TAOK2

TAO kinase 2, the group of Mitogen-activated protein kinase kinase kinases

Basic information

Region (hg38): 16:29973867-29992261

Links

ENSG00000149930 ∙ NCBI:9344 ∙ OMIM:613199 ∙ HGNC:16835 ∙ Uniprot:Q9UL54 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• immunodeficiency disease (Limited), mode of inheritance: AR
• autism spectrum disorder (Limited), mode of inheritance: AD

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TAOK2 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TAOK2 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			2	196	15	213
missense			333	15	2	350
nonsense			4			4
start loss						0
frameshift			6			6
inframe indel			17	2		19
splice donor/acceptor (+/-2bp)			2			2
splice region			11	28		39
non coding			3	45	3	51
Total	0	0	367	258	20

Variants in TAOK2

This is a list of pathogenic ClinVar variants found in the TAOK2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
16-29977786-G-T			Uncertain significance (Jan 09, 2024)
16-29977788-C-T			Uncertain significance (Jan 26, 2024)
16-29977789-G-C		not specified	Uncertain significance (Jan 26, 2023)
16-29977793-C-T			Benign (Apr 20, 2022)
16-29977794-G-A		not specified	Uncertain significance (Jan 18, 2024)
16-29977795-G-C			Uncertain significance (Aug 09, 2021)
16-29977812-G-A			Uncertain significance (May 04, 2022)
16-29977817-G-A			Likely benign (Mar 27, 2023)
16-29977850-G-A			Likely benign (May 20, 2023)
16-29977850-G-T		not specified	Uncertain significance (Jan 05, 2022)
16-29977859-T-C		TAOK2-related disorder	Likely benign (Nov 25, 2023)
16-29977866-C-T			Uncertain significance (Apr 19, 2021)
16-29977895-C-T			Benign (Jan 29, 2024)
16-29977901-C-T			Likely benign (Jul 17, 2023)
16-29977916-C-G			Likely benign (Dec 18, 2023)
16-29978069-C-T			Likely benign (Mar 16, 2022)
16-29978071-T-C			Likely benign (Sep 02, 2022)
16-29978095-G-A			Uncertain significance (Jan 12, 2023)
16-29978107-A-G			Uncertain significance (Oct 18, 2022)
16-29978136-C-T			Likely benign (Jan 22, 2024)
16-29978156-A-G			Uncertain significance (Apr 20, 2023)
16-29978173-C-T			Likely benign (Dec 22, 2023)
16-29978178-C-T			Likely benign (Dec 31, 2023)
16-29978238-C-T			Likely benign (Jun 16, 2023)
16-29978245-C-G			Uncertain significance (Apr 09, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TAOK2	protein_coding	protein_coding	ENST00000308893	15	18621

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.000245	125703	0	42	125745	0.000167

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.21	518	768	0.674	0.0000511	7825
Missense in Polyphen		146	281.25	0.51911		2859
Synonymous	-1.09	331	307	1.08	0.0000176	2673
Loss of Function	5.97	7	54.7	0.128	0.00000294	576

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000391	0.000387
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.000741	0.000739
European (Non-Finnish)	0.000134	0.000132
Middle Eastern	0.0000544	0.0000544
South Asian	0.0000333	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Serine/threonine-protein kinase involved in different processes such as membrane blebbing and apoptotic bodies formation DNA damage response and MAPK14/p38 MAPK stress-activated MAPK cascade. Phosphorylates itself, MBP, activated MAPK8, MAP2K3, MAP2K6 and tubulins. Activates the MAPK14/p38 MAPK signaling pathway through the specific activation and phosphorylation of the upstream MAP2K3 and MAP2K6 kinases. In response to DNA damage, involved in the G2/M transition DNA damage checkpoint by activating the p38/MAPK14 stress-activated MAPK cascade, probably by mediating phosphorylation of upstream MAP2K3 and MAP2K6 kinases. Isoform 1, but not isoform 2, plays a role in apoptotic morphological changes, including cell contraction, membrane blebbing and apoptotic bodies formation. This function, which requires the activation of MAPK8/JNK and nuclear localization of C-terminally truncated isoform 1, may be linked to the mitochondrial CASP9-associated death pathway. Isoform 1 binds to microtubules and affects their organization and stability independently of its kinase activity. Prevents MAP3K7-mediated activation of CHUK, and thus NF-kappa-B activation, but not that of MAPK8/JNK. May play a role in the osmotic stress-MAPK8 pathway. Isoform 2, but not isoform 1, is required for PCDH8 endocytosis. Following homophilic interactions between PCDH8 extracellular domains, isoform 2 phosphorylates and activates MAPK14/p38 MAPK which in turn phosphorylates isoform 2. This process leads to PCDH8 endocytosis and CDH2 cointernalization. Both isoforms are involved in MAPK14 phosphorylation. {ECO:0000269|PubMed:10660600, ECO:0000269|PubMed:11279118, ECO:0000269|PubMed:12639963, ECO:0000269|PubMed:12665513, ECO:0000269|PubMed:13679851, ECO:0000269|PubMed:16893890, ECO:0000269|PubMed:17158878, ECO:0000269|PubMed:17396146}.
• Pathway: MAPK signaling pathway - Homo sapiens (human);EGF-Core;MAPK Signaling Pathway;p38 MAPK signaling pathway (Consensus)

Recessive Scores

• pRec: 0.185

Intolerance Scores

• loftool: 0.267
• rvis_EVS: -2.85
• rvis_percentile_EVS: 0.6

Haploinsufficiency Scores

• pHI: 0.654
• hipred: Y
• hipred_score: 0.652
• ghis: 0.675

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.992

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Taok2
• Phenotype: behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); homeostasis/metabolism phenotype; growth/size/body region phenotype

Zebrafish Information Network

• Gene name: taok2b
• Affected structure: ventricular system
• Phenotype tag: abnormal
• Phenotype quality: decreased size

Gene ontology

• Biological process: activation of MAPKK activity;activation of MAPK activity;regulation of cell growth;protein targeting to membrane;apoptotic process;cellular response to DNA damage stimulus;mitotic G2 DNA damage checkpoint;axonogenesis;regulation of cell shape;cell migration;signal transduction by protein phosphorylation;actin cytoskeleton organization;stress-activated protein kinase signaling cascade;positive regulation of protein autophosphorylation;activation of protein kinase activity;positive regulation of stress-activated MAPK cascade;regulation of actin cytoskeleton organization;positive regulation of JNK cascade;protein autophosphorylation;focal adhesion assembly;stress-activated MAPK cascade;basal dendrite morphogenesis;basal dendrite arborization
• Cellular component: nucleus;nucleolus;cytoplasm;cytosol;actin cytoskeleton;integral component of membrane;axon;cytoplasmic vesicle membrane;cytoplasmic vesicle;neuron projection;receptor complex;dendritic growth cone;axonal growth cone
• Molecular function: protein serine/threonine kinase activity;MAP kinase kinase kinase activity;ATP binding;mitogen-activated protein kinase kinase binding;neuropilin binding;tau protein binding;tau-protein kinase activity