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General Information
Name
myeloproliferative disorders, JAK2-related
FlyBase ID
FBhh0000189
Disease Ontology Term
Parent Disease
OMIM
Overview

This report describes fly models of JAK2-related myeloproliferative disorders or myeloproliferative neoplasias (MPNs); see the OMIM report for JAK2 (OMIM:147796). The JAK2 gene encodes a non-receptor tyrosine kinase that plays a role in the JAK-STAT signaling pathway and is involved in regulation of many developmental processes. There is a single fly ortholog of JAK2, Dmel\hop, for which classical amorphic and hypomorphic alleles, RNAi-targeting constructs, and alleles caused by insertional mutagenesis have been generated. Several other human genes, including JAK1, TYK2, and JAK3, are also orthologous to Dmel\hop.

The human JAK2 gene has not been introduced into flies. The pathogenic allele V617F, which exhibits constitutive tyrosine kinase activity, is responsible for the majority of identified JAK2-related myeloproliferative disorders.

Amorphic mutations of Dmel\hop, when homozygous, result in lethality at the larval or pupal stages; mutant animals exhibit segmentation defects. A well-characterized gain-of-function mutation is dominant; heterozygous animals exhibit additional cellular proliferation in the larval lymph glands, a massive increase in circulating haemocytes, and formation of melanotic tumors in both larvae and adults. Phenotypic assays using Dmel\hop mutations have allowed characterization of genetic interactions. Physical interactions of the hop protein have been described; see below and in the gene report for hop.

See the pathway report 'JAK-STAT Signaling Pathway' (FBgg0000883) for a listing of genes encoding core components and regulators of this pathway in flies.

[updated Jun. 2018 by FlyBase; FBrf0222196]

Disease Summary Information
Disease Summary: myeloproliferative disorders, JAK2-related
OMIM report
Human gene(s) implicated
Symptoms and phenotype
Genetics

The JAK2 V617F allele has been found in most cases of polycythemia vera and half of the cases of essential thrombocythemia and primary myelofibrosis (Baxter et al., 2005; pubmed:15781101).

Mutations in the Janus kinase 2 (JAK2) gene are implicated in multiple myeloproliferative disorders, including acute myeloid leukemia (OMIM:601626), erythrocytosis (OMIM:133100), thrombocythemia-3 (OMIM:614521), polycythemia vera (OMIM:263300), and myelofibrosis (OMIM:254450).

The pathogenic allele JAK2V617F, which exhibits constitutive tyrosine kinase activity, is responsible for the majority of JAK2-related myeloproliferative disorders. (Levine and Gilliland, 2007; pubmed:17133099).

Cellular phenotype and pathology
Molecular information

The JAK2 gene encodes a non-receptor tyrosine kinase that plays a role in the JAK-STAT signaling pathway; it is involved in regulation of many developmental processes, including hematopoiesis. [From Gene Cards, JAK2; 2016.03.11]

JAK2 kinase is a member of a family of tyrosine kinases involved in cytokine receptor signaling. [from OMIM:147796; 2016.03.10]

External links
Disease synonyms
MPN
MPN, JAK2-related
myeloproliferative neoplasias
Ortholog Information
Human gene(s) in FlyBase
    Human gene (HGNC)
    D. melanogaster ortholog (based on DIOPT)
    Comments on ortholog(s)

    Many to one: 4 human to 1 Drosophila; the other orthologous human genes are JAK1, TYK2, and JAK3; additional lower scoring orthologs also exist in humans.

    Other mammalian ortholog(s) used
      D. melanogaster Gene Information (1)
      Gene Snapshot
      hopscotch (hop) encodes a non-receptor tyrosine kinase for interleukin-like ligands (encoded by upd1, upd2, and upd3) and functions in the JAK-STAT signaling pathway. It is involved in embryonic segmentation, cell proliferation, and cell migration. [Date last reviewed: 2019-03-07]
      Gene Groups / Pathways
      Comments on ortholog(s)

      Moderate-scoring ortholog of human JAK1 and JAK2; low-to-moderate-scoring ortholog of human TYK2 and JAK3 (1 Drosophila to 4 human); additional lower scoring orthologs exist in humans. Dmel\hop shares 24% identity and 39-41% similarity with JAK1 and JAK2.

      Orthologs and Alignments from DRSC
      DIOPT - DRSC Integrative Ortholog Prediction Tool - Click the link below to search for orthologs in Humans
      Other Genes Used: Viral, Bacterial, Synthetic (0)
        Summary of Physical Interactions (9 groups)
        RNA-protein
        Interacting group
        Assay
        References
        anti tag coimmunoprecipitation, quantitative reverse transcription pcr
        protein-protein
        Interacting group
        Assay
        References
        experimental knowledge based
        experimental knowledge based
        anti tag coimmunoprecipitation, anti tag western blot
        anti tag coimmunoprecipitation, anti tag western blot
        anti tag coimmunoprecipitation, anti tag western blot
        anti tag coimmunoprecipitation, anti tag western blot
        anti tag coimmunoprecipitation, anti tag western blot
        anti tag coimmunoprecipitation, anti tag western blot
        Alleles Reported to Model Human Disease (Disease Ontology) (7 alleles)
        Models Based on Experimental Evidence ( 5 )
        Modifiers Based on Experimental Evidence ( 5 )
        Allele
        Disease
        Interaction
        References
        Alleles Representing Disease-Implicated Variants
        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
        loss of function allele
        P-element activity
        amorphic allele - genetic evidence
        ethyl methanesulfonate
        loss of function allele
        X ray
        amorphic allele - genetic evidence
        ethyl methanesulfonate
        amorphic allele - genetic evidence
        ethyl methanesulfonate
        amorphic allele - genetic evidence
        ethyl methanesulfonate
        loss of function allele
        gamma ray
        amorphic allele - genetic evidence
        ethyl methanesulfonate
        ethyl methanesulfonate
        amorphic allele - genetic evidence
        ethyl methanesulfonate
        loss of function allele
        gamma ray
        amorphic allele - genetic evidence
        ethyl nitrosourea
        loss of function allele
        gamma ray
        amorphic allele - genetic evidence
        X ray
        ethyl methanesulfonate
        amorphic allele - genetic evidence
        ethyl nitrosourea
        amorphic allele - genetic evidence
        ethyl nitrosourea
        amorphic allele - genetic evidence
        ethyl methanesulfonate
        amorphic allele - genetic evidence
        ethyl methanesulfonate
        loss of function allele
        gamma ray
        amorphic allele - genetic evidence
        X ray
        loss of function allele
        gamma ray
        amorphic allele - genetic evidence
        ethyl methanesulfonate
        amorphic allele - genetic evidence
        ethyl nitrosourea
        References (23)