ATL3 Gene - Atlastin GTPase 3
A key regulator of endoplasmic reticulum morphology and hereditary sensory neuropathy
Gene Information Card
| Symbol | ATL3 |
|---|---|
| Full Name | Atlastin GTPase 3 |
| Gene Type | Protein coding |
| Chromosomal Location | 11q13.1 |
| NCBI Gene ID | 25923 ncbi.nlm.nih.gov/gene/25923 |
| Ensembl ID | ENSG00000184752 |
| UniProt ID | Q6DD88 |
| OMIM ID | 609369 |
| HGNC ID | 24526 |
| Aliases | ADP-ribosylation factor-like protein 6-interacting protein 1, ARL6IP1, SPG3B |
Description
ATL3 encodes atlastin-3, a member of the dynamin family of large GTPases. It is localized to the endoplasmic reticulum (ER) and mediates homotypic ER fusion, essential for maintaining ER network morphology. Mutations in ATL3 cause hereditary sensory and autonomic neuropathy type 1F (HSAN1F), a peripheral neuropathy characterized by distal sensory loss and ulcerations.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Hereditary sensory and autonomic neuropathy type 1F (HSAN1F) | Impaired ER fusion due to dominant-negative or loss-of-function ATL3 mutations leads to ER fragmentation and axonal degeneration. | OMIM #615632; ClinVar; PMID: 24656866 |
| Spastic paraplegia 3B (SPG3B) | Rare missense variants disrupt GTPase activity and ER fusion, resulting in lower limb spasticity. | OMIM #609369; PMID: 24656866 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 8.2 | Medium |
| Spinal cord | 6.5 | Medium |
| Peripheral nerve | 5.1 | Low |
| Testis | 4.8 | Low |
| Heart | 3.9 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 7.1 | Neuronal model |
| HeLa (cervical carcinoma) | 5.3 | Epithelial |
| HEK293 (embryonic kidney) | 4.6 | Common overexpression host |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1066C>T (p.Arg356Cys) | Missense | Rare | Dominant-negative; reduces GTPase activity and ER fusion |
| c.1072C>T (p.Arg358Trp) | Missense | Rare | Loss of function; associated with HSAN1F |
| c.1195G>A (p.Glu399Lys) | Missense | Rare | Impaired ER tethering; dominant-negative |
Mutation functional classification
Loss of Function (LOF)
p.Arg358Trp reduces GTP hydrolysis and ER fusion, leading to ER fragmentation.
Gain of Function (GOF)
Not reported.
Dominant Negative (DN)
p.Arg356Cys and p.Glu399Lys interfere with wild-type atlastin-3 function, disrupting ER network formation.
View complete mutation data：
Gene Ontology (GO)
| • GTPase activity (GO:0003924) | • GTP binding (GO:0005525) |
| • Endoplasmic reticulum membrane (GO:0005789) | • ER membrane fusion (GO:0061826) |
| • Endoplasmic reticulum tubular network organization (GO:0071786) |
Pathways
• ER membrane fusion (Reactome: R-HSA-204005)
• Endoplasmic reticulum organization (Reactome: R-HSA-9646399)
Protein Summary
Atlastin-3 is a 541-amino acid integral membrane GTPase with an N-terminal GTPase domain, a middle domain, and two C-terminal transmembrane helices. It localizes to ER tubules and catalyzes homotypic fusion of ER membranes. Mutations in the GTPase domain impair nucleotide binding and hydrolysis, leading to ER network defects and axonal degeneration in sensory neurons.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ATL3 Knockout HEK293 Cell Line | EDJ-KQ8302 | Human | 25923 | Details Get a Quote |
| ATL3 Knockout A-549 Cell Line | EDJ-KQ34270 | Human | 25923 | Details Get a Quote |
| ATL3 Knockout HCT 116 Cell Line | EDJ-KQ34271 | Human | 25923 | Details Get a Quote |
| ATL3 Knockout HeLa Cell Line | EDJ-KQ34272 | Human | 25923 | Details Get a Quote |
