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Gene Symbol CBL
Synonyms C-CBL | CBL2 | FRA11B | NSLL | RNF55
Gene Description CBL, Cbl proto-oncogene C, is an E3 ubiquitin-protein ligase involved in cell signaling and ubiquitination of tyrosine kinases (PMID: 23085373). CBL mutations, often resulting in a loss of function, have been identified primarily in myeloid neoplasms, including myelodysplastic syndrome, acute myeloid leukemia, chronic myeloid leukemia, myelofibrosis, and juvenile myelomonocytic leukemia (PMID: 25477533).

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Variant Impact Protein Effect Variant Description Associated with drug Resistance
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, Jul 2020).
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, Jul 2020).
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: 30337359, PMID: 29866652, PMID: 24728327), but has not been biochemically characterized and therefore, its effect on Cbl protein function is unknown (PubMed, Jul 2020).
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: 26580448, PMID: 20126411), but has not been biochemically characterized and therefore, its effect on Cbl protein function is unknown (PubMed, Jul 2020).
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, Apr 2020).
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, Jul 2020).
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, Jul 2020).
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, Jul 2020).
act mut unknown gain of function CBL act mut indicates that this variant results in a gain of function in the Cbl protein. However, the specific amino acid change has not been identified.
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 the 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 is predicted to disrupt Cbl stability by computational modeling (PMID: 26676746), but has not been biochemically characterized and therefore, its effect on Cbl protein function is unknown (PubMed, Jul 2020).
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).
C381Y missense unknown CBL C381Y lies within the RING-type zinc finger domain of the Cbl protein (UniProt.org). C381Y has been identified in sequencing studies (PMID: 25426837, PMID: 19387008), but has not been biochemically characterized and therefore, its effect on Cbl protein function is unknown (PubMed, Jul 2020).
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).
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).
C384W missense unknown CBL C384W lies within the RING-type zinc finger domain of the Cbl protein (UniProt.org). C384W has been identified in sequencing studies (PMID: 26343386), but has not been biochemically characterized and therefore, its effect on Cbl protein function is unknown (PubMed, Jul 2020).
C384Y missense unknown CBL C384Y lies within the RING-type zinc finger domain of the Cbl protein (UniProt.org). C384Y is predicted to disrupt Cbl stability by computational modeling (PMID: 26676746), but has not been biochemically characterized, and therefore, its effect on Cbl protein function is unknown.
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).
C396Y missense unknown CBL C396Y lies within the RING-type zinc finger domain of the Cbl protein (UniProt.org). C396Y is predicted to disrupt Cbl stability by computational modeling (PMID: 26676746), but has not been biochemically characterized and therefore, its effect on Cbl protein function is unknown (PubMed, Jul 2020).
C401F missense unknown CBL C401F lies within the RING-type zinc finger domain of the Cbl protein (UniProt.org). C401F is predicted to disrupt Cbl stability by computational modeling (PMID: 26676746), but has not been biochemically characterized and therefore, its effect on Cbl protein function is unknown (PubMed, Jul 2020).
C401R missense unknown CBL C401R lies within the RING-type zinc finger domain of the Cbl protein (UniProt.org). C401R is predicted to disrupt Cbl stability by computational modeling (PMID: 26676746), but has not been biochemically characterized and therefore, its effect on Cbl protein function is unknown (PubMed, Jul 2020).
C401Y missense unknown CBL C401Y lies within the RING-type zinc finger domain of the Cbl protein (UniProt.org). C401Y is predicted to disrupt Cbl stability by computational modeling (PMID: 26676746), but has not been biochemically characterized and therefore, its effect on Cbl protein function is unknown (PubMed, Jul 2020).
C404R missense unknown CBL C404R lies within the RING-type zinc finger domain of the Cbl protein (UniProt.org). C404R is predicted to disrupt Cbl stability by computational modeling (PMID: 26676746), but has not been biochemically characterized and therefore, its effect on Cbl protein function is unknown (PubMed, Jul 2020).
C404Y missense unknown CBL C404Y lies within the RING-type zinc finger domain of the Cbl protein (UniProt.org). C404Y is predicted to disrupt Cbl stability by computational modeling (PMID: 26676746), but has not been biochemically characterized and therefore, its effect on Cbl protein function is unknown (PubMed, Jul 2020).
C416R missense unknown CBL C416R lies within the RING-type zinc finger domain of the Cbl protein (UniProt.org). C416R is predicted to disrupt Cbl stability by computational modeling (PMID: 26676746), but has not been biochemically characterized and therefore, its effect on Cbl protein function is unknown (PubMed, Jul 2020).
C416S missense unknown CBL C416S lies within the RING-type zinc finger domain of the Cbl protein (UniProt.org). C416S has been identified in the scientific literature (PMID: 22071139, PMID: 31004019, PMID: 29872864), but has not been biochemically characterized and therefore, its effect on Cbl protein function is unknown (PubMed, Apr 2020).
C416W missense unknown CBL C416W lies within the RING-type zinc finger domain of the Cbl protein (UniProt.org). C416W results in increased cell proliferation compared to wild-type Cbl in cells overexpressing wild-type FLT3 (PMID: 22315494), but has not been individually characterized and therefore, its effect on Cbl protein function is unknown.
C416Y missense unknown CBL C416Y lies within the RING-type zinc finger domain of the Cbl protein (UniProt.org). C416Y is predicted to disrupt Cbl stability by computational modeling (PMID: 26676746), but has not been biochemically characterized and therefore, its effect on Cbl protein function is unknown (PubMed, Jul 2020).
C419R missense unknown CBL C419R lies within the RING-type zinc finger domain of the Cbl protein (UniProt.org). C419R is predicted to disrupt Cbl stability by computational modeling (PMID: 26676746), but has not been biochemically characterized and therefore, its effect on Cbl protein function is unknown (PubMed, Jul 2020).
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, Jul 2020).
D460del deletion unknown CBL D460del results in the deletion of one amino acid of the Cbl protein at amino acid 460 (UniProt.org). D460del has been identified in sequencing studies (PMID: 28098136, PMID: 25186949, PMID: 24817963), but has not been biochemically characterized and therefore, its effect on Cbl protein function is unknown (PubMed, Aug 2020).
D501H missense unknown CBL D501H does not lie within any known functional domains of the Cbl protein (UniProt.org). D501H has not been characterized and therefore, its effect on Cbl protein function is unknown (PubMed, Jul 2020).
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.
del exon8 deletion gain of function CBL del exon8 is a CBL splice variant caused by a mutation resulting in the deletion of exon 8 (PMID: 18698078). Del exon8 results in ligand-independent Flt3 autophosphorylation, and activation of Stat5 and Akt, and leads to increased ligand-dependent proliferation, and IL-3 independent proliferation of cells in culture (PMID: 19276253).
del exon9 deletion loss of function CBL del exon9 is a CBL splice variant caused by a mutation resulting in the deletion of exon 9 (PMID: 19276253). Del exon9 demonstrates increased ubiquitination and reduced protein stability of Cbl, and failure to suppress Erk phosphorylation in cell culture (PMID: 26152360).
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, Jul 2020).
E276K missense unknown CBL E276K lies within the Cbl-PTB domain of the Cbl protein (UniProt.org). E276K has been identified in sequencing studies (PMID: 29338072, PMID: 27389057), but has not been biochemically characterized and therefore, its effect on Cbl protein function is unknown (PubMed, Jul 2020).
E366K missense unknown CBL E366K lies within the linker region of the Cbl protein (UniProt.org). E366K has been identified in sequencing studies (PMID: 27029036, PMID: 20678218), but has not been biochemically characterized and therefore, its effect on Cbl protein function is unknown (PubMed, Jul 2020).
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).
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, Jul 2020).
E815D missense unknown CBL E815D lies within the CD2AP-interacting region of the Cbl protein (UniProt.org). E815D has been identified in sequencing studies (PMID: 24816253), but has not been biochemically characterized and therefore, its effect on Cbl protein function is unknown (PubMed, Jul 2020).
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 and therefore, its effect on Cbl protein function is unknown (PubMed, Jul 2020).
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, Jul 2020).
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, Jul 2020).
exon8 unknown unknown CBL exon 8 indicates an unspecified mutation has occurred in exon 8 of the CBL gene.
exon9 unknown unknown CBL exon 9 indicates an unspecified mutation has occurred in exon 9 of the CBL gene.
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, Jul 2020).
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, Jul 2020).
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, Jul 2020).
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).
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: 27997717, PMID: 23010802), but has not been biochemically characterized and therefore, its effect on Cbl protein function is unknown (PubMed, Jul 2020).
G413R missense unknown CBL G413R lies within the RING-type zinc finger domain of the Cbl protein (UniProt.org). C413R is predicted to disrupt Cbl stability by computational modeling (PMID: 26676746), but has not been biochemically characterized and therefore, its effect on Cbl protein function is unknown (PubMed, Jul 2020).
G415S missense unknown CBL G415S lies within the RING-type zinc finger domain of the Cbl protein (UniProt.org). G415S is predicted to disrupt Cbl stability by computational modeling (PMID: 26676746), but has not been biochemically characterized and therefore, its effect on Cbl protein function is unknown (PubMed, Jul 2020).
G415V missense unknown CBL G415V lies within the RING-type zinc finger domain of the Cbl protein (UniProt.org). C415V is predicted to disrupt Cbl stability by computational modeling (PMID: 26676746), but has not been biochemically characterized and therefore, its effect on Cbl protein function is unknown (PubMed, Jul 2020).
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, Jul 2020).
G868E missense unknown CBL G868E lies within the UBA domain of the Cbl protein (UniProt.org). G868E has not been characterized and therefore, its effect on Cbl protein function is unknown (PubMed, Jul 2020).
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, Jul 2020).
H398P missense unknown CBL H398P lies within the RING-type zinc finger domain of the Cbl protein (UniProt.org). H398P is predicted to disrupt Cbl stability by computational modeling (PMID: 26676746), but has not been biochemically characterized and therefore, its effect on Cbl protein function is unknown (PubMed, Jul 2020).
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).
H398R missense unknown CBL H398R lies within the RING-type zinc finger domain of the Cbl protein (UniProt.org). H398R is predicted to disrupt Cbl stability by computational modeling (PMID: 26676746), but has not been biochemically characterized and therefore, its effect on Cbl protein function is unknown (PubMed, Jul 2020).
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).
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, Jul 2020).
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, Jul 2020).
H94Y missense unknown CBL H94Y lies within the Cbl-PTB domain of the Cbl protein (UniProt.org). H94Y in combination with S80N results in ubiquitin activity similar to wild-type Cbl (PMID: 26676746), altered cell cycle, and increased cell viability and motility in cell culture (PMID: 20126411), however, has not been individually characterized and therefore, its effect on Cbl protein function is unknown.
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).
I98T missense unknown CBL I98T lies within the Cbl-PTB domain of the Cbl protein (UniProt.org). I98T is predicted to disrupt Cbl stability by computational modeling (PMID: 26676746), but has not been biochemically characterized and therefore, its effect on Cbl protein function is unknown (PubMed, Jul 2020).
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.
K322T missense unknown CBL K322T lies within the Cbl-PTB domain of the Cbl protein (UniProt.org). K322T has not been characterized and therefore, its effect on Cbl protein function is unknown (PubMed, Jul 2020).
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).
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, Jul 2020).
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, Jul 2020).
L380P missense unknown CBL L380P lies within the linker region of the Cbl protein (UniProt.org). L380P has been identified in the scientific literature (PMID: 19387008), but has not been biochemically characterized and therefore, its effect on Cbl protein function is unknown (PubMed, Jun 2020).
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).
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).
L405P missense unknown CBL L405P lies within the RING-type zinc finger domain of the Cbl protein (UniProt.org). L405P is predicted to disrupt Cbl stability by structural modeling (PMID: 26676746), but has not been biochemically characterized and therefore, its effect on Cbl protein function is unknown (PubMed, Jun 2020).
L405R missense unknown CBL L405R lies within the RING-type zinc finger domain of the Cbl protein (UniProt.org). L405R has been identified in sequencing studies (PMID: 31107544), but has not been biochemically characterized and therefore, its effect on Cbl protein function is unknown (PubMed, Jul 2020).
L467V missense unknown CBL L467V does not lie within any known functional domains of the Cbl protein (UniProt.org). L467V has been identified in sequencing studies (PMID: 29338072), but has not been biochemically characterized and therefore, its effect on Cbl protein function is unknown (PubMed, Jul 2020).
L620F missense unknown CBL L620F does not lie within any known functional domains 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, Jul 2020).
L857* nonsense loss of function CBL L857* results in a premature truncation of the Cbl protein at amino acid 857 of 946 (UniProt.org). L857* results in a loss of Cbl protein function as demonstrated by reduced Cbl dimerization, lack of nuclear translocation, and failure to ubiquitinate beta-catenin in cell culture (PMID: 23744067).
L878F missense unknown CBL L878F lies within the UBA domain of the Cbl protein (UniProt.org). L878F has not been characterized and therefore, its effect on Cbl protein function is unknown (PubMed, Jul 2020).
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, Jul 2020).
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 function.
M400R missense unknown CBL M400R lies within the RING-type zinc finger domain of the Cbl protein (UniProt.org). M400R is predicted to disrupt Cbl stability by computational modeling (PMID: 26676746), but has not been biochemically characterized and therefore, its effect on Cbl protein function is unknown (PubMed, Jul 2020).
M469I missense unknown CBL M469I does not lie within any known functional domains of the Cbl protein (UniProt.org). M469I has not been characterized and therefore, its effect on Cbl protein function is unknown (PubMed, Jul 2020).
M487V missense unknown CBL M487V does not lie within any known functional domains of the Cbl protein (UniProt.org). M487V has not been characterized and therefore, its effect on Cbl protein function is unknown (PubMed, Jul 2020).
mutant unknown unknown CBL mutant indicates an unspecified mutation in the CBL gene.
N832I missense unknown CBL N832I lies within the CD2AP-interacting region of the Cbl protein (UniProt.org). N832I has been identified in sequencing studies (PMID: 24121792), but has not been biochemically characterized and therefore, its effect on Cbl protein function is unknown (PubMed, Jul 2020).
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, Jul 2020).
P201S missense unknown CBL P201S lies within the Cbl-PTB domain of the Cbl protein (UniProt.org). P201S has been identified in sequencing studies (PMID: 25303977, PMID: 24265154), but has not been biochemically characterized and therefore, its effect on Cbl protein function is unknown (PubMed, Aug 2020).
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).
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).
P417H missense unknown CBL P417H lies within the RING-type zinc finger domain of the Cbl protein (UniProt.org). P417H has been identified in sequencing studies (PMID: 27011036, PMID: 23010802), but has not been biochemically characterized and therefore, its effect on Cbl protein function is unknown (PubMed, Jul 2020).
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: 27997717, PMID: 26214590, PMID: 24030381), but has not been biochemically characterized and therefore, its effect on Cbl protein function is unknown (PubMed, Jul 2020).
P428L missense no effect - predicted CBL P428L does not lie within any known functional domains of the Cbl protein (UniProt.org). P428L demonstrates 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.
P433Q missense unknown CBL P433Q does not lie within any known functional domains of the Cbl protein (UniProt.org). P433Q has been identified in sequencing studies (PMID: 30171174), but has not been biochemically characterized and therefore, its effect on Cbl protein function is unknown (PubMed, Jul 2020).
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, Jul 2020).
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, Jul 2020).
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, Jul 2020).
P703L missense unknown CBL P703L lies within the CD2AP-interacting region of the Cbl protein (UniProt.org). P703L has not been characterized and therefore, its effect on Cbl protein function is unknown (PubMed, Jul 2020).
Q249E missense gain of function - predicted CBL Q249E lies within the Cbl-PTB domain of the Cbl protein (UniProt.org). Q249E results in increased Cbl activity, as demonstrated by increased ubiquitination of Egfr compared to wild-type in cultured cells (PMID: 26676746), and therefore, is predicted to result in a gain of Cbl protein function.
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).
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).
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).
Q367R missense unknown CBL Q367R lies within the linker region of the Cbl protein (UniProt.org). Q367R has been identified in sequencing studies (PMID: 26956871, PMID: 30836094, PMID: 24896186), but has not been biochemically characterized and therefore, its effect on Cbl protein function is unknown (PubMed, Aug 2020).
Q867* nonsense unknown CBL Q867* results in a premature truncation of the Cbl protein at amino acid 867 of 906 (UniProt.org). Q867* has been identified in sequencing studies (PMID: 28027327), but has not been biochemically characterized and therefore, its effect on Cbl protein function is unknown (PubMed, Jul 2020).
Q875* nonsense unknown CBL Q875* results in a premature truncation of the Cbl protein at amino acid 875 of 906 (UniProt.org). Q875* has been identified in sequencing studies (PMID: 26214590), but has not been biochemically characterized and therefore, its effect on Cbl protein function is unknown (PubMed, Jul 2020).
Q882H missense unknown CBL Q882H lies within the UBA domain of the Cbl protein (UniProt.org). Q882H has been identified in sequencing studies (PMID: 30352278), but has not been biochemically characterized and therefore, its effect on Cbl protein function is unknown (PubMed, Jul 2020).
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, Jul 2020).
R343* nonsense loss of function - predicted CBL R343* results in a premature truncation of the Cbl protein at amino acid 343 of 906 (UniProt.org). R343* has not been characterized however, due to the effects of other truncation mutations downstream of R343 (PMID: 23744067, PMID: 10617633), R343* is predicted to lead to a loss of Cbl protein function.
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). R420* has not been characterized however, due to the effect of other truncation mutations downstream of R420 (PMID: 23744067), R420* is predicted to lead to a loss of Cbl protein function.
R420G missense unknown CBL R420G lies within the RING-type zinc finger domain of the Cbl protein (UniProt.org). R420G is predicted to disrupt Cbl stability by computational modeling (PMID: 26676746), but has not been biochemically characterized and therefore, its effect on Cbl protein function is unknown (PubMed, Jul 2020).
R420L missense unknown CBL R420L lies within the RING-type zinc finger domain of the Cbl protein (UniProt.org). R420L is predicted to disrupt Cbl stability by computational modeling (PMID: 26676746), but has not been biochemically characterized and therefore, its effect on Cbl protein function is unknown (PubMed, Jul 2020).
R420P missense unknown CBL R420P lies within the RING-finger domain of the Cbl protein (PMID: 20501843) R420P has not been biochemically characterized, but leads to destabilization of Cbl-E2 binding in computational models (PMID: 26676746), and therefore its effect on Cbl protein function is unknown.
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).
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, Jul 2020).
R499Q missense unknown CBL R499Q does not lie within any known functional domains of the Cbl protein (UniProt.org). R499Q has been identified in sequencing studies (PMID: 27149842), but has not been biochemically characterized and therefore, its effect on Cbl protein function is unknown (PubMed, Jul 2020).
R559Q missense unknown CBL R559Q does not lie within any known functional domains of the Cbl protein (UniProt.org). R559Q has been identified in sequencing studies (PMID: 28270683), but has not been biochemically characterized and therefore, its effect on Cbl protein function is unknown (PubMed, Apr 2020).
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, Jul 2020).
R788Q missense unknown CBL R788Q lies within the CD2AP-interacting region of the Cbl protein (UniProt.org). R788Q has been identified in sequencing studies (PMID: 29057546, PMID: 26580448), but has not been biochemically characterized and therefore, its effect on Cbl protein function is unknown (PubMed, Apr 2020).
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, Jul 2020).
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, Jul 2020).
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, Jul 2020).
R893L missense unknown CBL R893L lies within the UBA domain of the Cbl protein (UniProt.org). R893L has been identified in sequencing studies (PMID: 28157713), but has not been biochemically characterized and therefore, its effect on Cbl protein function is unknown (PubMed, Jul 2020).
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, Jul 2020).
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, Jul 2020).
S217Y missense unknown CBL S217Y lies within the Cbl-PTB domain of the Cbl protein (UniProt.org). S217Y 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, Jul 2020).
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, Jul 2020).
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).
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, Jul 2020).
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, Jul 2020).
S80N missense unknown CBL S80N lies within the Cbl-PTB domain of the Cbl protein (UniProt.org). S80N in combination with H94Y demonstrates ubiquitin ligase activity similar to wild-type Cbl towards Egfr (PMID: 26676746) and increased cell viability and motility in cell culture (PMID: 20126411), however, has not been individually characterized and therefore, its effect on Cbl protein function is unknown.
T426A missense unknown CBL T426A does not lie within any known functional domains of the Cbl protein (UniProt.org). T426A has not been characterized and therefore, its effect on Cbl protein function is unknown (PubMed, Jul 2020).
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).
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.
V478L missense unknown CBL V478L does not lie within any known functional domains of the Cbl protein (UniProt.org). V478L has been identified in sequencing studies (PMID: 26960398), but has not been biochemically characterized and therefore, its effect on Cbl protein function is unknown (PubMed, Apr 2020).
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, Jul 2020).
W408L missense unknown CBL W408L lies within the RING-type zinc finger domain of the Cbl protein (UniProt.org). W408L is predicted to disrupt Cbl stability by computational modeling (PMID: 26676746), but has not been biochemically characterized and therefore, its effect on Cbl protein function is unknown (PubMed, Jul 2020).
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). W802* has not been characterized however, due to the effect of other truncation mutations downstream of 802 (PMID: 23744067), W802* is predicted to lead to a loss of Cbl protein function.
wild-type none no effect Wild-type CBL indicates that no mutation has been detected within the CBL gene.
Y274F missense no effect - predicted CBL Y274F lies within the Cbl-PTB domain of the Cbl protein (UniProt.org). Y274F does not impair E3 ubiquitin ligase activity and demonstrates similar levels of Egfr ubiquitination compared to wild-type Cbl in cell culture (PMID: 10635327), and therefore, is predicted to have no effect on Cbl protein function.
Y291F missense no effect - predicted CBL Y291F lies within the Cbl-PTB domain of the Cbl protein (UniProt.org). Y291F does not impair E3 ubiquitin ligase activity and demonstrates similar levels of Egfr ubiquitination compared to wild-type Cbl in cell culture (PMID: 10635327), and therefore, is predicted to have no effect on Cbl protein function.
Y307F missense no effect - predicted CBL Y307F lies within the Cbl-PTB domain of the Cbl protein (UniProt.org). Y307F does not impair E3 ubiquitin ligase activity and demonstrates similar levels of Egfr ubiquitination compared to wild-type Cbl in cell culture (PMID: 10635327), and therefore, is predicted to have no effect on Cbl protein function.
Y337F missense no effect - predicted CBL Y337F lies within the Cbl-PTB domain of the Cbl protein (UniProt.org). Y337F does not impair E3 ubiquitin ligase activity and demonstrates similar levels of Egfr ubiquitination compared to wild-type Cbl in cell culture (PMID: 10635327), and therefore, is predicted to have no effect on Cbl protein function.
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).
Y368F missense no effect - predicted CBL Y368F lies within the linker region of the Cbl protein (UniProt.org). Y368F does not impair E3 ubiquitin ligase activity and demonstrates similar levels of Egfr ubiquitination compared to wild-type Cbl in cell culture (PMID: 10635327), and therefore, is predicted to have no effect on Cbl protein function.
Y368_K382del deletion unknown CBL Y368_K382del results in the deletion of 15 amino acids within 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, Jul 2020).
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).
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) and therefore, is predicted to confer a loss of function on the Cbl protein.
Y371del deletion loss of function - predicted CBL Y371del results in the deletion of one amino acid in the linker region of the Cbl protein at amino acid 371 (UniProt.org). Y371del results in decreased apoptosis, increased cell cycle progression, and transformation of cultured cells in the presence of FLT3 (PMID: 20622007, PMID: 31943762), and therefore is predicted to result in a loss of Cbl protein function.
Y371F missense loss of function CBL Y371F lies within the linker region of the Cbl protein (UniProt.org). Y371F impairs E3 ubiquitin ligase activity and demonstrates reduced levels of Egfr ubiquitination compared to wild-type Cbl in cell culture and an in vitro assay (PMID: 10635327).
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).
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).
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 been identified in sequencing studies (PMID: 25017477), but has not been biochemically characterized and therefore, its effect on Cbl protein function is unknown (PubMed, Apr 2020).
Y92A missense no effect - predicted CBL Y92A lies within the Cbl-PTB domain of the Cbl protein (UniProt.org). Y92A does not impair E3 ubiquitin ligase activity and demonstrates similar levels of Egfr ubiquitination compared to wild-type Cbl in cell culture (PMID: 10635327), and therefore, is predicted to have no effect on Cbl protein function.