Human Gene Module / Chromosome 18 / KATNAL2

KATNAL2Katanin p60 subunit A-like 2

Score
1
High Confidence Criteria 1.1
Autism Reports / Total Reports
6 / 7
Rare Variants / Common Variants
16 / 0
Aliases
KATNAL2, DKFZp667C165,  MGC33211
Associated Syndromes
-
Genetic Category
Rare Single Gene Mutation
Chromosome Band
18q21.1
Associated Disorders
-
Relevance to Autism

De novo variants in the KATNAL2 gene was been identified in autistic probands from simplex families in two separate reports (Sanders et al., 2012; O'Roak et al., 2012).

Molecular Function

Severs microtubules in vitro in an ATP-dependent manner. This activity may promote rapid reorganization of cellular microtubule arrays

Reports related to KATNAL2 (7 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary De novo mutations revealed by whole-exome sequencing are strongly associated with autism. Sanders SJ , et al. (2012) Yes -
2 Support Sporadic autism exomes reveal a highly interconnected protein network of de novo mutations. O'Roak BJ , et al. (2012) Yes -
3 Recent recommendation Synaptic, transcriptional and chromatin genes disrupted in autism. De Rubeis S , et al. (2014) Yes -
4 Support Whole-genome sequencing of quartet families with autism spectrum disorder. Yuen RK , et al. (2015) Yes -
5 Recent recommendation Low load for disruptive mutations in autism genes and their biased transmission. Iossifov I , et al. (2015) Yes -
6 Recent recommendation A Retroviral CRISPR-Cas9 System for Cellular Autism-Associated Phenotype Discovery in Developing Neurons. Williams MR , et al. (2016) No -
7 Support Targeted sequencing identifies 91 neurodevelopmental-disorder risk genes with autism and developmental-disability biases. Stessman HA , et al. (2017) Yes -
Rare Variants   (16)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type Author, Year
c.510+1G>A - splice_site_variant De novo - Simplex Sanders SJ , et al. (2012)
- - splice_site_variant De novo - Simplex O'Roak BJ , et al. (2012)
del(G) - frameshift_variant Familial Maternal Simplex De Rubeis S , et al. (2014)
c.310C>T p.Arg104Trp missense_variant Familial Paternal Simplex De Rubeis S , et al. (2014)
AC/A - frameshift_variant Unknown - Unknown De Rubeis S , et al. (2014)
c.673+1G>A - splice_site_variant Unknown - Unknown De Rubeis S , et al. (2014)
c.436C>T p.Arg146Ter stop_gained Unknown - Unknown De Rubeis S , et al. (2014)
c.730T>C p.Phe244Leu missense_variant Unknown - Unknown De Rubeis S , et al. (2014)
c.428G>A p.Arg143Gln missense_variant Unknown - Unknown De Rubeis S , et al. (2014)
c.740C>T p.Ala248Val missense_variant Unknown - Unknown De Rubeis S , et al. (2014)
c.1022G>A p.Arg341His missense_variant Unknown - Unknown De Rubeis S , et al. (2014)
c.1045G>A p.Asp349Asn missense_variant Unknown - Unknown De Rubeis S , et al. (2014)
c.907C>T p.Arg303Trp missense_variant Unknown - Unknown De Rubeis S , et al. (2014)
c.157C>T p.Gln53Ter stop_gained Familial Maternal Multiplex Yuen RK , et al. (2015)
c.429del p.Ser144GlnfsTer5 frameshift_variant De novo - - Stessman HA , et al. (2017)
c.727T>C p.Phe243Leu missense_variant De novo - - Stessman HA , et al. (2017)
Common Variants  

No common variants reported.

SFARI Gene score
1

High Confidence

De novo variants in the KATNAL2 gene have been identified in autistic probands from simplex families in two separate reports (PMIDs 22495306 and 22495309). Two of these variants are stop-gains and many are missense variants in EVS. Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) identified KATNAL2 as a gene meeting high statistical significance with a FDR ?0.01, meaning that this gene had a ?99% chance of being a true autism gene (PMID 25363760). A third de novo loss-of-function variant and a likely damaging de novo missense variant in KATNAL2 were identified in probands from the Autism Genetic Resource Exchange (AGRE) in Stessman et al., 2017.

1

High Confidence

See all Category 1 Genes

We considered a rigorous statistical comparison between cases and controls, yielding genome-wide statistical significance, with independent replication, to be the strongest possible evidence for a gene. These criteria were relaxed slightly for category 2.

01-01-2017
1

Initial score established: 1

Description

De novo variants in the KATNAL2 gene have been identified in autistic probands from simplex families in two separate reports (PMIDs 22495306 and 22495309). Two of these variants are stop-gains and many are missense variants in EVS. Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) identified KATNAL2 as a gene meeting high statistical significance with a FDR ?0.01, meaning that this gene had a ?99% chance of being a true autism gene (PMID 25363760). A third de novo loss-of-function variant and a likely damaging de novo missense variant in KATNAL2 were identified in probands from the Autism Genetic Resource Exchange (AGRE) in Stessman et al., 2017.

Reports Added
[]
CNVs associated with KATNAL2(4 CNVs)
13q14.12 3 Deletion 6  /  15
14q12-q21.3 1 Duplication 2  /  1
15q15.3-q21.1 1 Duplication 2  /  1
17q21.32-q21.33 1 Deletion 2  /  2
Interaction Table
Interactor Symbol Interactor Name Interactor Organism Interactor Type Entrez ID Uniprot ID
STRIP1 striatin interacting protein 1 Human Protein Binding 85369 Q5VSL9
Submit New Gene

Report an Error