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10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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MS4A6A
membrane spanning 4-domains A6A
Chromosome 11 · 11q12.2
NCBI Gene: 64231Ensembl: ENSG00000110077.16HGNC: HGNC:13375UniProt: B4DUN6
28PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Receptor
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein bindingtrans-Golgi networkcell surface receptor signaling pathwayplasma membraneAlzheimer diseasecoronary artery diseasedementiaIschemic stroke
✦AI Summary

MS4A6A (membrane spanning 4-domains A6A) is a tetraspan transmembrane protein involved in immune cell signaling and inflammatory responses. As a component of multimeric receptor complexes 1, MS4A6A functions in signal transduction at the plasma membrane and trans-Golgi network, demonstrating protein binding capacity consistent with its role in receptor assembly [GO Annotations]. The gene is predominantly expressed in immune cells, particularly microglia, macrophages, and endothelial cells 234. MS4A6A regulates inflammatory signaling through the IKK/NF-κB pathway 5, controlling endothelial dysfunction and monocyte adhesion. In Alzheimer's disease, MS4A6A expression in microglia promotes amyloid-beta clearance and neuroprotective responses; MS4A6d deficiency impairs microglial phagocytosis of amyloid plaques and exacerbates neuroinflammation 4. The protective MS4A6A variant rs610932 is associated with reduced Alzheimer's disease risk 6. In lung cancer and lupus nephritis, MS4A6A serves as a driver gene linked to immune cell infiltration and disease severity 78. Additionally, MS4A6A compensates functionally for FcεRIβ in human mast cells, supporting IgE-mediated allergic responses 1, suggesting its role in allergy susceptibility.

Sources cited
1
MS4A6A expression changes during THP-1 monocyte-to-macrophage differentiation induced by PMA
PMID: 37459313
2
MS4A6A is a microglial AD risk gene showing differential expression correlated with amyloid-beta and phospho-tau pathology
PMID: 34767070
3
MS4A6A is a hub driver gene in lupus nephritis with high diagnostic value (AUC=0.994) and highest expression in macrophages
PMID: 38130724
4
MS4A6A is a differentiation-related gene in tumor-associated macrophages with prognostic value in non-small cell lung cancer
PMID: 36969247
5
MS4a6d deficiency impairs amyloid clearance and microglial phagocytosis while exacerbating NF-κB-mediated neuroinflammation in Alzheimer's disease models
PMID: 40877951
6
MS4A6A promotes endothelial dysfunction and monocyte adhesion through IKK/NF-κB pathway activation in atherosclerosis
PMID: 40090082
7
MS4A6A compensates functionally for FcεRIβ in human mast cells to support FcεRI trafficking and IgE-mediated degranulation
PMID: 36424895
8
MS4A6A rs610932 variant is protective against late-onset Alzheimer's disease in meta-analysis of 24,771 patients and 35,324 controls
PMID: 29504051
Disease Associationsⓘ20
Alzheimer diseaseOpen Targets
0.54Moderate
coronary artery diseaseOpen Targets
0.40Weak
dementiaOpen Targets
0.38Weak
Ischemic strokeOpen Targets
0.34Weak
venous thromboembolismOpen Targets
0.33Weak
hypertrophic cardiomyopathyOpen Targets
0.33Weak
neurodegenerative diseaseOpen Targets
0.31Weak
deep vein thrombosisOpen Targets
0.28Weak
Lewy body dementiaOpen Targets
0.24Weak
late-onset Alzheimers diseaseOpen Targets
0.17Weak
Abruptio PlacentaeOpen Targets
0.14Weak
vitamin B deficiencyOpen Targets
0.13Weak
gliomaOpen Targets
0.08Suggestive
cardiomyopathyOpen Targets
0.05Suggestive
glioblastoma multiformeOpen Targets
0.05Suggestive
central nervous system cancerOpen Targets
0.04Suggestive
clear cell renal carcinomaOpen Targets
0.02Suggestive
lung adenocarcinomaOpen Targets
0.02Suggestive
Acute hepatic failureOpen Targets
0.02Suggestive
neoplasmOpen Targets
0.02Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
MS4A18Shared pathway100%MS4A13Shared pathway100%ADGRD2Shared pathway100%MS4A6EShared pathway100%MS4A15Shared pathway100%ADGRA3Shared pathway100%
Tissue Expression6 tissues
Bone Marrow
100%
Lung
78%
Liver
54%
Heart
37%
Ovary
11%
Brain
11%
Gene Interaction Network
Click a node to explore
MS4A6AMS4A18MS4A13ADGRD2MS4A6EMS4A15ADGRA3
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt Q9H2W1
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
1.33LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.90 [0.62–1.33]
RankingsWhere MS4A6A stands among ~20K protein-coding genes
  • #12,389of 20,598
    Most Researched28
  • #13,962of 17,882
    Most Constrained (LOEUF)1.33
Genes detectedMS4A6A
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Optimization of differentiation and transcriptomic profile of THP-1 cells into macrophage by PMA.
PMID: 37459313
PLoS One · 2023
1.00
2
Diverse human astrocyte and microglial transcriptional responses to Alzheimer's pathology.
PMID: 34767070
Acta Neuropathol · 2022
0.90
3
Identification of driver genes in lupus nephritis based on comprehensive bioinformatics and machine learning.
PMID: 38130724
Front Immunol · 2023
0.80
4
Differentiation-related genes in tumor-associated macrophages as potential prognostic biomarkers in non-small cell lung cancer.
PMID: 36969247
Front Immunol · 2023
0.70
5
MS4A6A/Ms4a6d deficiency disrupts neuroprotective microglia functions and promotes inflammation in Alzheimer's disease model.
PMID: 40877951
Mol Neurodegener · 2025
0.60