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General Information
Name
juvenile myelomonocytic leukemia, PTPN11-related
FlyBase ID
FBhh0000578
Disease Ontology Term
Parent Disease
OMIM
Overview

This report describes juvenile myelomonocytic leukemia, PTPN11-related (JMML, PTPN11-related). The human gene

implicated in this disease is PTPN11, which encodes a protein-tyrosine phosphatase. This gene is also associated with Noonan syndrome 1 (OMIM:163950, FBhh0000040), Noonan syndrome with multiple lentigines 1 (OMIM:151100, FBhh0000041), and metachondromatosis (OMIM:156250). There is one high-scoring fly ortholog, csw , for which RNAi targeting constructs, alleles caused by insertional mutagenesis, and classical amorphic alleles have been generated.

A transgenic construct of the wild-type human Hsap\PTPN11 gene under the control of a heat-shock promoter has been introduced into flies. Partial heterologous rescue (functional complementation) has been demonstrated: rescue of some, but not all, phenotypes of Dmel\csw null mutants is observed.

A UAS construct of Dmel\csw bearing a mutation corresponding to a JMML PTPN11 mutation has been introduced into flies. Variant(s) implicated in human disease tested (as analogous mutation in fly gene): E76K in the fly csw gene (corresponds to E76K in the human PTPN11 gene). This pathogenic variant produces dominant gain-of-function phenotypes in the fly, which recapitulates observations in human. GOF variants of PTPN11 implicated in JMML have also been used in flies to characterize the spacing effect for long-term memory induction. In addition to the variant described above, D61Y in the fly csw gene (corresponds to D61Y in the human PTPN11 gene) and T73I in the fly csw gene (corresponds to T73I in the human PTPN11 gene), were used in this study.

Animals homozygous for amorphic mutations of Dmel\csw die during larval and pupal stages. Germline clones in females result in maternal-effect lethality during during the embryonic stage; the embryos exhibit severe anatomical defects. Physical and genetic interactions of Dmel\csw have been described; see below and in the csw gene report.

[updated Aug. 2020 by FlyBase; FBrf0222196]

Disease Summary Information
Disease Summary: juvenile myelomonocytic leukemia, PTPN11-related
OMIM report
Human gene(s) implicated
Symptoms and phenotype

See report for juvenile myelomonocytic leukemia (FBhh0000028).

Genetics
Cellular phenotype and pathology
Molecular information
External links
Disease synonyms
Ortholog Information
Human gene(s) in FlyBase
Human gene (HGNC)
D. melanogaster ortholog (based on DIOPT)
Comments on ortholog(s)

Many to one: 2 human to 1 Drosophila; the second human gene is PTPN6.

Other mammalian ortholog(s) used
    D. melanogaster Gene Information (1)
    Gene Snapshot
    corkscrew (csw) encodes a non receptor tyrosine phosphatase acting downstream of receptor tyrosine kinases (RTKs) such as Egfr, tor and FGF RTKs. The product of csw contributes to growth regulation, cell survival and developmental patterning. [Date last reviewed: 2018-09-06]
    Cellular component (GO)
    Gene Groups / Pathways
    Comments on ortholog(s)

    Ortholog of human PTPN11 and human PTPN6 (1 Drosophila to 2 human). Dmel\csw shares 40% identity and 52% similarity with human PTPN11, and 36% identity and 49% similarity with human PTPN6.

    Orthologs and Alignments from DRSC
    DIOPT - DRSC Integrative Ortholog Prediction Tool - Click the link below to search for orthologs in Humans
    Synthetic Gene(s) Used (0)
    Summary of Physical Interactions (27 groups)
    protein-protein
    Interacting group
    Assay
    References
    anti tag coimmunoprecipitation, peptide massfingerprinting
    anti tag coimmunoprecipitation, peptide massfingerprinting
    anti tag coimmunoprecipitation, peptide massfingerprinting
    anti tag coimmunoprecipitation, peptide massfingerprinting
    anti tag coimmunoprecipitation, peptide massfingerprinting
    anti tag coimmunoprecipitation, peptide massfingerprinting, pull down, western blot
    anti tag coimmunoprecipitation, peptide massfingerprinting
    anti bait coimmunoprecipitation, anti tag western blot
    anti tag coimmunoprecipitation, peptide massfingerprinting
    anti tag coimmunoprecipitation, peptide massfingerprinting
    anti tag coimmunoprecipitation, peptide massfingerprinting
    anti tag coimmunoprecipitation, peptide massfingerprinting
    anti tag coimmunoprecipitation, peptide massfingerprinting
    two hybrid, pull down, western blot, anti bait coimmunoprecipitation
    anti tag coimmunoprecipitation, peptide massfingerprinting
    anti tag coimmunoprecipitation, peptide massfingerprinting
    anti tag coimmunoprecipitation, Identification by mass spectrometry, peptide massfingerprinting
    anti tag coimmunoprecipitation, peptide massfingerprinting
    anti tag coimmunoprecipitation, peptide massfingerprinting
    anti tag coimmunoprecipitation, peptide massfingerprinting
    anti tag coimmunoprecipitation, peptide massfingerprinting
    anti tag coimmunoprecipitation, peptide massfingerprinting
    anti bait coimmunoprecipitation, western blot
    anti tag coimmunoprecipitation, anti tag western blot
    anti tag coimmunoprecipitation, peptide massfingerprinting
    anti tag coimmunoprecipitation, peptide massfingerprinting
    Alleles Reported to Model Human Disease (Disease Ontology) (0 alleles)
    Genetic Tools, Stocks and Reagents
    Sources of Stocks
    Contact lab of origin for a reagent not available from a public stock center.
    Bloomington Stock Center Disease Page
    Selected mammalian transgenes
    Allele
    Transgene
    Publicly Available Stocks
    Selected Drosophila transgenes
    Allele
    Transgene
    Publicly Available Stocks
    RNAi constructs available
    Allele
    Transgene
    Publicly Available Stocks
    Selected Drosophila classical alleles
    Allele
    Allele class
    Mutagen
    Publicly Available Stocks
    amorphic allele - genetic evidence
    X ray
    amorphic allele - genetic evidence
    ethyl methanesulfonate
    amorphic allele - genetic evidence
    1,2-dichloroethane
    amorphic allele - genetic evidence
    spontaneous
    amorphic allele - genetic evidence
    ethyl methanesulfonate
    amorphic allele - genetic evidence
    ethyl methanesulfonate
    References (7)