Gene Variant Detail

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Gene SRSF2
Variant P95H
Impact List missense
Protein Effect loss of function
Gene Variant Descriptions SRSF2 P95H is a hotspot mutation that lies within the linker region between the RRM and RS domains of the Srsf2 protein (PMID: 26261309). P95H results in similar cell proliferation and viability levels to wild-type Srsf2 (PMID: 29533785), however, results in altered binding affinity of Srsf2 to specific RNA sites, and leads to disrupted regulation of splicing events (PMID: 26261309, PMID: 31040863) and enhanced mRNA decay in cell culture (PMID: 32001512).
Associated Drug Resistance

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Transcript NM_001195427.1
gDNA chr17:g.76736877G>T
cDNA c.284C>A
Protein p.P95H
Source Database RefSeq
Genome Build GRCh38/hg38
Transcript gDNA cDNA Protein Source Database Genome Build
XM_017024942.2 chr17:g.76736877G>T c.284C>A p.P95H RefSeq GRCh38/hg38
XM_017024942 chr17:g.76736877G>T c.284C>A p.P95H RefSeq GRCh38/hg38
NM_003016.4 chr17:g.76736877G>T c.284C>A p.P95H RefSeq GRCh38/hg38
NM_001195427.1 chr17:g.76736877G>T c.284C>A p.P95H RefSeq GRCh38/hg38
NM_003016 chr17:g.76736877G>T c.284C>A p.P95H RefSeq GRCh38/hg38
NM_001195427 chr17:g.76736877G>T c.284C>A p.P95H RefSeq GRCh38/hg38

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Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
SRSF2 P95H acute myeloid leukemia sensitive Indisulam Preclinical - Cell culture Actionable In a preclinical study, an acute myeloid leukemia cell line engineered to express SRSF2 P95H from the endogenous locus demonstrated increased sensitivity to Indisulam (E7070) induced growth inhibition compared to parental cells in culture (PMID: 30799057). 30799057
SRSF2 P95H chronic myeloid leukemia sensitive E7107 + GSK3203591 + MS023 Preclinical - Cell culture Actionable In a preclinical study, E7107, MS023, and GSK3203591 triple combination potently inhibited survival of a chronic myeloid leukemia cell line with knockin SRSF2 P95H in culture (PMID: 31408619). 31408619
SRSF2 P95H acute myeloid leukemia sensitive E7820 Preclinical - Cell culture Actionable In a preclinical study, an acute myeloid leukemia cell line engineered to express SRSF2 P95H from the endogenous locus demonstrated increased sensitivity to E7820 induced growth inhibition compared to parental cells in culture (PMID: 30799057). 30799057
SRSF2 P95H 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 SRSF2 P95H in culture (PMID: 31408619). 31408619
SRSF2 P95H acute myeloid leukemia sensitive H3B-8800 Preclinical - Cell line xenograft Actionable In a preclinical study, H3B-8800 inhibited tumor growth in a cell line xenograft model of acute myeloid leukemia harboring SRSF2 P95H (PMID: 29457796). 29457796
SRSF2 P95H acute myeloid leukemia sensitive GSK3203591 + MS023 Preclinical - Patient cell culture Actionable In a preclinical study, GSK3203591 and MS023 synergistically inhibited survival of patient-derived acute myeloid leukemia cell lines harboring SRSF2 P95H in culture (PMID: 31408619). 31408619
KMT2A - MLLT3 SRSF2 P95H acute myeloid leukemia sensitive MS023 Preclinical Actionable In a preclinical study, MS023 inhibited survival of murine KMT2A-MLLT3 ( reported as MLL-AF9)-driven acute myeloid leukemia cells harboring SRSF2 P95H in culture and delayed disease progression in mouse models, but not in wild-type SRSF2 models (PMID: 31408619). 31408619
KMT2A - MLLT3 SRSF2 P95H acute myeloid leukemia sensitive E7107 Preclinical - Cell culture Actionable In a preclinical study, murine KMT2A-MLLT3 ( reported as MLL-AF9)-driven acute myeloid leukemia cells expressing SRSF2 P95H demonstrated increased sensitivity to E7107 compared to cells expressing wild-type SRSF2 in culture (PMID: 31408619). 31408619
KMT2A - MLLT3 SRSF2 P95H acute myeloid leukemia sensitive E7107 Preclinical Actionable In a preclinical study, E7107 treatment decreased tumor burden and prolonged survival in an isogenic mouse model of acute myeloid leukemia expressing KMT2A-MLLT3 (reported as MLL-AF9) and SRSF2 P95H, but not in a model expressing KMT2A-MLLT3 and wild-type SRSF2 (PMID: 27135740). 27135740
KMT2A - MLLT3 SRSF2 P95H acute myeloid leukemia sensitive H3B-8800 Preclinical Actionable In a preclinical study, H3B-8800 inhibited tumor growth in transplant animal models of mouse acute myeloid leukemia cells harboring SRSF2 P95H and KMT2A-MLLT3 (MLL-AF9) while had no effect in SRSF2 wild-type controls (Blood 2016 128:966). detail...
KMT2A - MLLT3 SRSF2 P95H acute myeloid leukemia sensitive GSK3203591 Preclinical - Cell culture Actionable In a preclinical study, murine KMT2A-MLLT3 ( reported as MLL-AF9)-driven acute myeloid leukemia cells expressing SRSF2 P95H demonstrated increased sensitivity to GSK3203591 compared to cells expressing wild-type SRSF2 in culture (PMID: 31408619). 31408619
KMT2A - MLLT3 SRSF2 P95H acute myeloid leukemia sensitive EPZ015666 Preclinical Actionable In a preclinical study, EPZ015666 (GSK3235025) treatment decreased SDMA levels and prolonged survival in a mouse model of KMT2A-MLLT3 (MLL-AF9)-driven acute myeloid leukemia harboring SRSF2 P95H, but not in a SRSR2 wild-type model (PMID: 31408619). 31408619
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
SRSF2 P95X myelodysplastic syndrome not applicable N/A Guideline Prognostic SRSF2 P95X is associated with a poor prognosis in patients with myelodysplastic syndrome (NCCN.org). detail...
SRSF2 mutant myelodysplastic syndrome not applicable N/A Clinical Study Prognostic In multiple clinical studies, SRSF2 mutations were associated with shortened survival in patients with myelodysplastic syndrome (PMID: 26769228, PMID: 26508027). 26508027 26769228
SRSF2 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 (NCCN.org). detail...
SRSF2 mutant myelofibrosis not applicable N/A Guideline Prognostic SRSF2 mutations are associated with inferior overall survival and leukemia-free survival in patients with myelofibrosis (NCCN.org). detail...
SRSF2 mutant acute myeloid leukemia predicted - sensitive CG-806 Preclinical - Patient cell culture Actionable In a preclinical study, patient-derived acute myeloid leukemia cells harboring SRSF2 mutations were sensitive to CG-806 in culture (Proceedings of the American Association for Cancer Research, Vol 60, Mar 2019, Abstract #1323). detail...
SRSF2 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
SRSF2 mutant polycythemia vera not applicable N/A Guideline Prognostic SRSF2 mutations are associated with inferior overall survival in patients with polycythemia vera (NCCN.org). detail...
SRSF2 mutant chronic myelomonocytic leukemia sensitive H3B-8800 Preclinical - Pdx Actionable In a preclinical study, H3B-8800 inhibited tumor growth in patient-derived xenograft (PDX) models of chronic myelomonocytic leukemia harboring SRSF2 mutations, but not in SRSF2 wild-type PDX models (PMID: 29457796). 29457796
Molecular Profile Protein Effect Treatment Approaches
SRSF2 P95H loss of function
KMT2A - MLLT3 SRSF2 P95H