TBC1D22A: TBC1 Domain Family Member 22A
A Rab GTPase-activating protein implicated in vesicular trafficking and potential links to cancer and developmental disorders.
Gene Information Card
| Symbol | TBC1D22A |
|---|---|
| Full Name | TBC1 domain family member 22A |
| Gene Type | protein-coding |
| Chromosomal Location | 22q13.33 |
| NCBI Gene ID | 25771 ncbi.nlm.nih.gov/gene/25771 |
| Ensembl ID | ENSG00000100253 |
| UniProt ID | Q8WUA4 |
| OMIM ID | 617778 |
| HGNC ID | 29188 |
| Aliases | TBC1D22, FLJ12681, MGC131831 |
Description
TBC1D22A encodes a member of the TBC1 domain-containing family of Rab GTPase-activating proteins (RabGAPs). The protein contains a conserved TBC (Tre-2/Bub2/Cdc16) domain that catalyzes the conversion of active Rab-GTP to inactive Rab-GDP, thereby regulating intracellular vesicle trafficking and membrane transport. TBC1D22A is widely expressed and has been implicated in endosomal recycling and autophagy. Alterations in TBC1D22A expression or function may contribute to cancer progression and neurodevelopmental phenotypes.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Breast cancer | Altered expression may disrupt Rab-mediated vesicle trafficking, affecting cell proliferation and migration. | NCBI Gene, COSMIC |
| Colorectal cancer | Somatic mutations and copy number alterations observed in tumor samples. | COSMIC |
| Neurodevelopmental disorder | Rare variants reported in patients with intellectual disability; functional studies suggest impaired RabGAP activity. | ClinVar, OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Lung | 8.3 | Low |
| Liver | 6.1 | Low |
| Kidney | 9.7 | Low |
| Testis | 15.2 | Medium |
| Thyroid | 11.0 | Medium |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 10.5 | Cervical cancer line |
| HEK293 | 9.8 | Embryonic kidney line |
| MCF7 | 7.2 | Breast cancer line |
| A549 | 6.5 | Lung cancer line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1015C>T (p.Arg339Trp) | Missense | <0.01% | Unknown; predicted damaging by SIFT/PolyPhen |
| c.1420G>A (p.Glu474Lys) | Missense | <0.01% | Unknown; located in TBC domain |
| c.1789_1790insA (p.Thr597Asnfs*12) | Frameshift | <0.01% | Loss of function |
Mutation functional classification
Loss of Function (LOF)
Frameshift and nonsense mutations are predicted to cause loss of RabGAP activity.
Gain of Function (GOF)
No evidence for gain-of-function mutations.
Dominant Negative (DN)
Missense variants in the TBC domain may act in a dominant-negative manner by sequestering Rab substrates.
View complete mutation data：
Gene Ontology (GO)
| • GTPase activator activity (GO:0005096) | • Rab GTPase binding (GO:0017137) |
| • endocytic recycling (GO:0032456) | • intracellular protein transport (GO:0006886) |
| • cytoplasm (GO:0005737) |
Pathways
• Rab regulation of trafficking (Reactome: R-HSA-9007101)
• Membrane trafficking (Reactome: R-HSA-199991)
Protein Summary
TBC1D22A is a 746-amino acid protein containing a central TBC domain (residues ~350–550) that mediates RabGAP activity. It localizes to the cytoplasm and endosomal membranes. The protein interacts with Rab GTPases such as Rab5 and Rab11 to regulate endosome-to-plasma membrane recycling. Structural studies indicate that the TBC domain adopts a helical fold with a conserved arginine finger essential for GTP hydrolysis. Post-translational modifications include phosphorylation at Ser/Thr residues, which may modulate activity.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| TBC1D22A Knockout HEK293 Cell Line | EDJ-KQ8219 | Human | 25771 | Details Get a Quote |
| TBC1D22A Knockout HCT 116 Cell Line | EDJ-KQ34111 | Human | 25771 | Details Get a Quote |
| TBC1D22A Knockout HeLa Cell Line | EDJ-KQ34112 | Human | 25771 | Details Get a Quote |
| TBC1D22A Knockout A-549 Cell Line | EDJ-KQ32797 | Human | 25771 | Details Get a Quote |
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