FlyBase Allele Report: Dmel\Vap33[ALS8]

Genomic fragment including Vap-33A which has been mutated to contain the amino acid replacement P58S. This mutation is equivalent to the P56S mutation in Hsap\VAPB which is associated with the ALS8 disease in humans.

(Moustaqim-Barrette et al., 2014)

Allele components

Component

Use(s)

Regulatory region(s)

Vap33

Encoded product / tool

Vap33

Mutations Mapped to the Genome

Curation Data

Type

Location

Additional Notes

References

point_mutation

X:3,951,522..3,951,522 [+]

Nucleotide change:

C3951522T

Amino acid change:

P58S | Vap33-PA; P58S | Vap33-PB; P58S | Vap33-PC; P58S | Vap33-PE

Reported amino acid change:

P58S

Comment:

Analogous mutation in human VAPB implicated in amyotrophic lateral sclerosis 8 and spinal muscular atrophy, late onset, Finkel type; mutation carried on in vitro construct; site of nucleotide substitution in fly gene inferred by FlyBase curator.

(Moustaqim-Barrette et al., 2014)

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 type 8

CEA with Vap33^Δ31

(Moustaqim-Barrette et al., 2014)

CEA

(Thulasidharan et al., 2024, Mao et al., 2019)

CEA with Vap33^Δ166

(Thulasidharan et al., 2024)

model of autosomal dominant adult-onset proximal spinal muscular atrophy

CEA

(Mao et al., 2019)

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.

(Moustaqim-Barrette et al., 2014)

VAPB:p.Pro56Ser

(FlyBase curators, 2019-)

Variants Synonym(s)

Associated human disease model(s)

External database links

ClinVar: VAPB_4806

Comments concerning this variant

Phenotypic Data

Phenotypic Class

abnormal flight | progressive, with Vap33^Δ31

(Moustaqim-Barrette et al., 2014)

abnormal neuroanatomy | adult stage, with Vap33^Δ31

(Moustaqim-Barrette et al., 2014)

abnormal neurophysiology | adult stage | progressive, with Vap33^Δ31

(Moustaqim-Barrette et al., 2014)

short lived, with Vap33^Δ31

(Moustaqim-Barrette et al., 2014)

Phenotype Manifest In

adult cerebrum, with Vap33^Δ31

(Moustaqim-Barrette et al., 2014)

adult optic lobe, with Vap33^Δ31

(Moustaqim-Barrette et al., 2014)

endoplasmic reticulum, with Vap33^Δ31

(Moustaqim-Barrette et al., 2014)

Detailed Description

Statement

Reference

Vap-33A^Δ31 animals carrying Vap-33A^ALS8 have a severely reduced lifespan. The flies show a progressive flight defect which worsens with age. The brains of 12 day old Vap-33A^Δ31; Vap-33A^ALS8 adults have numerous vacuoles in the optic lobe and central brain (defects are more common in the central lobe). The ability of the TTM muscles to maintain a response to 200Hz stimulation of the giant fiber system is reduced compared to wild type at day 6 and this ability declines over time in Vap-33A^Δ31 ; Vap-33A^ALS8 adults. 12 day old flies show accumulation of ubiquitinated proteins and markers of endoplasmic reticulum stress are significantly upregulated compared to wild type.

(Moustaqim-Barrette et al., 2014)

External Data

Linkouts

Interactions

Show genetic interaction network for Enhancers & Suppressors

Phenotypic Class

Suppressed by

Statement

Reference

Vap33^Δ31, Vap33^ALS8 has abnormal flight | progressive phenotype, suppressible by Hsap\OSBPL8^UAS.Tag:HA/Scer\GAL4^C164

(Moustaqim-Barrette et al., 2014)

Vap33^Δ31, Vap33^ALS8 has short lived phenotype, suppressible | partially by Hsap\OSBPL8^UAS.Tag:HA/Scer\GAL4^C164

(Moustaqim-Barrette et al., 2014)

Vap33^Δ31, Vap33^ALS8 has abnormal flight | progressive phenotype, suppressible by Hsap\OSBPL8^UAS.Tag:HA/Scer\GAL4^Toll-6-D42

(Moustaqim-Barrette et al., 2014)

Vap33^Δ31, Vap33^ALS8 has short lived phenotype, suppressible | partially by Hsap\OSBPL8^UAS.Tag:HA/Scer\GAL4^Toll-6-D42

(Moustaqim-Barrette et al., 2014)

Phenotype Manifest In

Additional Comments

Genetic Interactions

Statement

Reference

Xenogenetic Interactions

Statement

Reference

The reduction in lifespan and the flight defects seen in 12 day old Vap-33A^Δ31; Vap-33A^ALS8 flies are significantly suppressed by expression of Hsap\OSBPL8^{Scer\UAS.T:Ivir\HA1} under the control of either Scer\GAL4^C164 or Scer\GAL4^Toll-6-D42.

(Moustaqim-Barrette et al., 2014)

Complementation and Rescue Data

Rescued by

Vap33^Δ31/Vap33^ALS8 is rescued by Vap33^+tMa

(Moustaqim-Barrette et al., 2014)

Partially rescues

Vap33^ALS8 partially rescues Vap33^Δ31

(Moustaqim-Barrette et al., 2014)

Comments

Vap-33A^ALS8 insertion lines usually (8/11 lines) rescue the lethality of Vap-33A^Δ31 animals, but the rescued adults have a significantly reduced lifespan.

Vap-33A^+tMa rescues the lethality, reduced lifespan, progressive flight defects and central nervous system defects seen in Vap-33A^Δ31 ; Vap-33A^ALS8 animals.

(Moustaqim-Barrette et al., 2014)

Images (0)

Mutant

Wild-type

Stocks (0)

Notes on Origin

Discoverer

External Crossreferences and Linkouts ( 0 )

Synonyms and Secondary IDs (3)

Reported As

Symbol Synonym

Vap-33A^ALS8

Vap33^ALS8

gVAP^P58S

(Tendulkar et al., 2022)

Name Synonyms

Secondary FlyBase IDs

References (5)

Report Sections

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