SH3KBP1 (SH3-Domain Kinase-Binding Protein 1) was first reported in relation to X-linked Recessive Immunodeficiency 61 in 2018 by Keller et al (PMID: 29636373). Immunodeficiency 61 is a primary immunodeficiency characterized by the onset of recurrent bacterial infections in early childhood due to impaired antibody production. Affected individuals have normal numbers of circulating B and T cells, but B cells have an intrinsic defect in antibody production. At least 1 unique variant (an intragenic deletion encompassing exon 2 to exon 6) has been reported in humans (PMID: 29636373). Evidence supporting this gene-disease relationship includes case-level and experimental data. Summary of Case Level Data (1.5 points): Variants in this gene have been reported in 2 siblings in 1 publication (PMID: 29636373). Phenotypes described in the siblings include hypogammaglobulinemia (decreased IgG2, IgG4 and IgM in sibling 1 and almost complete absence of all Ig isotypes in sibling 2) and recurrent bacterial infections (in early childhood in sibling 1 and until death at age 15 years in sibling 2). Summary of experimental data (4 points): SH3KBP1-knockout mice were found to recapitulate the cellular and molecular phenotype seen in the human patient with impaired response to immunization (PMID: 21708930). Additionally, interaction with BLNK (PMID: 11071869) indicate a potential role of CIN85 in the B cell receptor-mediated signaling pathway, which was altered in SH3KBP1 deficient cells both from patients and non-patient sources (PMID: 29636373). In summary, there is limited evidence to support this gene-disease relationship. While more evidence is needed to establish this relationship definitively, no convincing contradictory evidence has emerged.
The GenCC data are available free of restriction under a CC0 1.0 Universal (CC0 1.0) Public Domain Dedication. The GenCC requests that you give attribution to GenCC and the contributing sources whenever possible and appropriate. The accepted Flagship manuscript is now available from Genetics in Medicine (https://www.gimjournal.org/article/S1098-3600(22)00746-8/fulltext).
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