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.

SFARI Genomic Platforms
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

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

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 29 Deletion-Duplication 44  /  116
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