Human Gene Module / Chromosome 17 / TAOK1

TAOK1TAO kinase 1

SFARI Gene Score
1S
High Confidence, Syndromic Criteria 1.1, Syndromic
Autism Reports / Total Reports
8 / 13
Rare Variants / Common Variants
55 / 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. Three novel de novo variants in the TAOK1 gene (two likely gene-disruptive variants, one missense variant predicted to be probably damaging as defined by an MPC score > 2) were identified in ASD probands from the Autism Sequencing Consortium in Satterstrom et al., 2020; subsequent TADA analysis of de novo variants from the Simons Simplex Collection and the Autism Sequencing Consortium and protein-truncating variants from iPSYCH in this report identified TAOK1 as a candidate gene with a false discovery rate between 0.05 and 0.1 (0.05 < FDR 0.1). Additional de novo loss-of-function variants and potentially damaging missense variants in the TAOK1 gene were reported in ASD probands from the Simons Simplex Collection and the SPARK cohort in Zhou et al., 2022; a two-stage analysis of rare de novo and inherited coding variants in 42,607 ASD cases, including 35,130 new cases from the SPARK cohort, in this report identified TAOK1 as a gene reaching exome-wide significance (P < 2.5E-06).

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.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to TAOK1 (13 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 -
7 Recent Recommendation - Zhou X et al. (2022) Yes -
8 Recent Recommendation - Beeman N et al. (2023) Yes -
9 Support - Miyake N et al. (2023) Yes -
10 Support - Wang J et al. (2023) Yes -
11 Recent Recommendation - Wang J et al. (2023) Yes -
12 Support - Marketa Wayhelova et al. (2024) Yes -
13 Support - Anna Cavalli et al. (2024) No Autistic features
Rare Variants   (55)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
- - copy_number_loss De novo - - 33565190 van Woerden GM et al. (2021)
- - copy_number_loss Unknown - - 33565190 van Woerden GM et al. (2021)
c.2125C>T p.Arg709Ter stop_gained De novo - - 35982159 Zhou X et al. (2022)
- - copy_number_loss De novo - Simplex 33565190 van Woerden GM et al. (2021)
- - copy_number_loss Familial Maternal - 33565190 van Woerden GM et al. (2021)
c.470T>G p.Ile157Ser missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.497A>C p.Lys166Thr missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.557C>T p.Pro186Leu missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.704A>G p.Tyr235Cys missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.449+1G>C - splice_site_variant De novo - - 33565190 van Woerden GM et al. (2021)
c.831+1dup - splice_site_variant De novo - - 33565190 van Woerden GM et al. (2021)
c.999+1dup - splice_site_variant De novo - - 33565190 van Woerden GM et al. (2021)
c.2361C>T p.Ala787%3D synonymous_variant De novo - - 35982159 Zhou X et al. (2022)
c.132+3_132+6del - splice_site_variant De novo - - 35091509 Hunter JM et al. (2022)
c.1203+8T>G - splice_region_variant De novo - Simplex 35982159 Zhou X et al. (2022)
c.1813C>T p.Arg605Ter stop_gained Unknown - - 33565190 van Woerden GM et al. (2021)
c.1819C>T p.Gln607Ter stop_gained De novo - - 33565190 van Woerden GM et al. (2021)
c.2083C>T p.Arg695Ter stop_gained De novo - - 33565190 van Woerden GM et al. (2021)
c.2104C>T p.Arg702Ter stop_gained Unknown - - 33565190 van Woerden GM et al. (2021)
c.1630C>T p.Gln544Ter stop_gained De novo - - 31230721 Dulovic-Mahlow M , et al. (2019)
c.2341G>T p.Glu781Ter stop_gained De novo - - 31230721 Dulovic-Mahlow M , et al. (2019)
c.2488G>T p.Glu830Ter stop_gained De novo - - 31230721 Dulovic-Mahlow M , et al. (2019)
c.449G>T p.Arg150Ile missense_variant De novo - - 33565190 van Woerden GM et al. (2021)
c.500T>G p.Leu167Arg missense_variant De novo - - 33565190 van Woerden GM et al. (2021)
c.691A>G p.Met231Val missense_variant Unknown - - 33565190 van Woerden GM et al. (2021)
c.943C>T p.Leu315Phe missense_variant De novo - - 33565190 van Woerden GM et al. (2021)
c.1671dup p.Glu558ArgfsTer3 frameshift_variant De novo - - 35982159 Zhou X et al. (2022)
c.655G>A p.Ala219Thr missense_variant De novo - Simplex 36973392 Miyake N et al. (2023)
c.245_247del p.Arg82del inframe_deletion De novo - - 25363760 De Rubeis S , et al. (2014)
c.1643T>C p.Leu548Pro missense_variant De novo - - 33565190 van Woerden GM et al. (2021)
c.136C>T p.Arg46Ter stop_gained De novo - Simplex 31981491 Satterstrom FK et al. (2020)
c.50A>G p.Glu17Gly missense_variant De novo - - 31230721 Dulovic-Mahlow M , et al. (2019)
c.1287del p.Lys429AsnfsTer42 frameshift_variant De novo - - 35982159 Zhou X et al. (2022)
c.1324C>T p.Arg442Trp missense_variant De novo - Simplex 35091509 Hunter JM et al. (2022)
c.332C>T p.Ser111Phe missense_variant De novo - - 31230721 Dulovic-Mahlow M , et al. (2019)
c.892A>G p.Lys298Glu missense_variant De novo - - 31230721 Dulovic-Mahlow M , et al. (2019)
c.914A>C p.Asp305Ala missense_variant De novo - - 31230721 Dulovic-Mahlow M , et al. (2019)
c.881_884del p.Ile294ArgfsTer7 frameshift_variant De novo - - 35982159 Zhou X et al. (2022)
c.2125C>T p.Arg709Ter stop_gained Familial Paternal - 33565190 van Woerden GM et al. (2021)
c.1414C>T p.Arg472Ter stop_gained Unknown Not maternal - 38443934 Anna Cavalli et al. (2024)
c.806G>A p.Arg269Gln missense_variant De novo - Simplex 31981491 Satterstrom FK et al. (2020)
c.825_826insCT p.Lys277Ter frameshift_variant De novo - - 33565190 van Woerden GM et al. (2021)
c.2520C>T p.Leu840= synonymous_variant De novo - Simplex 31981491 Satterstrom FK et al. (2020)
c.1941dup p.Glu648ArgfsTer10 frameshift_variant De novo - Simplex 37393044 Wang J et al. (2023)
c.393dup p.Thr132TyrfsTer19 frameshift_variant De novo - - 33565190 van Woerden GM et al. (2021)
c.564G>A p.Trp188Ter stop_gained Familial Paternal Multiplex 35907405 Vitobello A et al. (2022)
c.1287del p.Lys429AsnfsTer42 frameshift_variant De novo - - 33565190 van Woerden GM et al. (2021)
c.2442del p.Tyr815IlefsTer31 frameshift_variant De novo - - 33565190 van Woerden GM et al. (2021)
c.232_233del p.Lys78ValfsTer20 frameshift_variant De novo - - 33565190 van Woerden GM et al. (2021)
c.593A>C p.Asp198Ala missense_variant Familial Paternal - 38321498 Marketa Wayhelova et al. (2024)
c.658G>T p.Glu220Ter stop_gained Familial Maternal Multiplex 33565190 van Woerden GM et al. (2021)
c.941_950delinsTGTG p.Lys314_Phe317delinsMetCys inframe_indel De novo - - 35982159 Zhou X et al. (2022)
c.2366_2367insC p.Leu790PhefsTer3 frameshift_variant De novo - - 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 - 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

criteria met
See SFARI Gene'scoring criteria
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.

S

Syndromic

See all Category S Genes

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.

Reports Added
[TAOK1 is associated with neurodevelopmental disorder and essential for neuronal maturation and cortical development2021]
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.

Reports Added
[Large-Scale Exome Sequencing Study Implicates Both Developmental and Functional Changes in the Neurobiology of Autism2020]
10/1/2019
icon
1

Increased from to 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.
Original Source
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
Original Source
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).
Original Source
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.
Original Source
CNVs associated with TAOK1(1 CNVs)
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17q11.2 29 Deletion-Duplication 44  /  116
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