FB2026_01 , released March 12, 2026
FB2026_01 , released March 12, 2026
Allele: Hsap\FUSR521C.UAS.Tag:HA
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General Information
Symbol
Hsap\FUSR521C.UAS.Tag:HA
Species
H. sapiens
Name
FlyBase ID
FBal0261075
Feature type
allele
Associated gene
Associated Insertion(s)
Carried in Construct
Also Known As
FUS R521C, FUSR521C, UAS-FUS-hR521C
Key Links
Transgenic product class
Nature of the Allele
Transgenic product class
Progenitor genotype
Carried in construct
Cytology
Description

Amino acid replacement: R521C.

UAS regulatory sequences drive expression of mutated Hsap\FUS coding sequences.

Allele components
Component
Use(s)
Encoded product / tool
Mutations Mapped to the Genome
Curation Data
Type
Location
Additional Notes
References
Variant Molecular Consequences
Associated Sequence Data
DNA sequence
Protein sequence
 
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 )
Modifiers Based on Experimental Evidence ( 1 )
Disease
Interaction
References
is exacerbated by mblC.UAS
is exacerbated by SmnGL00581
is ameliorated by mblGD13374
is ameliorated by mblKK107778
is ameliorated by Ube4BJF02691
is ameliorated by Atx-1f01201
is ameliorated by Rgld03208
is ameliorated by Setxf05408
is exacerbated by Stripe04482
is ameliorated by glof02674
is ameliorated by hecad10800
is exacerbated by orbd06989
is exacerbated by pumd04225
is ameliorated by sasd07239
is ameliorated by Nup214GD11084
is ameliorated by Nup54KK102105
is ameliorated by Nup62KK108318
is exacerbated by Nup62UAS.cAa
Comments on Models/Modifiers Based on Experimental Evidence ( 0 )
 
Disease-implicated variant(s)
 
This allele represents a human variant implicated in disease.
FUS:p.Arg521Cys
Variants Synonym(s)
FUS:p.Arg517Cys
FUS:p.Arg520Cys
External database links
Comments concerning this variant
Phenotypic Data
Phenotypic Class
Phenotype Manifest In
Detailed Description
Statement
Reference

The expression of Hsap\FUSR521C.UAS.Tag:HA under the control of Scer\GAL4GMR.PU results in eye degeneration. Adulthood-only expression under the control of Scer\GAL4elav.Switch.PO and induced by RU486 results in a decrease in climbing ability.

Expressing Hsap\FUSR521C.UAS.Tag:HA under the control of Scer\GAL4GMR.PU leads to eye defects - rough-eye phenotype, eye degeneration and loss of pigmentation .

Expressing Hsap\FUSR521C.UAS.Tag:HA under the control of Scer\GAL4GMR.PF results in progressive eye degeneration: rough eye with loss of pigmentation; retinal degradation, length reduction, and separation from the lamina at the basal membrane.

Expressing Hsap\FUSR521C.UAS.Tag:HA under the control of Scer\GAL4Toll-6-D42 leads to more satellite boutons (but no change in the number of mature boutons or boutons size) in the larval neuromuscular junction.

The expression of Hsap\FUSR521C.UAS.Tag:HA under the control of Scer\GAL4GMR.PF leads to a rough eye phenotype, with depigmentation.

Expression of Hsap\FUSR521C.Scer\UAS.T:Ivir\HA1 under the control of Scer\GAL4GMR.PU induces age-dependent eye degeneration, manifested by loss of eye pigmentation in adult flies. Scer\GAL4RapGAP1-OK6-driven expression results in wing expansion defects (but no eclosion defects) and severely impaired climbing ability.

Expression of Hsap\FUSR521C.Scer\UAS.T:Ivir\HA1 in motor neurons under the control of Scer\GAL4VGlut-OK371 causes impaired larval motility.

Expression of Scer\GAL4VGlut-OK371>Hsap\FUSR521C.Scer\UAS.T:Ivir\HA1 results in an approximately three-fold increase in the number of inter-bouton regions at third instar larval neuromuscular junctions compared with wild-type.

Scer\GAL4VGlut-OK371>Hsap\FUSR521C.Scer\UAS.T:Ivir\HA1-expressing animals display an approximately 50% reduction in the number of presynaptic active zones compared with wild-type.

Compared with wild-type, third instar larvae expressing Hsap\FUSR521C.Scer\UAS.T:Ivir\HA1 under the control of Scer\GAL4VGlut-OK371 display an approximately 25% reduction in evoked excitatory junction potential (EJP) amplitude. Compared with wild-type, a greater than two-fold increase in mEJP frequency is observed in the transgenic flies. Hsap\FUSR521C.Scer\UAS.T:Ivir\HA1-expression does not cause a significant alteration in EJP kinetics.

Motor neuron expression of Hsap\FUSR521C.Scer\UAS.T:Ivir\HA1 using Scer\GAL4VGlut-OK371 leads to larval paralysis and pupal lethality.

Expression of Hsap\FUSR521C.Scer\UAS.T:Ivir\HA1 in motor neurons under the control of Scer\GAL4VGlut-OK371 causes smaller brain size due to atrophy in third instar larvae.

Over-shooting action potentials can be evoked in neurons expressing Hsap\FUSR521C.Scer\UAS.T:Ivir\HA1 under the control of Scer\GAL4VGlut-OK371 by injection of depolarising current via a recording electrode. Neurons fire repetitively in response to a sustained stimulus, with no apparent accommodation. In contrast to the evoked cell body action potentials, there is no statistically significant difference in the frequency of the spontaneous orthodromic action potentials recorded from the axons of Hsap\FUSR521C.Scer\UAS.T:Ivir\HA1-expressing larvae and wild-type.

Neuronal expression of Hsap\FUSR521C.Scer\UAS.T:Ivir\HA1 under the control of Scer\GAL4VGlut-OK371 appears to have little effect on the fast inward currents evoked by membrane depolarisation. The large, voltage-dependent outward currents are very similar in wild-type and Hsap\FUSR521C.Scer\UAS.T:Ivir\HA1 larvae and the conductance-voltage relationships of the peak outward currents are indistinguishable between Hsap\FUSR521C.Scer\UAS.T:Ivir\HA1 and wild-type larvae.

Pre-synaptic expression of Hsap\FUSR521C.Scer\UAS.T:Ivir\HA1 (under the control of Scer\GAL4VGlut-OK371) leads to a dramatic decrease in the amplitude of the excitatory junctional current. The rate of EJC decay in markedly increased in Hsap\FUSR521C.Scer\UAS.T:Ivir\HA1 expressing mutants compared to controls (decay time constants are approximately 35% of those in controls). This substantial change in decay kinetics, in combination with the decrease in EJC amplitude, results in an even more profound decrease in the integrated synaptic current. Synaptic transmission at the larval neuromuscular junction is severely impaired in Hsap\FUSR521C.Scer\UAS.T:Ivir\HA1 mutant flies.

The structure and shape of presynaptic active zones is aberrant in flies expressing Hsap\FUSR521C.Scer\UAS.T:Ivir\HA1 under the control of Scer\GAL4VGlut-OK371.

Expression of Hsap\FUSR521C.Scer\UAS.T:Ivir\HA1 in the developing eye under the control of Scer\GAL4GMR.PF results in a severe neurodegeneration in the eye, characterised by disorganised ommatidia and loss of mechanosensory bristles, correlated with vacuolar neurodegeneration with severe disruption of the retinal organization and thinning of the retina.

Expression of Hsap\FUSR521C.Scer\UAS.T:Ivir\HA1 in the nervous system under the control of Scer\GAL4Appl.G1a causes pupal lethality.

Induction of Hsap\FUSR521C.Scer\UAS.T:Ivir\HA1 expression in adult neurons under the control of Scer\GAL4elav.Switch.PO causes a severe decline in the survival rate after approximately 10 days RU486 treatment and exhibit drastically shortened life span when compared with untreated Hsap\FUSR521C.Scer\UAS.T:Ivir\HA1 and Scer\GAL4elav.Switch.PO alone. Approximately 50% of the Scer\GAL4elav.Switch.PO; Hsap\FUSR521C.Scer\UAS.T:Ivir\HA1 flies are dead within 18 days of RU486 treatment with all of the flies dead within 30 days (with an average life span of 17.4 days).

Induction of Hsap\FUSR521C.Scer\UAS.T:Ivir\HA1 expression in adult neurons under the control of Scer\GAL4elav.Switch.PO causes an age-dependent decline in climbing ability. These flies start showing impairment in the climbing behavior by day 10 and at day 20 less than 3% of these flies treated with RU486 are able to climb.

Expression of Hsap\FUSR521C.Scer\UAS.T:Ivir\HA1 in motor neurons under the control of Scer\GAL4VGlut-OK371 causes a larval-crawling defect. These mutants display normal numbers of synaptic boutons.

External Data
Interactions
Show genetic interaction network for Enhancers & Suppressors
Phenotypic Class
Enhanced by
Statement
Reference
NOT Enhanced by
Suppressed by
Statement
Reference
NOT suppressed by
Phenotype Manifest In
Enhanced by
NOT Enhanced by
Suppressed by
Statement
Reference

Hsap\FUSR521C.UAS.Tag:HA, Scer\GAL4GMR.PU has eye phenotype, suppressible by Mnre00651/CG32521[+]

Hsap\FUSR521C.UAS.Tag:HA, Scer\GAL4GMR.PU has eye phenotype, suppressible by SNF4Aγd05297/SNF4Agamma[+]

Hsap\FUSR521C.UAS.Tag:HA, Scer\GAL4GMR.PU has eye phenotype, suppressible by CG8036[+]/Tktd05884

NOT suppressed by
Additional Comments
Genetic Interactions
Statement
Reference
Xenogenetic Interactions
Statement
Reference

The age-dependent eye pigmentation loss characteristic for adult flies expressing Hsap\FUSR521C.Scer\UAS.T:Ivir\HA1 under the control of Scer\GAL4GMR.PU is exacerbated by co-expression of CG5445NIG.5445R and ameliorated by co-expression of either Rpn11Scer\UAS.cTa or CG5445Scer\UAS.cUa but not by co-expression of CG5445ΔUBA.Scer\UAS or CG5445ΔFW.Scer\UAS.

The wing expansion defects observed in flies expressing Hsap\FUSR521C.Scer\UAS.T:Ivir\HA1 with the Scer\GAL4RapGAP1-OK6 driver are not rescued by co-expression of CG5445Scer\UAS.cUa, whereas their poor climbing ability is significantly improved.

Complementation and Rescue Data
Comments
Images (0)
Mutant
Wild-type
Stocks (0)
Notes on Origin
Discoverer
External Crossreferences and Linkouts ( 0 )
Synonyms and Secondary IDs (2)
Reported As
Symbol Synonym
Hsap\FUSR521C.Scer\UAS.T:Ivir\HA1
Hsap\FUSR521C.UAS.Tag:HA
Name Synonyms
Secondary FlyBase IDs
    References (16)