Citron Rho-Interacting Serine/Threonine Kinase

Alternative Names

  • CIT
  • Serine/Threonine Protein Kinase 21
  • STK21
  • Citron Rho-Interacting Kinase
  • CRIK
  • Rho-Interacting Serine/Threonine Kinase
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OMIM Number


Gene Map Locus


The CIT gene encodes a kinase that catalyzes the phosphorylation of serine and threonine residues in proteins.  The CIT protein localizes to the cleavage furrow and midbody of mitotic cells where it is needed for the positive regulation of cell cytokinesis.  It is also required for the regulation of actin polymerization and depolymerization.

Furthermore, by playing a role in the generation of neurons and the neuron apoptotic process, CIT is involved in the development of the central nervous system.  The gene is hence associated with Microcephaly 17, Primary, Autosomal Recessive (MCPH17), a congenital neurologic disorder characterized by reduced head circumference, facial dysmorphia, delayed psychomotor development, intellectual disability, axial hypotonia, spasticity and a failure to thrive.

Molecular Genetics

Located on the long arm of chromosome 12, the CIT gene spans a length of 191.5 kb of DNA.  Its coding sequence is spread across 50 exons and it encodes a 231 kDa protein consisting of 2027 amino acids.  Multiple isoforms of the CIT protein exist due to alternative splicing.  The gene is found to be overexpressed in the frontal cortex and basal ganglia of the brain.  Homozygous mutations in the CIT gene are associated with MCPH17.  Missense mutations, splice site mutations and deletions resulting in frameshift and termination have all been found in MCPH17 affected patients. 

Epidemiology in the Arab World

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Other Reports

Saudi Arabia

Basit et al. (2016) carried out a study to identify the underlying gene defect in four Saudi siblings suffering from microcephaly, sloping foreheads, intellectual disability and simplified gyral patterns in the brain.  Whole exome sequencing found a novel, homozygous splice donor site variant (c.753+3A>T) in the CIT gene.  Sanger sequencing confirmed that the mutation segregated with the phenotype in all affected members.  The variant was not found in dbSNP, ExAC or 64 in-house exomes.  In-silico analysis using eight different splice site effect prediction tools anticipated the variant to abolish the splice donor site.  The authors confirmed this by carrying out cDNA analysis that showed the presence of intronic sequences in the mRNA of the patients’ blood.  This retention of intronic sequence in the mRNA was predicted to add six additional amino acids in the catalytic domain of CIT and result in immediate truncation of the protein.

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