Human Gene Module / Chromosome 16 / KCTD13

KCTD13Potassium channel tetramerisation domain containing 13

Score
3
Suggestive Evidence Criteria 3.1
Autism Reports / Total Reports
2 / 7
Rare Variants / Common Variants
4 / 0
Aliases
KCTD13, FKSG86,  PDIP1,  POLDIP1,  hBACURD1
Associated Syndromes
-
Genetic Category
Rare Single Gene Mutation, Functional
Chromosome Band
16p11.2
Associated Disorders
-
Relevance to Autism

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.

Reports related to KCTD13 (7 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary KCTD13 is a major driver of mirrored neuroanatomical phenotypes of the 16p11.2 copy number variant. Golzio C , et al. (2012) Yes -
2 Recent Recommendation Spatiotemporal 16p11.2 protein network implicates cortical late mid-fetal brain development and KCTD13-Cul3-RhoA pathway in psychiatric diseases. Lin GN , et al. (2015) No -
3 Recent Recommendation A Potential Contributory Role for Ciliary Dysfunction in the 16p11.2 600 kb BP4-BP5 Pathology. Migliavacca E , et al. (2015) No -
4 Support Identification of rare variants in KCTD13 at the schizophrenia risk locus 16p11.2. Degenhardt F , et al. (2016) No -
5 Support Targeted sequencing and functional analysis reveal brain-size-related genes and their networks in autism spectrum disorders. Li J , et al. (2017) Yes -
6 Recent Recommendation Kctd13 deletion reduces synaptic transmission via increased RhoA. Escamilla CO , et al. (2017) No -
7 Recent Recommendation CRISPR/Cas9-mediated Knockout of the Neuropsychiatric Risk Gene KCTD13 Causes Developmental Deficits in Human Cortical Neurons Derived from Induced... Kizner V , et al. (2019) No -
Rare Variants   (4)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
- - copy_number_loss De novo NA - 22596160 Golzio C , et al. (2012)
c.6G>T p.Ser2%3D synonymous_variant Unknown - - 27668412 Degenhardt F , et al. (2016)
c.256A>C p.Ile86Leu missense_variant Familial - Simplex 28831199 Li J , et al. (2017)
c.405G>A p.Leu135%3D missense_variant Unknown Not maternal Multiplex 27668412 Degenhardt F , et al. (2016)
Common Variants  

No common variants reported.

SFARI Gene score
3

Suggestive Evidence

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 (PMID 22596160). An autistic proband with a de novo deletion including exons 3-5 of the KCTD13 gene was also identified in this report.

Score Delta: Decreased from 4 to 3

3

Suggestive Evidence

See all Category 3 Genes

The literature is replete with relatively small studies of candidate genes, using either common or rare variant approaches, which do not reach the criteria set out for categories 1 and 2. Genes that had two such lines of supporting evidence were placed in category 3, and those with one line of evidence were placed in category 4. Some additional lines of "accessory evidence" (indicated as "acc" in the score cards) could also boost a gene from category 4 to 3.

10/1/2019
4
icon
3

Decreased from 4 to 3

New Scoring Scheme
Description

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 (PMID 22596160). An autistic proband with a de novo deletion including exons 3-5 of the KCTD13 gene was also identified in this report.

Reports Added
[New Scoring Scheme]
7/1/2019
4
icon
4

Decreased from 4 to 4

Description

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 (PMID 22596160). An autistic proband with a de novo deletion including exons 3-5 of the KCTD13 gene was also identified in this report.

10/1/2017
4
icon
4

Decreased from 4 to 4

Description

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 (PMID 22596160). An autistic proband with a de novo deletion including exons 3-5 of the KCTD13 gene was also identified in this report.

10/1/2016
4
icon
4

Decreased from 4 to 4

Description

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 (PMID 22596160). An autistic proband with a de novo deletion including exons 3-5 of the KCTD13 gene was also identified in this report.

4/1/2015
4
icon
4

Decreased from 4 to 4

Description

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 (PMID 22596160). An autistic proband with a de novo deletion including exons 3-5 of the KCTD13 gene was also identified in this report.

1/1/2015
4
icon
4

Decreased from 4 to 4

Description

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 (PMID 22596160). An autistic proband with a de novo deletion including exons 3-5 of the KCTD13 gene was also identified in this report.

7/1/2014
No data
icon
4

Increased from No data to 4

Description

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 (PMID 22596160). An autistic proband with a de novo deletion including exons 3-5 of the KCTD13 gene was also identified in this report.

4/1/2014
No data
icon
4

Increased from No data to 4

Description

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 (PMID 22596160). An autistic proband with a de novo deletion including exons 3-5 of the KCTD13 gene was also identified in this report.

Krishnan Probability Score

Score 0.49345763911132

Ranking 4138/25841 scored genes


[Show Scoring Methodology]
Krishnan and colleagues generated probability scores genome-wide by using a machine learning approach on a human brain-specific gene network. The method was first presented in Nat Neurosci 19, 1454-1462 (2016), and scores for more than 25,000 RefSeq genes can be accessed in column G of supplementary table 3 (see: http://www.nature.com/neuro/journal/v19/n11/extref/nn.4353-S5.xlsx). A searchable browser, with the ability to view networks of associated ASD risk genes, can be found at asd.princeton.edu.
ExAC Score

Score 0.79196093357248

Ranking 3989/18225 scored genes


[Show Scoring Methodology]
The Exome Aggregation Consortium (ExAC) is a summary database of 60,706 exomes that has been widely used to estimate 'constraint' on mutation for individual genes. It was introduced by Lek et al. Nature 536, 285-291 (2016), and the ExAC browser can be found at exac.broadinstitute.org. The pLI score was developed as measure of intolerance to loss-of- function mutation. A pLI > 0.9 is generally viewed as highly constrained, and thus any loss-of- function mutations in autism in such a gene would be more likely to confer risk. For a full list of pLI scores see: ftp://ftp.broadinstitute.org/pub/ExAC_release/release0.3.1/functional_gene_constraint/fordist_cle aned_exac_nonTCGA_z_pli_rec_null_data.txt
Sanders TADA Score

Score 0.92946760507709

Ranking 11175/18665 scored genes


[Show Scoring Methodology]
The TADA score ('Transmission and De novo Association') was introduced by He et al. PLoS Genet 9(8):e1003671 (2013), and is a statistic that integrates evidence from both de novo and transmitted mutations. It forms the basis for the claim of 65 individual genes being strongly associated with autism risk at a false discovery rate of 0.1 (Sanders et al. Neuron 87, 1215-1233 (2015)). The calculated TADA score for 18,665 RefSeq genes can be found in column P of Supplementary Table 6 in the Sanders et al. paper (the column headed 'tadaFdrAscSscExomeSscAgpSmallDel'), which represents a combined analysis of exome data and small de novo deletions (see www.cell.com/cms/attachment/2038545319/2052606711/mmc7.xlsx).
Zhang D Score

Score 0.41571474409261

Ranking 1277/20870 scored genes


[Show Scoring Methodology]
The DAMAGES score (disease-associated mutation analysis using gene expression signatures), or D score, was developed to combine evidence from de novo loss-of- function mutation with evidence from cell-type- specific gene expression in the mouse brain (specifically translational profiles of 24 specific mouse CNS cell types isolated from 6 different brain regions). Genes with positive D scores are more likely to be associated with autism risk, with higher-confidence genes having higher D scores. This statistic was first presented by Zhang & Shen (Hum Mutat 38, 204- 215 (2017), and D scores for more than 20,000 RefSeq genes can be found in column M in supplementary table 2 from that paper.
CNVs associated with KCTD13(1 CNVs)
16p11.2 111 Deletion-Duplication 174  /  1556
Interaction Table
Interactor Symbol Interactor Name Interactor Organism Interactor Type Entrez ID Uniprot ID
ARMC7 armadillo repeat containing 7 Human Protein Binding 79637 Q9H6L4
C6orf55 Vps20-associated 1 homolog (S. cerevisiae) Human Protein Binding 51534 Q9NP79
FLJ22494 nudix (nucleoside diphosphate linked moiety X)-type motif 18 Human Protein Binding 79873 Q6ZVK8
LAMB4 laminin, beta 4 Human Protein Binding 22798 A4D0S4
LNX ligand of numb-protein X 1, E3 ubiquitin protein ligase Human Protein Binding 84708 Q8TBB1
NUDT18 nudix (nucleoside diphosphate linked moiety X)-type motif 18 Human Protein Binding 79873 Q6ZVK8
SPRTN SprT-like N-terminal domain Human Protein Binding 83932 Q9H040
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SFARI Gene Update

We are pleased to announce some changes to the ongoing curation of the data in SFARI Gene. In the context of a continued effort to develop the human gene module and its manually curated list of autism risk genes, we are modifying other aspects of the site to focus on the information that is of greatest interest to the research community. The version of SFARI Gene that has been developed until now will be frozen and will remain available as “SFARI Gene Archive”. Please see the announcement for more details.
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