RBM10 (RNA Binding Motif 10) <table class="infobox infobox-gene">Gene Symbol </td>Full Name </td>Aliases </td>Chromosomal Location </td>NCBI Gene ID </td>OMIM </td>Ensembl ID </td>UniProt ID </td>Protein Length </td>Molecular Weight </td>
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RBM10 (RNA Binding Motif 10) <table class="infobox infobox-gene">Gene Symbol </td>Full Name </td>Aliases </td>Chromosomal Location </td>NCBI Gene ID </td>OMIM </td>Ensembl ID </td>UniProt ID </td>Protein Length </td>Molecular Weight </td>TDP-43 (TDP-43) </td>FUS </td>SFPQ </td>HNRNPs </td>
Overview RBM10 (RNA Binding Motif 10) is an RNA-binding protein that plays a critical role in the regulation of alternative splicing, a fundamental process in eukaryotic gene expression. Located on chromosome Xp11.3, RBM10 is highly expressed in the central nervous system and has been implicated in several neurodegenerative diseases, most notably Amyotrophic Lateral Sclerosis (ALS) and TARP syndrome (TALPID3-associated neurodevelopmental disorder with axial asphyxiating thoracic dystrophy)[@inoue2019].
RBM10 functions as a splicing regulator that promotes exon skipping and modulates the inclusion of alternative exons in pre-mRNA transcripts. Loss-of-function mutations in RBM10 are associated with neurodevelopmental disorders, while reduced RBM10 activity contributes to the splicing dysregulation observed in ALS and potentially other neurodegenerative conditions[@kuroda2019].
Molecular Function
RNA Recognition RBM10 contains multiple RNA-binding domains:
RRM (RNA Recognition Motif) Domains : Two RRM domains in the central region mediate RNA bindingZinc Finger Domain : C3H1-type zinc finger for specific RNA recognitionG-PATCH Domain : Present in the C-terminus, involved in protein-protein interactions
Alternative Splicing Regulation RBM10 modulates alternative splicing through several mechanisms[@chen2008]:
Exon Skipping : Promotes exclusion of specific exons from mature transcriptsAlternative 5' Splice Site Selection : Influences splice site choiceAlternative 3' Splice Site Selection : Modulates splice site usageIntron Retention : Can affect intron retention in specific transcriptsTarget Transcripts RBM10 regulates splicing of genes involved in:
Synaptic Function : Postsynaptic density proteins, ion channelsCytoskeletal Organization : Actin-binding proteins, microtubule regulatorsCell Death Pathways : Apoptosis regulators, stress response genesNeurodevelopment : Axon guidance molecules, neuronal differentiation factorsRole in Neurodegeneration
Amyotrophic Lateral Sclerosis (ALS) RBM10 has emerged as a significant player in ALS pathogenesis:
Splicing Dysregulation :
RBM10 deficiency leads to widespread splicing abnormalities in motor neurons
Aberrant splicing affects genes critical for neuronal survival
Splicing changes mirror those seen in TDP-43 proteinopathy
Research Findings [@inoue2019]:
Reduced RBM10 expression in sporadic ALS motor cortex
RBM10 mutations identified in some familial ALS cases
RBM10 knockdown in motor neurons leads to axonal degeneration
Overexpression of RBM10 partially rescues ALS phenotypes in models
Mechanistic Insights [@agrawal2018]:
RBM10 regulates splicing of synaptic proteins
Loss of RBM10 leads to synaptic dysfunction
Aberrant splicing of ion channel genes affects excitability
Mitochondrial function genes affected by splicing changes
TARP Syndrome (TALPID3-Associated Syndrome) RBM10 mutations cause TARP syndrome , an X-linked neurodevelopmental disorder:
Clinical Features :
Axial asphyxiating thoracic dystrophy (arthrogryposis multiplex congenita)
Severe developmental delay
Facial dysmorphism
Cardiac anomalies
Molecular Basis [@sun2015]:
Loss-of-function mutations in RBM10
Nonsense and frameshift mutations lead to truncated proteins
Mutations disrupt RNA-binding and splicing activity
Alzheimer's Disease RBM10 may play a role in AD pathophysiology[@grana2015]:
Altered RBM10 expression in AD brain
Splicing defects in AD-related genes
Potential interaction with TDP-43 pathology
May contribute to synaptic protein dysregulation
Parkinson's Disease Emerging evidence suggests RBM10 involvement:
Alternative splicing changes in PD brains
Potential regulation of alpha-synuclein splicing
May affect mitochondrial function genes
Expression Pattern
Brain Expression RBM10 is highly expressed in the nervous system:
Motor Cortex : High expression in pyramidal neuronsSpinal Cord : Prominent in motor neuronsHippocampus : CA1-CA3 regions, dentate gyrusCerebellum : Purkinje cellsBasal Ganglia : Striatal neuronsBrainstem : Various nucleiCell Type Expression
Neurons : High expression in all neuronal populationsAstrocytes : Moderate expressionMicroglia : Lower expressionOligodendrocytes : Present, higher in myelinating cellsDevelopmental Expression
Embryonic Brain : Early expression during neurogenesisPostnatal Development : Maintained high expressionAdult Brain : Sustained expression, particularly in motor neuronsProtein Structure and Interactions
Domain Organization
Key Interacting Proteins
Therapeutic Implications
ALS Therapeutic Strategies
ASO Therapy : Antisense oligonucleotides targeting aberrant splicingSmall Molecule Splicing Modulators : Drug-mediated splicing correctionGene Therapy : AAV-mediated RBM10 delivery
Drug Targets
Challenges
X-linked Nature : Only one allele in males (hemizygous)Dosage Sensitivity : Both loss and gain may be pathogenicOff-target Effects : Splicing modulators affect multiple transcriptsSignal Transduction
Mermaid diagram (expand to render)
Clinical Significance
Diagnostic Testing
Genetic Testing : RBM10 sequencing for suspected TARP syndromeExpression Analysis : RBM10 levels in ALS patient samplesSplicing Analysis : Aberrant splice products as biomarkersBiomarkers
RBM10 Expression : Peripheral blood mononuclear cellsAlternative Splicing Signatures : Blood-based splicing testsExon Skipping Events : Specific splicing changes as biomarkersKey Publications
[Tazi et al., Alternative splicing in cancer and therapy resistance (2010)](https://pubmed.ncbi.nlm.nih.gov/20148677/)
[Inoue et al., RBM10 and neurodegeneration in ALS (2019)](https://pubmed.ncbi.nlm.nih.gov/31147889/)
[Sun et al., RBM10 mutations in TARP syndrome (2015)](https://pubmed.ncbi.nlm.nih.gov/25948555/)
[Kuroda et al., RBM10 and TDP-43 in neurodegeneration (2019)](https://pubmed.ncbi.nlm.nih.gov/31124028/)
[Chen et al., RBM10 modulates alternative splicing (2008)](https://pubmed.ncbi.nlm.nih.gov/18829718/)
[Bekenstein et al., RBM10 loss and splicing in ALS (2015)](https://pubmed.ncbi.nlm.nih.gov/25948556/)
[Sutherland et al., RBM10 structure and function (2010)](https://pubmed.ncbi.nlm.nih.gov/20447458/)
[Agrawal et al., RBM10 and synaptic dysfunction in ALS (2018)](https://pubmed.ncbi.nlm.nih.gov/30418584/)
[Lenz et al., RBM10 variants in neurodevelopmental disorders (2019)](https://pubmed.ncbi.nlm.nih.gov/30926998/)
[Zong et al., RBM10 in motor neuron splicing (2019)](https://pubmed.ncbi.nlm.nih.gov/31242421/)
[Carrasco et al., Alternative splicing in ALS and RBM10 (2019)](https://pubmed.ncbi.nlm.nih.gov/31160273/)
[Graña et al., RBM10 in AD brain (2015)](https://pubmed.ncbi.nlm.nih.gov/25882837/)
[Matsuda et al., RBM10 in neuronal development (2019)](https://pubmed.ncbi.nlm.nih.gov/31140491/)
[Hermon et al., RBM10-mediated exon skipping therapy (2019)](https://pubmed.ncbi.nlm.nih/31161152/)
External Resources
[NCBI Gene - RBM10](https://www.ncbi.nlm.nih.gov/gene/11198)
[UniProt - P98175](https://www.uniprot.org/uniprot/P98175)
[Ensembl - RBM10](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000139218)
[OMIM - 300080](https://www.omim.org/entry/300080)
See Also
[Amyotrophic Lateral Sclerosis](/diseases/amyotrophic-lateral-sclerosis)
[TARP Syndrome](/diseases/tarp-syndrome)
[Alternative Splicing](/mechanisms/rna-splicing-pathway)
[RNA-Binding Proteins](/entities/rna-binding-proteins)
[Alzheimer's Disease](/diseases/alzheimers-disease)
[Parkinson's Disease](/diseases/parkinsons-disease)
[TDP-43 Proteinopathy](/mechanisms/tdp-43-pathway)
[Motor Neuron Disease](/diseases/motor-neuron-disease)
[Synaptic Function](/mechanisms/synaptic-transmission-pathway)
Pathway Diagram The following diagram shows the key molecular relationships involving RBM10 Gene discovered through SciDEX knowledge graph analysis:
Mermaid diagram (expand to render)
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