Gene Variant Detail

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Gene BTK
Variant C481S
Impact List missense
Protein Effect no effect
Gene Variant Descriptions BTK C481S lies within the protein kinase domain of the Btk protein (UniProt.org). C481S demonstrates kinase activity similar to wild-type Btk, but confers Imbruvica (ibrutinib) resistance in cell culture (PMID: 27282255, PMID: 28573668) through interference of drug binding (PMID: 25189416, PMID: 23940282).
Associated Drug Resistance Y

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Transcript NM_000061.2
gDNA chrX:g.101356177A>T
cDNA c.1441T>A
Protein p.C481S
Source Database RefSeq
Genome Build GRCh38/hg38
Transcript gDNA cDNA Protein Source Database Genome Build
NM_000061.2 chrX:g.101356177A>T c.1441T>A p.C481S RefSeq GRCh38/hg38
NM_000061 chrX:g.101356177A>T c.1441T>A p.C481S RefSeq GRCh38/hg38

Filtering

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  • Simple literal full or partial string matches
  • Separate multiple filter terms with a spaces, order doesn't matter (a b c and c b a are equivalent )
  • Filtering will only apply to rows that are already loaded on the page, filtering has no impact on query parameters
  • Use quotes to match a longer phrase which contains spaces "mtor c1483f"

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Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
BTK C481S diffuse large B-cell lymphoma activated B-cell type predicted - sensitive NX-5948 Preclinical - Cell line xenograft Actionable In a preclinical study, NX-5948 treatment resulted in degradation of BTK C481S and inhibited proliferation of an activated B-cell type diffuse large B-cell lymphoma (ABC-DLBCL) cell line harboring BTK C481S in culture and inhibited tumor growth in a cell line xenograft model (Blood 2021 138 (Supp 1):2251). detail...
BTK C481S diffuse large B-cell lymphoma sensitive Fenebrutinib Preclinical - Cell culture Actionable In a preclinical study, Fenebrutinib (GDC-0853) treatment inhibited viability of a diffuse large B-cell lymphoma cell line harboring BTK C481S in culture (PMID: 35196427). 35196427
BTK C481S chronic lymphocytic leukemia sensitive ARQ 531 Preclinical - Patient cell culture Actionable In a preclinical study, ARQ 531 treatment inhibited activation of BCR signaling and induced cytotoxicity in Imbruvica (ibrutinib)-resistant patient-derived chronic lymphocytic leukemia cells harboring BTK C481S in culture (PMID: 30093506). 30093506
BTK C481S diffuse large B-cell lymphoma sensitive Vecabrutinib Preclinical - Cell culture Actionable In a preclinical study, Vecabrutinib (SNS-062) treatment inhibited viability of a diffuse large B-cell lymphoma cell line harboring BTK C481S in culture (PMID: 35196427). 35196427
BTK C481S chronic lymphocytic leukemia/small lymphocytic lymphoma resistant Acalabrutinib Guideline Actionable Calquence (acalabrutinib) is not indicated for use in patients with Imbruvica (ibrutinib)-refractory chronic lymphocytic leukemia/small lymphocytic lymphoma harboring BTK C481S (NCCN.org). detail...
BTK C481S chronic lymphocytic leukemia predicted - sensitive Fenebrutinib Case Reports/Case Series Actionable In a Phase I trial, Fenebrutinib (GDC-0853) treatment resulted in clinical activity in patients with chronic lymphocytic leukemia harboring BTK C481S including one patient with a partial response with lymphocytosis and duration of response of 2.5 months and two patients with stable disease, each with a decrease in tumor size from baseline of -44.0% and -23.0% (PMID: 29560128; NCT01991184). 29560128
BTK C481S diffuse large B-cell lymphoma resistant Ibrutinib Preclinical - Cell culture Actionable In a preclinical study, a diffuse large B-cell lymphoma cell line expressing BTK C481S demonstrated resistance to Imbruvica (ibrutinib) in culture (PMID: 35196427). 35196427
BTK C481S diffuse large B-cell lymphoma sensitive ARQ 531 Preclinical - Cell culture Actionable In a preclinical study, ARQ 531 treatment inhibited viability of a diffuse large B-cell lymphoma cell line harboring BTK C481S in culture (PMID: 35196427). 35196427
BTK C481S Advanced Solid Tumor predicted - sensitive RN486 Preclinical - Biochemical Actionable In a preclinical study, treatment with RN486 resulted in reduced Btk activity in a cell line expressing BTK C481S in culture (PMID: 33526860). 33526860
BTK C481S chronic lymphocytic leukemia predicted - resistant Venetoclax Case Reports/Case Series Actionable In a clinical case study, a patient with chronic lymphocytic leukemia who had relapsed on treatment with Imbruvica (ibrutinib) was treated with Venclexta (venetoclax), but progressed and was found to harbor BTK C481S (PMID: 32232486). 32232486
BTK C481S mantle cell lymphoma predicted - resistant Edralbrutinib Preclinical - Cell culture Actionable In a preclinical study, Edralbrutinib (TG-1701) treatment resulted in reduced sensitivity in a mantle cell lymphoma cell line expressing BTK C481S compared to the parental wild-type BTK cell line in culture (PMID: 34551904). 34551904
BTK C481S mantle cell lymphoma resistant Ibrutinib Case Reports/Case Series Actionable In a clinical study, BTK C418S was identified as an acquired mutation that confers resistance to Imbruvica (ibrutinib) in two patients with mantle cell lymphoma who relapsed after a durable response (PMID: 25082755). 25082755
BTK C481S hematologic cancer predicted - sensitive RXC005 Preclinical - Cell culture Actionable In a preclinical study, hematological cancer cell lines that are dependent on Btk signaling demonstrated sensitivity to RXC005 in culture (Blood 2016 128:4399). detail...
BTK C481S diffuse large B-cell lymphoma sensitive LOXO-305 Preclinical - Cell culture Actionable In a preclinical study, LOXO-305 treatment inhibited viability of a diffuse large B-cell lymphoma cell line harboring BTK C481S in culture (PMID: 35196427). 35196427
BTK C481S Advanced Solid Tumor predicted - sensitive Fenebrutinib Preclinical - Biochemical Actionable In a preclinical study, treatment with Fenebrutinib resulted in reduced Btk activity in a cell line expressing BTK C481S in culture (PMID: 33526860). 33526860
BTK C481S chronic lymphocytic leukemia/small lymphocytic lymphoma resistant Zanubrutinib Guideline Actionable Brukinsa (zanubrutinib) is not indicated for use in patients with Imbruvica (ibrutinib)-refractory chronic lymphocytic leukemia/small lymphocytic lymphoma harboring BTK C481S (NCCN.org). detail...
BTK C481S diffuse large B-cell lymphoma sensitive Ibrutinib + Venetoclax Preclinical - Cell culture Actionable In a preclinical study, a diffuse large B-cell lymphoma cell line expressing BTK C481S resulting in Imbruvica (ibrutinib) resistance demonstrated increased sensitivity to Imbruvica (ibrutinib) when also treated with Venclexta (venetoclax), demonstrating decreased cell growth in culture (PMID: 28428442). 28428442
BTK C481S chronic lymphocytic leukemia resistant Ibrutinib Clinical Study - Cohort Actionable In a clinical study, BTK C418S was identified as an acquired mutation that confers resistance to Imbruvica by preventing irreversible binding of ibrutinib to BTK in patients with chronic lymphocytic leukemia who relapsed while on Imbruvica (ibrutinib)(PMID: 24869598). 24869598
BTK C481S chronic lymphocytic leukemia resistant Ibrutinib Preclinical - Patient cell culture Actionable In a preclinical study, primary chronic lymphocytic leukemia cells derived from patients who acquired BTK C481S following Imbruvica (ibrutinib) treatment demonstrated resistance to Imbruvica (ibrutinib) in culture (PMID: 30093506). 30093506
BTK C481S lymphoma resistant Ibrutinib Preclinical - Cell culture Actionable In a preclinical study, lymphoma cells expressing BTK C481S were resistant to Imbruvica (ibrutinib) in culture (PMID: 27626698) 27626698
BTK C481S diffuse large B-cell lymphoma sensitive NX-2127 Preclinical - Cell line xenograft Actionable In a preclinical study, NX-2127 inhibited proliferation of a diffuse large B-cell lymphoma cell line expressing BTK C481S in culture, and resulted in tumor growth inhibition in a cell line xenograft model (62nd ASH Annual Meeting and Exposition, Dec 2020, Abstract 2788). detail...
BTK T474A BTK C481S Advanced Solid Tumor predicted - sensitive Ibrutinib Preclinical - Biochemical Actionable In a preclinical study, treatment with Imbruvica (ibrutinib) resulted in reduced Btk activity in cell lines expressing BTK variants T474A and C481S in culture (PMID: 33526860). 33526860
BTK T474A BTK C481S Advanced Solid Tumor predicted - resistant Fenebrutinib Preclinical - Biochemical Actionable In a preclinical study, treatment with Fenebrutinib (GDC-0853) failed to inhibit Btk activity in a cell line expressing BTK variants T474A and C481S in culture (PMID: 33526860). 33526860
BTK T474S BTK C481S Advanced Solid Tumor predicted - sensitive Ibrutinib Preclinical - Biochemical Actionable In a preclinical study, treatment with Imbruvica (ibrutinib) resulted in reduced Btk activity in a cell line expressing BTK variants T474S and C481S in culture (PMID: 33526860). 33526860
BTK T474S BTK C481S Advanced Solid Tumor predicted - sensitive Fenebrutinib Preclinical - Biochemical Actionable In a preclinical study, treatment with Fenebrutinib (GDC-0853) resulted in reduced Btk activity in a cell line expressing BTK variants T474S and C481S in culture (PMID: 33526860). 33526860
BTK T474I BTK C481S Advanced Solid Tumor predicted - sensitive Fenebrutinib Preclinical - Biochemical Actionable In a preclinical study, treatment with Fenebrutinib (GDC-0853) resulted in reduced Btk activity in a cell line expressing BTK variants T474I and C481S in culture (PMID: 33526860). 33526860
BTK T474I BTK C481S Advanced Solid Tumor predicted - resistant Acalabrutinib Preclinical - Biochemical Actionable In a preclinical study, treatment with Calquence (acalabrutinib) failed to inhibit Btk activity in a cell line expressing BTK variants T474I and C481S in culture (PMID: 33526860). 33526860
BTK T474I BTK C481S Advanced Solid Tumor predicted - sensitive RN486 Preclinical - Biochemical Actionable In a preclinical study, treatment with RN486 resulted in reduced Btk activity in a cell line expressing BTK variants T474I and C481S in culture (PMID: 33526860). 33526860
BTK T474I BTK C481S Advanced Solid Tumor predicted - resistant Ibrutinib Preclinical - Biochemical Actionable In a preclinical study, treatment with Imbruvica (ibrutinib) failed to inhibit Btk activity in a cell line expressing BTK variants T474I and C481S in culture (PMID: 33526860). 33526860
BTK T474I BTK C481S Advanced Solid Tumor predicted - resistant Zanubrutinib Preclinical - Biochemical Actionable In a preclinical study, treatment with Brukinsa (zanubrutinib) failed to inhibit Btk activity in a cell line expressing BTK variants T474I and C481S in culture (PMID: 33526860). 33526860
BTK T474I BTK C481S Advanced Solid Tumor predicted - resistant CGI1746 Preclinical - Biochemical Actionable In a preclinical study, treatment with CGI1746 failed to inhibit Btk activity in a cell line expressing BTK variants T474I and C481S in culture (PMID: 33526860). 33526860
BTK T474M BTK C481S Advanced Solid Tumor predicted - resistant Zanubrutinib Preclinical - Biochemical Actionable In a preclinical study, treatment with Brukinsa (zanubrutinib) failed to inhibit Btk activity in a cell line expressing BTK variants T474M and C481S in culture (PMID: 33526860). 33526860
BTK T474M BTK C481S Advanced Solid Tumor predicted - resistant Ibrutinib Preclinical - Biochemical Actionable In a preclinical study, treatment with Imbruvica (ibrutinib) failied to inhibit Btk activity in a cell line expressing BTK variants T474M and C481S in culture (PMID: 33526860). 33526860
BTK T474M BTK C481S Advanced Solid Tumor predicted - sensitive Fenebrutinib Preclinical - Biochemical Actionable In a preclinical study, treatment with Fenebrutinib (GDC-0853) resulted in reduced Btk activity in a cell line expressing BTK variants T474M and C481S in culture (PMID: 33526860). 33526860
BTK T474M BTK C481S Advanced Solid Tumor predicted - resistant CGI1746 Preclinical - Biochemical Actionable In a preclinical study, treatment with CGI1746 failed to inhibit Btk activity in a cell line expressing BTK variants T474M and C481S in culture (PMID: 33526860). 33526860
BTK T474M BTK C481S Advanced Solid Tumor predicted - resistant Acalabrutinib Preclinical - Biochemical Actionable In a preclinical study, treatment with Calquence (acalabrutinib) failed to inhibit Btk activity in a cell line expressing BTK variants T474M and C481S in culture (PMID: 33526860). 33526860
BTK T474M BTK C481S Advanced Solid Tumor predicted - sensitive RN486 Preclinical - Biochemical Actionable In a preclinical study, treatment with RN486 resulted in reduced Btk activity in a cell line expressing BTK variants T474M and C481S in culture (PMID: 33526860). 33526860
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
BTK C481X chronic lymphocytic leukemia predicted - resistant Ibrutinib Phase II Actionable In a Phase II trial, BTK C481X and/or PLCG2 mutations were identified in 80% (8/10) of patients with progressive disease and in 20% (1/5) of patients with prolymphocytic transformation of chronic lymphocytic leukemia while on Imbruvica (ibrutinib) treatment (PMID: 28049639, NCT01500733). 28049639