FlyBase Allele Report: Hsap\FUS[R518K.UAS.Tag:HA]

General Information

Symbol

Hsap\FUS^{R518K.UAS.Tag:HA}

Species

H. sapiens

Name

FlyBase ID

FBal0261074

Feature type

allele

Associated gene

Hsap\FUS

Associated Insertion(s)

Carried in Construct

P{UAS-hFUS.R518K.HA}

Also Known As

FUS R518K, FUS^R518K

Key Links

Transgenic product class

missense_variant

(Lanson et al., 2011)

Mutagen

in vitro construct

Nature of the Allele

Transgenic product class

missense_variant

(Lanson et al., 2011)

Mutagen

in vitro construct

(Lanson et al., 2011)

Progenitor genotype

Carried in construct

P{UAS-hFUS.R518K.HA}

Cytology

Description

Amino acid replacement: R518K.

(Lanson et al., 2011)

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

(Lanson et al., 2011)

Allele components

Component

Use(s)

Regulatory region(s)

UAS

binary expression system - regulatory region

Encoded product / tool

Hsap\FUS

Tagged with

Tag:HA

epitope tag

Mutations Mapped to the Genome

Curation Data

Type

Location

Additional Notes

References

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

model of amyotrophic lateral sclerosis

CEA

(Daigle et al., 2013, Lanson et al., 2011)

model of amyotrophic lateral sclerosis type 6

CEC

(Casci et al., 2019)

CEA

(Fortuna et al., 2021, Lin et al., 2021, Guo et al., 2018, Mallik et al., 2018)

Modifiers Based on Experimental Evidence ( 1 )

Disease

Interaction

References

model of amyotrophic lateral sclerosis type 6

is exacerbated by Smn^GL00581

(Casci et al., 2019)

is ameliorated by Smn^UAS.Tag:FLAG

(Casci et al., 2019)

is exacerbated by mbl^C.UAS

(Casci et al., 2019)

is ameliorated by mbl^GD13374

(Casci et al., 2019)

is ameliorated by mbl^KK107778

(Casci et al., 2019)

is ameliorated by Tnpo^GD33

(Guo et al., 2018)

is ameliorated by Xrp1^HMS00053

(Mallik et al., 2018)

is ameliorated by Nup62^KK108318

(Lin et al., 2021)

is exacerbated by Nup62^UAS.cAa

(Lin et al., 2021)

is ameliorated by Nup98-96^KK100388

(Lin et al., 2021)

is ameliorated by Nup214^GD11084

(Lin et al., 2021)

is ameliorated by Nup54^KK102105

(Lin et al., 2021)

is ameliorated by Rm62^UAS.cUa

(Fortuna et al., 2021)

is exacerbated by Rm62^RNAi.UAS.cUa

(Fortuna et al., 2021)

is exacerbated by Rm62^unspecified

(Fortuna et al., 2021)

is ameliorated by abs^KK101165

(Fortuna et al., 2021)

is ameliorated by vas^KK100929

(Fortuna et al., 2021)

Comments on Models/Modifiers Based on Experimental Evidence ( 0 )

Disease-implicated variant(s)

This allele represents a human variant implicated in disease.

(Lanson et al., 2011)

FUS:p.Arg518Lys

(FlyBase curators, 2019-)

Variants Synonym(s)

FUS:p.Arg514Lys

FUS:p.Arg517Lys

Associated human disease model(s)

amyotrophic lateral sclerosis 6 with or without frontotemporal dementia

External database links

ClinVar: FUS_16223

Comments concerning this variant

Phenotypic Data

Phenotypic Class

abnormal eye color, with Scer\GAL4^GMR.PF

(Kim et al., 2018)

abnormal eye color, with Scer\GAL4^GMR.PU

(Kim et al., 2023)

abnormal locomotor behavior, with Scer\GAL4^VGlut-OK371

(Lanson et al., 2011)

abnormal locomotor behavior | adult stage, with Scer\GAL4^{elav.Switch.PO}

(Fortuna et al., 2021)

abnormal locomotor behavior | adult stage | progressive, with Scer\GAL4^Toll-6-D42

(Mallik et al., 2018)

abnormal locomotor behavior | larval stage, with Scer\GAL4^Toll-6-D42

(Casci et al., 2019)

abnormal locomotor behavior | third instar larval stage, with Scer\GAL4^VGlut-OK371

(Daigle et al., 2013)

abnormal neuroanatomy | larval stage, with Scer\GAL4^Toll-6-D42

(Casci et al., 2019)

lethal - all die before end of P-stage, with Scer\GAL4^VGlut-OK371

(Daigle et al., 2013)

lethal - all die before end of pupal stage, with Scer\GAL4^Appl.G1a

(Lanson et al., 2011)

short lived, with Scer\GAL4^{elav.Switch.PO}

(Fortuna et al., 2021)

short lived, with Scer\GAL4^Toll-6-D42

(Mallik et al., 2018)

some die during pupal stage, with Scer\GAL4^Appl.G1a

(Lanson et al., 2011)

visible, with Scer\GAL4^GMR.PF

(Kim et al., 2018, Daigle et al., 2013)

visible | adult stage, with Scer\GAL4^GMR.PU

(Fortuna et al., 2021, Zhu et al., 2017)

visible | adult stage | progressive, with Scer\GAL4^GMR.PF

(Casci et al., 2019)

Phenotype Manifest In

embryonic/larval brain | third instar larval stage, with Scer\GAL4^VGlut-OK371

(Daigle et al., 2013)

embryonic/larval neuromuscular junction | larval stage, with Scer\GAL4^Toll-6-D42

(Casci et al., 2019)

eye, with Scer\GAL4^GMR.PF

(Casci et al., 2019, Kim et al., 2018, Daigle et al., 2013, Lanson et al., 2011)

eye, with Scer\GAL4^GMR.PU

(Kim et al., 2023, Fortuna et al., 2021, Zhu et al., 2017)

interommatidial bristle, with Scer\GAL4^GMR.PF

(Lanson et al., 2011)

NMJ bouton | larval stage, with Scer\GAL4^Toll-6-D42

(Casci et al., 2019)

ommatidium, with Scer\GAL4^GMR.PF

(Lanson et al., 2011)

retina, with Scer\GAL4^GMR.PF

(Casci et al., 2019, Lanson et al., 2011)

Detailed Description

Statement

Reference

The expression of Hsap\FUS^{R518K.UAS.Tag:HA} under the control of Scer\GAL4^GMR.PU induces a decrease in climbing ability and eye degeneration.

(Fortuna et al., 2021)

Expressing Hsap\FUS^{R518K.UAS.Tag:HA} under the control of Scer\GAL4^GMR.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. There is a decrease in adult climbing activity.

Expressing Hsap\FUS^{R518K.UAS.Tag:HA} under the control of Scer\GAL4^Toll-6-D42 leads to more satellite boutons (but no change in the number of mature boutons or boutons size) in the larval neuromuscular junction.

(Casci et al., 2019)

The expression of Hsap\FUS^{R518K.UAS.Tag:HA} under the control of Scer\GAL4^GMR.PF leads to a rough eye phenotype, with depigmentation.

(Kim et al., 2018)

Adults expressing Hsap\FUS^{R518K.UAS.Tag:HA} under the control of Scer\GAL4^Toll-6-D42 show a significant and progressive decrease in locomotor ability (i.e. speed), as compared to controls.

(Mallik et al., 2018)

Expressing Hsap\FUS^{R518K.UAS.Tag:HA} under the control of Scer\GAL4^GMR.PU causes a severe rough eye phenotype with patchy red pigmentation.

(Zhu et al., 2017)

Motor neuron expression of Hsap\FUS^{R518K.Scer\UAS.T:Ivir\HA1} using Scer\GAL4^VGlut-OK371 leads to larval paralysis and pupal lethality.

Expression of Hsap\FUS^{R518K.Scer\UAS.T:Ivir\HA1} in motor neurons under the control of Scer\GAL4^VGlut-OK371 causes smaller brain size in third instar larvae.

(Daigle et al., 2013)

Expression of Hsap\FUS^{R518K.Scer\UAS.T:Ivir\HA1} in the developing eye under the control of Scer\GAL4^GMR.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\FUS^{R518K.Scer\UAS.T:Ivir\HA1} in the nervous system under the control of Scer\GAL4^Appl.G1a causes pupal lethality.

Expression of Hsap\FUS^{R518K.Scer\UAS.T:Ivir\HA1} in motor neurons under the control of Scer\GAL4^VGlut-OK371 causes a larval-crawling defect.

(Lanson et al., 2011)

External Data

Linkouts

Interactions

Show genetic interaction network for Enhancers & Suppressors

Phenotypic Class

Enhanced by

Statement

Reference

Hsap\FUS^{R518K.UAS.Tag:HA}, Scer\GAL4^GMR.PU has visible | adult stage phenotype, enhanceable by Rm62^unspecified