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Background  Immunoglobulin A nephropathy (IgAN) is one of the most common primary glomerulonephritis and a serious health concern worldwide; though still the underlying molecular mechanisms of IgAN are yet to be known and there is no efficient treatment for this disease. The main goal of this study was to explore the IgAN underlying pathogenic pathways, plus identifying the disease correlated modules and genes using the weighted gene co-expression network analysis (WGCNA) algorithm.    Results  GSE104948 dataset (the expression data from glomerular tissue of IgAN patients) was analyzed and the identified differentially expressed genes (DEGs) were introduced to the WGCNA algorithm for building co-expression modules. Genes were classified into six co-expression modules. Genes of the disease’s most correlated module were mainly enriched in the immune system, cell–cell communication and transmembrane cell signaling pathways. The PPI network was constructed by genes in all the modules and after hub-gene identification and validation steps, 11 genes, mostly transmembrane proteins ( CD44 ,  TLR1 ,  TLR2 ,  GNG11 ,  CSF1R ,  TYROBP ,  ITGB2 ,  PECAM1 ), as well as  DNMT1 ,  CYBB  and  PSMB9  were identified as potentially key players in the pathogenesis of IgAN. In the constructed regulatory network,  hsa-miR-129-2-3p ,  hsa-miR-34a-5p  and  hsa-miR-27a-3p , as well as  STAT3  were spotted as top molecules orchestrating the regulation of the hub genes.    Conclusions  The excavated hub genes from the hearts of co-expressed modules and the PPI network were mostly transmembrane signaling molecules. These genes and their upstream regulators could deepen our understanding of IgAN and be considered as potential targets for hindering its progression.    Supplementary Information  The online version contains supplementary material available at 10.1186/s12865-021-00468-y.

Transmembrane signaling molecules play a key role in the pathogenesis of IgA nephropathy: a weighted gene co-expression network analysis study