RAB23: A Key Regulator of Vesicular Trafficking and Hedgehog Signaling
Comprehensive genomic and functional analysis of RAB23, a RAS oncogene family member implicated in developmental disorders and cancer
Gene Information Card
| Symbol | RAB23 |
|---|---|
| Full Name | RAB23, member RAS oncogene family |
| Gene Type | protein-coding |
| Chromosomal Location | 6p12.1 |
| NCBI Gene ID | 51715 ncbi.nlm.nih.gov/gene/51715 |
| Ensembl ID | ENSG00000112210 |
| UniProt ID | Q9ULC3 |
| OMIM ID | 606144 |
| HGNC ID | 14263 |
| Aliases | HSPC137, RAB23, member RAS oncogene family |
Description
RAB23 encodes a member of the RAB family of small GTPases, which are key regulators of intracellular vesicle trafficking. RAB23 is specifically involved in the transport of proteins to the primary cilium and modulates Hedgehog signaling by controlling the ciliary localization of signaling components. Mutations in RAB23 cause Carpenter syndrome, an autosomal recessive disorder characterized by craniosynostosis, polysyndactyly, and other developmental anomalies. RAB23 is also implicated in certain cancers, where altered expression or mutation may disrupt Hedgehog pathway regulation.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Carpenter syndrome (ACPS2) | Loss-of-function mutations in RAB23 impair ciliary trafficking, leading to aberrant Hedgehog signaling during development. | OMIM #201000; multiple homozygous/compound heterozygous mutations reported in patients. |
| Hedgehog pathway-related cancers (e.g., medulloblastoma, basal cell carcinoma) | RAB23 acts as a negative regulator of Hedgehog signaling; loss of function may contribute to ligand-independent pathway activation. | COSMIC; functional studies (PMID: 17003056, 19536131). |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 5.2 | Low |
| Heart | 3.8 | Low |
| Liver | 2.1 | Not detected |
| Kidney | 4.5 | Low |
| Testis | 8.9 | Medium |
| Lung | 3.0 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 6.1 | Embryonic kidney cells; moderate expression |
| HeLa | 4.8 | Cervical cancer cells; low expression |
| SH-SY5Y | 7.3 | Neuroblastoma cells; medium expression |
| HepG2 | 2.5 | Hepatocellular carcinoma; low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.166C>T (p.Arg56*) | Nonsense | Rare (Carpenter syndrome) | Loss of function; premature stop codon leads to truncated protein. |
| c.533G>A (p.Arg178Gln) | Missense | Rare (Carpenter syndrome) | Loss of function; disrupts GTP binding and membrane localization. |
| c.232_233delAG (p.Ser78fs) | Frameshift | Rare (Carpenter syndrome) | Loss of function; frameshift introduces premature stop. |
| c.1A>G (p.Met1?) | Start loss | Rare (Carpenter syndrome) | Loss of function; abolishes translation initiation. |
Mutation functional classification
Loss of Function (LOF)
Most reported mutations in Carpenter syndrome are loss-of-function (nonsense, frameshift, missense affecting GTP binding). These impair RAB23's ability to regulate ciliary trafficking and Hedgehog signaling.
Gain of Function (GOF)
No confirmed gain-of-function mutations reported in human disease. Overexpression in some cancers may contribute to oncogenesis but not via activating mutations.
Dominant Negative (DN)
Not described for RAB23; all disease-associated mutations are recessive.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Hedgehog signaling pathway (Reactome: R-HSA-5358351)
• RAB GEFs exchange GTP for GDP on RABs (Reactome: R-HSA-8876198)
• Membrane trafficking (Reactome: R-HSA-199991)
Protein Summary
RAB23 is a small GTPase (approx. 26 kDa) belonging to the RAS superfamily. It cycles between an active GTP-bound and inactive GDP-bound state, regulating vesicle transport from the Golgi to the plasma membrane and primary cilium. RAB23 localizes to the ciliary base and controls the entry and exit of Hedgehog signaling components (e.g., Smoothened, Gli transcription factors). Loss of RAB23 function leads to constitutive activation of Hedgehog signaling, causing developmental defects and potentially promoting tumorigenesis.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| RAB23 Knockout HEK293 Cell Line | EDJ-KQ11203 | Human | 51715 | Details Get a Quote |
| RAB23 Knockout A-549 Cell Line | EDJ-KQ39267 | Human | 51715 | Details Get a Quote |
| RAB23 Knockout HCT 116 Cell Line | EDJ-KQ39268 | Human | 51715 | Details Get a Quote |
| RAB23 Knockout HeLa Cell Line | EDJ-KQ39269 | Human | 51715 | Details Get a Quote |
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