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Gene Symbol | CBLB | ||||||||||
Synonyms | Cbl-b | Nbla00127 | RNF56 | ||||||||||
Gene Description | CBLB, Cbl proto-oncogene B, is an E3 ubiquitin ligase that negatively regulates receptor tyrosine kinase signaling through targeted degradation of active kinases, and is a key regulator of the immune system (PMID: 25477533, PMID: 30442330). CBLB mutations have been observed in myeloid neoplasms, and loss of CBLB in mouse models results in increased anti-tumor immunity (PMID: 19901108, PMID: 25477533). | ||||||||||
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Variant | Impact | Protein Effect | Variant Description | Associated with drug Resistance |
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A215T | missense | unknown | CBLB A215T lies within the Cbl-PTB domain of the Cblb protein (UniProt.org). A215T has been identified in sequencing studies (PMID: 22895193), but has not been biochemically characterized and therefore, its effect on Cblb protein function is unknown (PubMed, Jan 2021). | |
A914* | nonsense | loss of function - predicted | CBLB A914* results in a premature truncation of the Cblb protein at amino acid 914 of 982 (UniProt.org). A914* retains the ability to deregulate Egfr and activated cSrc, but abolishes the binding to high molecular weight ubiquitinated proteins in culture (PMID: 15273720), and therefore, is predicted to lead to a loss of Cblb protein function. | |
C224F | missense | unknown | CBLB C224F lies within the Cbl-PTB domain of the Cblb protein (UniProt.org). C224F has not been characterized in the scientific literature and therefore, its effect on Cblb protein function is unknown (PubMed, Jan 2021). | |
C373A | missense | loss of function | CBLB C373A lies within the RING-type zing finger domain of the Cblb protein (UniProt.org). C373A retains the ability to bind high molecular weight ubiquitinated proteins, but abolishes the E3 ligase activity of Cblb, and fails to deregulate Egfr and activated cSrc in culture (PMID: 15273720, PMID: 11375397). | |
D221Y | missense | unknown | CBLB D221Y lies within the Cbl-PTB domain of the Cblb protein (UniProt.org). D221Y has not been characterized in the scientific literature and therefore, its effect on Cblb protein function is unknown (PubMed, Jan 2021). | |
D430N | missense | unknown | CBLB D430N does not lie within any known functional domains of the Cblb protein (UniProt.org). D430N has not been characterized in the scientific literature and therefore, its effect on Cblb protein function is unknown (PubMed, Jan 2021). | |
D448N | missense | unknown | CBLB D448N does not lie within any known functional domains of the Cblb protein (UniProt.org). D448N has been identified in sequencing studies (PMID: 24755471), but has not been biochemically characterized and therefore, its effect on Cblb protein function is unknown (PubMed, Jan 2021). | |
D448Y | missense | unknown | CBLB D448Y does not lie within any known functional domains of the Cblb protein (UniProt.org). D448Y has not been characterized and therefore, its effect on Cblb protein function is unknown (PubMed, Jan 2021). | |
D452N | missense | unknown | CBLB D452N does not lie within any known functional domains of the Cblb protein (UniProt.org). D452N has not been characterized and therefore, its effect on Cblb protein function is unknown (PubMed, Jan 2021). | |
D759E | missense | unknown | CBLB D759E does not lie within any known functional domains of the Cblb protein (UniProt.org). D759E has been identified in sequencing studies (PMID: 21720365), but has not been biochemically characterized and therefore, its effect on Cblb protein function is unknown (PubMed, Jan 2021). | |
dec exp | none | no effect | CBLB dec exp indicates decreased expression of the Cblb protein. However, the mechanism causing the decreased expression is unspecified. | |
del | deletion | loss of function | CBLB del indicates a deletion of the CBLB gene. | |
E127* | nonsense | loss of function - predicted | CBLB E127* results in a premature truncation of the Cblb protein at amino acid 127 of 982 (UniProt.org). Due to the loss of all known functional domains (UniProt.org), E127* is predicted to lead to a loss of Cblb protein function. | |
E135D | missense | unknown | CBLB E135D lies within the Cbl-PTB domain of the Cblb protein (UniProt.org). E135D has been identified in sequencing studies (PMID: 22895193), but has not been biochemically characterized and therefore, its effect on Cblb protein function is unknown (PubMed, Jan 2021). | |
E358G | missense | unknown | CBLB E358G lies within the linker region of the Cblb protein (UniProt.org). E358G has not been characterized in the scientific literature and therefore, its effect on Cblb protein function is unknown (PubMed, Jan 2021). | |
F197Y | missense | unknown | CBLB F197Y lies within the Cbl-PTB domain of the Cblb protein (UniProt.org). F197Y has not been characterized in the scientific literature and therefore, its effect on Cblb protein function is unknown (PubMed, Jan 2021). | |
F814C | missense | unknown | CBLB F814C does not lie within any known functional domains of the Cblb protein (UniProt.org). F814C has not been characterized in the scientific literature and therefore, its effect on Cblb protein function is unknown (PubMed, Jan 2021). | |
F814L | missense | unknown | CBLB F814L does not lie within any known functional domains of the Cblb protein (UniProt.org). F814L has been identified in sequencing studies (PMID: 22941189), but has not been biochemically characterized and therefore, its effect on Cblb protein function is unknown (PubMed, Jan 2021). | |
G323V | missense | unknown | CBLB G323V lies within the Cbl-PTB domain of the Cblb protein (UniProt.org). G323V has not been characterized in the scientific literature and therefore, its effect on Cblb protein function is unknown (PubMed, Jan 2021). | |
G658A | missense | unknown | CBLB G658A does not lie within any known functional domains of the Cblb protein (UniProt.org). G658A has been identified in sequencing studies (PMID: 22810696), but has not been biochemically characterized and therefore, its effect on Cblb protein function is unknown (PubMed, Jan 2021). | |
G943A | missense | unknown | CBLB G943A lies within the UBA domain of the Cblb protein (UniProt.org). G943A abolishes ubiquitin binding of the UBA domain of Cblb when combined with Y944Q in an in vitro assay (PMID: 15273720), but has not been individually characterized and therefore, its effect on Cblb protein function is unknown. | |
G943_Y944delinsAQ | indel | loss of function - predicted | CBLB G943_Y944delinsAQ results in a deletion of two amino acids in the UBA domain of the Cblb protein from amino acids 943 to 944, combined with the insertion of an alanine (A) and a glutamine (G) at the same site (UniProt.org). G943_Y944delinsAQ abolishes ubiquitin binding of the UBA domain as compared to wild-type Cblb in an in vitro assay (PMID: 15273720), and therefore, is predicted to lead to a loss of Cblb protein function. | |
H152L | missense | unknown | CBLB H152L lies within the Cbl-PTB domain of the Cblb protein (UniProt.org). H152L has not been characterized in the scientific literature and therefore, its effect on Cblb protein function is unknown (PubMed, Jan 2021). | |
H257Y | missense | unknown | CBLB H257Y lies within the Cbl-PTB domain of the Cblb protein (UniProt.org). H257Y has not been characterized in the scientific literature and therefore, its effect on Cblb protein function is unknown (PubMed, Jan 2021). | |
I149M | missense | unknown | CBLB I149M lies within the Cbl-PTB domain of the Cblb protein (UniProt.org). I149M has not been characterized in the scientific literature and therefore, its effect on Cblb protein function is unknown (PubMed, Jan 2021). | |
I619M | missense | unknown | CBLB I619M does not lie within any known functional domains of the Cblb protein (UniProt.org). I619M has not been characterized in the scientific literature and therefore, its effect on Cblb protein function is unknown (PubMed, Jan 2021). | |
I77V | missense | unknown | CBLB I77V lies within the Cbl-PTB domain of the Cblb protein (UniProt.org). I77V has not been characterized in the scientific literature and therefore, its effect on Cblb protein function is unknown (PubMed, Jan 2021). | |
inact mut | unknown | loss of function | CBLB inact mut indicates that this variant results in a loss of function of the Cblb protein. However, the specific amino acid change has not been identified. | |
K217T | missense | unknown | CBLB K217T lies within the Cbl-PTB domain of the Cblb protein (UniProt.org). K217T has not been characterized in the scientific literature and therefore, its effect on Cblb protein function is unknown (PubMed, Jan 2021). | |
L23W | missense | unknown | CBLB L23W does not lie within any known functional domains of the Cblb protein (UniProt.org). L23W has not been characterized in the scientific literature and therefore, its effect on Cblb protein function is unknown (PubMed, Jan 2021). | |
L743P | missense | unknown | CBLB L743P does not lie within any known functional domains of the Cblb protein (UniProt.org). L743P has not been characterized in the scientific literature and therefore, its effect on Cblb protein function is unknown (PubMed, Jan 2021). | |
L764V | missense | unknown | CBLB L764V does not lie within any known functional domains of the Cblb protein (UniProt.org). L764V has not been characterized in the scientific literature and therefore, its effect on Cblb protein function is unknown (PubMed, Jan 2021). | |
L967A | missense | unknown | CBLB L967A lies within the UBA domain of the Cblb protein (UniProt.org). L967A has been identified in the scientific literature (PMID: 15273720), but has not been biochemically characterized and therefore, its effect on Cblb protein function is unknown (PubMed, Jan 2021). | |
mutant | unknown | unknown | CBLB mutant indicates an unspecified mutation in the CBLB gene. | |
P428S | missense | unknown | CBLB P428S does not lie within any known functional domains of the Cblb protein (UniProt.org). P428S has not been characterized in the scientific literature and therefore, its effect on Cblb protein function is unknown (PubMed, Jan 2021). | |
P674L | missense | unknown | CBLB P674L does not lie within any known functional domains of the Cblb protein (UniProt.org). P674L has not been characterized in the scientific literature and therefore, its effect on Cblb protein function is unknown (PubMed, Jan 2021). | |
P674S | missense | unknown | CBLB P674S does not lie within any known functional domains of the Cblb protein (UniProt.org). P674S has not been characterized in the scientific literature and therefore, its effect on Cblb protein function is unknown (PubMed, Jan 2021). | |
P824S | missense | unknown | CBLB P824S does not lie within any known functional domains of the Cblb protein (UniProt.org). P824S has not been characterized in the scientific literature and therefore, its effect on Cblb protein function is unknown (PubMed, Jan 2021). | |
P858T | missense | unknown | CBLB P858T does not lie within any known functional domains of the Cblb protein (UniProt.org). P858T has not been characterized in the scientific literature and therefore, its effect on Cblb protein function is unknown (PubMed, Jan 2021). | |
Q318E | missense | unknown | CBLB Q318E lies within the Cbl-PTB domain of the Cblb protein (UniProt.org). Q318E has not been characterized in the scientific literature and therefore, its effect on Cblb protein function is unknown (PubMed, Jan 2021). | |
R141* | nonsense | loss of function - predicted | CBLB R141* results in a premature truncation of the Cblb protein at amino acid 141 of 982 (UniProt.org). Due to the loss of most known functional domains (UniProt.org), R141* is predicted to lead to a loss of Cblb protein function. | |
R141Q | missense | unknown | CBLB R141Q lies within the Cbl-PTB domain of the Cblb protein (UniProt.org). R141Q has been identified in sequencing studies (PMID: 24755471, PMID: 29937994), but has not been biochemically characterized and therefore, its effect on Cblb protein function is unknown (PubMed, Jan 2021). | |
R272Q | missense | unknown | CBLB R272Q lies within the Cbl-PTB domain of the Cblb protein (UniProt.org). R272Q has not been characterized in the scientific literature and therefore, its effect on Cblb protein function is unknown (PubMed, Jan 2021). | |
R325G | missense | unknown | CBLB R325G lies within the Cbl-PTB domain of the Cblb protein (UniProt.org). R325G has not been characterized in the scientific literature and therefore, its effect on Cblb protein function is unknown (PubMed, Jan 2021). | |
R468Q | missense | unknown | CBLB R468Q does not lie within any known functional domains of the Cblb protein (UniProt.org). R468Q has not been characterized in the scientific literature and therefore, its effect on Cblb protein function is unknown (PubMed, Jan 2021). | |
R58K | missense | unknown | CBLB R58K lies within the Cbl-PTB domain of the Cblb protein (UniProt.org). R58K has not been characterized in the scientific literature and therefore, its effect on Cblb protein function is unknown (PubMed, Jan 2021). | |
R670W | missense | unknown | CBLB R670W does not lie within any known functional domains of the Cblb protein (UniProt.org). R670W has not been characterized in the scientific literature and therefore, its effect on Cblb protein function is unknown (PubMed, Jan 2021). | |
R734W | missense | unknown | CBLB R734W does not lie within any known functional domains of the Cblb protein (UniProt.org). R734W has been identified in sequencing studies (PMID: 22980975), but has not been biochemically characterized and therefore, its effect on Cblb protein function is unknown (PubMed, Jan 2021). | |
R782M | missense | unknown | CBLB R782M does not lie within any known functional domains of the Cblb protein (UniProt.org). R782M has not been characterized in the scientific literature and therefore, its effect on Cblb protein function is unknown (PubMed, Jan 2021). | |
R884I | missense | unknown | CBLB R884I does not lie within any known functional domains of the Cblb protein (UniProt.org). R884I has not been characterized in the scientific literature and therefore, its effect on Cblb protein function is unknown (PubMed, Jan 2021). | |
R884K | missense | unknown | CBLB R884K does not lie within any known functional domains of the Cblb protein (UniProt.org). R884K has not been characterized in the scientific literature and therefore, its effect on Cblb protein function is unknown (PubMed, Jan 2021). | |
R979C | missense | unknown | CBLB R979C does not lie within any known functional domains of the Cblb protein (UniProt.org). R979C has not been characterized in the scientific literature and therefore, its effect on Cblb protein function is unknown (PubMed, Jan 2021). | |
S147F | missense | unknown | CBLB S147F lies within the Cbl-PTB domain of the Cblb protein (UniProt.org). S147F has not been characterized in the scientific literature and therefore, its effect on Cblb protein function is unknown (PubMed, Jan 2021). | |
S484* | nonsense | loss of function - predicted | CBLB S484* results in a premature truncation of the Cblb protein at amino acid 484 of 982 (UniProt.org). S484* results in the loss of binding to ubiquitinated proteins as compared to wild-type Cblb in culture (PMID: 15273720), and therefore, is predicted to lead to a loss of Cblb protein function. | |
S718F | missense | unknown | CBLB S718F does not lie within any known functional domains of the Cblb protein (UniProt.org). S718F has not been characterized in the scientific literature and therefore, its effect on Cblb protein function is unknown (PubMed, Jan 2021). | |
T687S | missense | unknown | CBLB T687S does not lie within any known functional domains of the Cblb protein (UniProt.org). T687S has been identified in sequencing studies (PMID: 24121792), but has not been biochemically characterized and therefore, its effect on Cblb protein function is unknown (PubMed, Jan 2021). | |
V654I | missense | unknown | CBLB V654I does not lie within any known functional domains of the Cblb protein (UniProt.org). V654I has been identified in sequencing studies (PMID: 22810696), but has not been biochemically characterized and therefore, its effect on Cblb protein function is unknown (PubMed, Jan 2021). | |
V932L | missense | unknown | CBLB V932L lies within the UBA domain of the Cblb protein (UniProt.org). V932L has not been characterized in the scientific literature and therefore, its effect on Cblb protein function is unknown (PubMed, Oct 2020). | |
W194C | missense | unknown | CBLB W194C lies within the Cbl-PTB domain of the Cblb protein (UniProt.org). W194C has not been characterized in the scientific literature and therefore, its effect on Cblb protein function is unknown (PubMed, Jan 2021). | |
W400L | missense | unknown | CBLB W400L lies within the RING-type zinc finger domain of the Cblb protein (UniProt.org). W400L has been identified in sequencing studies (PMID: 22980975), but has not been biochemically characterized and therefore, its effect on Cblb protein function is unknown (PubMed, Jan 2021). | |
W400R | missense | unknown | CBLB W400R lies within the RING-type zinc finger domain of the Cblb protein (UniProt.org). W400R has not been characterized in the scientific literature and therefore, its effect on Cblb protein function is unknown (PubMed, Jan 2021). | |
Y665C | missense | unknown | CBLB Y665C does not lie within any known functional domains of the Cblb protein (UniProt.org). Y665C has not been characterized in the scientific literature and therefore, its effect on Cblb protein function is unknown (PubMed, Jan 2021). | |
Y944Q | missense | unknown | CBLB Y944Q lies within the UBA domain of the Cblb protein (UniProt.org). Y944Q abolishes ubiquitin binding of the UBA domain of Cblb when combined with G943A in an in vitro assay (PMID: 15273720), but has not been individually characterized and therefore, its effect on Cblb protein function is unknown. |