FlyBase Allele Report: Hsap\CACNA1A[UAS.αACT.Q70]

General Information

Symbol

Hsap\CACNA1A^{UAS.αACT.Q70}

Species

H. sapiens

Name

FlyBase ID

FBal0319788

Feature type

allele

Associated gene

Hsap\CACNA1A

Associated Insertion(s)

Carried in Construct

P{UAS-αACT.Q70}

Also Known As

α1ACT(Q70)

Key Links

Transgenic product class

trinucleotide_repeat_expansion

(Tsou et al., 2015)

Mutagen

in vitro construct

Nature of the Allele

Transgenic product class

trinucleotide_repeat_expansion

(Tsou et al., 2015)

Mutagen

in vitro construct

(Tsou et al., 2015)

Progenitor genotype

Carried in construct

P{UAS-αACT.Q70}

Cytology

Description

UAS drives expression of the entire mRNA sequence of the transcription factor "α1ACT" (with its native start and stop codons), which is one product of the bicistronic Hsap\CACNA1A gene. The CAG repeat/polyQ region that is linked to spinocerebellar ataxia type 6 occurs within α1ACT, and this construct contains a pathogenic, polyQ-expanded version with a repeat of 70Q. (The wild type CAG repeat is between 4 and 18, whereas the SCA6-causing allele shows an expansion between 19 and 33 repeats.)

(Tsou et al., 2015)

Allele components

Component

Use(s)

Regulatory region(s)

UAS

binary expression system - regulatory region

Encoded product / tool

Hsap\CACNA1A

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 spinocerebellar ataxia 6

CEA

(Sujkowski et al., 2022, Johnson et al., 2021, Tsou et al., 2016, Tsou et al., 2015)

Modifiers Based on Experimental Evidence ( 1 )

Disease

Interaction

References

model of spinocerebellar ataxia 6

is exacerbated by DnaJ-1^RNAi.UAS.cUa

(Tsou et al., 2015)

is exacerbated by Hsap\ATXN3^{UAS.Tag:polyHis}

(Tsou et al., 2015)

is exacerbated by Hsap\ATXN3^{Scer\UAS.T:Zzzz\His6}

(Tsou et al., 2015)

is ameliorated by DnaJ-1^UAS.cKa

(Tsou et al., 2015)

is ameliorated by Kap-α3^D93

(Tsou et al., 2015)

is ameliorated by Kap-α3^JF02686

(Tsou et al., 2015)

is ameliorated by CG4968^GD11489

(Tsou et al., 2015)

is ameliorated by trbd^GD14218

(Tsou et al., 2015)

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

Disease-implicated variant(s)

This allele represents a human variant implicated in disease.

(Tsou et al., 2015)

This construct uses the α1ACT short isoform of CACNA1A; the primary variant description is relative to that isoform.

CACNA1A(α1ACT):p.Gln354[70]

(FlyBase curators, 2019-)

Variants Synonym(s)

CACNA1A:p.Gln2313[70Gln]

CACNA1A(&agr1ACT):p.Gln354[70Gln]

CACNA1A,(CAG)n REPEAT EXPANSION

CACNA1A:p.Gln2313[70]

CACNA1A(&agr1ACT):p.Gln354[70]

CACNA1A(α1ACT):p.Gln354[70Gln]

Associated human disease model(s)

spinocerebellar ataxia 6

External database links

ClinVar: CACNA1A_562099

Comments concerning this variant

Phenotypic Data

Phenotypic Class

abnormal eye color | adult stage | progressive, with Scer\GAL4^GMR.PU

(Tsou et al., 2015)

abnormal locomotor behavior | adult stage | progressive, with Scer\GAL4^elav.PU

(Tsou et al., 2015)

abnormal locomotor behavior | adult stage | progressive, with Scer\GAL4^repo.PU

(Tsou et al., 2015)

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

(Tsou et al., 2015)

abnormal neuroanatomy | adult stage | progressive, with Scer\GAL4^GMR.PU

(Tsou et al., 2015)

lethal - all die before end of P-stage, with Scer\GAL4^sqh.PW

(Tsou et al., 2016)

lethal - all die during pharate adult stage, with Scer\GAL4^sqh.PW

(Tsou et al., 2015)

short lived, with Scer\GAL4^elav.PU

(Tsou et al., 2015)

short lived, with Scer\GAL4^Mef2.PU

(Tsou et al., 2015)

short lived, with Scer\GAL4^repo.PU

(Tsou et al., 2015)

visible | progressive, with Scer\GAL4^GMR.PU

(Tsou et al., 2016)

Phenotype Manifest In

eye, with Scer\GAL4^GMR.PU

(Tsou et al., 2016)

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

(Tsou et al., 2015)

ommatidium, with Scer\GAL4^GMR.PU

(Tsou et al., 2016)

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

(Tsou et al., 2015)

Detailed Description

Statement

Reference

Expressing Hsap\CACNA1A^{UAS.αACT.Q70} under the control of Scer\GAL4^sqh.PW results in progressive eye degeneration, with loss of inter-ommatidial boundaries accumulation of densely-staining bodies.

(Tsou et al., 2016)

Expression of Hsap\CACNA1A^{Scer\UAS.αACT.Q70} driven by Scer\GAL4^sqh.PW leads to lethality before or while adults eclose from the pupal case. Expression of Hsap\CACNA1A^{Scer\UAS.αACT.Q70} driven by Scer\GAL4^elav.PU or Scer\GAL4^repo.PU leads to a significantly shortened lifespan and progressive (significant by 28 and 35 days post eclosion) loss of climbing ability compared to controls. Expression of Hsap\CACNA1A^{Scer\UAS.αACT.Q70} driven by Scer\GAL4^Mef2.PU leads to severely decreased lifespan, with adults dying soon after eclosion.

Expression of Hsap\CACNA1A^{Scer\UAS.αACT.Q70} driven by Scer\GAL4^GMR.PU does not cause clear anomalies in the external portion of the retina in young adults; by 4 weeks of age there is very mild dyspigmentation of the external retina. Scer\GAL4^GMR.PU>Hsap\CACNA1A^{Scer\UAS.αACT.Q70} flies show retinal degeneration as flies age (obvious at 4 weeks old), with separation of retinal structures, disappearance of ommatidial boundaries and in some cases restriction of retinal depth, along with presence of densely staining punctate structures. A more sensitive GFP-based method shows that expression of Hsap\CACNA1A^{Scer\UAS.αACT.Q70} driven by Scer\GAL4^GMR.PU is toxic in fly eyes (significant loss at day 1, 7 and 14).

(Tsou et al., 2015)

External Data

Linkouts

Interactions

Show genetic interaction network for Enhancers & Suppressors

Phenotypic Class

Enhanced by

Statement

Reference

Hsap\CACNA1A^{UAS.αACT.Q70}, Scer\GAL4^GMR.PU has abnormal neuroanatomy | adult stage | progressive phenotype, enhanceable by DnaJ-1^RNAi.UAS.cUa, Scer\GAL4^GMR.PU

(Tsou et al., 2015)

Hsap\CACNA1A^{UAS.αACT.Q70}, Scer\GAL4^GMR.PU has abnormal neuroanatomy | adult stage | progressive phenotype, enhanceable by Hsap\ATXN3^{UAS.Tag:polyHis}, Scer\GAL4^GMR.PU