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Cristaria plicata, a bivalve widespread in Eastern Asia fresh water, is utilized as the freshwater pearl mussel in China. With a high economic value in pearl production, it is also an ideal object used for the studies on biomineralization in freshwater. In the research, we performed a large-scale sequencing of Cristaria plicata mantle transcriptome using Illumina HiSeq™ 2500, obtaining 98,501 unigenes with 67,817,724 bases. 22.28 and 16.64% of the unigenes were annotated in the NR and Swiss-Prot databases, respectively. Most of the annotated unigenes were homologous with proteins of Crassostrea gigas (47.4%) and some were similar to proteins of Aplysia californica (16.7%). Here, we identified 109 homologous unigenes of 15 decided shell matrix proteins, including nacrein, Pif, perlucin, tyrosinase (Tyr), PfN44, PUSP1, chitinase, shell matrix protein, MSI80, fibronectin type III, AmOxCo, perlwapin, BMSP, PfCHS1 and CaLP. Two other mantle transcriptomes of Pinctada margaritifera and Pinctada fucata were also analyzed to perform a biomineralization protein comparison of the three molluscan transcriptomes. All the three compared mollusks shared four proteins, including nacrein, Pif, Tyr and PfCHS1. It was also discovered that Cristaria plicata shared more biomineralization proteins with Pinctada fucata than that with Pinctada margaritifera. Our study explored a whole draft of mantle transcriptome of freshwater mussel and unraveled genes involved in the formation of shell and pearl, making it possible to identify massive novel biomineralization proteins in mollusks. [ABSTRACT FROM AUTHOR]