Gene Variant Detail

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Gene SF3B1
Variant K700E
Impact List missense
Protein Effect loss of function
Gene Variant Descriptions SF3B1 K700E lies within HEAT repeat 5 of the Sf3b1 protein (UniProt.org). K700E confers a loss of function to the Sf3b1 protein as indicated by aberrant mRNA splicing of BRD9, resulting in Brd9 protein loss and disruption of the localization of the non-canonical BAF complex (PMID: 31597964), aberrant splicing of Sf3b1 in cell culture (PMID: 32168916), reduced binding to Sugp1 in an in vitro assay and aberrant splicing of target genes in cell culture and knock-in animal models (PMID: 31474574, PMID: 26565915, PMID: 27818134), and increased stability of Myc and impaired apoptosis in a knock-in mouse model (PMID: 32188705).
Associated Drug Resistance

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Transcript NM_012433
gDNA chr2:g.197402110T>C
cDNA c.2098A>G
Protein p.K700E
Source Database RefSeq
Genome Build GRCh38/hg38
Transcript gDNA cDNA Protein Source Database Genome Build
NM_012433 chr2:g.197402110T>C c.2098A>G p.K700E RefSeq GRCh38/hg38

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  • Simple literal full or partial string matches
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  • 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
SF3B1 K700E myelodysplastic syndrome not applicable N/A Guideline Prognostic SF3B1 K700E is associated with a more favorable prognosis in patients with myelodysplastic syndrome (NCCN.org). detail...
SF3B1 K700E pancreatic cancer sensitive H3B-8800 Preclinical - Cell culture Actionable In a preclinical study, H3B-8800 inhibited aberrant splicing and preferentially induced apoptosis in pancreatic cancer cells harboring SF3B1 K700E compared to SF3B1 wild-type cell lines in culture (PMID: 29457796). 29457796
SF3B1 K700E hematologic cancer sensitive E7107 Preclinical - Cell culture Actionable In a preclinical study, mouse cells expressing SF3B1 K700E demonstrated sensitivity to E7107 in culture, resulting in decreased viability of cells (PMID: 27622333). 27622333
SF3B1 K700E acute myeloid leukemia predicted - sensitive E7820 Preclinical - Cell culture Actionable In a preclinical study, an acute myeloid leukemia cell line engineered to express SF3B1 K700E from the endogenous locus demonstrated increased sensitivity to E7820 induced growth inhibition compared to parental cells in culture (PMID: 30799057). 30799057
SF3B1 K700E acute myeloid leukemia sensitive Indisulam Preclinical - Cell culture Actionable In a preclinical study, an acute myeloid leukemia cell line engineered to express SF3B1 K700E from the endogenous locus demonstrated increased sensitivity to Indisulam (E7070) induced growth inhibition compared to parental cells in culture (PMID: 30799057). 30799057
SF3B1 K700E B-cell acute lymphoblastic leukemia sensitive Indisulam Preclinical - Cell culture Actionable In a preclinical study, a B-cell acute lymphoblastic leukemia cell line engineered to express SF3B1 K700E from the endogenous locus demonstrated increased sensitivity to Indisulam (E7070) induced growth inhibition compared to parental cells in culture (PMID: 30799057). 30799057
SF3B1 K700E chronic myeloid leukemia sensitive GSK3203591 + MS023 Preclinical - Cell culture Actionable In a preclinical study, MS023 and GSK3203591 synergistically inhibited survival of a chronic myeloid leukemia cell line with knockin SF3B1 K700E in culture (PMID: 31408619). 31408619
SF3B1 K700E chronic myeloid leukemia sensitive H3B-8800 Preclinical - Cell line xenograft Actionable In a preclinical study, H3B-8800 inhibited tumor growth in cell line xenograft models of chronic myeloid leukemia harboring SF3B1 K700E while had no effect in SF3B1 wild-type controls (Blood 2016 128:966). detail...
SF3B1 K700E chronic myeloid leukemia sensitive H3B-8800 Preclinical - Cell line xenograft Actionable In a preclinical study, H3B-8800 preferentially induced cell death in a chronic myeloid leukemia cell line expressing SF3B1 K700E in culture, inhibited aberrant splicing and tumor growth in a cell line xenograft model (PMID: 29457796). 29457796
SF3B1 K700E B-cell acute lymphoblastic leukemia sensitive E7820 Preclinical - Cell culture Actionable In a preclinical study, a B-cell acute lymphoblastic leukemia cell line engineered to express SF3B1 K700E from the endogenous locus demonstrated increased sensitivity to E7820 induced growth inhibition compared to parental cells in culture (PMID: 30799057). 30799057
SF3B1 K700E acute myeloid leukemia sensitive H3B-8800 Preclinical - Pdx Actionable In a preclinical study, H3B-8800 inhibited aberrant splicing and tumor growth in a cell line xenograft and a patient-derived xenograft (PDX) model of acute myeloid leukemia harboring SF3B1 K700E (PMID: 29457796). 29457796
SF3B1 K700E acute myeloid leukemia sensitive H3B-8800 Preclinical - Cell culture Actionable In a preclinical study, H3B-8800 preferentially inhibited growth of mouse acute myeloid leukemia cells harboring SF3B1 K700E compared to SF3B1 wild-type cells in culture (Blood 2016 128:966). detail...
SF3B1 K700E pancreatic cancer sensitive Spliceostatin A Preclinical Actionable In a preclinical study, Spliceostatin A inhibited survival of pancreatic cancer cells harboring SF3B1 K700E in culture (PMID: 25424858). 25424858
SF3B1 K700E chronic lymphocytic leukemia predicted - sensitive Sudemycin D1 Preclinical - Patient cell culture Actionable In a preclinical study, Sudemycin D1 treatment resulted in increased cytotoxicity (p<0.05) in chronic lymphocytic leukemia cells derived from patients harboring mutations in SF3B1 (n=14) or other RNA splicing/processing genes (n=8) compared to cells derived from patients without mutations (n=10) in culture, including 2 cell lines harboring SF3B1 K700E (PMID: 26068951). 26068951
RUNX1 rearrange SF3B1 K700E acute myeloid leukemia sensitive EPZ015666 + MS023 Preclinical - Pdx Actionable In a preclinical study, MS023 and EPZ015666 (GSK3235025) combination treatment reduced tumor burden in a patient-derived xenograft (PDX) model of acute myeloid leukemia cells harboring RUNX1 rearrangement and SF3B1 K700E (PMID: 31408619). 31408619
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
SF3B1 mutant chronic lymphocytic leukemia predicted - sensitive Sudemycin D6 Preclinical - Pdx Actionable In a preclinical study, Sudemycin D6 treatment reduced tumor cells in the spleen and peripheral blood in patient-derived xenograft (PDX) models of chronic lymphocytic leukemia harboring SF3B1 mutations (PMID: 26068951). 26068951
SF3B1 mutant acute myeloid leukemia predicted - sensitive GSK3203591 Preclinical - Patient cell culture Actionable In a preclinical study, patient-derived acute myeloid leukemia cell lines harboring mutations in U2AF1 (n=3), SRSF2 (n=9), or SF3B1 (n=4) demonstrated increased sensitivity to GSK3203591 compared to spliceosomal wild-type cell lines in culture (PMID: 31408619). 31408619
SF3B1 mutant essential thrombocythemia not applicable N/A Guideline Prognostic The presence of at least one mutation in either SH2B3, IDH2, U2AF1, SRSF2, SF3B1, EZH2, TP53, or RUNX1 is associated with inferior overall survival in patients with essential thrombocythemia, SF3B1 mutations are also associated with inferior myelofibrosis-free survival (NCCN.org). detail...
SF3B1 mutant myelodysplastic syndrome not applicable N/A Clinical Study Prognostic In multiple clinical studies, SF3B1 mutations were associated with better overall survival in patients with myelodysplastic syndrome (PMID: 21998214, PMID: 22096241, PMID: 24220272), but may not have independent prognostic significance (PMID: 22096241). 22096241 21998214 24220272
SF3B1 mutant chronic lymphocytic leukemia predicted - sensitive Ibrutinib + Sudemycin D1 Preclinical - Patient cell culture Actionable In a preclinical study, Sudemycin D1 and Imbruvica (ibrutinib) combination treatment resulted in enhanced cytotoxicity in chronic lymphocytic leukemia cells derived from patients harboring SF3B1 mutations in culture (PMID: 26068951). 26068951
SF3B1 mutant uveal melanoma not applicable N/A Guideline Risk Factor SF3B1 mutations are associated with medium risk of developing distant metastasis in uveal melanoma (NCCN.org). detail...
SF3B1 mutant chronic lymphocytic leukemia predicted - sensitive Sudemycin D1 Preclinical - Patient cell culture Actionable In a preclinical study, Sudemycin D1 treatment resulted in increased cytotoxicity (p<0.05) in chronic lymphocytic leukemia cells derived from patients harboring mutations in SF3B1 (n=14) or other RNA splicing/processing genes (n=8) compared to cells derived from patients without mutations (n=10) in culture (PMID: 26068951). 26068951
Molecular Profile Protein Effect Treatment Approaches
SF3B1 K700E loss of function
RUNX1 rearrange SF3B1 K700E