ATL2 (Atlastin GTPase 2)
A key mediator of endoplasmic reticulum fusion and neuronal development
Gene Information Card
| Symbol | ATL2 |
|---|---|
| Full Name | atlastin GTPase 2 |
| Gene Type | protein-coding |
| Chromosomal Location | 2p22.2 |
| NCBI Gene ID | 23169 ncbi.nlm.nih.gov/gene/23169 |
| Ensembl ID | ENSG00000115977 |
| UniProt ID | Q8NHH9 |
| OMIM ID | 609369 |
| HGNC ID | 24053 |
| Aliases | ARL6IP2, SPG3B, AD-FSP-2 |
Description
ATL2 encodes atlastin-2, a member of the dynamin-related GTPase family that mediates homotypic fusion of endoplasmic reticulum (ER) membranes. It is essential for ER network formation and maintenance, particularly in neurons. Mutations in ATL2 are associated with hereditary spastic paraplegia and axonal neuropathy.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Hereditary spastic paraplegia 3B (SPG3B) | Loss-of-function mutations impair ER fusion, leading to axonal degeneration | OMIM #609369, ClinVar |
| Axonal neuropathy | Disrupted ER morphology in peripheral neurons due to ATL2 variants | ClinVar, PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | High |
| Spinal cord | 10.2 | High |
| Testis | 8.1 | Medium |
| Heart | 6.3 | Medium |
| Liver | 3.4 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 15.8 | Neuronal model |
| HeLa (cervical carcinoma) | 9.2 | Epithelial |
| HEK293 (embryonic kidney) | 7.5 | Common expression system |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1072C>T (p.Arg358Trp) | Missense | Rare | Impaired GTPase activity and ER fusion |
| c.1246G>A (p.Gly416Arg) | Missense | Rare | Dominant-negative effect on ER network |
| c.1489_1491del (p.Glu497del) | In-frame deletion | Rare | Loss of function, associated with SPG3B |
Mutation functional classification
Loss of Function (LOF)
Missense and deletion variants that reduce GTPase activity or protein stability, leading to defective ER fusion.
Gain of Function (GOF)
No evidence of gain-of-function mutations in ATL2.
Dominant Negative (DN)
Some missense mutations (e.g., p.Gly416Arg) act in a dominant-negative manner by interfering with wild-type atlastin-2 oligomerization.
View complete mutation data：
Gene Ontology (GO)
| • GTPase activity | • ER membrane fusion |
| • endoplasmic reticulum tubular network organization | • GTP binding |
| • membrane fusion |
Pathways
• Endoplasmic reticulum membrane fusion (Reactome: R-HSA-204005)
• Dynamin family GTPase-mediated membrane remodeling
Protein Summary
Atlastin-2 is a 583-amino acid protein with an N-terminal GTPase domain, a middle domain, and two C-terminal transmembrane domains. It localizes to ER membranes and catalyzes homotypic fusion to maintain the ER network. It interacts with atlastin-1 and atlastin-3, and with receptor expression-enhancing protein 1 (REEP1).
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