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.
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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.
Rescue Type:
RESCUE-Genetic
Rescue Paradigm:
100 pg each of wildtype human KCTD13 and CEP290 transcripts were injected into wild-type zebrafish embryos at the 1- to 2-cell stage.
Treatment does not improve measured phenotype (was expected to do so)
Ameliorated
Treatment provides partial correction or improvement of measured phenotype
No adverse effect
Treatment does not affect the parameter adversely
Sustained effect
Treatment has long term effect of restoration or amelioration, tested AFTER stopping administration (not applied for continuing long-term treatment) . Will be applied only where treatment has had restorative effects during administration or in the first battery of tests conducted.
No sustained effect
Treatment has no long term of restoration or amelioration detectable, after stopping administration. Will be applied only where treatment has had restorative effects during administration or in the first battery of tests conducted.
Description: Coinjection of kctd13 and cep290 transcripts rescued HuC/D expression compared to embryos injected with kctd13 transcript alone.
Exp Paradigm: Injected embryos were stained with HuC/D antibody. Anti-HuC/D is a marker for post- mitotic neurons, i.e., cells positive for HuC and HuD (also known as ELAVL3 and ELAVL4).
Description: Coinjection of cep290 mRNA and kctd13 mRNA reduced unilateral expression of HuC/D compared to embryos injected with Kctd13 mRNA alone.
Exp Paradigm: Injected embryos were stained with HuC/D antibody. Anti-HuC/D is a marker for post- mitotic neurons, i.e., cells positive for HuC and HuD (also known as ELAVL3 and ELAVL4).
Description: KCTD13 RNA and CEP290 RNA coinjection showed a significant rescue of bilateral HuC/D expression in the forebrain.
Exp Paradigm: Injected embryos were stained with HuC/D antibody. Anti-HuC/D is a marker for post- mitotic neurons, i.e., cells positive for HuC and HuD (also known as ELAVL3 and ELAVL4).
Description: Coinjection of kctd13 transcript and cep290 transcript showed no significant increase in ectopic HuC/D expression compared to embryos injected with kctd13 transcript alone.
Exp Paradigm: Injected embryos were stained with HuC/D antibody. Anti-HuC/D is a marker for post- mitotic neurons, i.e., cells positive for HuC and HuD (also known as ELAVL3 and ELAVL4).
Description: KCTD13 mRNA injection shows reduced bilateral HuC/D expression compared to controls. Exp Paradigm: Injected embryos were stained with HuC/D antibody. Anti-HuC/D is a marker for post- mitotic neurons, i.e., cells positive for HuC and HuD (also known as ELAVL3 and ELAVL4).
Description: Kctd13 mRNA injection increased unilateral HuC/D expression compared to controls. Exp Paradigm: Injected embryos were stained with HuC/D antibody. Anti-HuC/D is a marker for post- mitotic neurons, i.e., cells positive for HuC and HuD (also known as ELAVL3 and ELAVL4).
Description: Injection of kctd13 transcript reduced HuC/D expression compared to controls. Exp Paradigm: Injected embryos were stained with HuC/D antibody. Anti-HuC/D is a marker for post- mitotic neurons, i.e., cells positive for HuC and HuD (also known as ELAVL3 and ELAVL4).
