Gene Symbol: MS4A6A
Description: membrane spanning 4-domains A6A
Alias: 4SPAN3, 4SPAN3.2, CD20L3, CDA01, MS4A6, MST090, MSTP090, membrane-spanning 4-domains subfamily A member 6A, CD20 antigen-like 3, CD20-like precusor, HAIRB-iso, MS4A6A-polymorph, four-span transmembrane protein 3, four-span transmembrane protein 3.1, four-span transmembrane protein 3.2, membrane-spanning 4-domains, subfamily A, member 6A
Species: human
Products:     MS4A6A

Top Publications

  1. Liang Y, Buckley T, Tu L, Langdon S, Tedder T. Structural organization of the human MS4A gene cluster on Chromosome 11q12. Immunogenetics. 2001;53:357-68 pubmed
    ..polymorphisms were identified in the MS4A6E gene and common splice variants were observed for the MS4A4A, MS4A5, MS4A6A, and MS4A7 genes. Thus, the MS4A family currently includes 24 distinct human and mouse genes...
  2. McQuade A, Blurton Jones M. Microglia in Alzheimer's Disease: Exploring How Genetics and Phenotype Influence Risk. J Mol Biol. 2019;431:1805-1817 pubmed publisher
    ..By studying key Alzheimer's risk genes such as TREM2, CD33, ABCA7, and MS4A6A, we will be able to distinguish true disease-modulatory pathways from the full range of microglial-related ..
  3. Katsumata Y, Nelson P, Estus S, Fardo D. Translating Alzheimer's disease-associated polymorphisms into functional candidates: a survey of IGAP genes and SNPs. Neurobiol Aging. 2019;74:135-146 pubmed publisher
    ..For (2), the IGAP SNPs in CELF1 and MS4A6A were associated with expression of their neighboring genes, MYBPC3 and MS4A6A, respectively, in blood...
  4. Charchar F, Kaiser M, Bingham A, Fotinatos N, Ahmady F, Tomaszewski M, et al. Whole genome survey of copy number variation in the spontaneously hypertensive rat: relationship to quantitative trait loci, gene expression, and blood pressure. Hypertension. 2010;55:1231-8 pubmed publisher
    ..Transcriptomic experiments confirmed differences in the renal expression of several genes (including Ms4a6a, Ndrg3, Egln1, Cd36, Sema3a, Ugt2b, and Idi21) located in some of the CNVs between SHR and Wistar-Kyoto rats...
  5. Martiskainen H, Viswanathan J, Nykänen N, Kurki M, Helisalmi S, Natunen T, et al. Transcriptomics and mechanistic elucidation of Alzheimer's disease risk genes in the brain and in vitro models. Neurobiol Aging. 2015;36:1221.e15-28 pubmed publisher
    ..We observed that the expression of FRMD4A significantly decreased, and the expression of MS4A6A significantly increased in relation to increasing AD-related neurofibrillary pathology...
  6. Li J, Wang H, Zhu X, Sun F, Tan M, Tan C, et al. GWAS-Linked Loci and Neuroimaging Measures in Alzheimer's Disease. Mol Neurobiol. 2017;54:146-153 pubmed publisher
    ..As a result, single nucleotide polymorphisms (SNPs) at rs983392 within MS4A6A and rs11218343 within SOLR1 were both associated with the percentage of increase in the volume of left inferior ..
  7. Kunkle B, Jaworski J, Barral S, Vardarajan B, Beecham G, Martin E, et al. Genome-wide linkage analyses of non-Hispanic white families identify novel loci for familial late-onset Alzheimer's disease. Alzheimers Dement. 2016;12:2-10 pubmed publisher
    ..2-11q14.1, and 14q13.3), one of which replicates a genome-wide association LOAD locus, the MS4A6A-MS4A4E gene cluster at 11q12.2. Five of the 14 regions (3q25.31, 4q34.1, 8q22.3, 11q12.2-14.1, and 19q13...
  8. Wang Y, Tang B, Yang Y, Cui Y, Kang J, Liu Z, et al. Relationship between Alzheimer's disease GWAS-linked top hits and risk of Parkinson's disease with or without cognitive decline: a Chinese population-based study. Neurobiol Aging. 2016;39:217.e9-11 pubmed publisher
    ..function in PD, investigating 13 single-nucleotide polymorphisms in 9 genes (BIN1, CLU, ABCA7, CR1, PICALM, MS4A6A, CD33, MS4A4E, and CD2AP)...
  9. Barber R, Phillips N, Tilson J, Huebinger R, Shewale S, Koenig J, et al. Can Genetic Analysis of Putative Blood Alzheimer's Disease Biomarkers Lead to Identification of Susceptibility Loci?. PLoS ONE. 2015;10:e0142360 pubmed publisher
    ..Signals for several endophenotypes were observed in the vicinity of CR1, MS4A6A/MS4A4E, PICALM, CLU, and PTK2B...

More Information


  1. Almeida J, Dos Santos L, Trancozo M, de Paula F. Updated Meta-Analysis of BIN1, CR1, MS4A6A, CLU, and ABCA7 Variants in Alzheimer's Disease. J Mol Neurosci. 2018;64:471-477 pubmed publisher
    ..rs6656401 CR1, and rs744373 BIN1 were associated as risk factors for LOAD, while rs11136000 CLU and rs610932 MS4A6A were protective...
  2. Gölz L, Buerfent B, Hofmann A, Rühl H, Fricker N, Stamminger W, et al. Genome-wide transcriptome induced by nickel in human monocytes. Acta Biomater. 2016;43:369-382 pubmed publisher
    ..SLCs?), we identified new candidates implicated in Ni(2+)-elicited processes (various microRNAs?, INSIG1?, NAMPT?, MS4A6A?, DHRS9?)...
  3. Rosenberg R, Lambracht Washington D, Yu G, Xia W. Genomics of Alzheimer Disease: A Review. JAMA Neurol. 2016;73:867-74 pubmed publisher
    ..variants associated with late-onset AD have been identified including apolipoprotein E, BIN1, ABC7, PICALM, MS4A4E/MS4A6A, CD2Ap, CD33, EPHA1, CLU, CR1, and SORL1...
  4. Ramirez L, Goukasian N, Porat S, Hwang K, Eastman J, Hurtz S, et al. Common variants in ABCA7 and MS4A6A are associated with cortical and hippocampal atrophy. Neurobiol Aging. 2016;39:82-9 pubmed publisher
    ..Map-wise statistical significance was determined with permutations using threshold of p < 0.01. MS4A6A rs610932 and ABCA7 rs3764650 demonstrated significant associations with cortical and hippocampal atrophy...
  5. Carrasquillo M, Crook J, Pedraza O, Thomas C, Pankratz V, Allen M, et al. Late-onset Alzheimer's risk variants in memory decline, incident mild cognitive impairment, and Alzheimer's disease. Neurobiol Aging. 2015;36:60-7 pubmed publisher
    ..CLU-rs11136000-G associated with worse baseline memory and incident MCI/LOAD. MS4A6A-rs610932-C associated with increased incident MCI/LOAD and suggestively with lower baseline memory...
  6. Patel A, Rees S, Kelly M, Bain S, Barnett A, Prasher A, et al. Genetic variants conferring susceptibility to Alzheimer's disease in the general population; do they also predispose to dementia in Down's syndrome. BMC Res Notes. 2014;7:42 pubmed publisher
    ..SNPs, near or within the CR1 (rs3818361), BIN1 (rs744373), CD2AP (rs9349407), EPHA1 (rs11767557), CLU (rs1532278), MS4A6A/4A (rs610932), PICALM (rs561655), ABCA7 (rs3764650) and CD33 (rs3865444) genes were genotyped in 295 individuals ..
  7. Jamal S, Goyal S, Shanker A, Grover A. Computational Screening and Exploration of Disease-Associated Genes in Alzheimer's Disease. J Cell Biochem. 2017;118:1471-1479 pubmed publisher
    ..the pathogenic effects of non-synonymous single nucleotide polymorphisms (SNPs) associated with ABCA7, CR1, MS4A6A, CD2AP, PSEN1, PSEN2, and APP genes...
  8. Liang Y, Tedder T. Identification of a CD20-, FcepsilonRIbeta-, and HTm4-related gene family: sixteen new MS4A family members expressed in human and mouse. Genomics. 2001;72:119-27 pubmed
    ..1 along with CD20, FcepsilonRIbeta, and HTm4. Thus, like CD20 and FcepsilonRIbeta, the other MS4A family members are likely to be components of oligomeric cell surface complexes that serve diverse signal transduction functions. ..
  9. Fan K, Tang B, Wang Y, Kang J, Li K, Liu Z, et al. The GBA, DYRK1A and MS4A6A polymorphisms influence the age at onset of Chinese Parkinson patients. Neurosci Lett. 2016;621:133-136 pubmed publisher
    ..of the GBA L444P mutation and DYRK1A rs8126696 T allele with the earlier AAO in PD patients, and the A allele at MS4A6A rs610932 with the delayed AAO of PD...
  10. Caceres A, Vargas J, Gonzalez J. APOE and MS4A6A interact with GnRH signaling in Alzheimer's disease: Enrichment of epistatic effects. Alzheimers Dement. 2017;13:493-497 pubmed publisher
    ..of epistasis in gonadotropin-releasing hormone signaling with risk single-nucleotide polymorphisms in APOE and MS4A6A (P value = 3.7 × 10-5, P value = 5...
  11. Ghani M, Sato C, Kakhki E, Gibbs J, Traynor B, St George Hyslop P, et al. Mutation analysis of the MS4A and TREM gene clusters in a case-control Alzheimer's disease data set. Neurobiol Aging. 2016;42:217.e7-217.e13 pubmed publisher
  12. Lacher S, Alazizi A, Wang X, Bell D, Pique Regi R, Luca F, et al. A hypermorphic antioxidant response element is associated with increased MS4A6A expression and Alzheimer's disease. Redox Biol. 2018;14:686-693 pubmed publisher
    ..4-domains subfamily A) gene cluster is one of the most significant loci associated with AD risk, and MS4A6A expression is correlated with AD pathology...
  13. Ma J, Zhang W, Tan L, Wang H, Wan Y, Sun F, et al. MS4A6A genotypes are associated with the atrophy rates of Alzheimer's disease related brain structures. Oncotarget. 2016;7:58779-58788 pubmed publisher
    Membrane-spanning 4-domains, subfamily A, member 6A (MS4A6A) has been identified as susceptibility loci of Alzheimer's disease (AD) by several recent genome-wide association studies (GWAS), whereas little is known about the potential ..
  14. Sassi C, Nalls M, Ridge P, Gibbs J, Ding J, Lupton M, et al. ABCA7 p.G215S as potential protective factor for Alzheimer's disease. Neurobiol Aging. 2016;46:235.e1-9 pubmed publisher
    ..protein coding variants in 9 AD GWAS loci with the strongest effect sizes after APOE (BIN1, CLU, CR1, PICALM, MS4A6A, ABCA7, EPHA1, CD33, and CD2AP) in a cohort of 332 sporadic AD cases and 676 elderly controls of British and North-..
  15. Dos Santos L, Pimassoni L, Sena G, Camporez D, Belcavello L, Trancozo M, et al. Validating GWAS Variants from Microglial Genes Implicated in Alzheimer's Disease. J Mol Neurosci. 2017;62:215-221 pubmed publisher
    ..Among them, rs3865444 CD33, rs3764650 ABCA7, rs6656401 CR1, and rs610932 MS4A6A variants in microglial genes are associated with LOAD...
  16. Lefaucheur C, Viglietti D, Hidalgo L, Ratner L, Bagnasco S, Batal I, et al. Complement-Activating Anti-HLA Antibodies in Kidney Transplantation: Allograft Gene Expression Profiling and Response to Treatment. J Am Soc Nephrol. 2018;29:620-635 pubmed publisher
    ..and increased expression of five biologically relevant genes (CXCL11, CCL4, MS4A7, MS4A6A, and FCGR3A) indicative of endothelial activation, IFNγ response, CD16-mediated natural killer ..
  17. Hollingworth P, Harold D, Sims R, Gerrish A, Lambert J, Carrasquillo M, et al. Common variants at ABCA7, MS4A6A/MS4A4E, EPHA1, CD33 and CD2AP are associated with Alzheimer's disease. Nat Genet. 2011;43:429-35 pubmed publisher
    ..6 × 10(-9)), CD33 (GERAD+, P = 2.2 × 10(-4); including ADGC data, meta P = 1.6 × 10(-9)) and EPHA1 (GERAD+, P = 3.4 × 10(-4); including ADGC data, meta P = 6.0 × 10(-10)). ..
  18. Ishibashi K, Suzuki M, Sasaki S, Imai M. Identification of a new multigene four-transmembrane family (MS4A) related to CD20, HTm4 and beta subunit of the high-affinity IgE receptor. Gene. 2001;264:87-93 pubmed
    ..The identification of this relatively large gene family in various tissues will allow the further elucidation of physiological significance of this gene family, that is currently unclear. ..
  19. Kajiwara Y, McKenzie A, Dorr N, Gama Sosa M, Elder G, Schmeidler J, et al. The human-specific CASP4 gene product contributes to Alzheimer-related synaptic and behavioural deficits. Hum Mol Genet. 2016;25:4315-4327 pubmed publisher
    ..expression of caspase-4 was strongly correlated with AD risk genes including TYROBP, TREM2, CR1, PSEN1, MS4A4A and MS4A6A in LOAD brains...
  20. Proitsi P, Lee S, Lunnon K, Keohane A, Powell J, Troakes C, et al. Alzheimer's disease susceptibility variants in the MS4A6A gene are associated with altered levels of MS4A6A expression in blood. Neurobiol Aging. 2014;35:279-90 pubmed publisher
    ..risk of developing Alzheimer's disease (AD) has previously been found to be associated with variants at the MS4A6A locus...
  21. Deng Y, Liu L, Wang Y, Tang H, Ren R, Xu W, et al. The prevalence of CD33 and MS4A6A variant in Chinese Han population with Alzheimer's disease. Hum Genet. 2012;131:1245-9 pubmed publisher
    CD33 and MS4A6A genes play potential key roles in the pathogenesis of Alzheimer's disease (AD)...