Alt. symbols: CD20 | B1 | Bp35 | MS4A2

Approved name: membrane spanning 4-domains A1
Alt. names: membrane-spanning 4-domains, subfamily A, member 1

Location: 11q12.2: 60455846 - 60470752 (+)
Gene type: protein_coding, 12 transcripts.

Scores: LoFtool: 0.694000 | pLI: 0.01538817 | LOEUF: 1.266

HGNC: 7315

NCBI: 931, RefSeq: NG_023388.1

Ensembl: ENSG00000156738.18

LRG_140 | Status: public

OMIM: 112210

Expression | ProteinAtlas

Gene Ontology (GO)

• Molecular function:
• Cell component: external side of plasma membrane [GO:0009897]; plasma membrane [GO:0005886]
• Biological process: cell surface receptor signaling pathway [GO:0007166]

Normal function

MS4A1 encodes CD20, a human B-lymphocyte-specific membrane protein that is widely expressed during B-cell ontogeny, from early pre-B-cell through plasma cell stages of differentiation. CD21 functions as a store-operated Ca2+ (SOC) channel component to promote Ca2+ influx after BCR activation. As such, it helps regulate the cellular Ca2+ influx necessary for B cell development, differentiation, and T-dependent and -independent humoral responses (PMID: 3925015, 7684739, 12920111, 18474602).

Dysfunction and disease

Kuijpers et al. (2010) identified a homozygous MS4A1 splice donor site mutation in a Turkish girl, born of consanguineous parents, who developed recurrent respiratory infections and bronchopneumonia at age 2 years. She initially had low IgG and IgA levels that evolved into only low IgG levels 4 years later. Laboratory studies showed normal B cell counts, but persistent hypogammaglobulinemia, reduced circulating memory B cells, and absent CD20 expression on B cells. Moreover, each parent showed ~ 50% of the CD20 expression seen in controls. Further characterization found decreased SHM frequency in IgG heavy chain genes and impaired T-dependent and -independent IgG production in vitro, but patient B cells showed otherwise normal proliferation and IgM production, indicating intact early B cell development (PMID: 20038800). [Load More]