FB2026_01 , released March 12, 2026
FB2026_01 , released March 12, 2026
Human Disease Model Report: cancer, intestinal stem cell (postulated), SNX9,18,33-related
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General Information
Name
cancer, intestinal stem cell (postulated), SNX9,18,33-related
FlyBase ID
FBhh0001187
Disease Ontology Term
Parent Disease
OMIM
Overview

This report describes a model of colorectal cancer using the Drosophila sorting nexin SH3PX1; there are three genes orthologous to SH3PX1 in humans. Sorting nexins are a family of proteins that regulate membrane trafficking, endocytosis, and autophagy, and their dysregulation has been associated with cancer and other disorders. In a screen of Drosophila sorting nexins that regulate proliferation of intestinal stem cells (ISCs) in the gut, only SH3PX1 was identified as being critical to gut homeostasis. Many alleles of SH3PX1 have been generated, including amorphic alleles, alleles carrying RNAi targeting constructs, and alleles generated by insertional mutagenesis.

The high-ranking human orthologs of Dmel\SH3PX1 are the sorting nexins Hsap\SNX9, Hsap\SNX18, and Hsap\SNX33, all three of which have been introduced into flies.

Flies that are homozygous null for SH3PX1 show a strong increase in the rate of mitosis in ISCs, a cell-autonomous effect that generates larger-than-normal clones after 14 days. Flies lacking SH3PX1 have defects in autophagy, as seen by the lack of autophagosomes after 6 hours of starvation, and that knocking down Atg autophagy family genes (FBgg0000216) in SH3PX1 null flies further promotes ISC proliferation. In wild-type flies, autophagy restrains ISC proliferation by dampening EGFR-ERK activity (FBgg0000951), which has been implicated in several epithelial cancers (FBhh0000932). In SH3PX1 nulls, EGFR-ERK activation triggers an increased rate of ISC division. All three of the human orthologs of SH3PX1 (Hsap\SNX9, Hsap\SNX18, and Hsap\SNX33) are capable of heterologously rescuing (functionally complementing) SH3PX1-null phenotypes.

[updated Feb. 2020 by FlyBase; FBrf0222196]

Disease Summary Information
Disease Summary: cancer, intestinal stem cell (postulated), SNX9,18,33-related
OMIM report
Human gene(s) implicated
Symptoms and phenotype

Inflammation is now considered a dominant feature and a hallmark of cancer. (From Pesic and Greten 2016, pubmed:27521599.)

(FlyBase Curators, 2013-)
Genetics

In the intestine, genetic and epigenetic changes that dysregulate epithelial homeostasis contribute to common maladies such as colorectal cancer (CRC) and inflammatory bowel diseases (IBD). (From Zhang et al. 2019, FBrf0242427, citing Pesic and Greten 2016, pubmed:27521599.)

(FlyBase Curators, 2013-)
Cellular phenotype and pathology
Molecular information

The SORTING NEXIN (SNX) family consists of a diverse group of cytoplasmic and membrane-associated proteins that are involved in various aspects of endocytosis and protein trafficking through these membranous compartments. Endocytic pathways function to internalize extracellular components, and they participate in diverse signal-transduction pathways. (From Worby and Dixon 2002, pubmed:12461558.) Many sorting nexin proteins have been linked to cancers on the basis of differential expression and other criteria, both in oncogenic and tumor suppressor capacities. (Adapted from Teasdale and Collins 2012, pubmed:22168438.)

(FlyBase Curators, 2013-)
External links
Disease synonyms
cancer, intestinal stem cell, SH3PX1-related
Ortholog Information
Human gene(s) in FlyBase
Human gene (HGNC)
Symbol / Name
SNX9; sorting nexin 9
D. melanogaster ortholog (based on DIOPT)
Dmel\SH3PX1
(DIOPT, 2013-)
Comments on ortholog(s)

Many to one: 3 human genes to 1 Drosophila gene.

Human gene (HGNC)
Symbol / Name
SNX18; sorting nexin 18
D. melanogaster ortholog (based on DIOPT)
Dmel\SH3PX1
(DIOPT, 2013-)
Comments on ortholog(s)

Many to one: 3 human genes to 1 Drosophila gene.

Human gene (HGNC)
Symbol / Name
SNX33; sorting nexin 33
D. melanogaster ortholog (based on DIOPT)
Dmel\SH3PX1
(DIOPT, 2013-)
Comments on ortholog(s)

Many to one: 3 human genes to 1 Drosophila gene.

Other mammalian ortholog(s) used
    D. melanogaster Gene Information (1)
    Dmel\SH3PX1
    Gene Snapshot
    Contributions welcome
    Molecular function (GO)
    Cellular component (GO)
    Gene Groups / Pathways
    Comments on ortholog(s)

    Single, high- or moderate-ranking ortholog of three human genes: Hsap\SNX9, Hsap\SNX18, and Hsap\SNX33.

    Orthologs and Alignments from DRSC
    DIOPT - DRSC Integrative Ortholog Prediction Tool - Click the link below to search for orthologs in Humans
    H. sapiens (Human)
    Other Genes Used: Viral, Bacterial, Synthetic (0)
      Summary of Physical Interactions (12 groups)
      SH3PX1
      protein-protein
      Interacting group
      Assay
      References
      SH3PX1
      two hybrid
      (Worby et al., 2001)
      SH3PX1 - Ack
      two hybrid, pull down, western blot, enzymatic study, autoradiography, anti bait coimmunoprecipitation, anti tag coimmunoprecipitation, peptide massfingerprinting
      (Schoenherr et al., 2012, Worby et al., 2002)
      SH3PX1 - AP-2μ
      anti tag coimmunoprecipitation, western blot
      (Worby et al., 2001)
      SH3PX1 - Atg8a
      pull down, autoradiography
      (Knævelsrud et al., 2013)
      SH3PX1 - dock
      pull down, western blot, anti bait coimmunoprecipitation, two hybrid, edman degradation
      (Worby et al., 2002, Worby et al., 2001)
      SH3PX1 - Dscam1
      two hybrid
      (Worby et al., 2001)
      SH3PX1 - IPIP
      pull down, western blot
      (Carim et al., 2019)
      SH3PX1 - Nedd4
      pull down, anti tag western blot, anti tag coimmunoprecipitation, peptide massfingerprinting
      (Wasserman et al., 2019, Safi et al., 2016)
      SH3PX1 - nwk
      anti tag coimmunoprecipitation, anti tag western blot
      (Ukken et al., 2016)
      SH3PX1 - sau
      pull down, western blot, Identification by mass spectrometry
      (Sechi et al., 2021)
      SH3PX1 - Tab2
      anti tag coimmunoprecipitation, Identification by mass spectrometry, pull down, anti tag western blot
      (Tsapras et al., 2022)
      SH3PX1 - WASp
      two hybrid, pull down, western blot, anti tag coimmunoprecipitation
      (Worby et al., 2002, Worby et al., 2001)
      Alleles Reported to Model Human Disease (Disease Ontology) (8 alleles)
      SH3PX1
      Models Based on Experimental Evidence ( 4 )
      Modifiers Based on Experimental Evidence ( 4 )
      Hsap\SNX9
      Models Based on Experimental Evidence ( 0 )
      Allele
      Disease
      Evidence
      References
      Modifiers Based on Experimental Evidence ( 1 )
      Allele
      Disease
      Interaction
      References
      Hsap\SNX9UAS.Tag:V5
      ameliorates  colorectal cancer
      modeled by SH3PX1d1
      (Zhang et al., 2019)
      Hsap\SNX18
      Models Based on Experimental Evidence ( 0 )
      Allele
      Disease
      Evidence
      References
      Modifiers Based on Experimental Evidence ( 1 )
      Allele
      Disease
      Interaction
      References
      Hsap\SNX18UAS.Tag:V5
      ameliorates  colorectal cancer
      modeled by SH3PX1d1
      (Zhang et al., 2019)
      Hsap\SNX33
      Models Based on Experimental Evidence ( 0 )
      Allele
      Disease
      Evidence
      References
      Modifiers Based on Experimental Evidence ( 1 )
      Allele
      Disease
      Interaction
      References
      Hsap\SNX33UAS.Tag:V5
      ameliorates  colorectal cancer
      modeled by SH3PX1d1
      (Zhang et al., 2019)
      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
      Related mammalian, viral, bacterial, or synthetic transgenes
      Allele
      Transgene
      Publicly Available Stocks
      Hsap\SNX9UAS.Tag:V5
      P{UAS-hSNX9.V5}
      Hsap\SNX9UAS.Tag:HA
      PBac{UAS-hSNX9.HA}
      y1 w*; PBac{UAS-hSNX9.HA}VK00037/SM6a
      Hsap\SNX18UAS.Tag:V5
      P{UAS-hSNX18.V5}
      Hsap\SNX33UAS.Tag:V5
      P{UAS-hSNX33.V5}
      Selected Drosophila transgenes
      Allele
      Transgene
      Publicly Available Stocks
      RNAi constructs available
      Allele
      Transgene
      Publicly Available Stocks
      SH3PX1HMJ21528
      P{TRiP.HMJ21528}
      y1 v1; P{TRiP.HMJ21528}attP40/CyO
      SH3PX1GD12026
      P{GD12026}
      w1118; P{GD12026}v22412
      SH3PX1KK100618
      P{KK100618}
      P{KK100618}VIE-260B
      SH3PX1JF02730
      P{TRiP.JF02730}
      y1 v1; P{TRiP.JF02730}attP2/TM3, Sb1
      SH3PX1NIG.6757R
      P{NIG.6757R}
      P{NIG.6757R}8
      SH3PX1HMJ21552
      P{TRiP.HMJ21552}
      y1 v1; P{TRiP.HMJ21552}attP40/CyO
      SH3PX1GL01877
      P{TRiP.GL01877}
      y1 sc* v1 sev21; P{TRiP.GL01877}attP40/CyO
      Selected Drosophila classical alleles
      Allele
      Allele class
      Mutagen
      Publicly Available Stocks
      SH3PX1d1
      amorphic allele - molecular evidence
      P-element activity
      SH3PX1HK62b
      amorphic allele - molecular evidence
      P-element activity
      SH3PX110A
      amorphic allele - molecular evidence
      CRISPR/Cas9
      SH3PX1C1
      amorphic allele - molecular evidence
      CRISPR/Cas9
      w1118; P{UAS-Nedd4.Lo.FLAG}2/CyO; TI{TI}SH3PX1C1/TM3, P{ActGFP}JMR2, Ser1
      References (5)