Identified in a GWAS analysis of Chinese men with non-obstructive azoospermia, the human gene CDC42BPA is proposed as a candidate gene for involvement in human male fertility (FBrf0225129). CDC42BPA encodes a serine-threonine protein kinase which is a downstream effector of CDC42. There is a single high-scoring fly ortholog, gek, for which loss-of-function alleles, RNAi-targeting constructs, and alleles caused by insertional mutagenesis have been generated. Dmel\gek is orthologous to multiple additional genes in human, including CDC42BPG and CDC42BPB.
The CDC42BPA gene has not been introduced into flies.
Homozygous loss-of-function mutations of gek are lethal in embryonic or early larval stages. Using a GAL4 driver expressed in male accessory glands, testes sheath, and cyst cells, RNAi-effected knockdown of gek results in male sterility or semi-sterility. Physical interactions of Dmel\gek have been described; see below and in the gek gene report.
[updated May 2017 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).
Observation of non-obstructive azoospermia (NOA).
Locus identified in a genome-wide association study (GWAS) of non-obstructive azoospermia in Chinese men.
CDC42BPA is a serine-threonine protein kinase which is an important downstream effector of CDC42 and plays a role in the regulation of cytoskeleton reorganization and cell migration. [Gene Cards, CDC42BPA; 2017.05.16]
Many to one: 4 human to 1 Drosophila; additional orthologous human genes are CDC42BPG, CDC42BPB, and DMPK.
High-scoring ortholog of human CDC42BPA; also orthologous to CDC42BPG, CDC42BPB, and DMPK (1 Drosophila to 4 human). Dmel\gek shares 39-45% identity and 55-63% similarity with the human genes; human DMPK encodes a shorter protein.
