Overexpression of the KCTD13 gene in zebrafish resulted in induction of the microcephaly phenotype associated with 16p11.2 duplications, whereas suppression of KCTD13 expression resulted in the macrocephaly phenotype associated with 16p11.2 deletions (Golzio et al., 2012). An autistic proband with a de novo deletion including exons 3-5 of the KCTD13 gene was also identified in this report.
Molecular Function
Substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex required for synaptic transmission (PMID 19782033). The BCR(KCTD13) E3 ubiquitin ligase complex mediates the ubiquitination of RHOA, leading to its degradation by the proteasome (PMID 19782033) Degradation of RHOA regulates the actin cytoskeleton and promotes synaptic transmission.
External Links
References
Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
KCTD13 is a major driver of mirrored neuroanatomical phenotypes of the 16p11.2 copy number variant.
Ubiquitous knockdown of CG10465 results in decreased climbing behavior, increased occurrence of seizures, but no change in pupal or larval mortality. Tissue-specific knockdown results in abnormal eye morphogenesis, increased cell proliferation, and decreased gene expression. These effects are ameliorated or restored by simultaneous knockdown of other neurodevelopmental genes.
References
Type
Title
Author, Year
Primary
Pervasive genetic interactions modulate neurodevelopmental defects of the autism-associated 16p11.2 deletion in Drosophila melanogaster.
Model Type:
Genetic
Model Genotype:
Transgenic
Mutation:
Ubiquitous knockdown of CG10465 was generated using RNAi transgenic line on medium at 25C degrees.
Allele Type: Knockdown
Strain of Origin: Unreported
Genetic Background: Unreported
ES Cell Line: Mutant ES Cell Line: Model Source: VDRC 107131
Model Type:
Genetic
Model Genotype:
Transgenic
Mutation:
Ubiquitous knockdown of CG10465 was generated using RNAi transgenic line on medium at room temperature.
Allele Type: Knockdown
Strain of Origin: Unreported
Genetic Background: Unreported
ES Cell Line: Mutant ES Cell Line: Model Source: VDRC 107131
Model Type:
Genetic
Model Genotype:
Transgenic
Mutation:
Eye-specific knockdown of CG10465 was generated using RNAi transgenic line with the GMR-Gal4 driver on medium at 30C degrees.
Allele Type: Conditional knockdown
Strain of Origin: Unreported
Genetic Background: Unreported
ES Cell Line: Mutant ES Cell Line: Model Source: VDRC 107131
Model Type:
Genetic
Model Genotype:
Transgenic
Mutation:
Wing-specific knockdown of CG10465 was generated using RNAi transgenic line with the MS1096-Gal4 driver on medium at 25C degrees.
Allele Type: Conditional knockdown
Strain of Origin: Unreported
Genetic Background: Unreported
ES Cell Line: Mutant ES Cell Line: Model Source: VDRC 107131
Model Type:
Genetic
Model Genotype:
Transgenic
Mutation:
Neuron-specific knockdown of CG10465 was generated using RNAi transgenic line with the Elav-Gal4 driver on medium at 25C degrees.
Allele Type: Conditional knockdown
Strain of Origin: Unreported
Genetic Background: Unreported
ES Cell Line: Mutant ES Cell Line: Model Source: VDRC 107131
Model Type:
Genetic
Model Genotype:
Transgenic
Mutation:
Neuron-specific knockdown of CG10465 was generated using RNAi transgenic line with the Elav-Gal4 driver on medium at 25C degrees.
Allele Type: Conditional knockdown
Strain of Origin: Unreported
Genetic Background: Unreported
ES Cell Line: Mutant ES Cell Line: Model Source: Bloomington 57172
Model Type:
Genetic
Model Genotype:
Transgenic
Mutation:
Neuron-specific knockdown of CG10465 was generated using RNAi transgenic line with the Elav-Gal4 driver on medium at 25C degrees.
Allele Type: Conditional knockdown
Strain of Origin: Unreported
Genetic Background: Unreported
ES Cell Line: Mutant ES Cell Line: Model Source: Bloomington 26002
Description: Knockdowns showed abnormal eye development compared to controls. Specifically, over 80% of Knockdowns showed rough eyes phenotypes. Additional defects were observed in cone cells, primary cells, bristle group, secondary cells, tertiary cells, eye rotation, and hexagon structure of the eye. Moreover, Knockdowns showed an increase in ommatidial diameter, the number of photoreceptor cells, and eye area compared to controls.
Description: Knockdowns showed an increase in seizures compared to controls. This increase is evident in both the percentage of seizing flies per sample and the number of seizures per fly.
