TTBK2
Tau Tubulin Kinase 2: A Key Regulator of Ciliogenesis and Neurodegeneration
Gene Information Card
| Symbol | TTBK2 |
|---|---|
| Full Name | Tau Tubulin Kinase 2 |
| Gene Type | Protein coding |
| Chromosomal Location | 15q15.2 |
| NCBI Gene ID | 146057 ncbi.nlm.nih.gov/gene/146057 |
| Ensembl ID | ENSG00000128881 |
| UniProt ID | Q6IQ55 |
| OMIM ID | 611695 |
| HGNC ID | 19141 |
| Aliases | KIAA1764, TTBK, TTBK2 |
Description
TTBK2 (Tau Tubulin Kinase 2) encodes a serine/threonine kinase that phosphorylates tau and tubulin. It is essential for ciliogenesis, specifically for the removal of the CP110-CEP97 complex from the mother centriole to initiate cilium assembly. Mutations in TTBK2 cause spinocerebellar ataxia type 11 (SCA11), a neurodegenerative disorder. The gene is widely expressed, with highest levels in the brain and testis.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Spinocerebellar ataxia type 11 (SCA11) | Loss-of-function mutations in TTBK2 impair ciliogenesis, leading to progressive cerebellar degeneration. | OMIM #604432 |
| Primary microcephaly | Biallelic TTBK2 variants have been associated with microcephaly and intellectual disability. | ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 10.2 | Medium |
| Testis | 8.5 | Medium |
| Cerebellum | 12.1 | Medium |
| Heart | 3.4 | Low |
| Liver | 1.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y | 15.3 | Neuronal cell line |
| HeLa | 8.7 | Cervical carcinoma |
| HEK293 | 6.2 | Embryonic kidney |
| U-2 OS | 5.1 | Osteosarcoma |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1319_1320delAG | Frameshift | Rare | Loss of function; causes SCA11 |
| c.349C>T | Nonsense | Rare | Premature stop; loss of function |
| c.1070T>C | Missense | Rare | p.Leu357Pro; likely pathogenic |
Mutation functional classification
Loss of Function (LOF)
Frameshift and nonsense mutations in TTBK2 lead to truncated protein and loss of kinase activity, impairing ciliogenesis and causing SCA11.
Gain of Function (GOF)
No gain-of-function mutations have been reported for TTBK2.
Dominant Negative (DN)
Some missense mutations may act in a dominant-negative manner by disrupting the interaction with CP110, but evidence is limited.
View complete mutation data：
Gene Ontology (GO)
| • Protein serine/threonine kinase activity | • Cilium assembly |
| • Centrosome cycle | • Tau protein binding |
| • Microtubule binding |
Pathways
• Ciliogenesis
• Tau phosphorylation in Alzheimer disease
Protein Summary
TTBK2 is a 1244-amino acid serine/threonine kinase with an N-terminal kinase domain and a C-terminal domain that mediates localization to the centriole. It phosphorylates tau at Ser422 and tubulin, and is critical for the initiation of ciliogenesis by promoting the removal of CP110 from the mother centriole.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| TTBK2 Knockout HEK293 Cell Line | EDJ-KQ1018 | Human | 146057 | Details Get a Quote |
| TTBK2 Knockout A-549 Cell Line | EDJ-KQ20093 | Human | 146057 | Details Get a Quote |
| TTBK2 Knockout HCT 116 Cell Line | EDJ-KQ20094 | Human | 146057 | Details Get a Quote |
| TTBK2 Knockout HeLa Cell Line | EDJ-KQ20095 | Human | 146057 | Details Get a Quote |
| TTBK2 Knockout HAP1 Cell Line | EDC07905 | Human | 146057 | Details Get a Quote |
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