TBC1D12: TBC1 Domain Family Member 12
A Rab-GAP protein implicated in vesicular trafficking and potential roles in cancer and developmental disorders.
Gene Information Card
| Symbol | TBC1D12 |
|---|---|
| Full Name | TBC1 domain family member 12 |
| Gene Type | Protein coding |
| Chromosomal Location | 10q24.32 |
| NCBI Gene ID | 23232 ncbi.nlm.nih.gov/gene/23232 |
| Ensembl ID | ENSG00000107929 |
| UniProt ID | Q8TCX1 |
| OMIM ID | 618815 |
| HGNC ID | 29005 |
| Aliases | KIAA0608, MGC138499 |
Description
TBC1D12 encodes a member of the TBC1 domain family of Rab GTPase-activating proteins (Rab-GAPs). 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. TBC1D12 is widely expressed and has been implicated in endosomal recycling and autophagy. Alterations in TBC1D12 expression or function may contribute to cancer progression and neurodevelopmental phenotypes.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Neurodevelopmental disorder with hypotonia and brain anomalies | Loss-of-function variants disrupt Rab-GAP activity, impairing vesicle trafficking in neurons | ClinVar, OMIM |
| Breast cancer | Overexpression correlates with poor prognosis; potential role in tumor cell migration | COSMIC, literature |
| Lung adenocarcinoma | Somatic mutations and copy number alterations observed | COSMIC |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Lung | 8.3 | Low |
| Breast | 6.1 | Low |
| Testis | 15.2 | Medium |
| Kidney | 9.7 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 10.2 | Embryonic kidney |
| MCF7 | 7.8 | Breast cancer |
| A549 | 6.5 | Lung cancer |
| SH-SY5Y | 14.1 | Neuroblastoma |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1234C>T (p.Arg412*) | Nonsense | <0.01% | Premature truncation; loss of GAP domain |
| c.567_568del (p.Glu190fs) | Frameshift | <0.01% | Loss of function |
| c.890A>G (p.Tyr297Cys) | Missense | 0.02% | Unknown; predicted damaging |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift variants that truncate the TBC domain abolish Rab-GAP activity, leading to dysregulated vesicle trafficking.
Gain of Function (GOF)
No confirmed gain-of-function mutations reported.
Dominant Negative (DN)
Not established for TBC1D12.
View complete mutation data：
Gene Ontology (GO)
| • GTPase activator activity | • Rab GTPase binding |
| • intracellular protein transport | • vesicle-mediated transport |
| • endosome to lysosome transport | • autophagy |
Pathways
• Rab regulation of trafficking (Reactome: R-HSA-9007101)
• Endosomal recycling (Reactome: R-HSA-432722)
Protein Summary
TBC1D12 is a 1,200-amino-acid protein containing an N-terminal TBC domain (residues 50–400) that functions as a Rab-GAP. It localizes to endosomal membranes and regulates the recycling of receptors and lipids. The protein also harbors a coiled-coil region that may mediate dimerization or interactions with other trafficking proteins. Post-translational modifications include phosphorylation at Ser/Thr residues, which may modulate its GAP activity.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| TBC1D12 Knockout HEK293 Cell Line | EDJ-KQ7901 | Human | 23232 | Details Get a Quote |
| TBC1D12 Knockout HeLa Cell Line | EDJ-KQ32179 | Human | 23232 | Details Get a Quote |
| TBC1D12 Knockout A-549 Cell Line | EDJ-KQ33505 | Human | 23232 | Details Get a Quote |
| TBC1D12 Knockout HCT 116 Cell Line | EDJ-KQ33506 | Human | 23232 | Details Get a Quote |
