Table 2.
Main hubs in VA-CT and VA-PD networks*.
| Gene | Gene-gene links | Gene product and/or biological function | |
|---|---|---|---|
| CT | PD | ||
| FLYWCH1 | 23 | 6 | FLYWCH-type zinc finger 1. DNA binding. Involved in transcriptional regulation [25] |
| HRC | 21 | 4 | Histidine rich calcium binding protein. Regulator of Ca2+ homeostasis [26] |
| S100A4 | 20 | 0 | S100A4 Ca2+-binding protein involved in neuroprotection. It rescues neurons via the Janus kinase/STAT pathway and, partially, the interleukin-10 receptor [27, 28] |
| PGM3 | 19 | 2 | Phosphoglucomutase 3. PGM3 is involved in glycogenolysis and glycogenesis; these processes provide metabolic energy for cellular calcium homeostasis [29] and causes hypomyelination when mutated [30] |
| SOX10 | 18 | 6 | Transcription factor. Involved in regulatory network for myelination in oligodendrocytes [31] |
| CPNE2 | 18 | 0 | Calcium-dependent membrane binding protein. Ca2+ sensor in postsynaptic events [32] |
| LOC100128821 | 17 | 1 | Hypothetical protein LOC100128821 |
| AGBL4 | 17 | 0 | ATP/GTP binding protein-like 4. CCP6 (aliase). CCP6 catalyzes the shortening of the glutamate side chains, a critical process for neuron survival [33] |
| IFT88 | 16 | 26 | Key component of intraflagellar transport and involved in neuron migration and dendrite arborization [34] |
| ADAM15 | 11 | 26 | Metalloprotease-disintegrin expressed in brain and involved in neuroprotection [35] |
| SHARPIN | 5 | 25 | Ubiquitin-binding and ubiquitin-like-domain-containing protein. It modulates activation of NF-κB signaling pathway and controls cell survival and apoptosis [36–38] |
| GNL3L | 8 | 24 | Guanine nucleotide binding protein-like 3 nucleolar-like, paralogue of nucleostemin (NS). GNL3L, as NS, stabilizes MDM2 protein promoting neuron survival [39, 40] |
| UBTF | 3 | 24 | Upstream binding transcription factor, RNA polymerase I (aliase UBF), is a transcriptional activator regulating rRNA transcription. The activation of the nucleolar transcription is a response to proteotoxic stress in neurons [41] |
| ARS2 | 10 | 21 | Ars2 maintains neural stem cell identity via direct transcriptional activation of Sox2 [42] |
| PLA2G6 | 2 | 21 | Phospholipase A2, group VI (cytosolic, calcium-independent), PARK14 (aliase). PARK14 gene encodes iPLA2-VIA, a calcium independent phosphatase, catalyzing the hydrolysis of glycerophospholipids. Mutations in this gene can cause autosome recessive early-onset form of PD [43, 44] |
*Bold numbers indicate highly linked hubs in CT and/or PD networks.