PTEN Gene and Autism: Genetic Underpinnings and Neurodevelopmental Impacts
Abstract
1. Introduction
2. Materials and Methods
3. Results
4. Discussion
4.1. Genetic Underpinnings and Mechanisms of PTEN
4.2. Neurodevelopmental Impacts of PTEN Mutations
4.3. Neurobehavioral and Neuropsychiatric Impacts of PTEN Mutations
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Protein Symbol | Description |
---|---|
TP53 | Cellular tumor antigen p53 acts as a tumor suppressor in many tumor types and induces growth arrest or apoptosis, depending on physiological circumstances and cell type, with negative regulation of cell division. |
MAGI2 | It generates scaffold molecules at synaptic junctions and assembles neurotransmitter receptors, along with proteins, for cell adhesion required for nerve growth factor recruitment. |
MAST2 | It is linked to the dystrophin/utrophin network and involved with microtubule filaments using syntrophins that affect muscles and spermatid maturation. It is a representative member of the protein kinase superfamily. |
SPOP | It functions within the ubiquitin ligase complex pathway and is required for proteosomal degradation of targeted proteins. It is also involved in cell cycle regulation that plays a role in global development, behavior, head size, and craniofacial features. |
DLG1 | Disks large homolog 1 is an essential multidomain scaffolding protein required for normal development and function, including regulation of cardiac myocytes. |
PREX2 | It functions as a RAC1 guanine nucleotide exchange factor (GEF), which activates Rac proteins through exchanging bound GTP for free GTP. This encoded protein plays a role in the important mediation of Rac signaling, which is downstream to both G protein-coupled receptors and phosphoinositide 3-kinase. |
AKT1 | This encoded protein is one of three closely related serine/threonine kinases (AKT1, AK2, and AKT3) that generates specific inositol lipids that are implicated in the regulation of cell growth, survival, proliferation, and differentiation, along with cytoskeletal changes impacting cancer and cell overgrowth with the involvement of glucose transportation. |
PIK3R1 | Phosphatidylinositol 3-kinase is a lipid kinase that phosphorylates the inositol rig of phosphatidylinositol and related compounds at the 3-prime position thought to serve as second messengers in growth signaling pathways. |
PIK3R3 | This encoded protein binds phosphorylated Tyr kinases as an adapter that mediates an association with the p110 catalytic unit to the plasma membranes, which is necessary for the insulin-stimulated increase in glucose uptake, along with glycogen synthesis. It plays a vital role in the signaling of fibroblast growth factor receptors and for modulation of cellular response to stress. |
PIK3CG | Phosphatidylinositol 3-kinase, catalytic, gamma is thought to play a role in autoinflammation and immunodeficiency |
PIK3CA | The encoded protein generates cellular phosphorylation for the activation of signaling cascades for cellular growth, proliferation, survival, motility, and morphology-affecting diseases, such as breast, ovary, lung, liver, colorectal, and gastric cancer. Other disorders impacted by this protein when disturbed include Cowden syndrome, cerebral cavernous malformations, overgrowth, body and facial asymmetry, macrocephaly, skin and vascular malformations, lipomatous tumors, megalencephaly, CLOVE, and CLAPO syndromes. |
PIK3CB | Phosphatidylinositol 3-kinase, catalytic, 110-kd, beta is implicated in signaling pathways regulating cell growth in response to mitogenic stimuli. |
PIK3CD | Phosphatidylinositol 3-kinase, catalytic, 110-kd, delta displays a broad phosphoinositide lipid substrate specificity. |
PIK3R5 | Phosphatidylinositol 3-kinase, regulatory subunit 5 is involved with the recruitment and activation of cytosolic effectors involved in proliferation, survival, or chemotaxis. |
PIK3R6 | Phosphatidylinositol 3-kinase, regulatory subunit 6 is involved with phosphoinositide 3-kinase gamma and cellular function and regulation. |
P3R3URF | Readthrough transcript encodes a fusion protein that shares sequence identity with the PIK3R3 protein. |
INPP4B | Inositol polyphosphate-4-phosphatase, type II, 105-kD is a Mg(2+) independent phosphatase that catalyzes the hydrolysis of the 4-position phosphate from phosphatidylinositol 3,4-biphosphate, inositol 1,3,4-triphosphate, and inositol 3, 4-bisphosphate. |
PIP4P1 | Phosphatidylinositol 4,5-bisphosphate 4- phosphatase, type I catalyzes the degradation of phosphatidylinositol 4,5-bisphosphate. |
PIP4P2 | Phosphatidylinositol 4,5-bisphosphate 4- phosphatase, type II catalyzes the degradation of phosphatidylinositol 4,5-bisphosphate. |
PTK2 | This encoded protein is required for normal regulation of cell migration, adhesion, and spreading, with reorganization of cytoskeleton needed for early embryo and placenta development. It is also required to regulate embryonic angiogenesis, cardiomyocyte migration, and for proliferation of normal axon growth with neuronal cell migration, branching, and synapse formation. |
PIP4K2B | Phosphatidylinositol 5-phosphate 4-kinase, beta is required for the final step in the synthesis of the second messenger and phosphorylation of PIP. |
PIK3C2B | Phosphatidylinositol 3-kinase, class 2, beta is required to convert phosphoinositides as lipid molecules to crucial roles in diverse cellular functions. |
INPP5B | Inositol polyphosphate-5-phosphatase, 75-kD protein functions as an enzyme to regulate calcium signaling by inactivating inositol phosphates located in the cytosol, mitochondria, and cell membranes. |
PLCG2 | Phospholipase 2, gamma 2 acts as an enzyme to catalyze the hydrolysis of phospholipids and plays a role in autoinflammation and immune dysregulation. |
ERBB4 | ERB-B4 is a type 1 receptor tyrosine kinase subfamily that includes EGFR and ERBB3. |
CBLB | CAS-BR-M murine ecotropic retroviral transforming sequence B is a key regulator of peripheral immune tolerance by limiting T-cell activation and expansion through its E3 ubiquitin ligase activity. |
PRKCZ | Protein kinase C, zeta form is involved with secondary messengers that have N-terminal regular domains and C-terminal catalytic domains. |
IRS2 | Insulin receptor substrate 2 is involved with noninsulin-dependent diabetes mellitus. |
PIK3R2 | Phosphatidylinositol 3-kinase, regulatory subunit 2 is involved with phosphorylation, serving as a second messenger for growth signaling pathways, leading to megalencephaly and brain malformations when disturbed. |
P3R3URF-PIK3R3 | Readthrough transcript encodes a fusion protein that shares sequence identity with the PIK3R3 protein and is adjacent to the P3R3URF gene. |
Biological Process (Gene Ontology) [Count in Network] | Molecular Function (Gene Ontology) [Count in Network] | Cellular Component (Gene Ontology) [Count in Network] | KEGG Pathway [Count in Network] | Reactome Pathway [Count in Network] | Disease–Gene Association [Count in Network] |
---|---|---|---|---|---|
Phosphatidylinositol metabolic process [17 of 153 processes] | Phosphatidylinositol 3-kinase activity [7 of 12 functions] | Phosphatidylinositol 3-kinase complex, class 1A [9 of 9 components] | Phosphatidylinositol signaling system [14 of 94 pathways] | Synthesis of PIPs at the plasma membrane [13 of 53 pathways] | Head and neck cancer [4 of 12 associations] |
Phosphatidylinositol-3-kinase signaling [11 of 45] | 1-phosphatidylinositol-3-kinase activity [6 of 10] | Phosphatidylinositol 3-kinase complex [11 of 30] | ErbB signaling pathway [11 of 81] | PI metabolism [14 of 83] | Proteus syndrome [3 of 3] |
Phosphatidylinositol phosphate biosynthetic process [12 of 66] | Phosphatidylinositol phosphate kinase activity [6 of 15] | Phosphatidylinositol 3-kinase complex, class1B [4 of 4] | Glioma [10 of 71] | GPVI-mediated activation cascade [10 of 35] | Cowden syndrome [3 of 10] |
Phosphatidylinositol biosynthetic process [14 of 126] | 1-phosphatidylinositol -3-kinase regulator activity [6 of 16] | Extrinsic component of membrane [13 of 323] | Inositol phosphate metabolism [10 of 72] | Erythropoietin activates phosphoinositide-3-kianse (PI3K) [7 of 12] | Head and neck squamous cell carcinoma [3 of 11] |
Phosphatidylinositol -3-phosphate biosynthetic process [7 of 21] | Phosphatidylinositol -4,5-bisphosphate 3-kinase activity [5 of 7] | Transferase complex [12 of 847] | VEGF signaling pathway [9 of 56] | Signaling by erythropoietin [8 of 25] | Endometrial carcinoma [3 of 9] |
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Genovese, A.C.; Butler, M.G. PTEN Gene and Autism: Genetic Underpinnings and Neurodevelopmental Impacts. Genes 2025, 16, 1061. https://doi.org/10.3390/genes16091061
Genovese AC, Butler MG. PTEN Gene and Autism: Genetic Underpinnings and Neurodevelopmental Impacts. Genes. 2025; 16(9):1061. https://doi.org/10.3390/genes16091061
Chicago/Turabian StyleGenovese, Ann C., and Merlin G. Butler. 2025. "PTEN Gene and Autism: Genetic Underpinnings and Neurodevelopmental Impacts" Genes 16, no. 9: 1061. https://doi.org/10.3390/genes16091061
APA StyleGenovese, A. C., & Butler, M. G. (2025). PTEN Gene and Autism: Genetic Underpinnings and Neurodevelopmental Impacts. Genes, 16(9), 1061. https://doi.org/10.3390/genes16091061