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General Information
Name
familial adenomatous polyposis 1
FlyBase ID
FBhh0000135
Overview

This report describes familial adenomatous polyposis 1 (FAP1), which is a subtype of familial adenomatous polyposis. The human gene implicated in this disease is APC (Adenomatous Polyposis Coli), which encodes a tumor suppressor protein that acts as an antagonist of the Wnt signaling pathway. The APC protein is a component of the beta-catenin destruction complex, which regulates Wnt/β-catenin signaling. APC has multiple roles in processes that control cell growth and division and is also implicated in several other types of cancer (see OMIM:611731). There is a second related human gene, APC2; there are also two genes in Drosophila: Dmel\Apc and Dmel\Apc2. Classical loss-of-function alleles, RNAi-targeting constructs, and alleles caused by insertional mutagenesis have been generated for both fly genes.

UAS constructs of the human Hsap\APC gene have been introduced into flies; heterologous rescue has not been tested.

A disease model with flies carrying loss-of-function mutations in both Dmel\Apc and Dmel\Apc2 has been developed; cells in the adult midgut are assayed for epithelial hyperplasia, using somatic clones to produce cells homozygous for mutations in both genes. Candidate genes have been assessed for genetic interactions that modify the disease phenotype. Physical interactions for both Apc and Apc2 protein products have been described; see below and in the FlyBase gene reports for Dmel\Apc and Dmel\Apc2.

Early work assessed the behavior of somatic clones of the Apc-Apc2 double mutant in wing discs; such clones have an overgrowth phenotype which results due to the elimination of surrounding wild-type cells. Somatic clones of the fly Axin gene Axn, a scaffold protein for the beta-catenin destruction complex, exhibit similar overgrowth phenotypes. See the human disease model report 'cancer, multiple, AXIN-related' (FBhh0001045).

[updated May 2019 by FlyBase; FBrf0222196]

Disease Summary Information
Parent Disease Summary: familial adenomatous polyposis
Symptoms and phenotype

Familial adenomatous polyposis (FAP) is a disorder characterized by predisposition to cancer. Affected individuals usually develop hundreds to thousands of adenomatous polyps of the colon and rectum, a small proportion of which will progress to colorectal carcinoma if not surgically treated (Nishisho et al., 1991; pubmed:1651563). [from OMIM:175100; 2016.01.14]

Specific Disease Summary: familial adenomatous polyposis 1
OMIM report

[FAMILIAL ADENOMATOUS POLYPOSIS 1; FAP1](https://omim.org/entry/175100)

Human gene(s) implicated

[APC REGULATOR OF WNT SIGNALING PATHWAY; APC](https://omim.org/entry/611731)

Symptoms and phenotype

See description of familial adenomatous polyposis, above.

Genetics

Familial adenomatous polyposis 1 (FAP1) and its variant Gardner syndrome (GS) are caused by heterozygous mutation in the APC (Adenomatous Polyposis Coli) gene; an autosomal-dominant pattern of inheritance is observed. [from OMIM:175100; 2016.01.14]

Cellular phenotype and pathology
Molecular information

The APC gene encodes a multidomain protein that plays a major role in tumor suppression by antagonizing the WNT signaling pathway. Inappropriate activation of this pathway through loss of APC function contributes to cancer progression. The APC protein is also an integral part of the beta-catenin signaling pathway. [from OMIM:611731; 2016.01.14]

APC is a component of the beta-catenin destruction complex, which regulates the phosphorylation and subsequent proteolysis of the transcriptional regulator beta-catenin (Stamos and Weis, 2013; pubmed:23169527).

External links
Disease synonyms
FAP1
familial adenomatous polyposis-1
adenomatous polyposis of the colon
APC
familial polyposis of the colon
FPC
adenomatous intestinal polyposis
Gardner syndrome
GS
brain tumor-polyposis syndrome 2
BTPS2
Search term: colorectal cancer
Search term: colon cancer
Search term: beta-catenin destruction complex
Ortholog Information
Human gene(s) in FlyBase
Human gene (HGNC)
D. melanogaster ortholog (based on DIOPT)
Comments on ortholog(s)

Many to many: 2 human to 2 Drosophila. There are two orthologous genes in each species, APC and APC2 in humans, Apc and Apc2 in flies.

Other mammalian ortholog(s) used
    D. melanogaster Gene Information (2)
    Gene Snapshot
    APC-like (Apc) encodes one of two Drosophila APC family proteins. It is a key negative regulator of Wingless signaling, as a critical component of the destruction complex that phosphorylates beta-catenin and thus targets it for ubiquitination and proteasomal destruction. It is the primary family member during CNS and eye development, and functions redundantly with the product of Apc2 in adult development. [Date last reviewed: 2019-03-07]
    Gene Groups / Pathways
    Comments on ortholog(s)

    Ortholog of human genes APC and APC2 (2 Drosophila to 2 human). Dmel\Apc shares 25-26% identity and 37% similarity with both human genes; it lacks a microtubule-binding domain found at the C terminus of the human APC gene.

    Orthologs and Alignments from DRSC
    DIOPT - DRSC Integrative Ortholog Prediction Tool - Click the link below to search for orthologs in Humans
    Gene Snapshot
    Adenomatous polyposis coli 2 (Apc2) encodes one of two Drosophila APC family proteins. It is a key negative regulator of Wingless signaling, as a critical component of the destruction complex that phosphorylates beta-catenin and thus targets it for ubiquitination and proteasomal destruction. It is the primary APC family member during embryonic development, and functions redundantly with the product of Apc in adult development. [Date last reviewed: 2019-03-07]
    Gene Groups / Pathways
    Comments on ortholog(s)

    Ortholog of human genes APC and APC2 (2 Drosophila to 2 human). Dmel\Apc2 is significantly shorter than both human genes and the orthologous fly gene, Dmel\Apc. Dmel\Apc2 shares 26-27% identity and 37-38% similarity with both human genes; it lacks a microtubule-binding domain found at the C terminus of the human APC gene.

    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 (13 groups)
    protein-protein
    Interacting group
    Assay
    References
    colocalization, fluorescence microscopy, inferred by author, two hybrid
    pull down, autoradiography
    pull down, anti tag western blot
    protein-protein
    Interacting group
    Assay
    References
    anti tag coimmunoprecipitation, anti tag western blot, two hybrid, western blot
    colocalization, fluorescence microscopy, inferred by author, two hybrid
    anti tag coimmunoprecipitation, anti tag western blot, two hybrid, anti bait coimmunoprecipitation, western blot
    two hybrid, anti tag coimmunoprecipitation, western blot, anti tag western blot, bimolecular fluorescence complementation, fluorescence microscopy
    anti bait coimmunoprecipitation, western blot, pull down, anti tag western blot
    experimental knowledge based
    anti tag coimmunoprecipitation, anti tag western blot
    two hybrid, pull down, western blot, anti tag coimmunoprecipitation
    anti tag coimmunoprecipitation, anti tag western blot
    Alleles Reported to Model Human Disease (Disease Ontology) (7 alleles)
    Models Based on Experimental Evidence ( 2 )
    Modifiers Based on Experimental Evidence ( 1 )
    Allele
    Disease
    Interaction
    References
    is ameliorated by ewgP1
    Models Based on Experimental Evidence ( 4 )
    Modifiers Based on Experimental Evidence ( 1 )
    Allele
    Disease
    Interaction
    References
    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
    ethyl methanesulfonate
    amorphic allele - genetic evidence
    ethyl methanesulfonate
    loss of function allele
    ethyl methanesulfonate
    Delta2-3 transposase
    References (25)