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Gene Detail

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Gene Symbol BTK
Synonyms AGMX1 | AT | ATK | BPK | IGHD3 | IMD1 | PSCTK1 | XLA
Gene Description BTK, Bruton tyrosine kinase, is a non-receptor tyrosine kinase involved in B-cell activation and development (PMID: 24658273). BTK is commonly overexpressed in various hematological malignancies (PMID: 24658273) and BTK mutations have been linked to BTK inhibitor drug resistance (PMID: 28235842).
NCBI Gene ID Chromosome Map Location Canonical Transcript Gene Role
695 X Xq22.1 NM_000061 Both: Oncogene and Tumor suppressor (PMID: 30606230)

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Variant Impact Protein Effect Variant Description Associated with drug Resistance
A428D missense unknown BTK A428D lies within the protein kinase domain of the Btk protein (UniProt.org). A428D results in decreased Btk and Plcg2 phosphorylation and increased calcium ion flux but retains Akt and Erk phosphorylation and demonstrates resistance to BTK inhibitors in culture (PMID: 35196427), and therefore, its effect on Btk protein function is unknown. Y
A508T missense unknown BTK A508T lies within the protein kinase domain of the Btk protein (UniProt.org). A508T has been identified in sequencing studies (PMID: 26387629), but has not been biochemically characterized and therefore, its effect on Btk protein function is unknown (PubMed, Apr 2024).
A582T missense unknown BTK A582T lies within the protein kinase domain of the Btk protein (UniProt.org). A582T has not been characterized in the scientific literature and therefore, its effect on Btk protein function is unknown (PubMed, Apr 2024).
A582V missense loss of function BTK A582V lies within the protein kinase domain of the Btk protein (UniProt.org). A582V results in loss of Btk kinase activity in patient cells (PMID: 7554468).
A622P missense unknown BTK A622P lies within the protein kinase domain of the Btk protein (UniProt.org). A622P has not been characterized in the scientific literature and therefore, its effect on Btk protein function is unknown (PubMed, Apr 2024).
act mut unknown gain of function BTK act mut indicates that this variant results in a gain of function in the Btk protein. However, the specific amino acid change has not been identified.
C145* nonsense loss of function BTK C145* results in a premature truncation of the Btk protein at amino acid 145 of 659 (UniProt.org). C145* results in a loss of Btk function, as indicated by loss of Btk kinase activity and Btk protein expression in patient cells (PMID: 8898377).
C481A missense unknown BTK C481A lies within the protein kinase domain of the Btk protein (UniProt.org). C481A interferes with drug binding, leading to ibrutinib resistance (PMID: 24869597), but has not been biochemically characterized and therefore, its effect on Btk protein function is unknown (PubMed, Jun 2024). Y
C481F missense unknown BTK C481F lies within the protein kinase domain of the Btk protein (UniProt.org). C481F confers resistance to BTK inhibitors (PMID: 25189416, PMID: 28178345, PMID: 27282255, PMID: 35639855) and results in loss of autophosphorylation (PMID: 25189416, PMID: 28178345, PMID: 27282255), but maintains BCR signaling through activation of Hck in culture (PMID: 35639855), and therefore, its effect on Btk protein function is unknown. Y
C481R missense loss of function BTK C481R lies within the protein kinase domain of the Btk protein (UniProt.org). C481R confers a loss of function to the Btk protein as indicated by reduced enzymatic activity in vitro compared to wild-type Btk (PMID: 27571029, PMID: 27282255).
C481S missense no effect BTK C481S lies within the protein kinase domain of the Btk protein (UniProt.org). C481S demonstrates kinase activity similar to wild-type Btk (PMID: 38301010), but confers Imbruvica (ibrutinib) resistance in cell culture (PMID: 27282255, PMID: 28573668) through interference of drug binding (PMID: 25189416, PMID: 23940282). Y
C481T missense no effect BTK C481T lies within the protein kinase domain of the Btk protein (UniProt.org). C481T demonstrates kinase activity similar to wild-type Btk, but confers Imbruvica (ibrutinib) resistance in cell culture (PMID: 27282255). Y
C481X missense unknown BTK C481X indicates any BTK missense mutation that results in the replacement of the cysteine (C) at amino acid 481 by a different amino acid.
C481Y missense unknown BTK C481Y lies within the protein kinase domain of the Btk protein (UniProt.org). C481Y confers resistance to BTK inhibitors, results in a loss of Btk kinase activity in in vitro assays and in cell culture (PMID: 36183831, PMID: 35639855), but maintains BCR signaling through activation of Hck in culture (PMID: 35639855), and therefore, its effect on Btk protein function is unknown. Y
D539H missense loss of function BTK D539H lies within the protein kinase domain of the Btk protein (UniProt.org). D539H results in loss of kinase activity and reduced Btk and Plcg2 phosphorylation, increased Akt phosphorylation, and a greater sustained calcium influx upon IgM stimulation, and demonstrates resistance to BTK inhibitors in culture (PMID: 36661329). Y
D539N missense unknown BTK D539N lies within the protein kinase domain of the Btk protein (UniProt.org). D539N has been identified in the scientific literature (PMID: 31217352), but has not been biochemically characterized and therefore, its effect on Btk protein function is unknown (PubMed, May 2024).
D57N missense unknown BTK D57N lies within the PH domain of the Btk protein (UniProt.org). D57N has not been characterized in the scientific literature and therefore, its effect on Btk protein function is unknown (PubMed, Apr 2024).
del deletion loss of function BTK del indicates a deletion of the BTK gene.
E108K missense unknown BTK E108K lies within the PH domain of the Btk protein (UniProt.org). E108K has been identified in the scientific literature (PMID: 37257190), but has not been biochemically characterized and therefore, its effect on Btk protein function is unknown (PubMed, Apr 2024).
E280* nonsense loss of function - predicted BTK E280* results in a premature truncation of the Btk protein at amino acid 280 of 659 (UniProt.org). Due to the loss of the activation loop in the protein kinase domain (PMID: 19206206), E280* is predicted to lead to a loss of Btk protein function.
E41K missense gain of function BTK E41K lies within the pleckstrin homology domain of the Btk protein (UniProt.org). E41K confers a gain of function to the Btk protein as demonstrated by constitutive kinase activity (PMID: 20623551).
E445D missense unknown BTK E445D lies within the protein kinase domain of the Btk protein (UniProt.org). E445D is predicted to impact the catalytic function of the Btk protein based on structural modeling (PMID: 11527964), but has not been biochemically characterized and therefore, its effect on Btk protein function is unknown (PubMed, Apr 2024).
E567D missense unknown BTK E567D lies within the protein kinase domain of the Btk protein (UniProt.org). E567D has not been characterized and therefore, its effect on Btk protein function is unknown (PubMed, Apr 2024).
E589D missense unknown BTK E589D lies within the protein kinase domain of the Btk protein (UniProt.org). E589D is predicted to disrupt structural stability of Btk by structural modeling (PMID: 11527964), but has not been biochemically characterized and therefore, its effect on Btk protein function is unknown (PubMed, Apr 2024).
E589G missense unknown BTK E589G lies within the protein kinase domain of the Btk protein (UniProt.org). E589G is predicted to disrupt structural stability of Btk by structural modeling (PMID: 11527964, PMID: 32784026), but has not been biochemically characterized and therefore, its effect on Btk protein function is unknown (PubMed, Apr 2024).
E88K missense unknown BTK E88K lies within the PH domain of the Btk protein (UniProt.org). E88K has been identified in the scientific literature (PMID: 29735551), but has not been biochemically characterized and therefore, its effect on Btk protein function is unknown (PubMed, Apr 2024).
E90K missense unknown BTK E90K lies within the PH domain of the Btk protein (UniProt.org). E90K retains binding to Plcg2 and Cdc37, and demonstrates Plcg2 phosphorylation and Btk autophosphorylation levels similar to wild-type Btk, but results in decreased protein stability and expression, and elevated phosphorylation of Akt in anti-immunoglobulin treated cells in culture (PMID: 33419778), and therefore, its effect on Btk protein function is unknown.
G259W missense unknown BTK G259W lies within the SH3 domain of the Btk protein (UniProt.org). G259W has not been characterized in the scientific literature and therefore, its effect on Btk protein function is unknown (PubMed, Apr 2024).
G409R missense loss of function BTK G409R lies within the protein kinase domain of the Btk protein (UniProt.org). G409R results in loss of kinase activity and reduced Btk and Plcg2 phosphorylation, increased Akt phosphorylation, and a greater sustained calcium influx upon IgM stimulation, and demonstrates resistance to BTK inhibitors in culture (PMID: 36661329). Y
G480R missense loss of function BTK G480R lies within the protein kinase domain of the Btk protein (UniProt.org). G480R results in loss of kinase activity and reduced Btk and Plcg2 phosphorylation, increased Akt phosphorylation, and a greater sustained calcium influx upon IgM stimulation, and demonstrates resistance to BTK inhibitors in culture (PMID: 36661329). Y
G594E missense unknown BTK G594E lies within the protein kinase domain of the Btk protein (UniProt.org). G594E is predicted to affect the P-1 binding pocket based on structural modeling (PMID: 11527964), but has not been biochemically characterized and therefore, its effect on Btk protein function is unknown (PubMed, Apr 2024).
H364N missense unknown BTK H364N lies within the SH2 domain of the Btk protein (UniProt.org). H364N has not been characterized and therefore, its effect on Btk protein function is unknown (PubMed, Apr 2024).
H491D missense unknown BTK H491D lies within the protein kinase domain of the Btk protein (UniProt.org). H491D has been identified in the scientific literature (PMID: 25777788), but has not been biochemically characterized and therefore, its effect on Btk protein function is unknown (PubMed, Apr 2024).
H491Y missense unknown BTK H491Y lies within the protein kinase domain of the Btk protein (UniProt.org). H491Y has been identified in sequencing studies (PMID: 18772396), but has not been biochemically characterized and therefore, its effect on Btk protein function is unknown (PubMed, Apr 2024).
I167V missense unknown BTK I167V lies within the Btk-type zinc finger domain of the Btk protein (UniProt.org). I167V has not been characterized and therefore, its effect on Btk protein function is unknown (PubMed, Apr 2024).
I331M missense unknown BTK I331M lies within the SH2 domain of the Btk protein (UniProt.org). I331M has not been characterized and therefore, its effect on Btk protein function is unknown (PubMed, Apr 2024).
I370M missense loss of function - predicted BTK I370M lies within the SH2 domain of the Btk protein (UniProt.org). I370M reduces peptide binding affinity of Btk in cell culture (PMID: 11206059), and therefore, is predicted to lead to a loss of Btk protein function.
inact mut unknown loss of function BTK inact mut indicates that this variant results in a loss of function of the Btk protein. However, the specific amino acid change has not been identified.
K176Q missense unknown BTK K176Q does not lie within any known functional domains of the Btk protein (UniProt.org). K176Q has not been characterized and therefore, its effect on Btk protein function is unknown (PubMed, Apr 2024).
K218N missense unknown BTK K218N lies within the SH3 domain of the Btk protein (UniProt.org). K218N has not been characterized and therefore, its effect on Btk protein function is unknown (PubMed, Apr 2024).
K430E missense loss of function BTK K430E lies within the protein kinase domain of the Btk protein (PMID: 10373551). K430E results in loss of Btk kinase activity, inhibition of Btk-mediated phosphorylation of TFII-I, and TFII-I transcriptional activity in cell culture (PMID: 7538439, PMID: 10373551).
K430R missense loss of function BTK K430R lies within the protein kinase domain of the Btk protein (PMID: 7538439). K430R renders the Btk protein kinase-inactive, reducing TLR mediated activation of NFkB in cell culture (PMID: 7538439, PMID: 17932028, PMID: 15849198).
K433T missense loss of function BTK K433T lies within the protein kinase domain of the Btk protein (UniProt.org). K433T retains binding to Plcg2 and Cdc37, but results in decreased protein stability and expression, loss of Plcg2 phosphorylation and Btk autophosphorylation, and elevated phosphorylation of Akt in anti-immunoglobulin treated patient cells in culture (PMID: 33419778).
L233P missense unknown BTK L233P lies within the SH3 domain of the Btk protein (UniProt.org). L233P has not been characterized and therefore, its effect on Btk protein function is unknown (PubMed, Apr 2024).
L244* nonsense loss of function - predicted BTK L244* results in a premature truncation of the Btk protein at amino acid 244 of 659 (UniProt.org). Due to the loss of the activation loop in the protein kinase domain (PMID: 19206206), L244* is predicted to lead to a loss of Btk protein function.
L294M missense unknown BTK L294M lies within the SH2 domain of the Btk protein (UniProt.org). L294M has not been characterized and therefore, its effect on Btk protein function is unknown (PubMed, May 2024).
L295P missense loss of function - predicted BTK L295P lies within the SH2 domain of the Btk protein (UniProt.org). L295P results in decreased peptide binding affinity of Btk in cell culture (PMID: 11206059), and therefore, is predicted to lead to a loss of Btk protein function.
L369F missense loss of function BTK L369F lies within the SH2 linker region of the Btk protein (PMID: 16291652). L369F reduces Btk-mediated calcium signaling, PLC-gamma2 activation, and binding of Btk to phosphopeptides in cell culture (PMID: 16291652, PMID: 11206059).
L460* nonsense loss of function - predicted BTK L460* results in a premature truncation of the Btk protein at amino acid 460 of 659 (UniProt.org). Due to the loss of the activation loop in the protein kinase domain (PMID: 19206206), L460* is predicted to lead to a loss of Btk protein function.
L528S missense loss of function BTK L528S lies within the protein kinase domain of the Btk protein (UniProt.org). L528S results in loss of kinase activity and reduced Btk and Plcg2 phosphorylation, increased Akt phosphorylation, and a greater sustained calcium influx upon IgM stimulation, and demonstrates resistance to BTK inhibitors in culture (PMID: 36661329). Y
L528W missense unknown BTK L528W lies within the protein kinase domain of the Btk protein (UniProt.org). L528W confers resistance to BTK inhibitors in culture (PMID: 35196427, PMID: 36183831), results in decreased Btk and Plcg2 phosphorylation, increased calcium ion flux (PMID: 35196427), and loss of kinase activity in vitro (PMID: 36183831), but retains Akt and Erk phosphorylation in culture (PMID: 35196427), and therefore, its effect on Btk protein function is unknown. Y
L647F missense unknown BTK L647F lies within the protein kinase domain of the Btk protein (UniProt.org). L647F has not been characterized and therefore, its effect on Btk protein function is unknown (PubMed, Apr 2024).
M437R missense unknown BTK M437R lies within the protein kinase domain of the Btk protein (UniProt.org). M437R results in decreased Btk and Plcg2 phosphorylation and increased calcium ion flux but retains Akt and Erk phosphorylation and demonstrates resistance to BTK inhibitors in culture (PMID: 35196427), and therefore, its effect on Btk protein function is unknown. Y
M509I missense unknown BTK M509I lies within the protein kinase domain of the Btk protein (UniProt.org). M509I is predicted by structural modeling to affect Btk protein stability (PMID: 11527964), but has not been biochemically characterized and therefore, its effect on Btk protein function is unknown (PubMed, Apr 2024).
mutant unknown unknown BTK mutant indicates an unspecified mutation in the BTK gene.
N161fs frameshift loss of function - predicted BTK N161fs results in a change in the amino acid sequence of the Btk protein beginning at aa 161 of 659, likely resulting in premature truncation of the functional protein (UniProt.org). Due to the loss of the activation loop in the protein kinase domain (PMID: 19206206), N161fs is predicted to lead to a loss of Btk protein function.
over exp none no effect BTK over exp indicates an over expression of the Btk protein. However, the mechanism causing the over expression is unspecified.
P189A missense loss of function BTK P189A lies within the SH3 binding site in the TH domain of the Btk protein (PMID: 7657668). P189A abolishes binding between Btk and specific SH3 domain containing proteins, and results in reduced trans-phosphorylation of Btk (PMID: 7657668).
P190K missense unknown BTK P190K does not lie within any known functional domains of the Btk protein (UniProt.org). P190K has been identified in sequencing studies (PMID: 16140923), but has not been biochemically characterized and therefore, its effect on Btk protein function is unknown (PubMed, Apr 2024).
P204_Y263del deletion unknown BTK P204_Y263del results in a deletion of 60 amino acids of the Btk protein from amino acids 204 to 263 (UniProt.org). P204_Y263del has not been characterized in the scientific literature and therefore, its effect on Btk protein function is unknown (PubMed, May 2024).
P22H missense unknown BTK P22H lies within the PH domain of the Btk protein (UniProt.org). P22H has not been characterized in the scientific literature and therefore, its effect on Btk protein function is unknown (PubMed, Apr 2024).
P22L missense unknown BTK P22L lies within the PH domain of the Btk protein (UniProt.org). P22L has not been characterized in the scientific literature and therefore, its effect on Btk protein function is unknown (PubMed, Apr 2024).
P265L missense loss of function BTK P265L lies within the SH3 domain of the Btk protein (UniProt.org). P265L results in a loss of Btk function as indicated by abolished SH3 domain binding capacity (PMID: 9201297).
P376S missense unknown BTK P376S lies within the SH2 domain of the Btk protein (UniProt.org). P376S has not been characterized in the scientific literature and therefore, its effect on Btk protein function is unknown (PubMed, Apr 2024).
P566L missense loss of function BTK P566L lies within the protein kinase domain of the Btk protein (UniProt.org). P566L retains binding to Plcg2 and Cdc37, but results in decreased protein stability and expression, loss of Plcg2 phosphorylation and Btk autophosphorylation, and elevated phosphorylation of Akt in anti-immunoglobulin treated cells in culture (PMID: 33419778).
P597S missense loss of function BTK P597S lies within the protein kinase domain of the Btk protein (UniProt.org). P597S retains binding to Plcg2 and Cdc37, but results in decreased protein stability and expression, loss of Plcg2 phosphorylation and Btk autophosphorylation, leads to elevated phosphorylation of Akt in anti-immunoglobulin treated cells in culture (PMID: 33419778).
positive unknown unknown BTK positive indicates the presence of the BTK gene, mRNA, and/or protein.
Q15* nonsense loss of function - predicted BTK Q15* results in a premature truncation of the Btk protein at amino acid 15 of 659 (UniProt.org). Due to the loss of the activation loop in the protein kinase domain (PMID: 19206206), Q15* is predicted to lead to a loss of Btk protein function.
Q166* nonsense loss of function - predicted BTK Q166* results in a premature truncation of the Btk protein at amino acid 166 of 659 (UniProt.org). Due to the loss of the activation loop in the protein kinase domain (PMID: 19206206), Q166* is predicted to lead to a loss of Btk protein function.
Q166K missense unknown BTK Q166K lies within the Btk-type zinc finger domain of the Btk protein (UniProt.org). Q166K has not been characterized and therefore, its effect on Btk protein function is unknown (PubMed, Apr 2024).
Q497* nonsense loss of function - predicted BTK Q497* results in a premature truncation of the Btk protein at amino acid 497 of 659 (UniProt.org). Due to the loss of the activation loop in the protein kinase domain (PMID: 19206206), Q497* is predicted to lead to a loss of Btk protein function.
R13* nonsense loss of function - predicted BTK R13* results in a premature truncation of the Btk protein at amino acid 13 of 659 (UniProt.org). Due to the loss of the activation loop in the protein kinase domain (PMID: 19206206), R13* is predicted to lead to a loss of Btk protein function.
R171S missense unknown BTK R171S lies within the Btk-type zinc finger domain of the Btk protein (UniProt.org). R171S has not been characterized and therefore, its effect on Btk protein function is unknown (PubMed, Apr 2024).
R255* nonsense loss of function BTK R255* results in a premature truncation of the Btk protein at amino acid 255 of 659 (UniProt.org). R255* leads to a loss of Btk function, as indicated by lack of Btk protein expression and loss of Btk autokinase activity in patient cells (PMID: 9486400).
R255Q missense unknown BTK R255Q lies within the SH3 domain of the Btk protein (UniProt.org). R255Q has not been characterized and therefore, its effect on Btk protein function is unknown (PubMed, Apr 2024).
R288Q missense loss of function - predicted BTK R288Q lies within the SH2 domain of the Btk protein (UniProt.org). R288Q abolishes the peptide binding affinity of Btk in cell culture (PMID: 11206059), and therefore, is predicted tolead to a loss of Btk protein function.
R288W missense loss of function - predicted BTK R288W lies within the SH2 domain of the Btk protein (UniProt.org). R288W results in Btk protein expression and kinase activity similar to wild-type Btk, but decreased binding affinity to phosphopeptides (PMID: 9486400, PMID: 16159644, PMID: 11206059), and therefore, is predicted to lead to a loss of Btk protein function.
R28C missense loss of function BTK R28C lies within the PH domain of the Btk protein (UniProt.org). R28C results in decreased affinity of Btk protein to phosphoinositides (PMID: 9268346) and decreased phosphorylation of Btk in cell culture (PMID: 9391111).
R307G missense loss of function - predicted BTK R307G lies within the SH2 domain of the Btk protein (UniProt.org). R307G results in reduced binding of Btk to phosphotyrosine in cell culture (PMID: 11206059, PMID: 10754312), and therefore, is predicted to lead to a loss of Btk protein function.
R307K missense loss of function BTK R307K lies within the SH2 domain of the Btk protein (PMID: 9524119). R307K confers a loss of Btk function, as indicated by inability to enhance calcium signaling (PMID: 9524119) and decreased phosphorylation of BAP-135 in cell culture (PMID: 9012831).
R307T missense loss of function - predicted BTK R307T lies within the SH2 domain of the Btk protein (UniProt.org). R307T strongly reduces the peptide binding affinity of Btk in cell culture (PMID: 11206059), and therefore, is predicted to lead to a loss of Btk protein function.
R332H missense unknown BTK R332H lies within the SH2 domain of the Btk protein (UniProt.org). R332H has not been characterized in the scientific literature and therefore, its effect on Btk protein function is unknown (PubMed, Jan 2024).
R46C missense unknown BTK R46C lies within the PH domain of the Btk protein (UniProt.org). R46C has been identified in sequencing studies (PMID: 29338072, PMID: 36696464), but has not been biochemically characterized and therefore, its effect on Btk protein function is unknown (PubMed, May 2024).
R490C missense unknown BTK R490C lies within the protein kinase domain of the Btk protein (UniProt.org). R490C has been identified in sequencing studies (PMID: 19734198), but has not been biochemically characterized and therefore, its effect on Btk protein function is unknown (PubMed, May 2024).
R492H missense unknown BTK R492H lies within the protein kinase domain of the Btk protein (UniProt.org). R492H has been identified in sequencing studies (PMID: 24951259), but has not been biochemically characterized and therefore, its effect on Btk protein function is unknown (PubMed, May 2024).
R520* nonsense loss of function - predicted BTK R520* results in a premature truncation of the Btk protein at amino acid 520 of 659 (UniProt.org). Due to the loss of the activation loop in the protein kinase domain (PMID: 19206206), R520* is predicted to lead to a loss of Btk protein function.
R520Q missense unknown BTK R520Q lies within the protein kinase domain of the Btk protein (UniProt.org). R520Q has not been characterized and therefore, its effect on Btk protein function is unknown (PubMed, Apr 2024).
R525G missense unknown BTK R525G lies within the protein kinase domain of the Btk protein (UniProt.org). R525G has not been characterized and therefore, its effect on Btk protein function is unknown (PubMed, May 2024).
R544M missense unknown BTK R544M lies within the protein kinase domain of the Btk protein (UniProt.org). R544M has been identified in the scientific literature (PMID: 30240888), but has not been biochemically characterized and therefore, its effect on Btk protein function is unknown (PubMed, Jun 2024).
R544W missense unknown BTK R544W lies within the protein kinase domain of the Btk protein (UniProt.org). R544W has been identified in sequencing studies (PMID: 22980975), but has not been biochemically characterized and therefore, its effect on Btk protein function is unknown (PubMed, May 2024).
R562W missense unknown BTK R562W lies within the protein kinase domain of the Btk protein (UniProt.org). R562W has not been characterized and therefore, its effect on Btk protein function is unknown (PubMed, May 2024).
R77S missense unknown BTK R77S lies within the PH domain of the Btk protein (UniProt.org). R77S retains binding to Plcg2 and Cdc37, and demonstrates Plcg2 phosphorylation and Btk autophosphorylation levels similar to wild-type Btk, but results in decreased protein stability and expression, and elevated phosphorylation of Akt in anti-immunoglobulin treated cells in culture (PMID: 33419778), and therefore, its effect on Btk protein function is unknown.
S115F missense unknown BTK S115F lies within the PH domain of the Btk protein (PMID: 10196129). S115F is predicted to disrupt protein folding by structural modeling (PMID: 10196129), but has not been biochemically characterized and therefore, its effect on Btk protein function is unknown (PubMed, May 2024).
S180F missense unknown BTK S180F does not lie within any known functional domains of the Btk protein (UniProt.org). S180F has not been characterized in the scientific literature and therefore, its effect on Btk protein function is unknown (PubMed, May 2024).
S21* nonsense loss of function - predicted BTK S21* results in a premature truncation of the Btk protein at amino acid 21 of 659 (UniProt.org). Due to the loss of the activation loop in the protein kinase domain (PMID: 19206206), S21* is predicted to lead to a loss of Btk protein function.
S247N missense unknown BTK S247N lies within the SH3 domain of the Btk protein (UniProt.org). S247N has been identified in sequencing studies (PMID: 20668451), but has not been biochemically characterized and therefore, its effect on Btk protein function is unknown (PubMed, May 2024).
S289N missense unknown BTK S289N lies within the SH2 domain of the Btk protein (UniProt.org). S289N has not been characterized and therefore, its effect on Btk protein function is unknown (PubMed, May 2024).
S51N missense unknown BTK S51N lies within the PH domain of the Btk protein (UniProt.org). S51N has been identified in sequencing studies (PMID: 22810696), but has not been biochemically characterized and therefore, its effect on Btk protein function is unknown (PubMed, May 2024).
S553R missense unknown BTK S553R lies within the protein kinase domain of the Btk protein (UniProt.org). S553R has not been characterized and therefore, its effect on Btk protein function is unknown (PubMed, May 2024).
S55A missense unknown BTK S55A lies within the PH domain of the Btk protein (UniProt.org). S55A has been identified in sequencing studies (PMID: 22722201), but has not been biochemically characterized and therefore, its effect on Btk protein function is unknown (PubMed, May 2024).
S592F missense unknown BTK S592F lies within the protein kinase domain of the Btk protein (UniProt.org). S592F has not been characterized and therefore, its effect on Btk protein function is unknown (PubMed, May 2024).
T117P missense unknown BTK T117P lies within the PH domain of the Btk protein (UniProt.org). T117P has been identified in the scientific literature (PMID: 15466623, PMID: 28064239), but has not been biochemically characterized and therefore, its effect on Btk protein function is unknown (PubMed, Apr 2024).
T316A missense unknown BTK T316A lies within the SH2 domain of the Btk protein (UniProt.org). T316A has been demonstrated to confer resistance to resistance to Imbruvica (ibrutinib) in culture (PMID: 27626698), but has not been biochemically characterized and therefore, its effect on Btk protein function is unknown (PubMed, Jun 2024). Y
T474A missense loss of function - predicted BTK T474A lies within the protein kinase domain of the Btk protein (UniProt.org). T474A results in reduced kinase activity as demonstrated by reduced autophosphorylation of Y223 in cell culture (PMID: 33526860), and therefore, is predicted to lead to a loss of Btk protein function.
T474E missense no effect - predicted BTK T474E lies within the protein kinase domain of the Btk protein (UniProt.org). T474E results in kinase activity similar to wild-type Btk as demonstrated by autophosphorylation levels of Y223 similar to wild-type protein in cell culture (PMID: 33526860), and therefore, is predicted to have no effect on Btk protein function.
T474F missense no effect - predicted BTK T474F lies within the protein kinase domain of the Btk protein (UniProt.org). T474F results in kinase activity similar to wild-type Btk as demonstrated by autophosphorylation levels of Y223 similar to wild-type protein in cell culture (PMID: 33526860), and therefore, is predicted to have no effect on Btk protein function.
T474I missense no effect BTK T474I lies within the protein kinase domain of the Btk protein (UniProt.org). T474I demonstrates kinase activity similar to wild-type Btk in cultured cells (PMID: 27571029, PMID: 28573668, PMID: 33526860).
T474L missense gain of function - predicted BTK T474L lies within the protein kinase domain of the Btk protein (UniProt.org). T474L results in increased kinase activity as demonstrated by increased autophosphorylation of Y223 in cell culture (PMID: 33526860), and therefore, is predicted to lead to a gain of Btk protein function.
T474M missense no effect BTK T474M lies within the protein kinase domain of the Btk protein (UniProt.org). T474M demonstrates kinase activity similar to wild-type Btk as determined by in vitro autophosphorylation (PMID: 27571029, PMID: 28573668).
T474N missense loss of function - predicted BTK T474N lies within the protein kinase domain of the Btk protein (UniProt.org). T474N results in reduced kinase activity as demonstrated by decreased autophosphorylation of Y223 in cell culture (PMID: 33526860), and therefore, is predicted to lead to loss of Btk protein function.
T474P missense loss of function - predicted BTK T474P lies within the protein kinase domain of the Btk protein (UniProt.org). T474P results in reduced kinase activity as demonstrated by decreased autophosphorylation of Y223 in cell culture (PMID: 33526860), and therefore, is predicted to lead to loss of Btk protein function.
T474Q missense no effect - predicted BTK T474Q lies within the protein kinase domain of the Btk protein (UniProt.org). T474Q results in kinase activity similar to wild-type Btk as demonstrated by autophosphorylation levels of Y223 similar to wild-type protein in cell culture (PMID: 33526860), and therefore, is predicted to have no effect on Btk protein function.
T474S missense no effect - predicted BTK T474S lies within the protein kinase domain of the Btk protein (UniProt.org). T474S results in kinase activity similar to wild-type Btk as demonstrated by autophosphorylation levels of Y223 similar to wild-type protein in cell culture (PMID: 33526860), and therefore, is predicted to have no effect on Btk protein function.
T474V missense no effect - predicted BTK T474V lies within the protein kinase domain of the Btk protein (UniProt.org). T474V results in kinase activity similar to wild-type Btk as demonstrated by autophosphorylation levels of Y223 similar to wild-type protein in cell culture (PMID: 33526860), and therefore, is predicted to have no effect on Btk protein function.
V336L missense unknown BTK V336L lies within the SH2 domain of the Btk protein (UniProt.org). V336L has been identified in sequencing studies (PMID: 22980975), but has not been biochemically characterized and therefore, its effect on Btk protein function is unknown (PubMed, May 2024).
V416A missense unknown BTK V416A lies within the protein kinase domain of the Btk protein (UniProt.org). V416A has been identified in sequencing studies (PMID: 24816253), but has not been biochemically characterized and therefore, its effect on Btk protein function is unknown (PubMed, May 2024).
V416L missense unknown BTK V416L lies within the protein kinase domain of the Btk protein (UniProt.org). V416L results in decreased Btk and Plcg2 phosphorylation and increased calcium ion flux but retains Akt and Erk phosphorylation and demonstrates resistance to BTK inhibitors in culture (PMID: 35196427, PMID: 36661329), and therefore, its effect on Btk protein function is unknown. Y
V568I missense loss of function BTK V568I lies within the protein kinase domain of the Btk protein (UniProt.org). V568I retains binding to Plcg2 and Cdc37, but results in decreased protein stability and expression, loss of Plcg2 phosphorylation and Btk autophosphorylation, and leads to elevated phosphorylation of Akt in anti-immunoglobulin treated cells in culture (PMID: 33419778).
W124* nonsense loss of function - predicted BTK W124* results in a premature truncation of the Btk protein at amino acid 124 of 659 (UniProt.org). Due to the loss of the activation loop in the protein kinase domain (PMID: 19206206), W124* is predicted to lead to a loss of Btk protein function.
W251L missense no effect - predicted BTK W251L lies within the SH3 domain of the Btk protein (UniProt.org). W251L demonstrates binding to Sh3 similar to wild-type Btk in cultured cells (PMID: 7657668), and therefore, is predicted to have no effect on Btk protein function.
W251R missense unknown BTK W251R lies within the SH3 domain of the Btk protein (UniProt.org). W251R has not been characterized in the scientific literature and therefore, its effect on Btk protein function is unknown (PubMed, May 2024).
W252* nonsense loss of function - predicted BTK W252* results in a premature truncation of the Btk protein at amino acid 252 of 659 (UniProt.org). Due to the loss of the activation loop in the protein kinase domain (PMID: 19206206), W252* is predicted to lead to a loss of Btk protein function.
W588* nonsense unknown BTK W588* results in a premature truncation of the Btk protein at amino acid 588 of 659 (UniProt.org). W588* has not been characterized and therefore, its effect on Btk protein function is unknown (PubMed, May 2024).
W588C missense unknown BTK W588C lies within the protein kinase domain of the Btk protein (UniProt.org). W588C has been identified in sequencing studies (PMID: 18056464), but has not been biochemically characterized and therefore, its effect on Btk protein function is unknown (PubMed, May 2024).
wild-type none no effect Wild-type BTK indicates that no mutation has been detected within the BTK gene.
Y112* nonsense loss of function - predicted BTK Y112* results in a premature truncation of the Btk protein at amino acid 112 of 659 (UniProt.org). Due to the loss of the activation loop in the protein kinase domain (PMID: 19206206), Y112* is predicted to lead to a loss of Btk protein function.
Y223F missense loss of function BTK Y223F is a mutation of the major autophosphorylation site within the SH3 domain of the Btk protein (PMID: 8630736). Y223F enhances BTK E41K-mediated transformation (PMID: 8630736) and decreases phosphorylation of BAP-135 in cell culture (PMID: 9012831).
Y315* nonsense loss of function - predicted BTK Y315* results in a premature truncation of the Btk protein at amino acid 315 of 659 (UniProt.org). Due to the loss of the activation loop in the protein kinase domain (PMID: 19206206), Y315* is predicted to lead to a loss of Btk protein function.
Y315N missense unknown BTK Y315N lies within the SH2 domain of the Btk protein (UniProt.org). Y315N retains binding to Plcg2 and Cdc37 and demonstrates Plcg2 phosphorylation and Btk autophosphorylation levels similar to wild-type Btk, but results in decreased protein stability and expression, elevated phosphorylation of Akt in anti-immunoglobulin treated cells, and is associated with resistance to Btk inhibition in culture (PMID: 33419778), and therefore, its effect on Btk protein function is unknown. Y
Y334C missense unknown BTK Y334C lies within the SH2 domain of the Btk protein (UniProt.org). Y334C has not been characterized and therefore, its effect on Btk protein function is unknown (PubMed, May 2024).
Y334S missense loss of function - predicted BTK Y334S lies within the SH2 domain of the Btk protein (UniProt.org). Y334S results in a conformational change of the Btk protein and decreased affinity for phosphopeptides (PMID: 10754312, PMID: 11206059), and therefore, is predicted to lead to a loss of Btk protein function.
Y361C missense loss of function - predicted BTK Y361C lies within the SH2 domain of the Btk protein (UniProt.org). Y361C results in decreased stability of the Btk protein and decreased peptide binding affinity in culture (PMID: 8164701, PMID: 11206059), and therefore, is predicted to lead to a loss of Btk protein function.
Y361H missense unknown BTK Y361H lies within the SH2 domain of the Btk protein (UniProt.org). Y361H retains binding to Plcg2 and Cdc37, and demonstrates Plcg2 phosphorylation and Btk autophosphorylation levels similar to wild-type Btk, but results in decreased protein stability and expression, and elevated phosphorylation of Akt in anti-immunoglobulin treated cells in culture (PMID: 33419778), and therefore, its effect on Btk protein function is unknown.
Y375* nonsense loss of function - predicted BTK Y375* results in a premature truncation of the Btk protein at amino acid 375 of 659 (UniProt.org). Due to the loss of the activation loop in the protein kinase domain (PMID: 19206206), Y375* is predicted to lead to a loss of Btk protein function.
Y40C missense unknown BTK Y40C lies within the PH domain of the Btk protein (PMID: 10196129). Y40C has been identified in the scientific literature (PMID: 9260159), but has not been biochemically characterized and therefore, its effect on Btk protein function is unknown (PubMed, Jun 2024).
Y551F missense loss of function BTK Y551F is a mutation of a Src-like phosphorylation site within the protein kinase domain of the Btk protein (PMID: 8629002). Y551F inhibits Src family-mediated Btk phosphorylation and autokinase activity in cultured cells (PMID: 8629002).
Y591* nonsense unknown BTK Y591* results in premature truncation of the Btk protein at amino acid 591 of 659 (UniProt.org). Y591* has not been characterized in the scientific literature and therefore, its effect on Btk protein function is unknown (PubMed, Jun 2024).
Y627C missense unknown BTK Y627C lies within the protein kinase domain of the Btk protein (UniProt.org). Y627C has not been characterized and therefore, its effect on Btk protein function is unknown (PubMed, Jun 2024).