Disease relevance of CENTG2

• Using specific antisera directed against synthetic peptides representing portions of the predicted GGAPs, we found multiple GGAP forms in the endocrine cells of human fetal lung and in human small cell lung cancer cells (SCLC) [1].
• 509 placentas from women delivering SGA infants (SGAP) and 529 placentas from women delivering infants with birthweights appropriate for gestational age (AGAP) were examined using fixed protocols for macroscopic identification and microscopic confirmation of infarction [2].
• STUDY DESIGN: Five hundred nine placentas from women delivered of small-for-gestational-age infants (SGAP) and 529 placentas from women delivering infants with birth weights appropriate for gestational age (AGAP) were examined prospectively for VUE as part of a population-based case control study of SGA infants at term [3].

High impact information on CENTG2

• Furthermore, the most recent duplications, involving the KIAA1099 pseudogenes, have largely been confined to 10q11 [4].
• The largest differences were observed with a change of isoleucine 46 to aspartate ([I46D]Arf1), which reduced ASAP1-induced catalysis by approximately 10,000-fold but had a 3-fold effect on AGAP1 [5].
• Our findings may hint to a potential role of AGAP1 in integrating signals from Arf, NO/cGMP, and tyrosine kinase signaling pathways [6].
• Thus, AGAP1 is a phosphoinositide-dependent Arf GAP that impacts both the endocytic compartment and actin [7].
• AGAP1, an endosome-associated, phosphoinositide-dependent ADP-ribosylation factor GTPase-activating protein that affects actin cytoskeleton [7].

Biological context of CENTG2

• We therefore assessed CENTG2 for its involvement in autism by (1) screening its exons for variants in 199 autistic and 160 non-autistic individuals, and (2) genotyping and assessing intra-genic polymorphisms for linkage and linkage disequilibrium (LD) [8].
• Evaluation of the chromosome 2q37.3 gene CENTG2 as an autism susceptibility gene [8].
• In the presence of serum, various sub-maximal levels of cell adhesion were found for all matrices except for the matrix based on GGAP [9].
• The cross-linked polytetrapeptide matrices based on the repeating amino acid sequences, GGAP, GGVP and GGIP, were prepared and tested for cell adhesion promoting activity in both the absence and presence of fetal bovine serum [9].
• PROBLEM: The Glycosylation Gap (GGAP) based on fructosamine (F) measurement and the Hemoglobin Glycation Index (HGI) based on mean blood glucose (MBG) are two indices of between-individual differences in glycated hemoglobin (HbA1c) adjusted for glycemia [10].

Anatomical context of CENTG2

• However, distinct from other ASAP family members, AGAP1 also induced the loss of actin stress fibers [7].
• Cells overexpressing AGAP1 also exhibit increased LAMP1 trafficking via the plasma membrane [11].

Associations of CENTG2 with chemical compounds

• Overexpression of AGAP1 changes the cellular distribution of AP-3, and reduced expression of AGAP1 renders AP-3 resistant to brefeldin A [11].

Other interactions of CENTG2

• We conclude, therefore, that 2q37.3 continues to be a region of interest for autism susceptibility, and that CENTG2 is an intriguing candidate gene that merits further scrutiny for its role in autism [8].

References