Spatial superposition of the native and mutant TSPO structures.

<p>Native human TSPO structure depicted in grey, was aligned with <b>(A)</b> A147T (red), and <b>(B)</b> R162H (blue) TSPO mutant structures, respectively. Mutation at position A147T destabilized the whole protein, especially the loop LP1, which is involved in ligand binding pocket and loop LP2. Mutation R162H, on the other hand, affected the conformation of the C-terminus only.</p

Two known loci with significant age-difference in genetic effects on late stage AMD.

<p>Shown are the genome-wide significant (P_Agediff < 5 x 10⁻⁸) lead variant at the CFH locus and two of the 34 known variants from Fritsche et al [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0194321#pone.0194321.ref013" target="_blank">13</a>], which revealed significant age-dependency (P_Agediff < 0.05/34, corrected for 34 known lead variants from Fritsche et al). Age-stratified analyses included 17,031 younger (7,959 cases, 9,072 controls) and 16,587 older (7,934 cases, 8,653 controls) individuals.</p

Distribution of coding nsSNPs, coding sSNPs, intronic SNPs, and UTR SNPs in the human TSPO gene.

<p>Distribution of coding nsSNPs, coding sSNPs, intronic SNPs, and UTR SNPs in the human TSPO gene.</p

Identification of deleterious nsSNPs in human TSPO gene.

<p>Out of 52 nsSNPs analysed using a wide array of sequence and structure based computational methods, 21 were predicted to be deleterious. Non-deleterious (blue), and deleterious (red), nsSNPs were plotted onto topology model of human TSPO which was generated with PROTTER [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0195627#pone.0195627.ref018" target="_blank">18</a>]. Cholesterol recognition/interaction amino acid consensus sequence (CRAC) domain is highlighted in black.</p

Average structural properties calculated for full length wt, A147T, and R162H TSPO models and corresponding standard deviations (in parentheses).

<p>Average structural properties calculated for full length wt, A147T, and R162H TSPO models and corresponding standard deviations (in parentheses).</p

Manhattan and QQ plot of age-difference P-values.

<p>Shown are the age-difference P-Values for late AMD by their position on the genome (A, Manhattan plot) as well as their distribution (B, QQ plot). The 34 known genetic regions identified by Fritsche et al [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0194321#pone.0194321.ref013" target="_blank">13</a>] are colored blue in the Manhattan plot.</p