Human Gene Module / Chromosome 13 / KATNAL1

KATNAL1katanin catalytic subunit A1 like 1

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
3 / 4
Rare Variants / Common Variants
3 / 0
Aliases
-
Associated Syndromes
-
Chromosome Band
13q12.3
Associated Disorders
-
Relevance to Autism

A de novo frameshift variant in the KATNAL1 gene was identified by whole-genome sequencing in an ASD proband from a simplex family from the ASD: Genomes to Outcome Study cohort in Yuen et al., 2017. A mouse line with a loss-of-function missense mutation in the Katnal1 gene was shown in Banks et al., 2017 to exhibit behavioral deficits including decreased ultrasonic vocalizations, circadian rhythm and sleep anomalies, deficits in learning and memory, and hyperactivity, as well as defects in both neuronal migration and morphology and motile cilia of the ependymal lining of the lateral ventricle.

Molecular Function

Regulates microtubule dynamics in Sertoli cells, a process that is essential for spermiogenesis and male fertility. Severs microtubules in an ATP-dependent manner, promoting rapid reorganization of cellular microtubule arrays.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to KATNAL1 (4 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary Whole genome sequencing resource identifies 18 new candidate genes for autism spectrum disorder C Yuen RK et al. (2017) Yes -
2 Recent Recommendation A missense mutation in Katnal1 underlies behavioural, neurological and ciliary anomalies Banks G , et al. (2017) No -
3 Support - Zhou X et al. (2022) Yes -
4 Support - Cirnigliaro M et al. (2023) Yes -
Rare Variants   (3)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.19T>G p.Cys7Gly missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.597_598del p.Ser200GlnfsTer4 frameshift_variant De novo - Simplex 28263302 C Yuen RK et al. (2017)
c.401del p.Gly134AspfsTer3 frameshift_variant Familial Maternal Multiplex 37506195 Cirnigliaro M et al. (2023)
Common Variants  

No common variants reported.

SFARI Gene score
2

Strong Candidate

A de novo frameshift variant in the KATNAL1 gene was identified by whole-genome sequencing in an ASD proband from a simplex family from the ASD: Genomes to Outcome Study cohort in Yuen et al., 2017. A mouse line with a loss-of-function missense mutation in the Katnal1 gene was shown in Banks et al., 2017 to exhibit behavioral deficits including decreased ultrasonic vocalizations, circadian rhythm and sleep anomalies, deficits in learning and memory, and hyperactivity, as well as defects in both neuronal migration and morphology and motile cilia of the ependymal lining of the lateral ventricle.

Score Delta: Score remained at 2

criteria met
See SFARI Gene'scoring criteria
2

Strong Candidate

See all Category 2 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.

4/1/2022
3
icon
2

Decreased from 3 to 2

Description

A de novo frameshift variant in the KATNAL1 gene was identified by whole-genome sequencing in an ASD proband from a simplex family from the ASD: Genomes to Outcome Study cohort in Yuen et al., 2017. A mouse line with a loss-of-function missense mutation in the Katnal1 gene was shown in Banks et al., 2017 to exhibit behavioral deficits including decreased ultrasonic vocalizations, circadian rhythm and sleep anomalies, deficits in learning and memory, and hyperactivity, as well as defects in both neuronal migration and morphology and motile cilia of the ependymal lining of the lateral ventricle.

10/1/2019
4
icon
3

Decreased from 4 to 3

New Scoring Scheme
Description

A de novo frameshift variant in the KATNAL1 gene was identified by whole-genome sequencing in an ASD proband from a simplex family from the ASD: Genomes to Outcome Study cohort in Yuen et al., 2017. A mouse line with a loss-of-function missense mutation in the Katnal1 gene was shown in Banks et al., 2017 to exhibit behavioral deficits including decreased ultrasonic vocalizations, circadian rhythm and sleep anomalies, deficits in learning and memory, and hyperactivity, as well as defects in both neuronal migration and morphology and motile cilia of the ependymal lining of the lateral ventricle.

Reports Added
[New Scoring Scheme]
4/1/2017
icon
4

Increased from to 4

Description

A de novo frameshift variant in the KATNAL1 gene was identified by whole-genome sequencing in an ASD proband from a simplex family from the ASD: Genomes to Outcome Study cohort in Yuen et al., 2017. A mouse line with a loss-of-function missense mutation in the Katnal1 gene was shown in Banks et al., 2017 to exhibit behavioral deficits including decreased ultrasonic vocalizations, circadian rhythm and sleep anomalies, deficits in learning and memory, and hyperactivity, as well as defects in both neuronal migration and morphology and motile cilia of the ependymal lining of the lateral ventricle.

Krishnan Probability Score

Score 0.44770897739187

Ranking 12044/25841 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.
Original Source
ExAC Score

Score 0.94632658254645

Ranking 2751/18225 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
Original Source
Sanders TADA Score

Score 0.92609518952627

Ranking 10357/18665 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).
Original Source
Zhang D Score

Score 0.27440140560305

Ranking 3116/20870 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.
Original Source
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