TAOK3: A Key Regulator of Hippo Signaling and Cell Cycle Control
Comprehensive genomic and functional analysis of TAOK3 (MAP3K18) in cancer and development
Gene Information Card
| Symbol | TAOK3 |
|---|---|
| Full Name | TAO kinase 3 |
| Gene Type | protein-coding |
| Chromosomal Location | 12q24.23 |
| NCBI Gene ID | 51347 ncbi.nlm.nih.gov/gene/51347 |
| Ensembl ID | ENSG00000135090 |
| UniProt ID | Q9H2K8 |
| OMIM ID | 614907 |
| HGNC ID | 29265 |
| Aliases | MAP3K18, JIK, KDS, TAOK3alpha, TAOK3beta |
Description
TAOK3 (TAO kinase 3) encodes a serine/threonine kinase belonging to the STE20 family. It acts as a MAP3K in the Hippo signaling pathway, phosphorylating and activating MST1/2 kinases, and regulates cell cycle progression, cytoskeletal dynamics, and stress responses. TAOK3 is implicated in cancer, neurodevelopmental disorders, and immune regulation.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (multiple types) | Dysregulation of Hippo pathway via TAOK3 overexpression or mutation leads to altered cell proliferation and apoptosis | COSMIC, ClinVar |
| Intellectual disability | De novo missense variants in TAOK3 associated with neurodevelopmental phenotypes | ClinVar, OMIM |
| Hepatocellular carcinoma | TAOK3 overexpression correlates with poor prognosis and activation of YAP/TAZ | NCBI Gene, literature |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Liver | 8.3 | Low |
| Kidney | 15.2 | Medium |
| Testis | 22.1 | High |
| Lung | 9.7 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 18.4 | Embryonic kidney, high expression |
| HeLa | 14.2 | Cervical cancer, moderate |
| HepG2 | 11.0 | Hepatocellular carcinoma, moderate |
| K562 | 7.5 | Leukemia, low |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.154C>T (p.Arg52Cys) | Missense | 0.02% | Potential loss of kinase activity |
| c.1012G>A (p.Glu338Lys) | Missense | 0.01% | Unknown functional impact |
| c.1745_1746insA | Frameshift | <0.01% | Predicted loss of function |
Mutation functional classification
Loss of Function (LOF)
Frameshift and nonsense mutations in TAOK3 are predicted to truncate the kinase domain, impairing Hippo signaling and cell cycle control.
Gain of Function (GOF)
Missense mutations in the activation loop (e.g., p.Ser181Ala) may increase kinase activity, promoting oncogenic YAP/TAZ signaling.
Dominant Negative (DN)
Mutations in the dimerization domain could interfere with TAOK3-MST1/2 interactions, blocking pathway activation.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Hippo signaling pathway (KEGG: hsa04390)
• MAPK signaling pathway (KEGG: hsa04010)
• Regulation of actin cytoskeleton (KEGG: hsa04810)
Protein Summary
TAOK3 is a 1001-amino-acid serine/threonine kinase with an N-terminal kinase domain, a central coiled-coil region, and a C-terminal regulatory domain. It phosphorylates MST1/2 to activate Hippo signaling, leading to YAP/TAZ inhibition. TAOK3 also regulates microtubule stability and cell cycle progression through interaction with Cdc25C and Aurora kinases. Alternative splicing produces isoforms with distinct tissue expression and functions.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| TAOK3 Knockout HEK293 Cell Line | EDJ-KQ758 | Human | 51347 | Details Get a Quote |
| TAOK3 Knockout A-549 Cell Line | EDJ-KQ19430 | Human | 51347 | Details Get a Quote |
| TAOK3 Knockout HCT 116 Cell Line | EDJ-KQ19431 | Human | 51347 | Details Get a Quote |
| TAOK3 Knockout HeLa Cell Line | EDJ-KQ19432 | Human | 51347 | Details Get a Quote |
| TAOK3 Knockout HAP1 Cell Line | EDC08220 | Human | 51347 | Details Get a Quote |
