Human Gene Module / Chromosome 17 / TAOK1

TAOK1TAO kinase 1

SFARI Gene Score
1
High Confidence Criteria 1.1
Autism Reports / Total Reports
2 / 5
Rare Variants / Common Variants
39 / 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.

Reports related to TAOK1 (5 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
Rare Variants   (39)
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.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
1

High Confidence

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.

4/1/2022
1

Initial score established: 1

10/1/2021
1

Initial score established: 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.

7/1/2021
1

Initial score established: 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.

4/1/2021
1

Initial score established: 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.

1/1/2021
1

Initial score established: 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.

10/1/2020
1

Initial score established: 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.

7/1/2020
1

Initial score established: 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.

4/1/2020
1

Initial score established: 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

Initial score established: 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
1

Initial score established: 1

New Scoring Scheme
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.

Reports Added
[New Scoring Scheme]
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 24 Deletion-Duplication 38  /  103
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