Table 1.
Gene loci associated with a higher risk of developing primary psychosis.
| Gene Loci | Corresponding Transcript/Protein and Localization | Principal Known Functions | ||||
|---|---|---|---|---|---|---|
| General Description of the Function(s) | Central Nervous System (CNS) Development | Neuronal Morphology Regulation | Signal Transmission | |||
| NEUROTRANSMITTER RECEPTORS | DRD2 (Dopamine Receptor D2) | G protein-coupled membrane receptor | Dopamine signaling | Dopaminergic system | ||
| DRD1, 3, 4 (Dopamine Receptors D1, D3, D4) | G protein-coupled membrane receptor | Dopamine signaling | Dopaminergic system | |||
| HTR2A (5-Hydroxytryptamine -5-HT- Receptor 2A) [44] | G protein-coupled membrane receptor | Regulation of dopamine and glutamate release in the mesolimbic and mesocortical systems | Serotoninergic system Dopaminergic system Glutamatergic system |
|||
| GRM3 (Glutamate Metabotropic Receptor 3) | G protein-coupled membrane receptor | Glutamate signaling | Glutamatergic system | |||
| GRIN2B (Glutamate Ionotropic Receptor N-methyl-D-aspartate—NMDA—Type Subunit 2B) | Subunit of the NMDA membrane receptor—ion channel (NMDAR) | Neurodevelopment, circuit formation, synaptic plasticity, and cellular migration and differentiation | Neurogenesis Differentiation of neural progenitors |
Glutamatergic system | ||
| GABRB2 (Gamma-Aminobutyric Acid -GABA- Type A Receptor Subunit Beta2) | Subunit of the GABA-A membrane receptor—ion channel | Balance in excitatory/inhibitory signaling in the CNS | GABAergic system | |||
| NEUROTRASMITTER METABOLISM AND SIGNAL REGULATION | PDE4B (Phosphodiesterase 4B) | Intracellular enzyme | Cyclic AMP (cAMP)-specific phosphodiesterase (PDE), family IV. It modulates cAMP second messenger concentration in the transduction of the signal process |
Signal transmission in different systems | ||
| COMT (Catechol-O-Methyl-transferase) | Intracellular enzyme | Dopamine and noradrenaline metabolism | Dopaminergic system Noradrenergic system |
|||
| RGS-4 (Regulator of G Protein Signaling 4) [45] | Intracellular enzyme activator | Activate GTPase activity of G alpha subunits of heterotrimeric G proteins, thus deactivating them | Differentiation of neural progenitors—Axonogenesis in embryogenesis | Glutamatergic system (signal transduction) | ||
| SLC18A2 (Solute Carrier Family 18 Member A2) | ATP-dependent transmembrane transporter | ATP-dependent transporter of monoamines | Dopaminergic system Serotoninergic system Noradrenergic system |
|||
| DAOA (D-Amino Acid Oxidase Activator) and DAOA-AS1 (Antisense RNA 1) | Intracellular enzyme activator and corresponding long non-coding RNA | Metabolism of glial D-serine that regulates neuronal NDMAR signaling, mitochondrial function, dendritic arborization | Dendritic regulation | Glia-neuron communication Glutamatergic system |
||
| DTNBP1 (Dystrobrevin Binding Protein 1) and CMYA5 (Cardiomyopathy Associated 5) | Intracellular proteins that participate in the formation of the lysosome-related organelles complex 1 (BLOC-1) |
Synaptic vesicle trafficking and neurotransmitter release, in particular regulation of cell surface exposure of DRD2 and glutamatergic release. Actin cytoskeleton reorganization and neurite outgrowth. |
Neurite regulation | Dopaminergic system Glutamatergic system Synaptic regulation | ||
| CELL-CELL CONTACT AND NEURODEVELOPMENT | DISC1 (Disrupted In Schizophrenia 1) | Scaffold intracellular protein | Involved in neurogenesis (neural progenitor proliferation, neuron positioning), dendritic development, and synapse formation |
Neurogenesis | Dendritic regulation | Synaptic regulation |
| NRXN1 (Neurexin 1) | Membrane receptor | Binds neuroligins to form Ca(2+)-dependent neurexin/neuroligin complexes at synapses in the CNS | Synaptic regulation | |||
| ERBB4 (Erb-B2 Receptor Tyrosine Kinase 4) | Membrane receptor tyrosine kinases, epidermal growth factor subfamily. | Binds neuroregulins NMDAR pathway |
Regulation of CNS development | Glutamatergic system | ||
| NRG1 (Neuregulin 1) | Membrane glycoprotein | Mediates cell–cell signaling. Binds to ERBB receptors NMDAR pathway |
Neurogenesis Gliogenesis Differentiation of neural progenitors |
Glutamatergic system | ||
| AKT1 (AKT-8 retrovirus Serine/Threonine Kinase 1) [46] | Intracellular Serine/Threonine kinase | Known oncogene involved PI3K and mTOR signaling pathways Placentar and CNS development and functioning |
Neurogenesis | Dendritic regulation | Synaptic regulation | |
| RELN (Reelin) | Large extracellular matrix serine protease | Enzymatic activity modulates cell adhesion | CNS development (cellular migration) | Neuronal morphology regulation (microtubule functioning) | ||
| IMMUNE SYSTEM | IL1B (Interleukin 1 Beta) | Cytokine (extracellular messenger) | Potent proinflammatory cytokine, involved in neuroinflammation during neurodevelopment and adult life | Altered by neuroinflammation | ||
The genes presented are among the most studied and reported in different meta-analyses or systematic reviews [17,18,22,42,43]. To facilitate consultation of the table, we have divided these genes in relation to their structure, localization, and main function (first column). The last three columns summarize functions synoptically. The nomenclature, the description of the products of the genes and their function is that proposed by GeneCards® [47]. Specific references for the function of single genes are reported in the table.