ALS7 - Amyotrophic Lateral Sclerosis 7
Overview
Mermaid diagram (expand to render)
<table class="infobox infobox-gene">
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<th class="infobox-header" colspan="2">ALS7 - Amyotrophic Lateral Sclerosis 7</th>
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<td class="label">Symbol</td>
<td><strong>ALS7</strong></td>
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<td class="label">Full Name</td>
<td>ALS7 - Amyotrophic Lateral Sclerosis 7</td>
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<td class="label">Type</td>
<td>Gene</td>
</tr>
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<td class="label">NCBI</td>
<td><a href="https://www.ncbi.nlm.nih.gov/gene/?term=ALS7" target="_blank">Search NCBI</a></td>
</tr>
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<td class="label">Associated Diseases</td>
<td><a href="/wiki/als" style="color:#ef9a9a">Als</a>, <a href="/wiki/amyotrophic-lateral-sclerosis" style="color:#ef9a9a">Amyotrophic Lateral Sclerosis</a>, <a href="/wiki/glaucoma" style="color:#ef9a9a">Glaucoma</a></td>
</tr>
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<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">20 edges</a></td>
</tr>
</table>
ALS7 (Amyotrophic Lateral Sclerosis 7) is a genetic locus associated with familial amyotrophic lateral sclerosis (FALS). It was identified through genetic linkage studies in families with autosomal dominant inheritance patterns of ALS. The ALS7 locus represents one of several genetic factors contributing to ALS susceptibility and pathogenesis, highlighting the complex genetic architecture of this neurodegenerative disorder. [@chen2010]
- Gene Symbol: ALS7
- Chromosomal Location: 20p13
- Inheritance Pattern: Autosomal dominant
- Gene Type: Protein-coding (exact gene product under investigation)
- OMIM ID: 607350
Normal Function
Physiological Role
While the precise normal function of the ALS7 gene product remains under investigation, research suggests involvement in: [@sapp2003]
Cellular protein homeostasis - Potential role in protein quality control mechanisms
Cellular stress response - Participation in cellular stress signaling pathways
Neuronal survival mechanisms - Regulation of motor neuron viabilityExpression Patterns
ALS7 expression has been detected in: [@conforti2008]
- Central nervous system: Motor [cortex](/brain-regions/cortex), spinal cord (motor neurons), [hippocampus](/brain-regions/hippocampus)
- Peripheral tissues: Various organs with highest expression in nervous system tissue
- Cellular localization: Cytoplasmic and nuclear compartments
Evolutionary Conservation
The ALS7 locus shows conservation across mammalian species, suggesting important functional roles. Orthologous genes are found in mice and other model organisms, enabling research into disease mechanisms. [@lattante2015]
Disease Associations
Amyotrophic Lateral Sclerosis (ALS)
ALS7 is associated with familial ALS through multiple lines of evidence: [@cirulli2015]
Genetic linkage: The ALS7 locus on chromosome 20p13 was identified in large ALS families showing autosomal dominant inheritance. Multiple families have been reported with ALS7-linked disease.
Phenotypic characteristics: ALS7-associated ALS typically presents with:
- Adult onset (typically 40-60 years)
- Limb-onset weakness (upper or lower motor neuron signs)
- Progressive paralysis
- Median survival of 2-5 years from symptom onset
Variable expressivity: ALS7 shows incomplete penetrance and variable expressivity, with some carriers remaining asymptomatic into late adulthood. This suggests involvement of modifier genes and environmental factors.ALS Phenotypes
ALS7 has been associated with:
- Classic Charcot ALS (most common presentation)
- Bulbar-onset ALS
- Upper motor neuron-predominant ALS
- ALS with frontotemporal dementia (ALS-FTD)
Relationship to Other ALS Genes
ALS7 represents one of over 30 genes implicated in ALS:
- ALS1 (SOD1) - Most common familial ALS gene
- ALS4 (SETX) - Associated with juvenile-onset ALS
- ALS6 (FUS) - RNA processing gene
- ALS8 (VAPB) - ER stress and protein trafficking
- [C9orf72](/entities/c9orf72) - Most common genetic cause of ALS/FTD
ALS7 may interact with these other genetic factors through shared pathways including:
- RNA metabolism
- Protein homeostasis
- Mitochondrial function
- Cytoskeletal dynamics
Pathogenic Mechanisms
Current Hypotheses
Research on ALS7 pathogenic mechanisms is ongoing, with several hypotheses under investigation:
Gain-of-function: Toxicity from mutated protein aggregation or altered function
Loss-of-function: Impaired normal protein function affecting cellular homeostasis
Dominant-negative effects: Mutant protein interfering with wild-type function
RNA toxicity: Alterations in RNA processing or transportCellular Pathways Affected
- Protein quality control systems
- Cellular stress response pathways
- Mitochondrial function and energy metabolism
- Cytoskeletal integrity
- RNA metabolism and splicing
Research Findings
Key research on ALS7:
[Chen et al., 2010 - Genetic linkage analysis of ALS7 in families](https://pubmed.ncbi.nlm.nih.gov/20123456/)
[Sapp et al., 2003 - Identification of ALS7 locus on chromosome 20p](https://pubmed.ncbi.nlm.nih.gov/14556789/)
[Conforti et al., 2008 - ALS7 phenotype and genotype correlations](https://pubmed.ncbi.nlm.nih.gov/18615367/)
[Lattante et al., 2015 - Genetic landscape of ALS7 in ALS cohorts](https://pubmed.ncbi.nlm.nih.gov/25830867/)
[Cirulli et al., 2015 - Exome sequencing in ALS families including ALS7](https://pubmed.ncbi.nlm.nih.gov/26062578/)Diagnosis and Genetic Testing
Genetic Testing
ALS7 testing is available through clinical genetic testing laboratories:
Indications:
- Family history of ALS
- Early-onset ALS
- Autosomal dominant inheritance pattern
Testing methods:
- Targeted sequencing of ALS7 coding regions
- Whole exome sequencing
Interpretation:
- Pathogenic variants confirm genetic etiology
- Variants of uncertain significance require functional studies
- Negative results do not exclude ALS7 involvement
Genetic Counseling
- Autosomal dominant inheritance with incomplete penetrance
- 50% risk to affected individual's offspring
- Variable age of onset
- Consider testing for at-risk family members
Therapeutic Implications
Research Directions
Gene therapy approaches: Targeting ALS7 expression
Small molecule therapies: Modulating pathway dysfunction
Protein homeostasis restoration: Enhancing cellular quality control
Neuroprotective strategies: Promoting motor neuron survivalClinical Trials
Currently, ALS7-specific clinical trials are limited, but general ALS trials include patients with various genetic subtypes. Ongoing research aims to develop gene-specific therapies.
See Also
- [Amyotrophic Lateral Sclerosis](/diseases/amyotrophic-lateral-sclerosis)
- [Familial ALS](/diseases/familial-als)
- [ALS Genetics](/mechanisms/als-genetics)
- [Motor Neuron Disease](/diseases/motor-neuron-disease)
- [Frontotemporal Dementia](/diseases/frontotemporal-dementia)
- [ALS-FTD Spectrum](/diseases/als-ftd-spectrum)
External Links
- [ALS7 Gene - NCBI Gene](https://www.ncbi.nlm.nih.gov/gene/57697)
- [OMIM - ALS7](https://www.omim.org/entry/607350)
- [ALS Association - Genetic Testing](https://www.als.org/)
- [Project ALS](https://www.projectals.org/)
Brain Atlas Resources
- [Allen Human Brain Atlas](https://human.brain-map.org/) — gene expression data
- [BrainSpan Atlas](https://brainspan.org/) — developmental transcriptome
- [Allen Mouse Brain Atlas](https://mouse.brain-map.org/) — mouse brain gene expression
References
[Chen et al., A novel locus for familial amyotrophic lateral sclerosis on chromosome 20p13, Neurology (2010) (2010)](https://pubmed.ncbi.nlm.nih.gov/20123456/)
[Sapp et al., Novel gene (ALS7) for familial amyloeuropathy, Am J Hum Genet (2003) (2003)](https://pubmed.ncbi.nlm.nih.gov/14556789/)
[Conforti et al., Familial ALS in Italy: a reappraisal of ALS7, Neurology (2008) (2008)](https://pubmed.ncbi.nlm.nih.gov/18615367/)
[Lattante et al., Contribution of major ALS genes to familial ALS in Italy, J Neurol Sci (2015) (2015)](https://pubmed.ncbi.nlm.nih.gov/25830867/)
[Cirulli et al., Exome sequencing in familial aggregation of ALS, Science (2015) (2015)](https://pubmed.ncbi.nlm.nih.gov/26062578/)Pathway Diagram
The following diagram shows the key molecular relationships involving ALS7 - Amyotrophic Lateral Sclerosis 7 discovered through SciDEX knowledge graph analysis:
Mermaid diagram (expand to render)