TAOK2
TAO kinase 2, the group of Mitogen-activated protein kinase kinase kinases
Basic information
Region (hg38): 16:29973868-29992261
Links
Phenotypes
GenCC
Source:
- 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
- not_provided (752 variants)
- not_specified (137 variants)
- TAOK2-related_disorder (22 variants)
- See_cases (2 variants)
- Autism (1 variants)
- TAOK2-associated_neurodevelopmental_disorder (1 variants)
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. These statistics are base on transcript: NM_000016151.4. 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 | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 223 | 13 | 239 | |||
| missense | 426 | 14 | 441 | |||
| nonsense | 4 | |||||
| start loss | 0 | |||||
| frameshift | 6 | |||||
| splice donor/acceptor (+/-2bp) | 2 | |||||
| Total | 0 | 0 | 441 | 237 | 14 |
Loading clinvar variants...
GnomAD
Source:
| 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:
- 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