Alt. symbols: RES4-23 | CRBM

Approved name: SH3 domain binding protein 2
Alt. names: Cherubism

Location: 4p16.3: 2793023 - 2841291 (+)
Gene type: protein_coding, 31 transcripts.

Scores: LoFtool: 0.037600 | pLI: 0.00310190 | LOEUF: 1.135

HGNC: 10825

NCBI: 6452, RefSeq: NG_011609.1

Ensembl: ENSG00000087266.18

LRG_1334 | Status: public

OMIM: 602104

Expression | ProteinAtlas

The role of SH3BP2 is still unclear, although it has been suggested that it may be involved in the regulation and activation of signalling pathways in B cells, NK cells and macrophages, such as the BCR signalling pathway, the NK-cell-mediated cytotoxicity and the basophilic cell degranulation. SH3BP2 seems to interact with PLCG2, and it is supposedly an adaptor protein without catalytic activity. SH3BP2 is also involved in the production of osteoclasts, which are the cells that degrade bone tissue when it is no longer needed. Osteoclasts play a central role in bone remodelling.

Monoallelic mutations in SH3BP2 cause autosomal dominant cherubism [MIM:118400]. This is a disorder characterized by swelling of the lower face that begins around the third or fourth year of life and progresses until the late teens. Swelling is caused by excessive bone degradation of the upper and lower jaws and the development of fibrous tissue masses. Pathogenic missense mutations reported to date include p.Thr107Met, p.Arg415Gln/Pro, p.Pro418His/Arg/Leu/Thr, p.Gln419Gly/Asn and p.Gly420Glu/Ar g (Ueki et al. 2001; Lo et al. 2003; Li and Yu 2006; Lietman et al. 2006; de Lange et al. 2007; Carvalho et al. 2009). Moreover, Carvalho et al. reported in 2008 the frameshift mutation p.Arg49ArgfsX26 -occurring in the PH domain of the protein- in a patient with severe cherubism. The authors also reported a somatic mutation (p.Gln481Leu) in a patient with a giant cell granuloma. In addition, one patient with a mutation (p.Arg477Trp) in SH3BP2 was described in a cohort of patients with CVID (van Schouwenburg et al. 2015, PMID: 26122175) via application of whole genome and RNA sequencing. However, these mutations were not functionally tested. A combination of bone loss and inflammation -due to increased signalling- likely underlies the cyst-like growth characteristics of cherubism. [Load More]