated by lack of Cbl activity in cell culture (PMID: 26676746).
R420* nonsense loss of function - predicted CBL R420* results in a premature truncation of the Cbl protein at amino acid 420 of 906 (UniProt.org). Due to the loss of the UBA domain (UniProt.org), R420* is predicted to lead to a loss of Cbl protein function.
H398Q missense loss of function - predicted CBL H398Q lies within the RING-type zinc finger domain of the Cbl protein (UniProt.org). H398Q is predicted to confer a loss of function to the Cbl protein, as demonstrated by lack of Cbl activity in cell culture (PMID: 26676746).
C381G missense unknown CBL C381G lies within the RING-type zinc finger domain of the Cbl protein (UniProt.org). C381G has not been biochemically characterized, but is predicted to disrupt Cbl stability by computer modeling (PMID: 26676746).
G415V missense unknown CBL G415V lies within the RING-type zinc finger domain of the Cbl protein (UniProt.org). C415V has not been biochemically characterized, but is predicted to disrupt Cbl stability by computer modeling (PMID: 26676746).
I383L missense loss of function CBL I383L lies within the RING-type zinc finger domain of the Cbl protein (UniProt.org). I383L results in a loss of Cbl E3 ubiquitin ligase activity, is transforming in cell culture, and promotes tumor formation in animal models (PMID: 19620960).
E894G missense unknown CBL E894G lies within the UBA domain of the Cbl protein (UniProt.org). E894G has not been characterized in the scientific literature and therefore, its effect on Cbl protein function is unknown (PubMed, Jan 2018).
R559Q missense unknown CBL R559Q does not lie within any known functional domains of the Cbl protein (UniProt.org). R559Q has not been characterized in the scientific literature and therefore, its effect on Cbl protein function is unknown (PubMed, Jan 2018).
R437I missense unknown CBL R437I does not lie within any known functional domains of the Cbl protein (UniProt.org). R437I has not been characterized in the scientific literature and therefore, its effect on Cbl protein function is unknown (PubMed, Jan 2018).
L878F missense unknown CBL L878F lies within the UBA domain of the Cbl protein (UniProt.org). L878F has not been characterized in the scientific literature and therefore, its effect on Cbl protein function is unknown (PubMed, Jan 2018).
R893L missense unknown CBL R893L lies within the UBA domain of the Cbl protein (UniProt.org). R893L has not been characterized in the scientific literature and therefore, its effect on Cbl protein function is unknown (PubMed, Jan 2018).
M469I missense unknown CBL M469I does not lie within any known functional domains of the Cbl protein (UniProt.org). M469I has not been characterized in the scientific literature and therefore, its effect on Cbl protein function is unknown (PubMed, Jan 2018).
A881T missense unknown CBL A881T lies within the UBA domain of the Cbl protein (UniProt.org). A881T has not been characterized in the scientific literature and therefore, its effect on Cbl protein function is unknown (PubMed, Jun 2018).
Q875* nonsense unknown CBL Q875* results in a premature truncation of the Cbl protein at amino acid 875 of 906 (UniProt.org). Q875* has not been characterized in the scientific literature and therefore, its effect on Cbl protein function is unknown (PubMed, Jan 2018).
R420Q missense loss of function CBL R420Q lies within the RING domain of the Cbl protein (PMID: 17446348). R420Q disrupts Cbl ubiquitin ligase activity, leading to activation of Flt3 signaling, and is transforming in cell culture in the presence of Flt3 (PMID: 17446348).
C416Y missense unknown CBL C416Y lies within the RING-type zinc finger domain of the Cbl protein (UniProt.org). C4C404Y has not been biochemically characterized, but is predicted to disrupt Cbl stability by computer modeling (PMID: 26676746).
L405P missense unknown CBL L405P lies within the RING-type zinc finger domain of the Cbl protein (UniProt.org). L405P has not been biochemically characterized, but is predicted to disrupt Cbl stability by computer modeling (PMID: 26676746).
S217C missense unknown CBL S217C lies within the Cbl-PTB domain of the Cbl protein (UniProt.org). S217C has not been characterized in the scientific literature and therefore, its effect on Cbl protein function is unknown (PubMed, Jan 2018).
N832I missense unknown CBL N832I lies within the CD2AP-interacting region of the Cbl protein (UniProt.org). N832I has not been characterized in the scientific literature and therefore, its effect on Cbl protein function is unknown (PubMed, Jan 2018).
C396Y missense unknown CBL C396Y lies within the RING-type zinc finger domain of the Cbl protein (UniProt.org). C396Y has not been biochemically characterized, but is predicted to disrupt Cbl stability by computer modeling (PMID: 26676746).
R420G missense unknown CBL R420G does not lie within any known functional domains of the Cbl protein (UniProt.org). R420G has been associated with increased cell survival in culture (PMID: 19276253), but has not been fully biochemically characterized and therefore, its effect on Cbl protein function is unknown (PubMed, Jun 2018).
L399P missense loss of function CBL L399P does not lie within any known functional domains of the Cbl protein (UniProt.org). L399P results in a loss of Cbl E3 ubiquitin ligase activity, is transforming in cell culture, and promotes tumor formation in animal models (PMID: 19620960).
V430M missense no effect - predicted CBL V430M does not lie within any known functional domains of the Cbl protein (UniProt.org). V430M demonstrates activity comparable to wild-type Cbl in cell culture (PMID: 26676746) and therefore, is predicted to have no effect on Cbl protein function.
M487V missense unknown CBL M487V does not lie within any known functional domains of the Cbl protein (UniProt.org). M487V has not been characterized in the scientific literature and therefore, its effect on Cbl protein function is unknown (PubMed, Jan 2018).
A848T missense unknown CBL A848T lies within the CD2AP-interacting region of the Cbl protein (UniProt.org). A848T has been identified in sequencing studies (PMID: 20126411), but has not been biochemically characterized and therefore, its effect on Cbl protein function is unknown (PubMed, Jun 2018).
G816S missense unknown CBL G816S lies within the CD2AP-interacting region of the Cbl protein (UniProt.org). G816S has not been characterized in the scientific literature and therefore, its effect on Cbl protein function is unknown (PubMed, Jun 2018).
P484S missense unknown CBL P484S does not lie within any known functional domains of the Cbl protein (UniProt.org). P484S has not been characterized in the scientific literature and therefore, its effect on Cbl protein function is unknown (PubMed, Jan 2018).
R499Q missense unknown CBL R499Q does not lie within any known functional domains of the Cbl protein (UniProt.org). R499Q has not been characterized in the scientific literature and therefore, its effect on Cbl protein function is unknown (PubMed, Jan 2018).
C384Y missense unknown CBL C384Y lies within the RING-type zinc finger domain of the Cbl protein (UniProt.org). C384Y has not been biochemically characterized, but is predicted to disrupt Cbl stability by computer modeling (PMID: 26676746).
C404R missense unknown CBL C404R lies within the RING-type zinc finger domain of the Cbl protein (UniProt.org). C404R has not been biochemically characterized, but is predicted to disrupt Cbl stability by computer modeling (PMID: 26676746).
Y371C missense loss of function CBL Y371C lies within the linker region of the Cbl protein (UniProt.org). Y371C results in a loss of Cbl E3 ubiquitin ligase activity, is transforming in cell culture, and promotes tumor formation in animal models (PMID: 19620960).
P417L missense unknown CBL P417L lies within the RING-type zinc finger domain of the Cbl protein (UniProt.org). P417L has been identified in sequencing studies (PMID: 26214590, PMID: 24030381), but has not been biochemically characterized and therefore, its effect on Cbl protein function is unknown (PubMed, Jan 2018).
H903L missense unknown CBL H903L lies within the CD2AP-interacting region of the Cbl protein (UniProt.org). H903L has not been characterized in the scientific literature and therefore, its effect on Cbl protein function is unknown (PubMed, Jan 2018).
P703L missense unknown CBL P703L lies within the CD2AP-interacting region of the Cbl protein (UniProt.org). P703L has not been characterized in the scientific literature and therefore, its effect on Cbl protein function is unknown (PubMed, Jan 2018).
P395A missense loss of function - predicted CBL P395A lies within the RING-type zinc finger domain of the Cbl protein (UniProt.org). P395A is predicted to confer a loss of function to the Cbl protein, as demonstrated by reduced Cbl activity in culture (PMID: 26676746).
wild-type none no effect Wild-type CBL indicates that no mutation has been detected within the CBL gene.
L467V missense unknown CBL L467V does not lie within any known functional domains of the Cbl protein (UniProt.org). L467V has not been characterized in the scientific literature and therefore, its effect on Cbl protein function is unknown (PubMed, Jan 2018).
C381Y missense unknown CBL C381Y lies within the RING-type zinc finger domain of the Cbl protein (UniProt.org). C381Y has not been biochemically characterized, but is predicted to disrupt Cbl stability by computer modeling (PMID: 26676746).
W802* nonsense loss of function - predicted CBL W802* results in a premature truncation of the Cbl protein at amino acid 802 of 906 (UniProt.org). Due to the loss of the UBA domain (UniProt.org), W802* is predicted to lead to a loss of Cbl protein function.
P428L missense no effect - predicted CBL P428L does not lie within any known functional domains of the Cbl protein (UniProt.org). P428L displays ubiquitin ligase activity similar to wild-type Cbl towards Egfr in culture (PMID: 26676746) and therefore, is predicted to have no effect on Cbl protein function.
N890fs frameshift unknown CBL N890fs results in a change in the amino acid sequence of the Cbl protein beginning at aa 890 of 906, likely resulting in premature truncation of the functional protein (UniProt.org). N890fs has not been characterized in the scientific literature and therefore, its effect on Cbl protein function is unknown (PubMed, Jan 2018).
E366_K382del deletion loss of function CBL E366_K382del (also known as 70Z-Cbl or 70Z del) results in the deletion of 17 amino acids in the Cbl protein from aa 366 to 382 (UniProt.org). E366_K382del confers a loss of function to the Cbl protein as demonstrated by loss of E3 ubiquitin-protein ligase activity and oncogenic transformation in cultured cells (PMID: 7925293, PMID: 11239464).
V813I missense unknown CBL V813I lies within the CD2AP-interacting region of the Cbl protein (UniProt.org). V813I has not been characterized in the scientific literature and therefore, its effect on Cbl protein function is unknown (PubMed, Jun 2018).
A848V missense unknown CBL A848V lies within the CD2AP-interacting region of the Cbl protein (UniProt.org). A848V has not been characterized in the scientific literature and therefore, its effect on Cbl protein function is unknown (PubMed, Jun 2018).
D459V missense unknown CBL D459V does not lie within any known functional domains of the Cbl protein (UniProt.org). D459V has not been characterized in the scientific literature and therefore, its effect on Cbl protein function is unknown (PubMed, Jan 2018).
R420P missense loss of function - predicted CBL R420P lies within the RING-finger domain of the Cbl protein (PMID: 20501843) R420P has not been biochemically characterized, however, other mutations at R420 lead to loss of Cbl ubiquitinating activity in cell culture (PMID: 17446348), and R420P leads to destabilization of Cbl-E2 binding in computer models (PMID: 26676746), and is therefore predicted to lead to a loss of Cbl protein function.
H94Y missense unknown CBL H94Y lies within the Cbl-PTB domain of the Cbl protein (UniProt.org). H94Y in combination with S80N displayed activity comparable to wild-type Cbl (PMID: 26676746), however, has not been individually characterized and therefore, its effect on Cbl protein function is unknown.
D460del deletion unknown CBL D460del results in the deletion of one amino acid in the Cbl protein at amino acid 460 (UniProt.org). D460del has been identified in sequencing studies (PMID: 24817963), but has not been biochemically characterized and therefore, its effect on Cbl protein function is unknown (PubMed, Jun 2018).
S376F missense loss of function CBL S376F lies within the linker region of the Cbl protein (UniProt.org). S376F leads to decreased Cbl ubiquitin ligase activity, increased cell survival, and is transforming in cell culture (PMID: 19387008).
C384R missense loss of function CBL C384R lies within the RING-type zinc finger domain of the Cbl protein (UniProt.org). C384R results in a loss of Cbl function as indicated by decreased degradation of Jak2, and increased expression and signaling of Jak2 and Lyn kinase in cell culture (PMID: 23696637).
R822T missense unknown CBL R822T lies within the CD2AP-interacting region of the Cbl protein (UniProt.org). R822T has been identified in sequencing studies (PMID: 24190505), but has not been biochemically characterized and therefore, its effect on Cbl protein function is unknown (PubMed, Jan 2018).
A186V missense unknown CBL A186V lies within the Cbl-PTB domain of the Cbl protein (UniProt.org). A186V has not been characterized in the scientific literature and therefore, its effect on Cbl protein function is unknown (PubMed, Jun 2018).
L892F missense unknown CBL L892F lies within the UBA domain of the Cbl protein (UniProt.org). L892F has not been characterized in the scientific literature and therefore, its effect on Cbl protein function is unknown (PubMed, Jun 2018).
S675F missense unknown CBL S675F lies within the CD2AP-interacting region of the Cbl protein (UniProt.org). S675F has not been characterized in the scientific literature and therefore, its effect on Cbl protein function is unknown (PubMed, Jan 2018).
Molecular Profile Protein Effect Treatment Approaches
CBL Q249E gain of function - predicted
CBL P546L unknown
CBL C401R unknown
CBL G868E unknown
CBL P417H unknown
CBL G397V unknown
CBL Y368_K382del unknown
CBL C401Y unknown
CBL Y455_D456del unknown
CBL G375P loss of function - predicted FLT3 Inhibitor
CBL V391I loss of function FLT3 Inhibitor
CBL F622C unknown
CBL H398Y loss of function FLT3 Inhibitor
CBL C404Y unknown
CBL P433Q unknown
CBL Q367P loss of function FLT3 Inhibitor
CBL R830K unknown
CBL Y371H loss of function FLT3 Inhibitor
CBL E276K unknown
CBL F418V unknown
CBL L281H unknown
CBL P417A loss of function FLT3 Inhibitor
CBL E894* unknown
CBL Q367K loss of function FLT3 Inhibitor
CBL C401F unknown
CBL D501H unknown
CBL L620F unknown
CBL H661P unknown
CBL Q882H unknown
CBL L399V loss of function - predicted FLT3 Inhibitor
CBL dec exp no effect
CBL del loss of function FLT3 Inhibitor
CBL del CBLB del
CBL M374V no effect - predicted
CBL R822G unknown
CBL Y368C loss of function FLT3 Inhibitor
CBL Y371S loss of function FLT3 Inhibitor
CBL R709Q unknown
CBL Y371D loss of function - predicted FLT3 Inhibitor
CBL E366K unknown
CBL C419R unknown
CBL R788Q unknown
CBL S253F unknown
CBL V478L unknown
CBL E886* unknown
CBL C381A loss of function - predicted FLT3 Inhibitor
CBL A850V unknown
CBL C416R unknown
CBL W408L unknown
CBL R96S unknown
CBL E815D unknown
CBL C384W unknown
CBL Q365_E366insSK loss of function FLT3 Inhibitor
CBL C416S unknown
CBL M400R unknown
CBL A757T unknown
CBL C416W unknown
CBL K382E loss of function - predicted FLT3 Inhibitor
CBL R343* unknown
CBL R149Q unknown
CBL R420L unknown
CBL A678D unknown
CBL E369_Y371del unknown
CBL G868V unknown
CBL G413R unknown
CBL H398P unknown
CBL C381R loss of function - predicted FLT3 Inhibitor
CBL E143D unknown
CBL inact mut loss of function FLT3 Inhibitor
CBL H398R unknown
CBL Q867* unknown
CBL K322T unknown
CBL T426A unknown
CBL S80N unknown
CBL F418I unknown
CBL A877V unknown
CBL G415S unknown
CBL S217Y unknown
CBL Q367R unknown
CBL C384G loss of function FLT3 Inhibitor
CBL L405R unknown
CBL mutant unknown
CBL P201S unknown
CBL P532S unknown
CBL K477M unknown
CBL I98T unknown
CBL S403F unknown
CBL C396R loss of function - predicted FLT3 Inhibitor
CBL R420* loss of function - predicted FLT3 Inhibitor
CBL H398Q loss of function - predicted FLT3 Inhibitor
CBL C381G unknown
CBL G415V unknown
CBL I383L loss of function FLT3 Inhibitor
CBL E894G unknown
CBL R559Q unknown
CBL R437I unknown
CBL L878F unknown
CBL R893L unknown
CBL M469I unknown
CBL A881T unknown
CBL Q875* unknown
CBL R420Q loss of function FLT3 Inhibitor
CBL C416Y unknown
CBL L405P unknown
CBL S217C unknown
CBL N832I unknown
CBL C396Y unknown
CBL R420G unknown
CBL L399P loss of function FLT3 Inhibitor
CBL V430M no effect - predicted
CBL M487V unknown
CBL A848T unknown
CBL G816S unknown
CBL P484S unknown
CBL R499Q unknown
CBL C384Y unknown
CBL C404R unknown
CBL Y371C loss of function FLT3 Inhibitor
CBL P417L unknown
CBL H903L unknown
CBL P703L unknown
CBL P395A loss of function - predicted FLT3 Inhibitor
CBL wild-type no effect
CBL L467V unknown
CBL C381Y unknown
CBL W802* loss of function - predicted FLT3 Inhibitor
CBL P428L no effect - predicted
CBL N890fs unknown
CBL E366_K382del loss of function FLT3 Inhibitor
CBL V813I unknown
CBL A848V unknown
CBL D459V unknown
CBL R420P loss of function - predicted FLT3 Inhibitor
CBL H94Y unknown
CBL D460del unknown
CBL S376F loss of function FLT3 Inhibitor
CBL C384R loss of function FLT3 Inhibitor
CBL R822T unknown
CBL A186V unknown
CBL L892F unknown
CBL S675F unknown
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
CBL dec exp pancreatic ductal carcinoma predicted - sensitive Erlotinib + Gemcitabine Preclinical - Cell line xenograft Emerging In a preclinical study, addition of Tarceva (erlotinib) overcame Gemzar (gemcitabine)-resistance in pancreatic ductal carcinoma cell lines with reduced Cbl expression via shRNA, resulted in decreased viability in cell culture and reduced tumor growth in cell line xenograft models (PMID: 25348515). 25348515
CBL del CBLB del bone marrow cancer predicted - sensitive Fasudil Preclinical Actionable In a preclinical study, Fasudil (HA-1077) selectively inhibited proliferation of CBL and CBLB double knockout hematopoietic stem/progenitor cells in a mouse model of myeloproliferative disorder (PMID: 26177294). 26177294
CBL mutant myelodysplastic/myeloproliferative neoplasm not applicable N/A Clinical Study Prognostic In clinical analyses, mutations in CBL were associated with adverse prognosis in patients with chronic myelomonocytic leukemia (PMID: 26230957, PMID: 23690417, PMID: 19901108). 26230957 19901108 23690417
CBL mutant bone marrow cancer sensitive Quizartinib Preclinical Actionable In a preclinical study, Quizartinib (AC220) reduced white blood cell counts and decreased myeloid cell invasion in a CBL mutant mouse model with myeloproliferative disorder (PMID: 22990016). 22990016