Open Close
General Information
Name
cardiomyopathy, familial hypertrophic 11
FlyBase ID
FBhh0000744
Overview

This report describes cardiomyopathy, familial hypertrophic 11 (CMH11), one of several diseases associated with defects in the human cardiac muscle actin gene ACTC1; CMH11 is inherited as an autosomal dominant. Actins are extremely highly conserved; ACTC1 shares 92-94% identity with all six actins in Drosophila. Two fly genes have used to characterize this disease, Dmel\Act57B and Dmel\Act88F. Loss-of-function mutations and RNAi targeting constructs have been generated for both genes; a number of alleles of Act88F are described as antimorphic.

A UAS construct of the wild-type human Hsap\ACTC1 gene has been introduced into flies, but has not been characterized.

Dmel\Act57B is expressed in mesodermally derived tissues, including the larval and adult heart. Animals homozygous for loss-of-function mutations of Act57B typically die in the larval or pupal stage. Act88F is expressed at high levels in pupal muscle precusors and adult muscle, most prominently in the indirect flight muscle. Animals carring hypomorphic alleles of Act88F frequently survive to adulthood, but exhibit a flightless phenotype.

A mutational lesion analogous to one implicated in CMH11 (A297S in the human ACTC1 gene) has been studied as a model of hypertrophic cardiomyopathy in Drosophila; the analogous mutation has been characterized in both Dmel\Act57B and Dmel\Act88F. Variant(s) implicated in human disease tested (as analogous mutation in fly gene): A296S in the fly Act57B gene or Act88F gene [corresponds to A297S (A295S) in the human ACTC1 gene]. The mutation is shown to disrupt critical associations between nearby actin residues K326, K328, and R147, termed the A-triad, and tropomyosin.

[updated Mar. 2020 by FlyBase; FBrf0222196]

Disease Summary Information
Parent Disease Summary: cardiomyopathy, familial hypertrophic
Symptoms and phenotype

Familial hypertrophic cardiomyopathy is a heart condition characterized by thickening (hypertrophy) of cardiac muscle. Thickening usually occurs in the interventricular septum, the muscular wall that separates the left ventricle from the right ventricle. Cardiac hypertrophy often begins in adolescence or young adulthood, although it can develop at any time throughout life. The symptoms are variable, even within the same family. While most people this condition are symptom-free or have only mild symptoms, hypertrophic cardiomyopathy can cause abnormal heart rhythms (arrhythmias) that may be life threatening. People with familial hypertrophic cardiomyopathy have an increased risk of sudden death, even if they have no other symptoms of the condition. A small number of affected individuals develop potentially fatal heart failure, which may require heart transplantation. [from Genetics Home Reference, familial hypertrophic cardiomyopathy; 2016.10.13]

Hypertrophic cardiomyopathy in early stages produces a presystolic gallop due to an atrial heart sound, and EKG changes of ventricular hypertrophy. Progressive ventricular outflow obstruction may cause palpitation associated with arrhythmia, congestive heart failure, and sudden death. Hypertrophic cardiomyopathy accounts for a significant number (exceeding 25% in one study) of sudden deaths of young athletes. [from OMIM:192600; 2016.10.28]

Specific Disease Summary: cardiomyopathy, familial hypertrophic 11
OMIM report

[CARDIOMYOPATHY, FAMILIAL HYPERTROPHIC, 11; CMH11](https://omim.org/entry/612098)

Human gene(s) implicated

[ACTIN, ALPHA, CARDIAC MUSCLE; ACTC1](https://omim.org/entry/102540)

Symptoms and phenotype
Genetics

Familial hypertrophic cardiomyopathy 11 is caused by heterozygous mutation in the ACTC1 gene. [from OMIM:612098; 2018.02.23]

Cellular phenotype and pathology
Molecular information
External links
Disease synonyms
CMH11
Ortholog Information
Human gene(s) in FlyBase
Human gene (HGNC)
D. melanogaster ortholog (based on DIOPT)
Comments on ortholog(s)

Many to many: multiple related genes in both species. ACTC1 shares 92-94% identity with all six actins in Drosophila.

Other mammalian ortholog(s) used
    D. melanogaster Gene Information (2)
    Gene Snapshot
    Actin 57B (Act57B) is one of several actin genes in the Drosophila genome, and one of the few that encode myofibrillar actin. This essential gene is a transcriptional target of Mef2 and Cf2 and is expressed in all embryonic muscles and a subset of adult muscle. [Date last reviewed: 2018-09-06]
    Molecular function (GO)
      Cellular component (GO)
      Gene Groups / Pathways
      Comments on ortholog(s)

      Highly conserved ortholog of multiple actin genes in human, including ACTC1; Dmel\Act57B shares 93% identity and 96% similarity with human ACTC1; the two proteins differ in length by only one amino acid.

      Orthologs and Alignments from DRSC
      DIOPT - DRSC Integrative Ortholog Prediction Tool - Click the link below to search for orthologs in Humans
      Molecular function (GO)
        Gene Groups / Pathways
        Comments on ortholog(s)

        Highly conserved ortholog of multiple actin genes in human, including ACTC1; Dmel\Act88F shares 93% identity and 96% similarity with human ACTC1; the two proteins differ in length by only one amino acid.

        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 (56 groups)
        protein-protein
        Interacting group
        Assay
        References
        anti tag coimmunoprecipitation, Identification by mass spectrometry
        experimental knowledge based
        experimental knowledge based
        experimental knowledge based
        experimental knowledge based
        experimental knowledge based
        experimental knowledge based
        experimental knowledge based
        experimental knowledge based
        experimental knowledge based, two hybrid
        experimental knowledge based
        experimental knowledge based
        experimental knowledge based
        experimental knowledge based
        anti tag coimmunoprecipitation, Identification by mass spectrometry, two hybrid
        experimental knowledge based
        experimental knowledge based
        experimental knowledge based
        anti tag coimmunoprecipitation, Identification by mass spectrometry
        anti tag coimmunoprecipitation, Identification by mass spectrometry
        anti tag coimmunoprecipitation, Identification by mass spectrometry
        anti tag coimmunoprecipitation, Identification by mass spectrometry
        anti tag coimmunoprecipitation, peptide massfingerprinting
        experimental knowledge based
        experimental knowledge based
        experimental knowledge based
        protein-protein
        Interacting group
        Assay
        References
        experimental knowledge based
        experimental knowledge based
        experimental knowledge based
        experimental knowledge based
        experimental knowledge based
        experimental knowledge based
        experimental knowledge based
        experimental knowledge based
        experimental knowledge based
        experimental knowledge based
        experimental knowledge based
        experimental knowledge based
        experimental knowledge based
        anti tag coimmunoprecipitation, Identification by mass spectrometry
        anti tag coimmunoprecipitation, peptide massfingerprinting
        experimental knowledge based
        experimental knowledge based
        ion exchange chromatography, peptide massfingerprinting
        Alleles Reported to Model Human Disease (Disease Ontology) (15 alleles)
        Models Based on Experimental Evidence ( 3 )
        Modifiers Based on Experimental Evidence ( 0 )
        Allele
        Disease
        Interaction
        References
        Models Based on Experimental Evidence ( 11 )
        Modifiers Based on Experimental Evidence ( 1 )
        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
        spontaneous
        ethyl methanesulfonate
        amorphic allele - genetic evidence
        ethyl methanesulfonate
        References (6)