• PMID: 22897820
• Gene Name: CAMK4
• Condition: Oligoasthenoteratozoospermia (OAT), male infertility
• Association: Associated
• Mutation: g.150264_66delGCG
• Population size: 551
• Population details: 551 (283 infertile men, 268 fertile men)
• Sex: Male
• Infertility type: Male infertility
• Associated genes: CAMK4
• Other associated phenotypes: Oligoasthenoteratozoospermia (OAT), male infertility

Novel mutations in calcium/calmodulin-dependent protein kinase IV (CAMK4) gene in infertile men

Khattri A, Reddy VP, Pandey RK, Sudhakar DV, Gupta NJ, Chakravarty BN, Deenadayal M, Singh L, Thangaraj K.

Calcium/calmodulin-dependent protein kinase IV (CAMK4) is a multifunctional serine/threonine protein kinase, which plays an important role in the spermatogenesis by phosphorylating protamines. It has been shown to be involved in the regulation of human sperm motility. Moreover, the Camk4 knockout mice were infertile because of severely reduced sperm count and morphological abnormalities. As no study is available on the association of this gene with male infertility, we analysed all the exons of CAMK4 gene in ethnically matched 283 infertile and 268 fertile Indian men. We identified twenty nucleotide substitutions, of which twelve were novel. Of these novel variants, eight were exclusively detected in infertile men. Moreover, two infertile men-specific mutations were non-synonymous replacing amino acids at the highly conserved region. In silico analysis predicted both of these mutations as 'deleterious'. In addition to nucleotide substitutions, we identified five novel insertion-deletion mutations; of these, g.150264_66delGCG was exclusively found in two oligoasthenoteratozoospermic men. In silico analysis of infertile men exclusive mutations predicted that they can alter/diminish the potential binding sites of splicing factors, which may affect the mRNA splicing and protein translation. Our study suggests that the mutations in CAMK4 may lead to abnormal semen parameters. CI - © 2012 The Authors. International Journal of Andrology © 2012 European Academy of Andrology. FAU - Khattri, A AU - Khattri A AD - Centre for Cellular and Molecular Biology, Hyderabad, India. FAU - Reddy, V P AU - Reddy VP FAU - Pandey, R K AU - Pandey RK FAU - Sudhakar, D V S AU - Sudhakar DV FAU - Gupta, N J AU - Gupta NJ FAU - Chakravarty, B N AU - Chakravarty BN FAU - Deenadayal, M AU - Deenadayal M FAU - Singh, L AU - Singh L