ARL3 Gene: ADP Ribosylation Factor Like GTPase 3
Essential regulator of ciliary trafficking and photoreceptor function
Gene Information Card
| Symbol | ARL3 |
|---|---|
| Full Name | ADP Ribosylation Factor Like GTPase 3 |
| Gene Type | Protein coding |
| Chromosomal Location | 10q24.32 |
| NCBI Gene ID | 403 ncbi.nlm.nih.gov/gene/403 |
| Ensembl ID | ENSG00000138175 |
| UniProt ID | P36405 |
| OMIM ID | 604695 |
| HGNC ID | 694 |
| Aliases | ARFL3 |
Description
ARL3 (ADP Ribosylation Factor Like GTPase 3) encodes a member of the ARF-like family of small GTPases. The protein localizes to cilia and plays a critical role in ciliary trafficking, particularly the transport of lipidated cargo (e.g., prenylated proteins) to the photoreceptor outer segment. Mutations in ARL3 cause autosomal recessive retinitis pigmentosa (RP83) and Joubert syndrome, highlighting its essential function in ciliary biology and vision.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Retinitis pigmentosa 83 (RP83) | Loss-of-function mutations impair ciliary trafficking of prenylated proteins, leading to photoreceptor degeneration. | OMIM #618173; ClinVar |
| Joubert syndrome 38 (JBTS38) | Biallelic ARL3 mutations disrupt primary cilium function, causing cerebellar and retinal abnormalities. | OMIM #618175; ClinVar |
| Ciliopathy-related phenotypes | ARL3 dysfunction affects multiple ciliated tissues, including kidney and brain. | Literature review |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 19.2 | Medium |
| Retina | 15.8 | Medium |
| Brain (cerebellum) | 12.1 | Medium |
| Kidney | 9.5 | Low |
| Lung | 6.3 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| ARPE-19 (retinal pigment epithelium) | 18.5 | High expression; relevant for retinal function |
| HeLa (cervical carcinoma) | 12.3 | Moderate expression |
| HEK 293 (embryonic kidney) | 10.7 | Moderate expression |
| SH-SY5Y (neuroblastoma) | 8.9 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.296G>A (p.Arg99Gln) | Missense | Rare | Impaired GTP binding and ciliary localization; associated with RP83 |
| c.2T>C (p.Met1Thr) | Start loss | Rare | Loss of protein expression; causes Joubert syndrome |
| c.557G>A (p.Arg186His) | Missense | Rare | Reduced GTPase activity; reported in retinitis pigmentosa |
Mutation functional classification
Loss of Function (LOF)
Biallelic loss-of-function mutations (e.g., start loss, missense impairing GTP binding) cause retinitis pigmentosa and Joubert syndrome by disrupting ciliary trafficking.
Gain of Function (GOF)
No gain-of-function mutations reported in ARL3.
Dominant Negative (DN)
No dominant-negative mutations reported; all disease-associated variants are recessive.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Ciliary trafficking pathway (Reactome: R-HSA-5620912)
• ARF family GTPase cycle (Reactome: R-HSA-9007101)
• Retinoid cycle and photoreceptor maintenance (KEGG: hsa04744)
Protein Summary
ARL3 is a small GTPase of the ARF-like family, essential for ciliary trafficking. It cycles between GDP-bound (inactive) and GTP-bound (active) states. Active ARL3 recruits effector proteins (e.g., UNC119, PDE6D) to mediate the transport of lipidated cargo from the inner segment to the outer segment of photoreceptors. Loss of ARL3 function leads to accumulation of cargo in the inner segment and progressive photoreceptor degeneration. The protein is highly expressed in testis, retina, and brain, consistent with its role in ciliated tissues.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ARL3 Knockout HEK293 Cell Line | EDJ-KQ4091 | Human | 403 | Details Get a Quote |
| ARL3 Knockout A-549 Cell Line | EDJ-KQ26477 | Human | 403 | Details Get a Quote |
| ARL3 Knockout HCT 116 Cell Line | EDJ-KQ26478 | Human | 403 | Details Get a Quote |
| ARL3 Knockout HeLa Cell Line | EDJ-KQ26479 | Human | 403 | Details Get a Quote |
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