FlyBase Allele Report: Dmel\TER94[R152H.UAS.R]

General Information

Symbol

Dmel\TER94^R152H.UAS.R

Species

D. melanogaster

Name

FlyBase ID

FBal0261043

Feature type

allele

Associated gene

Dmel\TER94

Associated Insertion(s)

Carried in Construct

P{UAS-TER94.R152H}

Also Known As

UAS-dVCP R152H

Key Links

Genomic Maps

JBrowse

Transgenic product class

missense_variant

(Ritson et al., 2010)

Mutagen

in vitro construct

Nature of the Allele

Transgenic product class

missense_variant

(Ritson et al., 2010)

Mutagen

in vitro construct

(Ritson et al., 2010)

Progenitor genotype

Carried in construct

P{UAS-TER94.R152H}

Cytology

Description

Amino acid replacement: R152H.

(Ritson et al., 2010)

UAS regulatory sequences drive expression of mutated TER94 coding sequences.

(Ritson et al., 2010)

Allele components

Component

Use(s)

Regulatory region(s)

UAS

binary expression system - regulatory region

Encoded product / tool

TER94

Mutations Mapped to the Genome

Curation Data

Type

Location

Additional Notes

References

point_mutation

2R:9,990,994..9,990,994 [+]

Nucleotide change:

G9990994A

Amino acid change:

R152H | TER94-PA; R110H | TER94-PD; R177H | TER94-PE; R177H | TER94-PC

Reported amino acid change:

R152H

Comment:

R152H mutation reported relative to TER94-PA. Analogous mutation in human VCP implicated in IBMPFD1 and ALS14; mutation carried on in vitro construct; site of nucleotide substitution in fly gene and specific disease association inferred by FlyBase curator.

(Ritson et al., 2010)

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 neurodegenerative disease

CEA

(Ritson et al., 2010)

model of frontotemporal dementia and/or amyotrophic lateral sclerosis 6

CEA

(Chalmers et al., 2023, Tendulkar et al., 2022)

Modifiers Based on Experimental Evidence ( 1 )

Disease

Interaction

References

model of neurodegenerative disease

is ameliorated by TBPH^GD6943

(Ritson et al., 2010)

is ameliorated by Hrb27C^GD6964

(Ritson et al., 2010)

is exacerbated by TBPH^UAS.cRa

(Ritson et al., 2010)

is exacerbated by Hsap\TARDBP^{NESmut.UAS.Tag:MYC}

(Ritson et al., 2010)

is exacerbated by Hsap\TARDBP^UAS.Tag:MYC

(Ritson et al., 2010)

is ameliorated by x16^GD6898

(Ritson et al., 2010)

is exacerbated by Hsap\TARDBP^{NLSmut.UAS.Tag:MYC}

(Ritson et al., 2010)

model of frontotemporal dementia and/or amyotrophic lateral sclerosis 6

is ameliorated by Eip74EF^JF02515

(Chalmers et al., 2023)

is exacerbated by mir-34^{UAS.DsRed(Unk)}

(Chalmers et al., 2023)

is exacerbated by mir-34^UAS.pLUC

(Chalmers et al., 2023)

is exacerbated by mir-34^{sponge.V2.UAS.mCherry}

(Chalmers et al., 2023)

ameliorates amyotrophic lateral sclerosis type 8

modeled by Vap33^Δ166, Vap33^P58S.cRa.UAS

(Tendulkar et al., 2022)

Comments on Models/Modifiers Based on Experimental Evidence ( 2 )

Eye degeneration used to model disease. Point mutation in TER94^{R152H.Scer\UAS.R} models that most commonly found in Inclusion Body Myopathy associated with Paget’s Disease of Bone

(Ritson et al., 2010)

and Frontotemporal Dementia.

(Ritson et al., 2010)

Disease-implicated variant(s)

This allele represents a human variant implicated in disease.

(Ritson et al., 2010)

VCP:p.Arg155His

(FlyBase curators, 2019-)

Variants Synonym(s)

VCP:p.Arg110His

Associated human disease model(s)

External database links

ClinVar: VCP_8468

Comments concerning this variant

Phenotypic Data

Phenotypic Class

Phenotype Manifest In

eye, with Scer\GAL4^GMR.PF

(Casci et al., 2019, Ritson et al., 2010)

flight muscle cell, with Scer\GAL4^Mhc.PU

(Kim et al., 2013)

mitochondrion, with Scer\GAL4^Mhc.PU

(Kim et al., 2013)

NMJ bouton, with Scer\GAL4^VGlut-OK371

(Kim et al., 2013)

ommatidium, with Scer\GAL4^GMR.PF

(Ritson et al., 2010)

presynaptic active zone, with Scer\GAL4^VGlut-OK371

(Kim et al., 2013)

wing, with Scer\GAL4^Mhc.PU

(Kim et al., 2013)

Detailed Description

Statement

Reference

Expressing TER94^R152H.UAS.R under the control of Scer\GAL4^GMR.PF results in eye degeneration: rough eye with loss of pigmentation.

(Casci et al., 2019)

Expression of TER94^{R152H.Scer\UAS.R} under the control of Scer\GAL4^wor.PA induces the accumulation of ubiquitin conjugates in larval neuroblasts but does not cause neuroblast loss.

(Kuang et al., 2014)

Expression of TER94^{R152H.Scer\UAS.R} under the control of Scer\GAL4^VGlut-OK371 results in a high rate of pupal lethality. Those animals that do eclose die shortly thereafter.

Third instar larvae expressing TER94^{R152H.Scer\UAS.R} under the control of Scer\GAL4^VGlut-OK371 show locomotor defects. The neuromuscular junction is abnormal in these animals, with a significant reduction in the number of boutons, a significant increase in the number of ghost boutons (in which the presynaptic structure lacks an appositional postsynaptic structure) and a reduced active zone density.

Adults expressing TER94^{R152H.Scer\UAS.R} under the control of Scer\GAL4^Mhc.PU have a a dropped wing phenotype and show degeneration of thoracic flight muscles. Atrophy of individual flight muscles and loss of normal sarcomere architecture is seen. Numerous swollen mitochondria with disrupted cristae are seen in these muscles.

(Kim et al., 2013)

Expression of TER94^{R152H.Scer\UAS.R} in the developing eye under the control of Scer\GAL4^GMR.PF generates a severe rough eye phenotype with necrotic patches and histologically evident marked vacuolar degeneration.

(Ritson et al., 2010)

External Data

Linkouts

Interactions

Show genetic interaction network for Enhancers & Suppressors

Phenotypic Class

Enhanced by

Statement

Reference

Scer\GAL4^GMR.PF, TER94^R152H.UAS.R has increased cell death phenotype, enhanceable by Hsap\TARDBP^UAS.Tag:MYC, Scer\GAL4^GMR.PF

(Ritson et al., 2010)

NOT Enhanced by

Statement

Reference

Scer\GAL4^GMR.PF, TER94^R152H.UAS.R has increased cell death phenotype, non-enhanceable by Hsap\TARDBP^mutNES.UAS, Scer\GAL4^GMR.PF

(Ritson et al., 2010)

Suppressed by

Statement

Reference

Scer\GAL4^GMR.PF, TER94^R152H.UAS.R has increased cell death phenotype, suppressible by TBPH^GD6943/Scer\GAL4^GMR.PF

(Ritson et al., 2010)

Scer\GAL4^GMR.PF, TER94^R152H.UAS.R has increased cell death phenotype, suppressible by x16^GD6898/Scer\GAL4^GMR.PF

(Ritson et al., 2010)

Scer\GAL4^GMR.PF, TER94^R152H.UAS.R has increased cell death phenotype, suppressible by Hrb27C^GD6964, Scer\GAL4^GMR.PF

(Ritson et al., 2010)

NOT suppressed by

Statement

Reference

Scer\GAL4^GMR.PF, TER94^R152H.UAS.R has visible | adult stage phenotype, non-suppressible by mbl^KK107778/Scer\GAL4^GMR.PF

(Casci et al., 2019)

Scer\GAL4^GMR.PF, TER94^R152H.UAS.R has increased cell death phenotype, non-suppressible by Hsap\TARDBP^mutNES.UAS, Scer\GAL4^GMR.PF

(Ritson et al., 2010)

Enhancer of

Statement

Reference

TER94^R152H.UAS.R, Scer\GAL4^GMR.PF is an enhancer of increased cell death phenotype of Hsap\TARDBP^{M337V.UAS.Tag:MYC}, Scer\GAL4^GMR.PF

(Ritson et al., 2010)

Other

Statement

Reference

Hsap\TARDBP^{M337V.UAS.Tag:MYC}, Scer\GAL4^GMR.PF, TER94^R152H.UAS.R has lethal phenotype

(Ritson et al., 2010)

Phenotype Manifest In

Enhanced by

Statement

Reference

Scer\GAL4^GMR.PF, TER94^R152H.UAS.R has eye phenotype, enhanceable by Hsap\TARDBP^UAS.Tag:MYC, Scer\GAL4^GMR.PF

(Ritson et al., 2010)

Scer\GAL4^GMR.PF, TER94^R152H.UAS.R has ommatidium phenotype, enhanceable by Hsap\TARDBP^UAS.Tag:MYC, Scer\GAL4^GMR.PF

(Ritson et al., 2010)

NOT Enhanced by

Statement

Reference

Scer\GAL4^GMR.PF, TER94^R152H.UAS.R has eye phenotype, non-enhanceable by Hsap\TARDBP^mutNES.UAS, Scer\GAL4^GMR.PF

(Ritson et al., 2010)

Scer\GAL4^GMR.PF, TER94^R152H.UAS.R has ommatidium phenotype, non-enhanceable by Hsap\TARDBP^mutNES.UAS, Scer\GAL4^GMR.PF

(Ritson et al., 2010)

Suppressed by

Statement

Reference

Scer\GAL4^GMR.PF, TER94^R152H.UAS.R has ommatidium phenotype, suppressible by Hrb27C^GD6964, Scer\GAL4^GMR.PF

(Ritson et al., 2010)

Scer\GAL4^GMR.PF, TER94^R152H.UAS.R has eye phenotype, suppressible by TBPH^GD6943/Scer\GAL4^GMR.PF

(Ritson et al., 2010)

Scer\GAL4^GMR.PF, TER94^R152H.UAS.R has ommatidium phenotype, suppressible by TBPH^GD6943/Scer\GAL4^GMR.PF

(Ritson et al., 2010)

Scer\GAL4^GMR.PF, TER94^R152H.UAS.R has eye phenotype, suppressible by x16^GD6898/Scer\GAL4^GMR.PF

(Ritson et al., 2010)

Scer\GAL4^GMR.PF, TER94^R152H.UAS.R has ommatidium phenotype, suppressible by x16^GD6898/Scer\GAL4^GMR.PF

(Ritson et al., 2010)

Scer\GAL4^GMR.PF, TER94^R152H.UAS.R has eye phenotype, suppressible by Hrb27C^GD6964, Scer\GAL4^GMR.PF

(Ritson et al., 2010)

NOT suppressed by

Statement

Reference

Scer\GAL4^GMR.PF, TER94^R152H.UAS.R has eye phenotype, non-suppressible by mbl^KK107778/Scer\GAL4^GMR.PF

(Casci et al., 2019)

Scer\GAL4^GMR.PF, TER94^R152H.UAS.R has eye phenotype, non-suppressible by Hsap\TARDBP^mutNES.UAS, Scer\GAL4^GMR.PF

(Ritson et al., 2010)

Scer\GAL4^GMR.PF, TER94^R152H.UAS.R has ommatidium phenotype, non-suppressible by Hsap\TARDBP^mutNES.UAS, Scer\GAL4^GMR.PF

(Ritson et al., 2010)

Enhancer of

Statement

Reference

TER94^R152H.UAS.R, Scer\GAL4^GMR.PF is an enhancer of eye phenotype of Hsap\TARDBP^{M337V.UAS.Tag:MYC}, Scer\GAL4^GMR.PF

(Ritson et al., 2010)

TER94^R152H.UAS.R, Scer\GAL4^GMR.PF is an enhancer of ommatidium phenotype of Hsap\TARDBP^{M337V.UAS.Tag:MYC}, Scer\GAL4^GMR.PF

(Ritson et al., 2010)

Additional Comments

Genetic Interactions

Statement

Reference

Expression of TBPH^GD6943 in the developing eye dominantly suppresses the eye degeneration phenotype found upon expression of TER94^{R152H.Scer\UAS.R} (with both transgenes driven by Scer\GAL4^GMR.PF). This is concurrent with a significant reduction in the blinded phenotypic severity score.

Expression of x16^GD6898 in the developing eye dominantly suppresses the eye degeneration phenotype found upon expression of TER94^{R152H.Scer\UAS.R} (with both transgenes driven by Scer\GAL4^GMR.PF). This is concurrent with a significant reduction in the blinded phenotypic severity score.

Expression of Hrb27C^GD6964 in the developing eye dominantly suppresses the eye degeneration phenotype found upon expression of TER94^{R152H.Scer\UAS.R} (with both transgenes driven by Scer\GAL4^GMR.PF). This is concurrent with a significant reduction in the blinded phenotypic severity score.

A Df(2L)Dwee1-W05 or Df(2R)BSC136 background suppresses the eye degeneration phenotype found upon expression of TER94^{R152H.Scer\UAS.R} under the control of Scer\GAL4^GMR.PF. This is concurrent with a significant reduction in the blinded phenotypic severity score.

(Ritson et al., 2010)

Xenogenetic Interactions

Statement

Reference

The eye degeneration phenotype found upon expression of TER94^{R152H.Scer\UAS.R} under the control of Scer\GAL4^GMR.PF is strongly enhanced by co-expression of Hsap\TARDBP^Scer\UAS.cRa or Hsap\TARDBP^{mutNLS.Scer\UAS}.

The eye degeneration phenotype found upon expression of TER94^{R152H.Scer\UAS.R} under the control of Scer\GAL4^GMR.PF is unaffected by co-expression of Hsap\TARDBP^{mutNES.Scer\UAS}.

Co-expression of TER94^{R152H.Scer\UAS.R} with Hsap\TARDBP^{M337V.Scer\UAS} under the control of Scer\GAL4^GMR.PF results in lethality.

(Ritson et al., 2010)

Complementation and Rescue Data

Comments

Images (0)

Mutant

Wild-type

Stocks (1)

Bloomington

95266

w¹¹¹⁸; P{UAS-TER94.R152H}2

Notes on Origin