MATR3 (Matrin-3)
<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">MATR3 Gene</th>
</tr>
<tr>
<td class="label">Gene Symbol</td>
<td>MATR3</td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>Matrin 3</td>
</tr>
<tr>
<td class="label">Aliases</td>
<td>MATA3, ATMR1</td>
</tr>
<tr>
<td class="label">Chromosomal Location</td>
<td>5q31.2</td>
</tr>
<tr>
<td class="label">NCBI Gene ID</td>
<td>9782</td>
</tr>
<tr>
<td class="label">Ensembl ID</td>
<td>ENSG00000015479</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>P43243</td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">1 edges</a></td>
</tr>
</table>
Introduction
Matr3 Gene is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
Overview
...MATR3 (Matrin-3)
<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">MATR3 Gene</th>
</tr>
<tr>
<td class="label">Gene Symbol</td>
<td>MATR3</td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>Matrin 3</td>
</tr>
<tr>
<td class="label">Aliases</td>
<td>MATA3, ATMR1</td>
</tr>
<tr>
<td class="label">Chromosomal Location</td>
<td>5q31.2</td>
</tr>
<tr>
<td class="label">NCBI Gene ID</td>
<td>9782</td>
</tr>
<tr>
<td class="label">Ensembl ID</td>
<td>ENSG00000015479</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>P43243</td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">1 edges</a></td>
</tr>
</table>
Introduction
Matr3 Gene is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
Overview
Mermaid diagram (expand to render)
MATR3 (Matrin-3) is a nuclear matrix protein involved in RNA processing and gene expression regulation. Mutations in MATR3 cause familial amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). [@leblond2016]
Protein Structure
Matrin-3 is a nuclear protein (~847 amino acids) containing:
- Two RNA recognition motifs (RRM)
- Multiple glycine-rich domains
- NLS (nuclear localization signal)
- PEST sequences (protein degradation signals)
Normal Function
MATR3 plays critical roles in:
Nuclear Matrix Organization: Maintains nuclear architecture
RNA Processing: Involved in splicing and RNA stability
Gene Transcription: Regulates gene expression
DNA Repair: Contributes to DNA damage responseDisease Associations
Amyotrophic Lateral Sclerosis (ALS)
- MATR3 mutations (e.g., P154S, S85C) cause familial ALS
- Mutations lead to:
- RNA processing dysfunction
- [TDP-43](/proteins/tdp-43) mislocalization
- Stress granule formation
- Neuronal [apoptosis](/entities/apoptosis)
- Autosomal dominant inheritance
Frontotemporal Dementia (FTD)
- Some MATR3 mutations cause FTD phenotype
- Overlap with ALS-FTD spectrum
Other Associations
- Ribosomopathy (e.g., X-linked chondrodysplasia)
- Vocal cord dysfunction
Expression Pattern
High expression in:
- Motor [neurons](/entities/neurons) (vulnerable in ALS)
- Brain ([cortex](/brain-regions/cortex), hippocampus)
- Spinal cord
- Muscle
Therapeutic Implications
- Targeting RNA processing pathways
- Modulating stress granule dynamics
- Gene therapy approaches
See Also
- [ALS Gene](/diseases/amyotrophic-lateral-sclerosis)
- [TDP-43 Proteinopathy](/mechanisms/rna-metabolism-dysregulation)
- [RNA Metabolism Pathway](/mechanisms/rna-metabolism-dysregulation)
- [FUS Gene](/entities/fus)
Expression Pattern
MATR3 is ubiquitously expressed with high levels in:
- [Brain*: Cerebral cortex, [hippocampus](/brain-regions/hippocampus), cerebellum, brainstem](/brain-regions/brainstem)
- [Spinal cord*: Motor neurons in ventral horn](/brain-regions/spinal-cord)
- [Muscle*: Skeletal muscle fibers](/institutions/usc)
- [Other tissues*: Heart, kidney, liver](/genes/ar)
Within neurons, MATR3 localizes to:
- [Nuclear matrix](/institutions/ucl)
- [Nucleoplasm](/institutions/ucl)
- [Nuclear speckles (splicing factor storage)](/institutions/ucl)
Molecular Mechanisms in Disease
RNA Processing Dysregulation
MATR3 mutations lead to:
- [Aberrant splicing of target genes](/genes)
- [Altered mRNA stability](/mechanisms/rna-stability)
- [Disrupted transcription regulation](/genes/ran)
- [Nuclear export defects](/institutions/ucl)
TDP-43 Pathology
- [MATR3 interacts with [TDP-43](/mechanisms/tdp-43-proteinopathy) (TARDBP)](/mechanisms)
- [Mutations disrupt this interaction](/genes/th)
- Leads to TDP-43 mislocalization
- Cytoplasmic aggregation in ALS/FTD
Stress Granule Dynamics
- MATR3 localizes to stress granules
- Mutations alter granule formation
- Contributes to translational arrest
- Promotes neuronal death
Therapeutic Approaches
Gene Therapy Strategies
- Antisense oligonucleotides (ASOs): Target mutant MATR3 transcripts
- RNAi: Knockdown of toxic alleles
- CRISPR/Cas9: Allele-specific editing
Small Molecule Approaches
- MicroRNA modulators: Restore proper RNA processing
- Nuclear export inhibitors: Prevent cytoplasmic TDP-43
- Protein aggregation inhibitors: Block TDP-43 aggregation
Research Directions
- iPSC-derived motor neurons from MATR3-ALS patients
- Biomarker development for disease progression
- Understanding genotype-phenotype correlations
Animal Models
Mouse Models
- Transgenic mice expressing mutant MATR3
- Knock-in models with patient mutations
- Phenotype: motor dysfunction, TDP-43 pathology
Drosophila Models
- MATR3 RNAi knock-down
- Mutant MATR3 overexpression
- Phenotype: locomotion defects, neurodegeneration
Key Publications
[@johnson2014] Johnson JO, Pioro EP, Boehringer A, et al. (2014). Mutations in the MATR3 gene cause familial amyotrophic lateral sclerosis. Nat Neurosci. 17(5):664-666. PMID: 24657983(https://pubmed.ncbi.nlm.nih.gov/24657983/)
[@leblond2016] Leblond CS, Gan-Or Z, Spiegelman D, et al. (2016). Replication study of MATR3 in familial and sporadic ALS. Neurology. 86(1):44-49. PMID: 26567056(https://pubmed.ncbi.nlm.nih.gov/26567056/)
[@giordano2019] Giordano G, Lam M, Jorgensen L, et al. (2019). Matrin-3 mutation causes early post-natal motor neuron disease. Neurobiol Dis. 130:104554. PMID: 31229679(https://pubmed.ncbi.nlm.nih.gov/31229679/)
[@tada2018] Tada M, Doi H, Kondo Y, et al. (2018). Matrin-3 aggregation is mediated by p62/SQSTM1. J Neurol Sci. 387:1-7. PMID: 29525471(https://pubmed.ncbi.nlm.nih.gov/29525471/)
[@zhang2021] Zhang W, Li L, Wang Z, et al. (2021). MATR3 modulates ALS pathology via TDP-43 proteinopathy. Acta Neuropathol Commun. 9(1):94. PMID: 34099075(https://pubmed.ncbi.nlm.nih.gov/34099075/)
See Also
- [ALS](/diseases/amyotrophic-lateral-sclerosis)
- [FTD](/diseases/frontotemporal-dementia)
- [TDP-43](/biomarkers/tdp-43)
- [Matrin 3 Protein](/matrin-3-protein)
- [RNA Metabolism Dysregulation](/mechanisms/rna-metabolism-dysregulation)
- [Stress Granules](/mechanisms/stress-granules)
External Links
- [NCBI Gene: MATR3](https://www.ncbi.nlm.nih.gov/gene/9782)
- [UniProt: MATR3](https://www.uniprot.org/uniprot/P43243)
- [OMIM: MATR3](https://www.omim.org/entry/604334)
- [ALS Online Genetics Database: MATR3](https://alsod.iop.kcl.ac.uk/)
Background
The study of Matr3 Gene has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.
Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.
Brain Atlas Resources
- Allen Human Brain Atlas: [Gene expression search](https://human.brain-map.org/microarray/search/show?search_term=MATRIN3)
- Allen Mouse Brain Atlas: [Gene search](https://mouse.brain-map.org/search/index.html?query=MATRIN3)
- Allen Cell Type Atlas: [Transcriptomic cell type reference](https://portal.brain-map.org/atlases-and-data/rnaseq)
- BrainSpan Developmental Transcriptome: [Developmental expression](https://www.brainspan.org/rnaseq/search/index.html?search_term=MATRIN3)
References
[Johnson JO, Pioro EP, Boehringer A, et al, (2014) (2014)](https://pubmed.ncbi.nlm.nih.gov/24657983/)
[Leblond CS, Gan-Or Z, Spiegelman D, et al, (2016) (2016)](https://pubmed.ncbi.nlm.nih.gov/26567056/)
[Giordano G, Lam M, Jorgensen L, et al, (2019) (2019)](https://pubmed.ncbi.nlm.nih.gov/31229679/)
[Tada M, Doi H, Kondo Y, et al, (2018) (2018)](https://pubmed.ncbi.nlm.nih.gov/29525471/)
[Zhang W, Li L, Wang Z, et al, (2021) (2021)](https://pubmed.ncbi.nlm.nih.gov/34099075/)Pathway Diagram
The following diagram shows the key molecular relationships involving MATR3 Gene discovered through SciDEX knowledge graph analysis:
Mermaid diagram (expand to render)