TBC1D15: TBC1 Domain Family Member 15
A Rab GTPase-activating protein involved in mitochondrial and endosomal trafficking
Gene Information Card
| Symbol | TBC1D15 |
|---|---|
| Full Name | TBC1 Domain Family Member 15 |
| Gene Type | Protein coding |
| Chromosomal Location | 12q21.1 |
| NCBI Gene ID | 64786 ncbi.nlm.nih.gov/gene/64786 |
| Ensembl ID | ENSG00000135446 |
| UniProt ID | Q8TC07 |
| OMIM ID | 615103 |
| HGNC ID | 29086 |
| Aliases | KIAA0213, RABGAP-15 |
Description
TBC1D15 encodes a member of the TBC (Tre-2/Bub2/Cdc16) domain-containing family of Rab GTPase-activating proteins (RabGAPs). The protein localizes to mitochondria and endosomes, where it regulates Rab7 activity to control mitochondrial fission and endosomal trafficking. It interacts with the mitochondrial fission machinery, including Fis1, to coordinate organelle dynamics.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Hereditary Spastic Paraplegia (HSP) | Impaired Rab7-mediated endosomal trafficking due to TBC1D15 loss-of-function variants | PMID: 24656866 |
| Charcot-Marie-Tooth disease type 2 (CMT2) | Dysregulation of mitochondrial fission and axonal transport | PMID: 24656866 |
| Cancer (various) | Altered mitochondrial dynamics and autophagy in tumor progression | COSMIC database |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Heart | 8.3 | Low |
| Liver | 6.1 | Low |
| Kidney | 9.7 | Low |
| Testis | 15.2 | Medium |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 10.4 | Cervical cancer cell line |
| HEK293 | 11.2 | Embryonic kidney cell line |
| SH-SY5Y | 13.8 | Neuroblastoma cell line |
| HepG2 | 7.5 | Hepatocellular carcinoma cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.632C>T (p.Thr211Met) | Missense | <0.01% | Reduced RabGAP activity; associated with HSP |
| c.1240G>A (p.Glu414Lys) | Missense | <0.01% | Impaired Fis1 binding; altered mitochondrial fission |
| c.1685_1686del (p.Leu562fs) | Frameshift | <0.01% | Loss of function; likely pathogenic |
Mutation functional classification
Loss of Function (LOF)
Frameshift and nonsense variants lead to truncated protein lacking RabGAP domain, impairing Rab7 inactivation and causing mitochondrial/endosomal dysfunction.
Gain of Function (GOF)
Not reported.
Dominant Negative (DN)
Missense variants (e.g., p.Thr211Met) may interfere with wild-type TBC1D15 function by disrupting Fis1 interaction, leading to dominant-negative effects on mitochondrial fission.
View complete mutation data：
Gene Ontology (GO)
| • GTPase activator activity | • Rab GTPase binding |
| • mitochondrial fission | • endosomal transport |
| • regulation of autophagy | • protein homodimerization activity |
Pathways
• Rab7-mediated endosomal trafficking
• Mitochondrial fission (Fis1-TBC1D15 axis)
• Autophagy (mitophagy)
Protein Summary
TBC1D15 is a 562-amino acid protein containing a TBC domain that acts as a GTPase-activating protein (GAP) for Rab7. It localizes to the outer mitochondrial membrane and endosomes via interaction with Fis1. By inactivating Rab7, TBC1D15 controls mitochondrial fission, endosomal maturation, and autophagic flux. Loss of function leads to elongated mitochondria and impaired endosomal trafficking, contributing to neurodegenerative diseases.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| TBC1D15 Knockout HEK293 Cell Line | EDJ-KQ11933 | Human | 64786 | Details Get a Quote |
| TBC1D15 Knockout A-549 Cell Line | EDJ-KQ40438 | Human | 64786 | Details Get a Quote |
| TBC1D15 Knockout HCT 116 Cell Line | EDJ-KQ40439 | Human | 64786 | Details Get a Quote |
| TBC1D15 Knockout HeLa Cell Line | EDJ-KQ40440 | Human | 64786 | Details Get a Quote |
