TAOK1

TAO kinase 1, the group of Mitogen-activated protein kinase kinase kinases

Basic information

Region (hg38): 17:29390363-29551903

Links

ENSG00000160551 ∙ NCBI:57551 ∙ OMIM:610266 ∙ HGNC:29259 ∙ Uniprot:Q7L7X3 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autosomal dominant non-syndromic intellectual disability (Supportive), mode of inheritance: AD
• complex neurodevelopmental disorder (Moderate), mode of inheritance: AD
• developmental delay with or without intellectual impairment or behavioral abnormalities (Strong), mode of inheritance: AD
• syndromic intellectual disability (Definitive), mode of inheritance: AD
• developmental delay with or without intellectual impairment or behavioral abnormalities (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Developmental delay with or without intellectual impairment or behavioral abnormalities	AD	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Craniofacial; Neurologic	31230721; 33565190

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TAOK1 gene.

• not_provided (120 variants)
• Inborn_genetic_diseases (72 variants)
• Developmental_delay_with_or_without_intellectual_impairment_or_behavioral_abnormalities (57 variants)
• TAOK1-related_disorder (22 variants)
• Neurodevelopmental_disorder (10 variants)
• See_cases (3 variants)
• not_specified (3 variants)
• DEVELOPMENTAL_DELAY_WITHOUT_INTELLECTUAL_IMPAIRMENT_OR_BEHAVIORAL_ABNORMALITIES (2 variants)
• Global_developmental_delay (2 variants)
• TAOK1-related_neurodevelopmental_disorder (2 variants)
• Abnormality_of_the_face (1 variants)
• Neurodevelopmental_delay (1 variants)
• Macroglossia (1 variants)
• Global_developmental_delay_with_or_without_impaired_intellectual_development (1 variants)
• Short_5th_finger (1 variants)
• Intellectual_disability,_autosomal_dominant_1 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TAOK1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000020791.4. Only rare variants are included in the table.

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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			4	10	5	19
missense	1	14	150	9		174
nonsense	11	10	5			26
start loss						0
frameshift	11	7	2			20
splice donor/acceptor (+/-2bp)	2	9	2			13
Total	25	40	163	19	5

Highest pathogenic variant AF is 0.0000065703885

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TAOK1	protein_coding	protein_coding	ENST00000261716	19	161441

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.998	0.00213	125739	0	9	125748	0.0000358

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	4.82	234	553	0.423	0.0000300	6629
Missense in Polyphen		23	132.82	0.17317		1671
Synonymous	0.920	162	178	0.912	0.00000843	1801
Loss of Function	6.31	11	66.5	0.165	0.00000431	678

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000290	0.0000290
Ashkenazi Jewish	0.0000993	0.0000992
East Asian	0.0000553	0.0000544
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.0000265	0.0000264
Middle Eastern	0.0000553	0.0000544
South Asian	0.000133	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: 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. Phosphorylates MAP2K3, MAP2K6 and MARK2. Acts as an activator of the p38/MAPK14 stress-activated MAPK cascade by mediating phosphorylation and subsequent activation of the upstream MAP2K3 and MAP2K6 kinases. Involved in G-protein coupled receptor signaling to p38/MAPK14. 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 MAP2K3 and MAP2K6. Acts as a regulator of cytoskeleton stability by phosphorylating 'Thr-208' of MARK2, leading to activate MARK2 kinase activity and subsequent phosphorylation and detachment of MAPT/TAU from microtubules. Also acts as a regulator of apoptosis: regulates apoptotic morphological changes, including cell contraction, membrane blebbing and apoptotic bodies formation via activation of the MAPK8/JNK cascade. {ECO:0000269|PubMed:12665513, ECO:0000269|PubMed:13679851, ECO:0000269|PubMed:16407310, ECO:0000269|PubMed:17396146, ECO:0000269|PubMed:17900936}.
• Pathway: MAPK signaling pathway - Homo sapiens (human);EGF-Core;Regulation of Microtubule Cytoskeleton;MAPK Signaling Pathway;Signal Transduction;Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal;Amplification of signal from the kinetochores;Mitotic Spindle Checkpoint;Cell Cycle Checkpoints;RHO GTPases Activate Formins;RHO GTPase Effectors;Signaling by Rho GTPases;Mitotic Prometaphase;Separation of Sister Chromatids;Mitotic Anaphase;Mitotic Metaphase and Anaphase;M Phase;Cell Cycle;Resolution of Sister Chromatid Cohesion;Cell Cycle, Mitotic;p38 MAPK signaling pathway (Consensus)

Recessive Scores

• pRec: 0.145

Intolerance Scores

• loftool: 0.102
• rvis_EVS: -0.62
• rvis_percentile_EVS: 17.16

Haploinsufficiency Scores

• pHI: 0.277
• hipred: Y
• hipred_score: 0.696
• ghis: 0.623

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.975

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Taok1

Gene ontology

• Biological process: activation of MAPKK activity;activation of MAPK activity;microtubule cytoskeleton organization;DNA repair;protein phosphorylation;cellular response to DNA damage stimulus;negative regulation of microtubule depolymerization;mitotic G2 DNA damage checkpoint;activation of JUN kinase activity;signal transduction by protein phosphorylation;stress-activated protein kinase signaling cascade;activation of protein kinase activity;positive regulation of stress-activated MAPK cascade;regulation of actin cytoskeleton organization;positive regulation of JNK cascade;protein autophosphorylation;regulation of cytoskeleton organization;neuron cellular homeostasis;regulation of microtubule cytoskeleton organization;execution phase of apoptosis;positive regulation of protein acetylation
• Cellular component: nucleus;cytoplasm;cytosol;microtubule cytoskeleton;perinuclear region of cytoplasm;extracellular exosome
• Molecular function: protein kinase activity;protein serine/threonine kinase activity;MAP kinase kinase kinase activity;protein binding;ATP binding;kinase activity;transferase activity;alpha-tubulin binding;protein serine/threonine kinase activator activity;tau protein binding;beta-tubulin binding;tau-protein kinase activity