ALS2 Gene (Alsin Rho Guanine Nucleotide Exchange Factor)
Comprehensive genomic and functional analysis of ALS2, associated with juvenile amyotrophic lateral sclerosis and related motor neuron diseases.
Gene Information Card
| Symbol | ALS2 |
|---|---|
| Full Name | alsin Rho guanine nucleotide exchange factor |
| Gene Type | protein-coding |
| Chromosomal Location | 2q33.1 |
| NCBI Gene ID | 57679 ncbi.nlm.nih.gov/gene/57679 |
| Ensembl ID | ENSG00000138336 |
| UniProt ID | Q96Q42 |
| OMIM ID | 606352 |
| HGNC ID | 443 |
| Aliases | ALS2CR, ALSJ, IAHSP, KIAA1563, PLSJ |
Description
The ALS2 gene encodes alsin, a guanine nucleotide exchange factor (GEF) for the small GTPase Rab5, involved in endosomal trafficking and neurite outgrowth. Mutations in ALS2 cause juvenile amyotrophic lateral sclerosis (ALS2), primary lateral sclerosis, and infantile-onset ascending hereditary spastic paralysis. The protein contains multiple domains including RCC1-like, DH/PH, and VPS9, and is expressed predominantly in the central nervous system.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Juvenile amyotrophic lateral sclerosis (ALS2) | Loss-of-function mutations impair alsin-mediated endosomal trafficking, leading to motor neuron degeneration. | ClinVar, OMIM |
| Primary lateral sclerosis, juvenile | Homozygous or compound heterozygous mutations disrupt alsin function, causing upper motor neuron degeneration. | OMIM, NCBI |
| Infantile-onset ascending hereditary spastic paralysis (IAHSP) | Biallelic loss-of-function mutations in ALS2 result in progressive spasticity and paralysis. | OMIM, ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 3.2 | Low |
| Spinal cord | 2.8 | Low |
| Cerebellum | 2.5 | Low |
| Testis | 1.9 | Low |
| Heart | 1.1 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y | 2.1 | Neuroblastoma cell line |
| HeLa | 1.5 | Cervical carcinoma |
| HEK293 | 1.3 | Embryonic kidney |
| U-87 MG | 1.8 | Glioblastoma |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1548_1549insA (p.Gly517Argfs*13) | Frameshift | Rare | Loss of function; associated with juvenile ALS |
| c.2674C>T (p.Arg892*) | Nonsense | Rare | Premature stop; loss of function |
| c.3340C>T (p.Arg1114*) | Nonsense | Rare | Loss of function; IAHSP |
| c.3853_3854delAG (p.Ser1285Cysfs*6) | Frameshift | Rare | Loss of function; primary lateral sclerosis |
Mutation functional classification
Loss of Function (LOF)
Most ALS2 mutations are loss-of-function, leading to truncated or unstable alsin protein, impairing Rab5-mediated endosomal trafficking and causing motor neuron degeneration.
Gain of Function (GOF)
No evidence of gain-of-function mutations in ALS2.
Dominant Negative (DN)
No evidence of dominant-negative effects; inheritance is autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
| • GTPase activator activity | • guanyl-nucleotide exchange factor activity |
| • Rab5 guanyl-nucleotide exchange factor activity | • endosomal transport |
| • regulation of endocytosis | • neuron projection development |
| • intracellular protein transport | • cytosol |
| • early endosome | • cytoplasmic vesicle |
Pathways
• Endosomal trafficking (Rab5 pathway)
• Neurite outgrowth signaling
Protein Summary
Alsin is a 1657-amino acid protein with a molecular weight of ~184 kDa. It contains an N-terminal RCC1-like domain (RLD), a central Dbl homology (DH) domain, a pleckstrin homology (PH) domain, and a C-terminal VPS9 domain. The VPS9 domain acts as a GEF for Rab5, regulating early endosome fusion and trafficking. Alsin is predominantly cytoplasmic and enriched in neurons, where it supports endosomal dynamics essential for motor neuron survival.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PALS2 Knockout HEK293 Cell Line | EDJ-KQ2084 | Human | 51678 | Details Get a Quote |
| ALS2 Knockout HEK293 Cell Line | EDJ-KQ4049 | Human | 57679 | Details Get a Quote |
| LGALS2 Knockout HEK293 Cell Line | EDJ-KQ5115 | Human | 3957 | Details Get a Quote |
| ALS2CL Knockout HEK293 Cell Line | EDJ-KQ12338 | Human | 259173 | Details Get a Quote |
| ALS2CL Knockout HeLa Cell Line | EDJ-KQ39927 | Human | 259173 | Details Get a Quote |
| ALS2CL Knockout A-549 Cell Line | EDJ-KQ41185 | Human | 259173 | Details Get a Quote |
| ALS2CL Knockout HCT 116 Cell Line | EDJ-KQ41186 | Human | 259173 | Details Get a Quote |
| PALS2 Knockout A-549 Cell Line | EDJ-KQ23550 | Human | 51678 | Details Get a Quote |
| PALS2 Knockout HCT 116 Cell Line | EDJ-KQ23551 | Human | 51678 | Details Get a Quote |
| PALS2 Knockout HeLa Cell Line | EDJ-KQ23552 | Human | 51678 | Details Get a Quote |
| ALS2 Knockout A-549 Cell Line | EDJ-KQ26401 | Human | 57679 | Details Get a Quote |
| ALS2 Knockout HCT 116 Cell Line | EDJ-KQ26402 | Human | 57679 | Details Get a Quote |
| ALS2 Knockout HeLa Cell Line | EDJ-KQ26403 | Human | 57679 | Details Get a Quote |
| LGALS2 Knockout HeLa Cell Line | EDJ-KQ53789 | Human | 3957 | Details Get a Quote |
| LGALS2 Knockout A-549 Cell Line | EDJ-KQ62267 | Human | 3957 | Details Get a Quote |
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