TBC1D20: TBC1 Domain Family Member 20
A Rab GTPase-activating protein involved in Warburg Micro syndrome and cataract formation
Gene Information Card
| Symbol | TBC1D20 |
|---|---|
| Full Name | TBC1 Domain Family Member 20 |
| Gene Type | Protein coding |
| Chromosomal Location | 20p13 |
| NCBI Gene ID | 128637 ncbi.nlm.nih.gov/gene/128637 |
| Ensembl ID | ENSG00000125875 |
| UniProt ID | Q96BZ9 |
| OMIM ID | 611663 |
| HGNC ID | 16133 |
| Aliases | C20orf140, dJ1181N3.1, FLJ20366 |
Description
TBC1D20 encodes a member of the TBC (Tre-2/Bub2/Cdc16) domain-containing family of Rab GTPase-activating proteins (RabGAPs). The protein localizes to the Golgi apparatus and endosomes and regulates Rab1 and Rab2 GTPase activity, thereby controlling vesicle trafficking between the endoplasmic reticulum and Golgi. Mutations in TBC1D20 cause autosomal recessive Warburg Micro syndrome 4 (WARBM4) and are associated with congenital cataracts.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Warburg Micro syndrome 4 (WARBM4) | Loss-of-function mutations impair RabGAP activity, disrupting vesicle transport and leading to microcephaly, microphthalmia, and intellectual disability | OMIM #615663; multiple homozygous mutations reported |
| Congenital cataracts | Defective TBC1D20 disrupts lens fiber cell vesicle trafficking, causing cataract formation | ClinVar; case studies with biallelic variants |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Eye | 10.8 | Medium |
| Testis | 9.2 | Medium |
| Kidney | 7.1 | Low |
| Liver | 5.3 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 15.2 | High expression |
| HeLa | 11.4 | Medium expression |
| SH-SY5Y | 9.8 | Medium expression |
| HepG2 | 6.1 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G (p.Met1?) | Missense/start loss | Rare | Loss of protein initiation |
| c.232C>T (p.Arg78*) | Nonsense | Rare | Premature truncation, loss of function |
| c.494_495delAG (p.Glu165Valfs*2) | Frameshift | Rare | Frameshift, loss of function |
| c.631C>T (p.Arg211Trp) | Missense | Rare | Impaired RabGAP activity |
Mutation functional classification
Loss of Function (LOF)
Most reported mutations (nonsense, frameshift, start loss) lead to complete loss of RabGAP activity, causing Warburg Micro syndrome.
Gain of Function (GOF)
No gain-of-function mutations documented.
Dominant Negative (DN)
No dominant-negative mutations reported; disease is autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
| • GTPase activator activity (GO:0005096) | • Rab GTPase binding (GO:0017137) |
| • Golgi apparatus (GO:0005794) | • ER to Golgi vesicle-mediated transport (GO:0006888) |
| • regulation of Rab GTPase activity (GO:0032313) |
Pathways
• Rab regulation of trafficking (Reactome: R-HSA-9007101)
• Vesicle-mediated transport (Reactome: R-HSA-5653656)
Protein Summary
TBC1D20 is a 413-amino acid Rab GTPase-activating protein containing a TBC domain. It specifically inactivates Rab1 and Rab2 by stimulating GTP hydrolysis, thereby regulating ER-to-Golgi trafficking. The protein is widely expressed, with highest levels in brain and eye tissues. Loss of function leads to accumulation of inactive Rab-GTP and disrupted vesicle transport, underlying the pathogenesis of Warburg Micro syndrome and cataracts.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| TBC1D20 Knockout HEK293 Cell Line | EDJ-KQ2891 | Human | 128637 | Details Get a Quote |
| TBC1D20 Knockout A-549 Cell Line | EDJ-KQ23961 | Human | 128637 | Details Get a Quote |
| TBC1D20 Knockout HCT 116 Cell Line | EDJ-KQ23962 | Human | 128637 | Details Get a Quote |
| TBC1D20 Knockout HeLa Cell Line | EDJ-KQ23963 | Human | 128637 | Details Get a Quote |
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