2. Academic Validation
  3. Common exonic missense variants in the C2 domain of the human KIBRA protein modify lipid binding and cognitive performance

Common exonic missense variants in the C2 domain of the human KIBRA protein modify lipid binding and cognitive performance

  • Transl Psychiatry. 2013 Jun 18;3(6):e272. doi: 10.1038/tp.2013.49.
K Duning 1,  D O Wennmann,  A Bokemeyer,  C Reissner,  H Wersching,  C Thomas,  J Buschert,  K Guske,  V Franzke,  A Flöel,  H Lohmann,  S Knecht,  S-M Brand,  M Pöter,  U Rescher,  M Missler,  P Seelheim,  C Pröpper,  T M Boeckers,  L Makuch,  R Huganir,  T Weide,  E Brand,  H Pavenstädt,  J Kremerskothen
Affiliations

Affiliation

  • 1 Internal Medicine D, Department of Nephrology, Hypertension and Rheumatology, University Hospital Münster, Münster, Germany.
PMID: 23778582 DOI: 10.1038/tp.2013.49
Abstract

The human KIBRA gene has been linked to human cognition through a lead intronic single-nucleotide polymorphism (SNP; rs17070145) that is associated with episodic memory performance and the risk to develop Alzheimer's disease. However, it remains unknown how this relates to the function of the KIBRA protein. Here, we identified two common missense SNPs (rs3822660G/T [M734I], rs3822659T/G [S735A]) in exon 15 of the human KIBRA gene to affect cognitive performance, and to be in almost complete linkage disequilibrium with rs17070145. The identified SNPs encode variants of the KIBRA C2 domain with distinct CA(2+) dependent binding preferences for monophosphorylated phosphatidylinositols likely due to differences in the dynamics and folding of the lipid-binding pocket. Our results further implicate the KIBRA protein in higher brain function and provide direction to the cellular pathways involved.

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