CDK5RAP2 (CDK5 regulatory subunit-associated protein 2)

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Human Uniqueness Compared to "Great Apes": 
Likely Difference
Human Universality: 
Individual Universal (All Individuals Everywhere)
MOCA Domain: 
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CDK5 regulatory subunit associated protein 2 (CDK5RAP2) is a centrosomal protein involved in neuronal differentiation. CDK5RAP2 is also known as MCPH3, as it is one of seven genes causative of primary microcephaly. This gene has undergone accelerated evolution and positive selection throughout the anthropoid lineages and specifically in the human lineage. These changes have been associated with neonatal brain mass and have led to the hypothesis that CDK5RAP2 may be involved in human brain size evolution.


Timing of appearance of the difference in the Hominin Lineage as a defined date or a lineage separation event. The point in time associated with lineage separation events may change in the future as the scientific community agrees upon better time estimates. Lineage separation events are defined in 2017 as:

  • the Last Common Ancestor (LCA) of humans and old world monkeys was 25,000 - 30,000 thousand (25 - 30 million) years ago
  • the Last Common Ancestor (LCA) of humans and chimpanzees was 6,000 - 8,000 thousand (6 - 8 million) years ago
  • the emergence of the genus Homo was 2,000 thousand (2 million) years ago
  • the Last Common Ancestor (LCA) of humans and neanderthals was 500 thousand years ago
  • the common ancestor of modern humans was 100 - 300 thousand years ago

Definite Appearance (Lineage Separation Event): 
Genetics Topic Attributes
Gene symbols follow the HUGO Gene Nomenclature Committee standard.
Type of Human-Specific Changes
Accelerated Evolution, Amino Acid Change


  1. Adaptive evolution of four microcephaly genes and the evolution of brain size in anthropoid primates., Montgomery, Stephen H., Capellini Isabella, Venditti Chris, Barton Robert A., and Mundy Nicholas I. , Mol Biol Evol, 2011 Jan, Volume 28, Issue 1, p.625-38, (2011)
  2. Molecular evolution of the brain size regulator genes CDK5RAP2 and CENPJ, Evans, Patrick D., Vallender Eric J., and Lahn Bruce T. , Gene, Volume 375, p.75 - 79, (2006)