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Gene Symbol | CBLC | ||||||||||
Synonyms | CBL-3 | CBL-SL | RNF57 | ||||||||||
Gene Description | CBLC, Cbl proto-oncogene C, is an ubiquitin ligase that targets activated receptor kinases for degradation (PMID: 10362357). Overexpression of Cblc has been observed in non-small cell lung cancer (PMID: 29945960), mutations have been identified in myeloproliferative neoplasms (PMID: 22315494), and Cblc may modulate response to PARP inhibitors (PMID: 25883215). | ||||||||||
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Variant | Impact | Protein Effect | Variant Description | Associated with drug Resistance |
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A191T | missense | unknown | CBLC A191T lies within the Cbl-PTB domain and EF-hand-like region of the Cblc protein (UniProt.org). A191T has not been characterized in the scientific literature and therefore, its effect on Cblc protein function is unknown (PubMed, Oct 2020). | |
A232Gfs*14 | frameshift | loss of function - predicted | CBLC A232Gfs*14 indicates a shift in the reading frame starting at amino acid 232 and terminating 14 residues downstream causing a premature truncation of the 474 amino acid Cblc protein (UniProt.org). A232Gfs*14 does not lead to altered recruitment of wild-type Cbl, but demonstrates impaired ability to ubiquitinate and downregulate Egfr in cell culture (PMID: 31260484), and therefore, is predicted to lead to a loss of Cblc protein function. | |
A398V | missense | unknown | CBLC A398V lies within the RET-interacting region of the Cblc protein (UniProt.org). A398V has been identified in sequencing studies (PMID: 22395615), but has not been biochemically characterized and therefore, its effect on Cblc protein function is unknown (PubMed, Oct 2020). | |
A64T | missense | unknown | CBLC A64T lies within the 4H region of the Cbl-PTB domain of the Cblc protein (UniProt.org). A64T has not been characterized in the scientific literature and therefore, its effect on Cblc protein function is unknown (PubMed, Mar 2021). | |
A6T | missense | unknown | CBLC A6T does not lie within any known functional domains of the Cblc protein (UniProt.org). A6T has not been characterized in the scientific literature and therefore, its effect on Cblc protein function is unknown (PubMed, Mar 2021). | |
A6V | missense | unknown | CBLC A6V does not lie within any known functional domains of the Cblc protein (UniProt.org). A6V has not been characterized in the scientific literature and therefore, its effect on Cblc protein function is unknown (PubMed, Mar 2021). | |
D318N | missense | unknown | CBLC D318N lies within the SH2-like region of the Cbl-PTB domain of the Cblc protein (UniProt.org). D318N has been identified in sequencing studies (PMID: 25240281), but has not been biochemically characterized and therefore, its effect on Cblc protein function is unknown (PubMed, Mar 2021). | |
dec exp | none | no effect | CBLC dec exp indicates decreased expression of the Cblc protein. However, the mechanism causing the decreased expression is unspecified. | |
E14K | missense | unknown | CBLC E14K lies within the 4H region of the Cbl-PTB domain of the Cblc protein (UniProt.org). E14K has not been characterized in the scientific literature and therefore, its effect on Cblc protein function is unknown (PubMed, Mar 2021). | |
E162K | missense | unknown | CBLC E162K lies within the EF-hand-like region of the Cbl-PTB domain of the Cblc protein (UniProt.org). E162K has not been characterized in the scientific literature and therefore, its effect on Cblc protein function is unknown (PubMed, Mar 2021). | |
E186K | missense | unknown | CBLC E186K lies within the EF-hand-like region of the Cbl-PTB domain of the Cblc protein (UniProt.org). E186K has not been characterized in the scientific literature and therefore, its effect on Cblc protein function is unknown (PubMed, Mar 2021). | |
E356K | missense | unknown | CBLC E356K lies within the RING-type zinc finger domain of the Cblc protein (UniProt.org). E356K has not been characterized in the scientific literature and therefore, its effect on Cblc protein function is unknown (PubMed, Mar 2021). | |
E392K | missense | no effect - predicted | CBLC E392K lies within the RET-interacting region of the Cblc protein (UniProt.org). E392K supports cell proliferation to similar levels of wild-type Cblc protein in culture (PMID: 22315494) and therefore, is predicted to have no effect on Cblc protein function. | |
E88D | missense | unknown | CBLC E88D lies within the 4H region of the Cbl-PTB domain of the Cblc protein (UniProt.org). E88D has not been characterized in the scientific literature and therefore, its effect on Cblc protein function is unknown (PubMed, Mar 2021). | |
F111L | missense | unknown | CBLC F111L lies within the 4H region of the Cbl-PTB domain of the Cblc protein (UniProt.org). F111L has not been characterized in the scientific literature and therefore, its effect on Cblc protein function is unknown (PubMed, Mar 2021). | |
F214Sfs*65 | frameshift | unknown | CBLC F214Sfs*65 indicates a shift in the reading frame starting at amino acid 214 and terminating 65 residues downstream causing a premature truncation of the 474 amino acid Cblc protein (UniProt.org). F214Sfs*65 has not been characterized in the scientific literature and therefore, its effect on Cblc protein function is unknown (PubMed, Mar 2021). | |
G141R | missense | unknown | CBLC G141R lies within the 4H region of the Cbl-PTB domain of the Cblc protein (UniProt.org). G141R has been identified in sequencing studies (PMID: 22895193), but has not been biochemically characterized and therefore, its effect on Cblc protein function is unknown (PubMed, Mar 2021). | |
G165R | missense | unknown | CBLC G165R lies within the EF-hand-like region of the Cbl-PTB domain of the Cblc protein (UniProt.org). G165R has been identified in sequencing studies (PMID: 27149842), but has not been biochemically characterized and therefore, its effect on Cblc protein function is unknown (PubMed, Mar 2021). | |
G259C | missense | unknown | CBLC G259C lies within the SH2-like region of the Cbl-PTB domain of the Cblc protein (UniProt.org). G259C has not been characterized in the scientific literature and therefore, its effect on Cblc protein function is unknown (PubMed, Mar 2021). | |
G312E | missense | unknown | CBLC G312E lies within the Cbl-PTB domain of the Cblc protein (UniProt.org). G312E has been identified in sequencing studies (PMID: 24589925), but has not been biochemically characterized and therefore, its effect on Cblc protein function is unknown (PubMed, Oct 2020). | |
G395D | missense | unknown | CBLC G395D lies within the RET-interacting region of the Cblc protein (UniProt.org). G395D has not been characterized in the scientific literature and therefore, its effect on Cblc protein function is unknown (PubMed, Mar 2021). | |
G467* | nonsense | unknown | CBLC G467* results in a premature truncation of the Cblc protein at amino acid 467 of 474 (UniProt.org). G467* has not been characterized in the scientific literature and therefore, its effect on Cblc protein function is unknown (PubMed, Mar 2021). | |
G72S | missense | unknown | CBLC G72S lies within the 4H region of the Cbl-PTB domain of the Cblc protein (UniProt.org). G72S has not been characterized in the scientific literature and therefore, its effect on Cblc protein function is unknown (PubMed, Mar 2021). | |
H136L | missense | unknown | CBLC H136L lies within the Cbl-PTB domain of the Cblc protein (UniProt.org). H136L has not been characterized in the scientific literature and therefore, its effect on Cblc protein function is unknown (PubMed, Oct 2020). | |
H235P | missense | unknown | CBLC H235P lies within the SH2-like region of the Cbl-PTB domain of the Cblc protein (UniProt.org). H235P has not been characterized in the scientific literature and therefore, its effect on Cblc protein function is unknown (PubMed, Mar 2021). | |
H405Y | missense | unknown | CBLC H405Y lies within the RET-interacting region of the Cblc protein (UniProt.org). H405Y has been identified in sequencing studies (PMID: 25589003, PMID: 16741161), but has not been biochemically characterized and therefore, its effect on Cblc protein function is unknown (PubMed, Oct 2020). | |
I126L | missense | unknown | CBLC I126L lies within the 4H region of the Cbl-PTB domain of the Cblc protein (UniProt.org). I126L has not been characterized in the scientific literature and therefore, its effect on Cblc protein function is unknown (PubMed, Mar 2021). | |
I284Tfs*37 | frameshift | unknown | CBLC I284Tfs*37 indicates a shift in the reading frame starting at amino acid 284 and terminating 37 residues downstream causing a premature truncation of the 474 amino acid Cblc protein (UniProt.org). I284Tfs*37 has not been characterized in the scientific literature and therefore, its effect on Cblc protein function is unknown (PubMed, Mar 2021). | |
inact mut | unknown | loss of function | CBLC inact mut indicates that this variant results in a loss of function of the CBLC protein. However, the specific amino acid change has not been identified. | |
K143N | missense | unknown | CBLC K143N lies within the 4H region of the Cbl-PTB domain of the Cblc protein (UniProt.org). K143N has not been characterized in the scientific literature and therefore, its effect on Cblc protein function is unknown (PubMed, Mar 2021). | |
L178F | missense | unknown | CBLC L178F lies within the EF-hand-like region of the Cbl-PTB domain of the Cblc protein (UniProt.org). L178F has not been characterized in the scientific literature and therefore, its effect on Cblc protein function is unknown (PubMed, Mar 2021). | |
L442V | missense | unknown | CBLC L442V lies within the RET-interacting region of the Cblc protein (UniProt.org). L442V has been identified in sequencing studies (PMID: 24121792), but has not been biochemically characterized and therefore, its effect on Cblc protein function is unknown (PubMed, Mar 2021). | |
M131I | missense | unknown | CBLC M131I lies within the 4H region of the Cbl-PTB domain of the Cblc protein (UniProt.org). M131I has been identified in sequencing studies (PMID: 24686850), but has not been biochemically characterized and therefore, its effect on Cblc protein function is unknown (PubMed, Mar 2021). | |
M148L | missense | unknown | CBLC M148L lies within the EF-hand-like region of the Cbl-PTB domain of the Cblc protein (UniProt.org). M148L has not been characterized in the scientific literature and therefore, its effect on Cblc protein function is unknown (PubMed, Mar 2021). | |
M148R | missense | unknown | CBLC M148R lies within the EF-hand-like region of the Cbl-PTB domain of the Cblc protein (UniProt.org). M148R has been identified in sequencing studies (PMID: 21720365), but has not been biochemically characterized and therefore, its effect on Cblc protein function is unknown (PubMed, Mar 2021). | |
mutant | unknown | unknown | CBLC mutant indicates an unspecified mutation in the CBLC gene. | |
over exp | none | no effect | CBLC over exp indicates an over expression of the Cblc protein. However, the mechanism causing the over expression is unspecified. | |
P100S | missense | unknown | CBLC P100S lies within the 4H region of the Cbl-PTB domain of the Cblc protein (UniProt.org). P100S has not been characterized in the scientific literature and therefore, its effect on Cblc protein function is unknown (PubMed, Mar 2021). | |
P310L | missense | unknown | CBLC P310L lies within the SH2-like region of the Cbl-PTB domain of the Cblc protein (UniProt.org). P310L has not been characterized in the scientific literature and therefore, its effect on Cblc protein function is unknown (PubMed, Mar 2021). | |
P35S | missense | unknown | CBLC P35S lies within the 4H region of the Cbl-PTB domain of the Cblc protein (UniProt.org). P35S has not been characterized in the scientific literature and therefore, its effect on Cblc protein function is unknown (PubMed, Mar 2021). | |
P430L | missense | unknown | CBLC P430L lies within the RET-interacting region of the Cblc protein (UniProt.org). P430L has not been characterized in the scientific literature and therefore, its effect on Cblc protein function is unknown (PubMed, Oct 2020). | |
P434L | missense | unknown | CBLC P434L lies within the RET-interacting region of the Cblc protein (UniProt.org). P434L has not been characterized in the scientific literature and therefore, its effect on Cblc protein function is unknown (PubMed, Mar 2021). | |
P435S | missense | no effect - predicted | CBLC P435S lies within the RET-interacting region of the Cblc protein (UniProt.org). P435S supports cell proliferation to similar levels of wild-type Cblc protein in culture (PMID: 22315494) and therefore, is predicted to have no effect on Cblc protein function. | |
P444L | missense | unknown | CBLC P444L lies within the RET-interacting region of the Cblc protein (UniProt.org). P444L has been identified in sequencing studies (PMID: 21720365), but has not been biochemically characterized and therefore, its effect on Cblc protein function is unknown (PubMed, Mar 2021). | |
P463A | missense | unknown | CBLC P463A lies within the RET-interacting region of the Cblc protein (UniProt.org). P463A has not been characterized and therefore, its effect on Cblc protein function is unknown (PubMed, Mar 2021). | |
P473S | missense | unknown | CBLC P473S lies within the RET-interacting region of the Cblc protein (UniProt.org). P473S has been identified in sequencing studies (PMID: 25589618), but has not been biochemically characterized and therefore, its effect on Cblc protein function is unknown (PubMed, Oct 2020). | |
Q384K | missense | unknown | CBLC Q384K lies within the RING-type zinc finger domain of the Cblc protein (UniProt.org). Q384K has not been characterized in the scientific literature and therefore, its effect on Cblc protein function is unknown (PubMed, Mar 2021). | |
Q419Pfs*81 | frameshift | no effect - predicted | CBLC Q419Pfs*81 indicates a shift in the reading frame starting at amino acid 419 and terminating 81 residues downstream causing a premature truncation of the 474 amino acid Cblc protein (UniProt.org). Q419Pfs*81 supports cell proliferation to similar level of wild-type Cblc protein in culture (PMID: 22315494) and therefore, is predicted to have no effect on Cblc protein function. | |
R104K | missense | unknown | CBLC R104K lies within the 4H region of the Cbl-PTB domain of the Cblc protein (UniProt.org). R104K has not been characterized in the scientific literature and therefore, its effect on Cblc protein function is unknown (PubMed, Mar 2021). | |
R104N | missense | unknown | CBLC R104N lies within the 4H region of the Cbl-PTB domain of the Cblc protein (UniProt.org). R104N has not been characterized in the scientific literature and therefore, its effect on Cblc protein function is unknown (PubMed, Mar 2021). | |
R119Q | missense | unknown | CBLC R119Q lies within the 4H region of the Cbl-PTB domain of the Cblc protein (UniProt.org). R119Q has not been characterized and therefore, its effect on Cblc protein function is unknown (PubMed, Mar 2021). | |
R167G | missense | unknown | CBLC R167G lies within the EF-hand-like region of the Cbl-PTB domain of the Cblc protein (UniProt.org). R167G has not been characterized in the scientific literature and therefore, its effect on Cblc protein function is unknown (PubMed, Mar 2021). | |
R20Q | missense | unknown | CBLC R20Q lies within the 4H region in the Cbl-PTB domain of the Cblc protein (UniProt.org). R20Q has been identified in sequencing studies (PMID: 26000489), but has not been biochemically characterized and therefore, its effect on Cblc protein function is unknown (PubMed, Oct 2020). | |
R269C | missense | unknown | CBLC R269C lies within the SH2-like region of the Cbl-PTB domain of the Cblc protein (UniProt.org). R269C has not been characterized and therefore, its effect on Cblc protein function is unknown (PubMed, Mar 2021). | |
R390H | missense | unknown | CBLC R390H lies within the RING-type zinc finger domain of the Cblc protein (UniProt.org). R390H has not been characterized in the scientific literature and therefore, its effect on Cblc protein function is unknown (PubMed, Mar 2021). | |
R56* | nonsense | loss of function - predicted | CBLC R56* results in a premature truncation of the Cblc protein at amino acid 56 of 474 (UniProt.org). Due to the loss of all known functional domains (UniProt.org), R56* is predicted to lead to a loss of Cblc protein function. | |
R63W | missense | unknown | CBLC R63W lies within the 4H region of the Cbl-PTB domain of the Cblc protein (UniProt.org). R63W has not been characterized in the scientific literature and therefore, its effect on Cblc protein function is unknown (PubMed, Mar 2021). | |
S381L | missense | unknown | CBLC S381L lies within the RING-type zinc finger domain of the Cblc protein (UniProt.org). S381L has been identified in sequencing studies (PMID: 22895193), but has not been biochemically characterized and therefore, its effect on Cblc protein function is unknown (PubMed, Mar 2021). | |
S400Vfs*55 | frameshift | unknown | CBLC S400Vfs*55 indicates a shift in the reading frame starting at amino acid 400 and terminating 55 residues downstream causing a premature truncation of the 474 amino acid Cblc protein (UniProt.org). S400Vfs*55 has not been characterized in the scientific literature and therefore, its effect on Cblc protein function is unknown (PubMed, Mar 2021). | |
S43L | missense | unknown | CBLC S43L lies within the 4H region of the Cbl-PTB domain of the Cblc protein (UniProt.org). S43L has not been characterized in the scientific literature and therefore, its effect on Cblc protein function is unknown (PubMed, Mar 2021). | |
S76Y | missense | unknown | CBLC S76Y lies within the 4H region of the Cbl-PTB domain of the Cblc protein (UniProt.org). S76Y has not been characterized in the scientific literature and therefore, its effect on Cblc protein function is unknown (PubMed, Mar 2021). | |
T197del | deletion | unknown | CBLC T197del results in the deletion of one amino acid within the EF-hand-like region in the Cbl-PTB domain of the Cblc protein at amino acid 197 (UniProt.org). T197del has not been characterized in the scientific literature and therefore, its effect on Cblc protein function is unknown (PubMed, Oct 2020). | |
T215P | missense | unknown | CBLC T215P lies within the EF-hand-like region in the Cbl-PTB domain of the Cblc protein (UniProt.org). T215P has not been characterized in the scientific literature and therefore, its effect on Cblc protein function is unknown (PubMed, Oct 2020). | |
T385I | missense | unknown | CBLC T385I lies within the RING-type zinc finger domain of the Cblc protein (UniProt.org). T385I has not been characterized in the scientific literature and therefore, its effect on Cblc protein function is unknown (PubMed, Oct 2020). | |
V213L | missense | unknown | CBLC V213L lies within the EF-hand-like region in the Cbl-PTB domain of the Cblc protein (UniProt.org). V213L has not been characterized and therefore, its effect on Cblc protein function is unknown (PubMed, Oct 2020). | |
V247A | missense | unknown | CBLC V247A lies within the SH2-like region in the Cbl-PTB domain of the Cblc protein (UniProt.org). V247A has not been characterized in the scientific literature and therefore, its effect on Cblc protein function is unknown (PubMed, Oct 2020). | |
V247I | missense | unknown | CBLC V247I lies within the SH2-like region in the Cbl-PTB domain of the Cblc protein (UniProt.org). V247I has not been characterized in the scientific literature and therefore, its effect on Cblc protein function is unknown (PubMed, Oct 2020). | |
V247L | missense | unknown | CBLC V247L lies within the SH2-like region in the Cbl-PTB domain of the Cblc protein (UniProt.org). V247L has not been characterized and therefore, its effect on Cblc protein function is unknown (PubMed, Oct 2020). | |
V361A | missense | unknown | CBLC V361A lies within the RING-type zinc finger domain of the Cblc protein (UniProt.org). V361A has not been characterized in the scientific literature and therefore, its effect on Cblc protein function is unknown (PubMed, Oct 2020). | |
W378* | nonsense | unknown | CBLC W378* results in a premature truncation of the Cblc protein at amino acid 378 of 474 (UniProt.org). W378* has not been characterized in the scientific literature and therefore, its effect on Cblc protein function is unknown (PubMed, Oct 2020). | |
W378C | missense | unknown | CBLC W378C lies within the RET-interacting region of the Cblc protein (UniProt.org). W378C has been identified in the scientific literature (PMID: 31260484), but has not been biochemically characterized and therefore, its effect on Cblc protein function is unknown (PubMed, Oct 2020). | |
Y341C | missense | loss of function | CBLC Y341C lies within the linker region of the Cblc protein (UniProt.org). Y341C prevents Cbl recruitment to activated Egfr, and results in impaired ability to ubiquitinate and downregulate Egfr in cell culture (PMID: 31260484). |