Table 3.
Summary of the most significant findings predicted following application of a series of steps involving pathway analysis, as well as cross-checking through transcriptomics (Nephroseq concept association analysis), protein expression (Human Protein Atlas) and protein-protein interactions (STRING) databases and literature mining.
| Gene | Protein name | Function (UniProt) | Literature |
|---|---|---|---|
| Platelet activation, signalling and aggregation | |||
| ACTN1 | Alpha-actinin-1 | actin anchoring, bundling protein | Validated in IgAN kidney tissue37 |
| ACTN4 | Alpha-actinin-4 | actin anchoring, bundling protein | Validated in IgAN kidney tissue38 |
| CAP1 | Adenylyl cyclase-associated protein 1 | complex developmental and morphological processes, actin cytoskeleton organization | functional receptor for human resistin, inflammatory action of monocytes60 |
| GAS6 | Growth arrest-specific protein 6 | ligand, negative regulation of renal albumin absorption, cell growth and survival, implicated in hypertension | Validated in IgAN kidney tissue39 |
| GNAQ | Guanine Guanine nucleotide-binding protein G(q) subunit alpha | modulators or transducers in various transmembrane signalling systems, modulation of B-cell selection and survival | maintenance of B-cell tolerance, autoimmunity repression89 |
| PTPN1 | Tyrosine-protein phosphatase non-receptor type 1 | Tyrosine-protein phosphatase, regulator of endoplasmic reticulum unfolded protein response | control of B cell activation and the maintenance of immunological tolerance, induction of migratory podocyte response90–92 |
| SHC1 | SHC-transforming protein 1 | Signalling adapter, couples activated growth factor receptors to signalling pathways | pivotal regulator of oxidative stress (p66Shc isoform), putative marker of tubular oxidative injury in DN71 |
| WDR1 | WD repeat-containing protein 1 | disassembly of actin filaments | platelet-related complications in CKD93 |
| EPH-Ephrin signalling | |||
| ADAM10 | Disintegrin and metalloproteinase domain-containing protein 10 | protease | expressed in human podocytes, may be involved in the development of glomerular kidney diseases through Notch signalling pathway94 |
| EFNA4 | Ephrin-A4 | ligand for Eph receptors, interaction between activated B-lymphocytes and dendritic cells in tonsils | signalling in injury and inflammation95 |
| Collagen formation | |||
| BMP1 | Bone morphogenetic protein 1 | protease | involved in renal fibrosis96 |
| CTSS | Cathepsin S | thiol protease | promotes vascular inflammation and calcification97, 98 |
| PLOD2 | Procollagen-lysine,2-oxoglutarate 5-dioxygenase 2 | Collagen crosslinking enzyme | — |
| Integrin cell surface interactions | |||
| F11R | Junctional adhesion molecule A | epithelial tight junction formation, regulation of monocyte transmigration | possible pathogenic role in arterial hypertension99 |
| JAM3 | Junctional adhesion molecule C | cell-cell adhesion, mediator of angiogenesis, regulation of transepithelial migration of polymorphonuclear neutrophils | inflammation and vascular biology, mediation of leukocyte infiltration in response to ischemia reperfusion injury100 |
| Binding and Uptake of Ligands by Scavenger Receptors | |||
| SPARC | SPARC | regulation of cell growth through interactions with the extracellular matrix and cytokines | Validated in IgAN kidney tissue41 |
| STAB1 | Stabilin-1 | scavenger receptor for acetylated low density lipoprotein | Maintenance of tissue homeostasis68, 69 |
| Metabolism of Angiotensinogen to Angiotensins | |||
| ATP6AP2/PRR | Renin receptor | renin and prorenin cellular receptor, may play a role in the renin-angiotensin system (RAS) | Validated in IgAN kidney tissue40 |
| Formation of Fibrin Clot (Clotting Cascade) | |||
| PRCP | Prolylcarboxypeptidase | peptidase | activity associated with cardiovascular risk factors, such as atherosclerosis, inflammation, and diabetes75 |
| Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) | |||
| MMP2 | Matrix metalloproteinase-2 | protease, remodelling of the vasculature, angiogenesis, tissue repair, tumour invasion, inflammation, and atherosclerotic plaque rupture | Validated in IgAN kidney tissue42 |