Human Gene Module / Chromosome 17 / TAOK1

TAOK1TAO kinase 1

SFARI Gene Score
1S
High Confidence, Syndromic Criteria 1.1, Syndromic
Autism Reports / Total Reports
2 / 6
Rare Variants / Common Variants
40 / 0
Aliases
TAOK1, KFC-B,  MAP3K16,  MARKK,  PSK-2,  PSK2,  TAO1,  hKFC-B,  hTAOK1
Associated Syndromes
-
Chromosome Band
17q11.2
Associated Disorders
ASD
Relevance to Autism

A de novo in-frame deletion variant in the TAOK1 gene was identified in an ASD proband from the Autism Sequencing Consortium (De Rubeis et al., 2014). Dulovic-Mahlow et al., 2019 described eight individuals with de novo TAOK1 variants who presented with a neurodevelopmental disorder characterized by developmental delay and muscular hypotonia; autism was reported in two individuals.

Molecular Function

Serine/threonine-protein kinase involved in various processes such as p38/MAPK14 stress-activated MAPK cascade, DNA damage response and regulation of cytoskeleton stability.

SFARI Genomic Platforms
Reports related to TAOK1 (6 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary Synaptic, transcriptional and chromatin genes disrupted in autism De Rubeis S , et al. (2014) Yes -
2 Recent Recommendation De Novo Variants in TAOK1 Cause Neurodevelopmental Disorders Dulovic-Mahlow M , et al. (2019) No ASD
3 Support Large-Scale Exome Sequencing Study Implicates Both Developmental and Functional Changes in the Neurobiology of Autism Satterstrom FK et al. (2020) Yes -
4 Support - van Woerden GM et al. (2021) No ASD
5 Support - Hunter JM et al. (2022) No ASD or autistic features, stereotypy
6 Support - Vitobello A et al. (2022) No -
Rare Variants   (40)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
- - copy_number_loss Unknown - - 33565190 van Woerden GM et al. (2021)
- - copy_number_loss De novo NA - 33565190 van Woerden GM et al. (2021)
- - copy_number_loss Familial Maternal - 33565190 van Woerden GM et al. (2021)
- - copy_number_loss De novo NA Simplex 33565190 van Woerden GM et al. (2021)
c.1813C>T p.Arg605Ter stop_gained Unknown - - 33565190 van Woerden GM et al. (2021)
c.2104C>T p.Arg702Ter stop_gained Unknown - - 33565190 van Woerden GM et al. (2021)
c.449+1G>C - splice_site_variant De novo NA - 33565190 van Woerden GM et al. (2021)
c.831+1dup - splice_site_variant De novo NA - 33565190 van Woerden GM et al. (2021)
c.999+1dup - splice_site_variant De novo NA - 33565190 van Woerden GM et al. (2021)
c.132+3_132+6del - splice_site_variant De novo NA - 35091509 Hunter JM et al. (2022)
c.1819C>T p.Gln607Ter stop_gained De novo NA - 33565190 van Woerden GM et al. (2021)
c.2083C>T p.Arg695Ter stop_gained De novo NA - 33565190 van Woerden GM et al. (2021)
c.691A>G p.Met231Val missense_variant Unknown - - 33565190 van Woerden GM et al. (2021)
c.1630C>T p.Gln544Ter stop_gained De novo NA - 31230721 Dulovic-Mahlow M , et al. (2019)
c.2341G>T p.Glu781Ter stop_gained De novo NA - 31230721 Dulovic-Mahlow M , et al. (2019)
c.2488G>T p.Glu830Ter stop_gained De novo NA - 31230721 Dulovic-Mahlow M , et al. (2019)
c.449G>T p.Arg150Ile missense_variant De novo NA - 33565190 van Woerden GM et al. (2021)
c.500T>G p.Leu167Arg missense_variant De novo NA - 33565190 van Woerden GM et al. (2021)
c.943C>T p.Leu315Phe missense_variant De novo NA - 33565190 van Woerden GM et al. (2021)
c.245_247del p.Arg82del inframe_deletion De novo NA - 25363760 De Rubeis S , et al. (2014)
c.1643T>C p.Leu548Pro missense_variant De novo NA - 33565190 van Woerden GM et al. (2021)
c.136C>T p.Arg46Ter stop_gained De novo NA Simplex 31981491 Satterstrom FK et al. (2020)
c.50A>G p.Glu17Gly missense_variant De novo NA - 31230721 Dulovic-Mahlow M , et al. (2019)
c.1324C>T p.Arg442Trp missense_variant De novo NA Simplex 35091509 Hunter JM et al. (2022)
c.2125C>T p.Arg709Ter stop_gained Familial Paternal - 33565190 van Woerden GM et al. (2021)
c.332C>T p.Ser111Phe missense_variant De novo NA - 31230721 Dulovic-Mahlow M , et al. (2019)
c.892A>G p.Lys298Glu missense_variant De novo NA - 31230721 Dulovic-Mahlow M , et al. (2019)
c.914A>C p.Asp305Ala missense_variant De novo NA - 31230721 Dulovic-Mahlow M , et al. (2019)
c.806G>A p.Arg269Gln missense_variant De novo NA Simplex 31981491 Satterstrom FK et al. (2020)
c.564G>A p.Trp188Ter stop_gained Familial Paternal Multiplex 35907405 Vitobello A et al. (2022)
c.825_826insCT p.Lys277Ter frameshift_variant De novo NA - 33565190 van Woerden GM et al. (2021)
c.2520C>T p.Leu840= synonymous_variant De novo NA Simplex 31981491 Satterstrom FK et al. (2020)
c.393dup p.Thr132TyrfsTer19 frameshift_variant De novo NA - 33565190 van Woerden GM et al. (2021)
c.1287del p.Lys429AsnfsTer42 frameshift_variant De novo NA - 33565190 van Woerden GM et al. (2021)
c.2442del p.Tyr815IlefsTer31 frameshift_variant De novo NA - 33565190 van Woerden GM et al. (2021)
c.658G>T p.Glu220Ter stop_gained Familial Maternal Multiplex 33565190 van Woerden GM et al. (2021)
c.232_233del p.Lys78ValfsTer20 frameshift_variant De novo NA - 33565190 van Woerden GM et al. (2021)
c.2366_2367insC p.Leu790PhefsTer3 frameshift_variant De novo NA - 31230721 Dulovic-Mahlow M , et al. (2019)
c.2203del p.Arg735AspfsTer6 frameshift_variant Familial Maternal Multiplex 35091509 Hunter JM et al. (2022)
c.2366_2367insC p.Leu790PhefsTer3 frameshift_variant De novo NA Simplex 31981491 Satterstrom FK et al. (2020)
Common Variants  

No common variants reported.

SFARI Gene score
1S

High Confidence, Syndromic

Score Delta: Score remained at 1S

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.

The syndromic category includes mutations that are associated with a substantial degree of increased risk and consistently linked to additional characteristics not required for an ASD diagnosis. If there is independent evidence implicating a gene in idiopathic ASD, it will be listed as "#S" (e.g., 2S, 3S, etc.). If there is no such independent evidence, the gene will be listed simply as "S."

1/1/2021
1
icon
1

Score remained at 1

Description

A de novo in-frame deletion variant in the TAOK1 gene was identified in an ASD proband from the Autism Sequencing Consortium (De Rubeis et al., 2014). Dulovic-Mahlow et al., 2019 described eight individuals with de novo TAOK1 variants who presented with a neurodevelopmental disorder characterized by developmental delay and muscular hypotonia; autism was reported in two individuals.

1/1/2020
1
icon
1

Score remained at 1

Description

A de novo in-frame deletion variant in the TAOK1 gene was identified in an ASD proband from the Autism Sequencing Consortium (De Rubeis et al., 2014). Dulovic-Mahlow et al., 2019 described eight individuals with de novo TAOK1 variants who presented with a neurodevelopmental disorder characterized by developmental delay and muscular hypotonia; autism was reported in two individuals.

10/1/2019
icon
1

Increased from to 1

Description

A de novo in-frame deletion variant in the TAOK1 gene was identified in an ASD proband from the Autism Sequencing Consortium (De Rubeis et al., 2014). Dulovic-Mahlow et al., 2019 described eight individuals with de novo TAOK1 variants who presented with a neurodevelopmental disorder characterized by developmental delay and muscular hypotonia; autism was reported in two individuals.

Krishnan Probability Score

Score 0.49152857062357

Ranking 5452/25841 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 0.99999973928315

Ranking 231/18225 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 0.82507211518372

Ranking 2726/18665 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 0.094635452349369

Ranking 6252/20870 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 TAOK1(1 CNVs)
17q11.2 25 Deletion-Duplication 40  /  104
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