FB2024_03 , released June 25, 2024
Allele: Dmel\MhcP838L
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General Information
Symbol
Dmel\MhcP838L
Species
D. melanogaster
Name
FlyBase ID
FBal0319817
Feature type
allele
Associated gene
Dmel\Mhc
Associated Insertion(s)
Carried in Construct
P{Mhc.P838L}
Key Links
Genomic Maps

Transgenic product class
missense_variant
(Achal et al., 2016)
Mutagen
Nature of the Allele
Transgenic product class
missense_variant
(Achal et al., 2016)
Mutagen
in vitro construct
(Achal et al., 2016)
Progenitor genotype
Carried in construct
P{Mhc.P838L}
Cytology
Description

Contains Mhc carrying the amino acid replacement P836T. This mutation is equivalent to a mutation in the orthologous human gene (P838L) that causes dominant restrictive cardiomyopathy.

(Achal et al., 2016)
Allele components
Component
Use(s)
Regulatory region(s)
Mhc
Encoded product / tool
Mhc
Mutations Mapped to the Genome
Curation Data
Type
Location
Additional Notes
References
point_mutation
2L:16,780,776..16,780,776 [+]
Nucleotide change:

C16780776T

Reported nucleotide change:

C?T

Amino acid change:

P837L | Mhc-PC; P837L | Mhc-PD; P837L | Mhc-PV; P837L | Mhc-PK; P837L | Mhc-PP; P837L | Mhc-PM; P837L | Mhc-PA; P837L | Mhc-PN; P837L | Mhc-PG; P837L | Mhc-PL; P837L | Mhc-PI; P837L | Mhc-PB; P837L | Mhc-PQ; P837L | Mhc-PF; P837L | Mhc-PU; P837L | Mhc-PO; P837L | Mhc-PT; P837L | Mhc-PH; P837L | Mhc-PS; P837L | Mhc-PE; P837L | Mhc-PR

Reported amino acid change:

P836L

Comment:

Analogous mutation in human MYH7 implicated in cardiomyopathy, familial hypertrophic 1 and familial restrictive cardiomyopathy; mutation carried on in vitro construct.

(Achal et al., 2016)
Variant Molecular Consequences
Associated Sequence Data
DDBJ / EMBL / GenBank
DNA sequence
Protein sequence
 
UniProtKB/Swiss-Prot
    UniProtKB/TrEMBL
      Expression Data
      Reporter Expression
      Additional Information
      Statement
      Reference
       
      Marker for
      Reflects expression of
      Reporter construct used in assay
      Human Disease Associations
      Disease Ontology (DO) Annotations
      Models Based on Experimental Evidence ( 1 )
      Disease
      Evidence
      References
      DOES NOT model  restrictive cardiomyopathy
      CEA with Mhc1
      (Achal et al., 2016)
      CEA with Mhc1, Mhc5
      (Achal et al., 2016)
      Modifiers Based on Experimental Evidence ( 0 )
      Disease
      Interaction
      References
      Comments on Models/Modifiers Based on Experimental Evidence ( 0 )
       
      Disease-implicated variant(s)
       
      This allele represents a human variant implicated in disease.
      (Achal et al., 2016)
      MYH7:p.Pro838Leu
      (FlyBase curators, 2019-)
      Variants Synonym(s)
      Associated human disease model(s)
      External database links
      ClinVar: MYH7_42910
      Comments concerning this variant
      Phenotypic Data
      Phenotypic Class
      Phenotype Manifest In
      Detailed Description
      Statement
      Reference

      Flies expressing MhcP838L/MhcP838L in a Mhc10/Mhc10 background, exhibit impaired flight ability. The indirect flight muscles in 2 day old flies display largely normal myofibril morphology and sarcomeric structure, but a few show occasional minor abnormalities in Z-disk regularity. At 3 weeks post-eclosion, indirect flight muscles show areas with Z-band irregularities, sarcomere gaps, abnormalities in myofibrillar shape and orientation, and defects in myofilament packing, as compared with controls. 2-3 day old flies expressing MhcP838L/MhcP838L in a Mhc10/Mhc10 background show no significant difference in indirect flight muscle power, wing beat frequency, active stiffness, isometric tension or rigor stiffness as compared with controls (Mhc+t12.4/Mhc+t12.4 in a Mhc10/Mhc10 background).

      Expression of MhcP838L/MhcP838L in a Mhc1/Mhc1 background results in no significant difference in heart myofibril arrangement and morphology, myofilament arrays, Z-disc and sarcomere morphology, heart period, diastolic diameter, systolic diameter or fractional shortening, as compared with controls. Expression of MhcP838L/+ in a Mhc1/Mhc1 background also does not result in any significant difference in sarcomere structure, heart period, diastolic diameter, systolic diameter or fractional shortening, as compared with controls (Mhc+t12.4/Mhc+t12.4 or Mhc+t12.4/+ in a Mhc1/Mhc1 background).

      Expression of MhcP838L in a Mhc1/Mhc5 background does not result in any significant difference in heart period or diastolic diameter, but does cause a significant increase in systolic diameter and decrease in fractional shortening, as compared with controls (Mhc+t12.4 in a Mhc1/Mhc5 background).

      (Achal et al., 2016)
      External Data
      Interactions
      Show genetic interaction network for Enhancers & Suppressors
      Phenotypic Class
      Phenotype Manifest In
      Additional Comments
      Genetic Interactions
      Statement
      Reference
      Xenogenetic Interactions
      Statement
      Reference
      Complementation and Rescue Data
      Rescues

      MhcP838L rescues Mhc1

      (Achal et al., 2016)
      Comments

      Expression of two copies of MhcP838L rescues the lethality of Mhc1/Mhc1 mutants.

      (Achal et al., 2016)
      Images (0)
      Mutant
      Wild-type
      Stocks (0)
      Notes on Origin
      Discoverer
      External Crossreferences and Linkouts ( 0 )
      Synonyms and Secondary IDs (1)
      Reported As
      Symbol Synonym
      MhcP838L
      Name Synonyms
      Secondary FlyBase IDs
        References (2)