Novel mutations in calcium/calmodulin-dependent protein kinase IV (CAMK4) gene in infertile men.
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.
Centre for Cellular and Molecular Biology, Hyderabad.
A
A
Khattri
Centre for Cellular and Molecular Biology, Hyderabad.
V P
VP
Reddy
Centre for Cellular and Molecular Biology, Hyderabad.
R K
RK
Pandey
Centre for Cellular and Molecular Biology, Hyderabad.
D V S
DVS
Sudhakar
Institute of Reproductive Medicine, Salt Lake, Kolkata.
N J
NJ
Gupta
Institute of Reproductive Medicine, Salt Lake, Kolkata.
B N
BN
Chakravarty
Infertility Institute and Research Centre, Secunderabad.
M
M
Deenadayal
Centre for Cellular and Molecular Biology, Hyderabad.|Genome Foundation, Hyderabad.|Banaras Hindu University, Varanasi, India.
L
L
Singh
Centre for Cellular and Molecular Biology, Hyderabad.
K
K
Thangaraj
D000595:Amino Acid Sequence; D001483:Base Sequence; D054734:Calcium-Calmodulin-Dependent Protein Kinase Type 4 / Q000737:chemistry / Q000235:genetics*; D016022:Case-Control Studies; D003001:Cloning, Molecular; D017931:DNA Primers; D006801:Humans; D007248:Infertility, Male / Q000201:enzymology* / Q000235:genetics; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D016133:Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid
D017931:DNA Primers; C517683:CAMK4 protein, human; D054734:Calcium-Calmodulin-Dependent Protein Kinase Type 4