Human transporter database: comprehensive knowledge and discovery tools in the human transporter genes

Abstract

Transporters are essential in homeostatic exchange of endogenous and exogenous substances at the systematic, organic, cellular, and subcellular levels. Gene mutations of transporters are often related to pharmacogenetics traits. Recent developments in high throughput technologies on genomics, transcriptomics and proteomics allow in depth studies of transporter genes in normal cellular processes and diverse disease conditions. The flood of high throughput data have resulted in urgent need for an updated knowledgebase with curated, organized, and annotated human transporters in an easily accessible way. Using a pipeline with the combination of automated keywords query, sequence similarity search and manual curation on transporters, we collected 1,555 human non-redundant transporter genes to develop the Human Transporter Database (HTD) (http://htd.cbi.pku.edu.cn). Based on the extensive annotations, global properties of the transporter genes were illustrated, such as expression patterns and polymorphisms in relationships with their ligands. We noted that the human transporters were enriched in many fundamental biological processes such as oxidative phosphorylation and cardiac muscle contraction, and significantly associated with Mendelian and complex diseases such as epilepsy and sudden infant death syndrome. Overall, HTD provides a well-organized interface to facilitate research communities to search detailed molecular and genetic information of transporters for development of personalized medicine.

Figure 1. Web interface in HTD.

(A) A typical entry for transporter gene (B) Text search; (C) Browsing Human Transporter classification (D) BLAST interface; (E) Chromosome distribution for all the human transporter genes.

Figure 2. Distribution of nonsynonyous SNP and CNV density on ten categories of transporter genes in HTD.

The x-axis shows the ten transporter categories, and y-axis shows the corresponding value: (A) the density of nonsynonymous SNPs, normalized by dividing CDS length, (B) the density of CNVs, normalized by dividing gene total length. Both subfigures are notched boxplot along with scattered real sample points in purple. The thick band inside the box is the median, and the bottom and top of the box are the first quantile (Q1) and the third quantile (Q3). The ends of the whiskers represents data within 1.5 *IQR ( = Q3–Q1) from the lower quantile (Q1) or the upper quantile (Q3). The notch is always symmetric around the median, with deviation from median by 1.58 *IQR/sqrt(n), where n is the sample size. The notch approximately shows the confidence interval of median, so that if the notches of two boxes do not overlap, their medians are usually significantly different. Three horizontal orange lines behind the boxes show the median and notch range of the “Total” box.