TBCK Gene
TBCK (TBC1 Domain Containing Kinase) – A Key Regulator of mTOR Signaling and Neurodevelopment
Gene Information Card
| Symbol | TBCK |
|---|---|
| Full Name | TBC1 Domain Containing Kinase |
| Gene Type | Protein coding |
| Chromosomal Location | 4q24 |
| NCBI Gene ID | 93627 ncbi.nlm.nih.gov/gene/93627 |
| Ensembl ID | ENSG00000145332 |
| UniProt ID | Q8TBC4 |
| OMIM ID | 616900 |
| HGNC ID | 28361 |
| Aliases | HSPC302, MGC16169, TBCKINASE |
Description
The TBCK gene encodes a protein containing a TBC (Tre-2/Bub2/Cdc16) domain and a kinase-like domain. It is involved in regulating mTOR signaling, cell growth, and autophagy. Mutations in TBCK cause a severe autosomal recessive neurodevelopmental disorder characterized by intellectual disability, hypotonia, and facial dysmorphism.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| TBCK-related encephalopathy (neurodevelopmental disorder with hypotonia and intellectual disability) | Loss-of-function mutations impair mTOR pathway regulation, leading to defective neuronal development and function. | ClinVar, OMIM #616900 |
| Infantile hypotonia with psychomotor retardation and characteristic facies (IHPRF) | Biallelic TBCK mutations disrupt protein function, causing early-onset hypotonia and developmental delay. | OMIM #616900, PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Testis | 8.3 | Low |
| Heart | 6.1 | Low |
| Liver | 4.2 | Low |
| Kidney | 5.0 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 10.2 | Moderate expression |
| SH-SY5Y | 14.8 | Higher in neuronal lineage |
| HeLa | 7.5 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.148C>T (p.Arg50*) | Nonsense | Rare | Loss of function; premature stop codon |
| c.1000C>T (p.Arg334Trp) | Missense | Rare | Likely damaging; disrupts TBC domain |
| c.1675C>T (p.Arg559*) | Nonsense | Rare | Loss of function; associated with severe phenotype |
Mutation functional classification
Loss of Function (LOF)
Most reported TBCK mutations are loss-of-function (nonsense, frameshift, splice-site) leading to reduced or absent protein, impairing mTOR signaling and causing neurodevelopmental disease.
Gain of Function (GOF)
No gain-of-function mutations have been reported for TBCK.
Dominant Negative (DN)
No dominant-negative mutations have been described; disease is autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
| • protein binding (GO:0005515) | • protein kinase activity (GO:0004672) |
| • phosphorylation (GO:0016310) | • regulation of TOR signaling (GO:0032006) |
| • autophagy (GO:0006914) |
Pathways
• mTOR signaling pathway (Reactome: R-HSA-165159)
• Autophagy (Reactome: R-HSA-9612973)
Protein Summary
The TBCK protein (UniProt Q8TBC4) contains an N-terminal TBC domain that acts as a GTPase-activating protein (GAP) for Rab GTPases, and a C-terminal kinase-like domain. It localizes to endosomes and lysosomes, regulating mTORC1 activity and autophagy. Loss of TBCK leads to aberrant mTOR signaling, accumulation of autophagic vesicles, and neuronal dysfunction.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| TBCK Knockout HEK293 Cell Line | EDJ-KQ11245 | Human | 93627 | Details Get a Quote |
| TBCK Knockout A-549 Cell Line | EDJ-KQ39338 | Human | 93627 | Details Get a Quote |
| TBCK Knockout HCT 116 Cell Line | EDJ-KQ39339 | Human | 93627 | Details Get a Quote |
| TBCK Knockout HeLa Cell Line | EDJ-KQ39340 | Human | 93627 | Details Get a Quote |
