Ms4A6A 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.
MS4A6A (Membrane-Spanning 4-Domains A6A) encodes a member of the membrane-spanning 4-domain subfamily A. GWAS have identified MS4A6A as a risk gene for Alzheimer's disease. The protein is expressed in immune cells and is thought to modulate calcium signaling and immune responses.
| Property |
Value |
| Gene Symbol |
MS4A6A |
| Full Name |
Membrane Spanning 4-Domains A6A |
| Chromosomal Location |
11q12.2 |
| NCBI Gene ID |
64231 |
| Ensembl ID |
ENSG00000110079 |
| UniProt ID |
Q9H5Z1 |
| OMIM |
— |
| Property |
Value |
| Protein Name |
MS4A6A |
| Molecular Weight |
~28 kDa (243 amino acids) |
| Subcellular Localization |
Cell membrane |
| Protein Family |
MS4A family (MS4A1-15) |
¶ Domain Structure
- N-terminal extracellular domain: Short extracellular loop
- Transmembrane domains: Four transmembrane helices
- C-terminal cytoplasmic tail: Intracellular domain
- Membrane protein: Member of tetraspanin-like family
- Immune cell function: Expressed in B-cells, T-cells, myeloid cells
- Calcium signaling: Modulates store-operated calcium entry
- Cell adhesion: May participate in immune cell interactions
- MS4A6A variants identified as risk gene in GWAS
- Risk allele associated with increased AD risk (odds ratio ~1.10)
- Potential mechanisms:
- Altered immune cell function
- Effects on microglial activation
- Modulation of amyloid clearance
- Altered neuroinflammation
- Autoimmune diseases: Variants associated with multiple sclerosis
- Cardiovascular disease: Some association with lipid metabolism
| Approach |
Status |
Description |
| None direct |
— |
No current therapeutic approaches |
| Research |
— |
Understanding microglial role in AD |
- Naj AC, et al. (2011). Common variants at MS4A4/MS4A6E, CD2AP, CD33 and EPHA1 are associated with late-onset Alzheimer's disease. Nat Genet. 43(5):436-41. https://doi.org/10.1038/ng.801
- Proitsi P, et al. (2015). MS4A4A modifies Alzheimer's disease risk and tau pathology. Neurobiol Aging. 36(12):2846-54. https://doi.org/10.1016/j.neurobiolaging.2015.08.018
- Huang KL, et al. (2017). A common haplotype lowers MS4A4A expression and protects against Alzheimer's disease. Nat Neurosci. 20(8):1052-61. https://doi.org/10.1038/nn.4586
MS4A6A expression in the brain:
- Cerebral cortex: High expression in cortical layers
- Hippocampus: Moderate expression in pyramidal neurons
- White matter: Lower expression in oligodendrocytes
- Microglia: Cell-type specific expression
- Membrane: Type I membrane protein
- Extracellular domain: Ligand-binding region
- Intracellular: Signaling domains
- Risk variant: rs61020556 associated with increased AD risk
- Mechanism: Altered microglial signaling
- Pathology: Co-localizes with amyloid plaques
- Therapeutic target: Anti-MS4A6A antibodies in development
- Expression changes: Altered in MS lesions
- Microglial role: Immune modulation
- Therapeutic potential: Target for immunomodulation
- Ms4a6a overexpression: Altered microglial response
- Knockout models: Viable with immune phenotypes
- AD model crosses: Accelerated pathology in some studies
- CSF MS4A6A: Investigated as AD biomarker
- PET ligands: In development for microglial imaging
- Blood biomarkers: Under investigation
- Monoclonal antibodies: Target extracellular domain
- Small molecule modulators: Alter microglial activation
- Gene therapy: Modulate expression
The study of Ms4A6A 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] MS4A6A and Alzheimer disease risk. PMID:24162737