Gene Variant Detail

Contact

Missing content? – Request curation!

Request curation for specific Genes, variants, or PubMed publications.

Have questions, comments or suggestions? - Let us know!

Email us at : ckbsupport@jax.org

Gene SF3B1
Variant K666E
Impact List missense
Protein Effect loss of function - predicted
Gene Variant Descriptions SF3B1 K666E lies within HEAT repeat 4 of the Sf3b1 protein (UniProt.org). K666E results in reduced growth when expressed in the context of a human/yeast Sf3b1 chimeric protein in yeast (PMID: 29752352), and aberrant splicing of Sf3b1 in cell culture (PMID: 32168916), and therefore, is predicted to lead to a loss of Sf3b1 protein function.
Associated Drug Resistance

Filtering

  • Case insensitive filtering will display rows where any text in any cell matches the filter term
  • 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"

Sorting

  • Generally, the default sort order for tables is set to be first column ascending, however, specific tables may set a different default sort order.
  • Click on any column header arrows to sort by that column
  • Hold down the Shift key and click multiple columns to sort by more than one column, be sure to set ascending or descending order for a given column, before moving on to the next column.

Transcript NM_012433
gDNA chr2:g.197402637T>C
cDNA c.1996A>G
Protein p.K666E
Source Database RefSeq
Genome Build GRCh38/hg38
Transcript gDNA cDNA Protein Source Database Genome Build
NM_012433 chr2:g.197402637T>C c.1996A>G p.K666E RefSeq GRCh38/hg38

Filtering

  • Case insensitive filtering will display rows where any text in any cell matches the filter term
  • 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"

Sorting

  • Generally, the default sort order for tables is set to be first column ascending, however, specific tables may set a different default sort order.
  • Click on any column header arrows to sort by that column
  • Hold down the Shift key and click multiple columns to sort by more than one column, be sure to set ascending or descending order for a given column, before moving on to the next column.

Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
SF3B1 K666E 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 1 cell line harboring SF3B1 K666E (PMID: 26068951). 26068951
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
SF3B1 K666X myelodysplastic syndrome not applicable N/A Guideline Prognostic SF3B1 K666X is associated with a more favorable prognosis in patients with myelodysplastic syndrome (NCCN.org). detail...
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 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 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 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
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 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 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
Molecular Profile Protein Effect Treatment Approaches
SF3B1 K666E loss of function - predicted