TBC1D16: A Rab GTPase-Activating Protein in Vesicular Trafficking and Cancer
Comprehensive genomic and functional overview of TBC1D16, a TBC domain-containing protein implicated in melanoma and other cancers.
Gene Information Card
| Symbol | TBC1D16 |
|---|---|
| Full Name | TBC1 domain family member 16 |
| Gene Type | Protein coding |
| Chromosomal Location | 17q25.3 |
| NCBI Gene ID | 125058 ncbi.nlm.nih.gov/gene/125058 |
| Ensembl ID | ENSG00000167286 |
| UniProt ID | Q8TBP0 |
| OMIM ID | 616242 |
| HGNC ID | 29005 |
| Aliases | MGC16169, FLJ11273, TBC1D16A, TBC1D16B |
Description
TBC1D16 encodes a member of the TBC (Tre-2/Bub2/Cdc16) domain-containing family of Rab GTPase-activating proteins (RabGAPs). The protein functions as a GTPase activator for Rab proteins, regulating vesicular trafficking and membrane transport. TBC1D16 is implicated in melanoma and other cancers, with mutations and expression changes affecting tumor progression and drug resistance.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Melanoma | TBC1D16 mutations and altered expression contribute to melanoma development and progression through dysregulation of Rab-mediated vesicular trafficking, affecting cell signaling and invasion. | COSMIC, ClinVar, literature |
| Breast cancer | TBC1D16 overexpression is associated with poor prognosis and may promote tumor growth via Rab GTPase regulation. | COSMIC, literature |
| Lung cancer | Somatic mutations in TBC1D16 have been identified in lung adenocarcinoma, potentially impacting vesicular transport pathways. | COSMIC |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 5.2 | Low |
| Lung | 3.8 | Low |
| Liver | 2.1 | Low |
| Kidney | 4.5 | Low |
| Skin | 6.7 | Medium |
| Melanoma cell lines | 12.3 | High |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| A375 (melanoma) | 15.1 | High expression |
| SK-MEL-28 (melanoma) | 14.5 | High expression |
| MCF7 (breast cancer) | 8.2 | Medium expression |
| HEK293 (embryonic kidney) | 4.0 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1132C>T (p.Arg378Trp) | Missense | <0.01 | Alters RabGAP domain; potential loss of function |
| c.1456G>A (p.Glu486Lys) | Missense | <0.01 | Unknown functional effect |
| c.1789_1790insA (p.Thr597Asnfs*12) | Frameshift | <0.01 | Truncation; likely loss of function |
| c.2023C>T (p.Arg675*) | Nonsense | <0.01 | Premature stop; loss of function |
Mutation functional classification
Loss of Function (LOF)
Frameshift and nonsense mutations (e.g., p.Thr597Asnfs*12, p.Arg675*) are predicted to cause loss of RabGAP activity, disrupting vesicular trafficking.
Gain of Function (GOF)
No gain-of-function mutations have been reported.
Dominant Negative (DN)
No dominant-negative mutations have been characterized.
View complete mutation data：
Gene Ontology (GO)
| • GTPase activator activity (GO:0005096) | • Rab GTPase binding (GO:0017137) |
| • intracellular protein transport (GO:0006886) | • vesicle-mediated transport (GO:0016192) |
| • endocytic recycling (GO:0032456) | • cytoplasm (GO:0005737) |
Pathways
• Rab regulation of trafficking (Reactome: R-HSA-9007101)
• Vesicle-mediated transport (Reactome: R-HSA-5653656)
Protein Summary
TBC1D16 is a 720-amino acid protein containing a TBC domain that catalyzes GTP hydrolysis on Rab GTPases, thereby inactivating them. It localizes to the cytoplasm and is involved in endocytic recycling and vesicular trafficking. The protein has two isoforms (A and B) generated by alternative splicing. TBC1D16 is highly expressed in melanoma cell lines and skin, and its dysregulation is linked to cancer progression.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| TBC1D16 Knockout HEK293 Cell Line | EDJ-KQ7974 | Human | 125058 | Details Get a Quote |
| TBC1D16 Knockout A-549 Cell Line | EDJ-KQ34940 | Human | 125058 | Details Get a Quote |
| TBC1D16 Knockout HCT 116 Cell Line | EDJ-KQ34942 | Human | 125058 | Details Get a Quote |
| TBC1D16 Knockout HeLa Cell Line | EDJ-KQ34943 | Human | 125058 | Details Get a Quote |
