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    GENE:

    SH2B3 (SH2B Adaptor Protein 3)

    i
    Other names: SH2B3, SH2B Adaptor Protein 3, Lymphocyte-Specific Adapter Protein Lnk, Signal Transduction Protein Lnk, SH2B Adapter Protein 3, LNK, Lymphocyte Adapter Protein, Lymphocyte Adaptor Protein, IDDM20
    5d
    FT400-004: Evaluate the Safety, Efficacy and Pharmacokinetics of ThisCART19A in Patients With R/R B-ALL (clinicaltrials.gov)
    P1, N=10, Completed, Zhejiang University | Recruiting --> Completed | N=16 --> 10 | Trial completion date: Aug 2025 --> May 2025 | Trial primary completion date: Aug 2025 --> May 2025
    Trial completion • Enrollment change • Trial completion date • Trial primary completion date
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    ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • FGFR (Fibroblast Growth Factor Receptor) • JAK2 (Janus kinase 2) • PDGFRB (Platelet Derived Growth Factor Receptor Beta) • IKZF1 (IKAROS Family Zinc Finger 1) • JAK1 (Janus Kinase 1) • IL7R (Interleukin 7 Receptor) • TCF3 (Transcription Factor 3) • SH2B3 (SH2B Adaptor Protein 3)
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    SH2B3 mutation
    1m
    Non-HLA risk variants in a type 1 diabetes pediatric population: Clinical and autoimmune profiles. (PubMed, An Pediatr (Engl Ed))
    The analyzed variants in the PTPN22, CD226, and INS genes were overrepresented in pediatric patients with T1D, suggesting potential therapeutic targets for modulating the autoimmune process. Their associations with specific clinical and autoimmune profiles can be applied in the identification of high-risk patients and help optimize their follow-up.
    Journal
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    CTLA4 (Cytotoxic T-Lymphocyte Associated Protein 4) • SH2B3 (SH2B Adaptor Protein 3) • FUT2 (Fucosyltransferase 2) • PTPN22 (Protein Tyrosine Phosphatase Non-Receptor Type 22)
    2ms
    BCR::ABL-Negative Triple Negative Myeloproliferative Neoplasm --Review (PubMed, Zhongguo Shi Yan Xue Ye Xue Za Zhi)
    TN-MPN may carry non-classical driver mutations at JAK2 or MPL, or other gene mutations, including somatic mutations of chromatin structure, epigenetic modifiers (TET2, IDH1/2), splicing factors (SF3B1, SRSF2, U2AF1, ZRSR2), and cytokine signaling regulators (CBL, SH2B3), etc., and there is evidence of clonal hematopoiesis. This article reviews the latest research progress in the pathogenesis, diagnosis, clinical features, prognosis and treatment of TN-MPN.
    Review • Journal
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    IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • JAK2 (Janus kinase 2) • SF3B1 (Splicing Factor 3b Subunit 1) • TET2 (Tet Methylcytosine Dioxygenase 2) • SRSF2 (Serine and arginine rich splicing factor 2) • U2AF1 (U2 Small Nuclear RNA Auxiliary Factor 1) • CALR (Calreticulin) • SH2B3 (SH2B Adaptor Protein 3) • ZRSR2 (Zinc Finger CCCH-Type, RNA Binding Motif And Serine/Arginine Rich 2)
    2ms
    Molecular classification and outcomes in pediatric aplastic anemia with myeloid neoplasm-associated gene variants. (PubMed, Front Pediatr)
    There was no significant difference in the efficacy of IST among patients with different gene variants. Survival time was associated with disease severity, and the development of a hematological response-particularly when achieved at 3 months-was an independent key factor, whereas genotype was not.
    Journal
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    TP53 (Tumor protein P53) • FLT3 (Fms-related tyrosine kinase 3) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • JAK2 (Janus kinase 2) • RUNX1 (RUNX Family Transcription Factor 1) • SF3B1 (Splicing Factor 3b Subunit 1) • ASXL1 (ASXL Transcriptional Regulator 1) • TET2 (Tet Methylcytosine Dioxygenase 2) • ETV6 (ETS Variant Transcription Factor 6) • WT1 (WT1 Transcription Factor) • BCOR (BCL6 Corepressor) • GATA2 (GATA Binding Protein 2) • CALR (Calreticulin) • SH2B3 (SH2B Adaptor Protein 3) • BCORL1 (BCL6 Corepressor Like 1)
    3ms
    Germline Heterozygous SH2B3 p.Glu78Lys Variant: A Three-Patient Case Series with Myeloproliferative Neoplasms (MPNs). (PubMed, Exp Hematol)
    Although heterozygosity alone appears insufficient to drive disease, the enrichment of this variant in our MPN cohort and its occurrence in relatively young patients support a possible low-penetrance predisposition role. Functional assays, larger case-control series, and assessment of genetic/epigenetic modifiers are needed to define pathogenicity and clinical utility.
    Journal
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    TET2 (Tet Methylcytosine Dioxygenase 2) • SRSF2 (Serine and arginine rich splicing factor 2) • CALR (Calreticulin) • SH2B3 (SH2B Adaptor Protein 3)
    3ms
    Long-term Follow-up of Gastrointestinal CAR T-cell Lymphoma: Homing, Clonal Expansion, and Response to Cyclosporine. (PubMed, Blood)
    We found clinical, histological, and molecular evidence demonstrating the efficacy of cyclosporine in reducing the expanded malignant clone and achieving durable clinical remission for more than a year. Our findings highlight the complex interplay between CAR T-cell therapy, pre-existing genetic vulnerabilities, and the GI microenvironment, emphasizing the need for vigilant monitoring and tailored therapeutic strategies to address the risks associated with CAR-T lymphomagenesis.
    Journal • IO biomarker
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    SH2B3 (SH2B Adaptor Protein 3) • TFCP2 (Transcription Factor CP2)
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    SH2B3 mutation
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    cyclosporine
    4ms
    Lnk Deficiency Enhances Translesion Synthesis to Alleviate Replication Stress and Promote Hematopoietic Stem Cell Fitness. (PubMed, J Clin Invest)
    TLS polymerases are specialized to execute DNA replication in the presence of lesions or natural replication fork barriers that stall replicative polymerases. Our findings implicate elevated use of these specialized DNA polymerases as critical to the enhanced HSC function imparted by Lnk deficiency, which has important ramifications for stem cell therapy and regenerative medicine in general.
    Journal
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    SH2B3 (SH2B Adaptor Protein 3)
    4ms
    KAT2A-H3K79succ-Mediated SH2B3 Upregulation Promotes TNBC Metastasis Through Diminishing the Ubiquitin-Dependent Degradation of Vimentin. (PubMed, FASEB J)
    Mass spectrometry and co-immunoprecipitation (Co-IP) assays were designed to investigate the mechanism of SH2B3 involved in promoting aggressiveness. Altogether, our study indicated that KAT2A modulates the malignant phenotype of TNBC by mediating H3K79succ to regulate the transcription of the SH2B3 gene, and the KAT2A/SH2B3/vimentin axis might be the potential molecular targets for diagnosing and treating TNBC.
    Journal
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    VIM (Vimentin) • SH2B3 (SH2B Adaptor Protein 3)
    5ms
    Genome-wide analysis defines genetic determinants of MPN subtypes and identifies a sex-specific association at CDH22/CD40. (PubMed, Blood)
    A polygenic risk score consisting of 48 SNPs from 31 loci demonstrated moderate discriminative performance for ET and PV (AUC=0.718) and was improved by optimization for disease subtype (AUCET=0.724 and AUCPV=0.755). Overall, our results reveal that multiple germline variants influence MPN phenotype with HBS1L-MYB and a novel sex-specific association with CDH22/CD40 being the strongest determinants.
    Journal • Tumor mutational burden • IO biomarker
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    TMB (Tumor Mutational Burden) • JAK2 (Janus kinase 2) • TET2 (Tet Methylcytosine Dioxygenase 2) • CDH2 (Cadherin 2) • SH2B3 (SH2B Adaptor Protein 3) • CD40 (CD40 Molecule)
    5ms
    The watch-and-wait approach for patients with juvenile myelomonocytic leukemia: results of the French cohort. (PubMed, Blood)
    These findings support W&W as a viable alternative in up to 30% of JMML patients, potentially sparing them from HSCT-associated risks. Given the persistence of clonal hematopoiesis and the risk of extra-hematological complications, long-term monitoring remains essential.
    Journal
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    NRAS (Neuroblastoma RAS viral oncogene homolog) • PTPN11 (Protein Tyrosine Phosphatase Non-Receptor Type 11) • SH2B3 (SH2B Adaptor Protein 3)
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    NRAS mutation • CBL mutation