Although not described in OMIM, a subtype of Bardet-Biedl syndrome (BBS) caused by mutation in the SCAPER gene has been reported. OMIM describes SCAPER as implicated in a disease with overlapping phenotypes, intellectual developmental disorder and retinitis pigmentosa (IDDRP; MIM:618195). For some of the patients described as exhibiting Bardet-Biedl syndrome caused by mutation in SCAPER, male infertility has also been reported. The SCAPER protein has been described as associated with the ER and to interact with cyclins; it has also been reported to be a microtubule-associated protein expressed in primary cilia. There is a single orthologous gene in Drosophila, ssp3, for which amorphic mutations, RNAi-targeting constructs and alleles caused by insertional mutagenesis have been generated.
The human SCAPER gene has not been introduced into flies.
Animals homozygous or hemizygous for null alleles of ssp3 are viable to adulthood; females are fertile; however, males are completely sterile. The Dmel\ssp3 protein has been shown to be associated with microtubules. Using GAL4/UAS targeted expression to different cells and stages within the testis, it has been determined that ssp3 is is required during spermatogonial and early spermatocyte stages. In males homozygous for amorphic mutations, almost all gonadal meiotic divisions are abnormal and do not exhibit regular central spindles. It is postulated that a defect in microtubule dynamic behavior prevents proper microtubule–kinetochore interaction in the male germline.
[updated Mar. 2021 by FlyBase; FBrf0222196]
Non-obstructive azoospermia (NOA) is defined as absence of any measurable level of sperm in semen, resulting from a defect in the production of spermatozoa in the testes. [from MedGen, Non-obstructive azoospermia; MedGen UID: 866757]
Non-obstructive azoospermia (NOA), or failure of spermatogenesis within the testis, is diagnosed in approximately 10% of infertile men. NOA may be due to a lack of appropriate stimulation by gonadotropins, in which case hormonal therapy is usually effective. A larger category of non-obstructive azoospermia consists of men with an intrinsic testicular impairment. In these cases, the primary approach is to improve the quantity and quality of sperm retrieved from the testis for use for in vitro fertilization (Kumar, 2013; PMCID:PMC3583162).
The infertile male patients described in Wormser et al., 2021 (FBrf0248471), were reported to have Bardet-Biedl syndrome (see MIM:209900); see also Wormser et al., 2019 (pubmed:30723319).
SCAPER protein is localized primarily to the endoplasmic reticulum (ER) and interacts with cyclin A2/CDK2. [Gene Cards, SCAPER; 2021.03.29]
SCAPER is expressed in primary cilia; the SCAPER protein is associated with microtubules (Wormser et al., 2019; pubmed:30723319).
Assessed in S2 cells, the Drosophila ortholog of SCAPER, ssp3, has been shown to be a microtubule-associated protein that regulates spindle formation (FBrf0201458).
One to one: 1 human gene to 1 Drosophila gene.
High-scoring ortholog of human SCAPER (1 Drosophila to 1 human).
