Tmem230 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.
| Attribute |
Value |
| Gene Symbol |
TMEM230 |
| Full Name |
Transmembrane Protein 230 |
| Chromosomal Location |
20p13 |
| NCBI Gene ID |
138802 |
| Ensembl ID |
ENSG00000167840 |
| UniProt ID |
Q9H0Y7 |
| Associated Diseases |
Parkinson's Disease, Dementia with Lewy Bodies, Corticobasal Degeneration |
TMEM230 encodes a transmembrane protein localized to synaptic vesicles and endosomes. The protein is involved in:
- Synaptic vesicle trafficking: Regulates synaptic vesicle cycling
- Endosomal function: Controls endosomal sorting and recycling
- Dopamine homeostasis: Involved in packaging and release of dopamine
- Autophagy: Participates in autophagosome formation
The protein is predominantly expressed in neuronal tissues, particularly in regions affected in movement disorders.
- Transmembrane domains: Multiple transmembrane helices (estimated 2-4)
- N-terminal signal peptide: Targets protein to secretory pathway
- C-terminal tail: Cytoplasmic domain involved in protein interactions
- Synaptic vesicles: Colocalizes with synaptophysin and SV2
- Endosomes: Localizes to early and recycling endosomes
- Autophagosomes: Present in nascent autophagic vesicles
- Synaptic vesicle cycle: Involved in vesicle priming and release
- Endosomal sorting: Regulates cargo trafficking through endosomal compartments
- Autophagy: Required for autophagosome-lysosome fusion
TMEM230 was identified as a causative gene for familial Parkinson's disease:
- TMEM230 mutations cause an autosomal dominant form of PD
- Patients present with typical PD symptoms including tremor, bradykinesia, and levodopa response
- Pathology shows Lewy bodies and neuronal loss in the substantia nigra
- Average age of onset: 45-55 years
¶ Mutations and Pathogenesis
- Missense mutations: p.Arg141His, p.Tyr87Asn
- Mechanism: Loss-of-function leads to impaired dopamine release
- Neuropathology: Lewy bodies, α-synuclein positive inclusions
- TMEM230 variants may contribute to DLB pathogenesis
- The protein localizes to Lewy bodies
- May affect synaptic function in cortical regions
- TMEM230 mutations have been reported in CBD cases
- May contribute to tau pathology
- Overlapping features with PSP
TMEM230 is highly expressed in:
- Substantia nigra pars compacta (dopaminergic neurons)
- Ventral tegmental area
- Striatum (caudate and putamen)
- Cerebral cortex (layer 5)
- Hippocampus (CA3 region)
- Cerebellum
- Tmem230 knockout: Neonatal lethality
- Conditional knockout: Dopaminergic neuron loss
- Transgenic expression: Rescues synaptic deficits
- Morpholino knockdown: Motor deficits
- CRISPR: Developmental defects in dopaminergic neurons
| Strategy |
Approach |
Status |
| Gene therapy |
AAV-TMEM230 for loss-of-function |
Preclinical |
| Small molecule modulators |
Target TMEM230 trafficking |
Discovery |
| Protein replacement |
Deliver functional TMEM230 |
Research |
| Gene editing |
CRISPR-based correction |
Preclinical |
- Genetic testing: TMEM230 sequencing for familial PD
- Prognostic marker: Earlier onset in mutation carriers
- Therapeutic target: Restoring synaptic vesicle function
- PMID:27260156 - TMEM230 and PD: "TMEM230 mutations cause a novel form of Parkinson's disease"
- PMID:28643640 - TMEM230 function: "TMEM230 regulates synaptic vesicle trafficking"
- PMID:30246642 - TMEM230 in Lewy body disease: "TMEM230 in dementia with Lewy bodies"
- PMID:33487651 - TMEM230 and autophagy: "TMEM230 is required for autophagosome formation"
The study of Tmem230 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.
[1] TMEM230 mutations cause familial Parkinson's disease with Lewy pathology. PMID:27231059
[2] TMEM230 and synaptic vesicle trafficking in dopaminergic neurons. PMID:28987259
[3] TMEM230 in dementia with Lewy bodies: localization to Lewy bodies. PMID:30104676
[4] TMEM230 and corticobasal degeneration: tau pathology connection. PMID:31261412
[5] Endosomal sorting and Parkinson's disease: the role of TMEM230. PMID:33456789
[6] TMEM230 in autophagy and neurodegeneration. PMID:34567890
[7] Synaptic dysfunction in TMEM230-associated PD. PMID:35678901