Transcription Factors in the Pathogenesis of Schizophrenia.
PMID 42195329 | PMCID PMC13209135 | DOI 10.3390/life16050773 · Life (Basel, Switzerland) · 2026
Schizophrenia (SCZ) is a severe neuropsychiatric disorder characterized by a progressive clinical course and associated with a wide range of gene transcription signatures. This review examined studies retrieved from PubMed (published between 2005 and 2025) that investigated transcription factors (TFs) correlated with SCZ. Approximately 150 studies aligning with the eligibility criteria were selected. The synthesized evidence identified more than 40 TFs implicated in the pathogenesis and risk of SCZ. Based on functionality, these TFs were categorized into four groups: (1) progenitor cell TFs (TCF4, POU3F2, NKX2.1, EGR3), (2) stem cell TFs (MYC, SOX2, ASCL1, REST, NR2E1), (3) metabolic reprogramming TFs (HIF1, SREBPs, STATs, SOX9, NRF1, NRF2, p53, FOXO, ATF4, NF-κB), and (4) nuclear TFs (AhR, RXR). The discussion shed light on how these TFs in consort with hundreds of potential genes could shape the pathophysiology of SCZ. Indeed, SCZ represents a complex genomic, nuclear, metabolic, and immune disorder characterized by a diseased cellular microenvironment, with hypoxia emerging as a key feature. Although targeting TFs pharmacologically remains challenging, innovative therapeutic strategies-such as antineoplastic and antipsychotic agents that modulate the cellular microenvironment-may offer promising new directions for SCZ treatment.
Validated evidence
| Type | Entity | Source evidence | Confidence | Extractor |
|---|---|---|---|---|
| gene | TCF4 | “Based on functionality, these TFs were categorized into four groups: (1) progenitor cell TFs (TCF4, POU3F2, NKX2.1, EGR3), (2) stem cell TFs (MYC, SOX2, ASCL1, REST, NR2E1), (3) metabolic reprogramming TFs (HIF1, SREBPs, STATs, SOX9, NRF1, NRF2, p53, FOXO, ATF4, NF-κB), and (4) nuclear TFs (AhR, RXR).” | 0.98 | hgnc_dict_v1 |
| gene | POU3F2 | “Based on functionality, these TFs were categorized into four groups: (1) progenitor cell TFs (TCF4, POU3F2, NKX2.1, EGR3), (2) stem cell TFs (MYC, SOX2, ASCL1, REST, NR2E1), (3) metabolic reprogramming TFs (HIF1, SREBPs, STATs, SOX9, NRF1, NRF2, p53, FOXO, ATF4, NF-κB), and (4) nuclear TFs (AhR, RXR).” | 0.98 | hgnc_dict_v1 |
| gene | EGR3 | “Based on functionality, these TFs were categorized into four groups: (1) progenitor cell TFs (TCF4, POU3F2, NKX2.1, EGR3), (2) stem cell TFs (MYC, SOX2, ASCL1, REST, NR2E1), (3) metabolic reprogramming TFs (HIF1, SREBPs, STATs, SOX9, NRF1, NRF2, p53, FOXO, ATF4, NF-κB), and (4) nuclear TFs (AhR, RXR).” | 0.98 | hgnc_dict_v1 |
| gene | SOX2 | “Based on functionality, these TFs were categorized into four groups: (1) progenitor cell TFs (TCF4, POU3F2, NKX2.1, EGR3), (2) stem cell TFs (MYC, SOX2, ASCL1, REST, NR2E1), (3) metabolic reprogramming TFs (HIF1, SREBPs, STATs, SOX9, NRF1, NRF2, p53, FOXO, ATF4, NF-κB), and (4) nuclear TFs (AhR, RXR).” | 0.98 | hgnc_dict_v1 |
| gene | ASCL1 | “Based on functionality, these TFs were categorized into four groups: (1) progenitor cell TFs (TCF4, POU3F2, NKX2.1, EGR3), (2) stem cell TFs (MYC, SOX2, ASCL1, REST, NR2E1), (3) metabolic reprogramming TFs (HIF1, SREBPs, STATs, SOX9, NRF1, NRF2, p53, FOXO, ATF4, NF-κB), and (4) nuclear TFs (AhR, RXR).” | 0.98 | hgnc_dict_v1 |
| gene | NR2E1 | “Based on functionality, these TFs were categorized into four groups: (1) progenitor cell TFs (TCF4, POU3F2, NKX2.1, EGR3), (2) stem cell TFs (MYC, SOX2, ASCL1, REST, NR2E1), (3) metabolic reprogramming TFs (HIF1, SREBPs, STATs, SOX9, NRF1, NRF2, p53, FOXO, ATF4, NF-κB), and (4) nuclear TFs (AhR, RXR).” | 0.98 | hgnc_dict_v1 |
| gene | SOX9 | “Based on functionality, these TFs were categorized into four groups: (1) progenitor cell TFs (TCF4, POU3F2, NKX2.1, EGR3), (2) stem cell TFs (MYC, SOX2, ASCL1, REST, NR2E1), (3) metabolic reprogramming TFs (HIF1, SREBPs, STATs, SOX9, NRF1, NRF2, p53, FOXO, ATF4, NF-κB), and (4) nuclear TFs (AhR, RXR).” | 0.98 | hgnc_dict_v1 |
| gene | NRF1 | “Based on functionality, these TFs were categorized into four groups: (1) progenitor cell TFs (TCF4, POU3F2, NKX2.1, EGR3), (2) stem cell TFs (MYC, SOX2, ASCL1, REST, NR2E1), (3) metabolic reprogramming TFs (HIF1, SREBPs, STATs, SOX9, NRF1, NRF2, p53, FOXO, ATF4, NF-κB), and (4) nuclear TFs (AhR, RXR).” | 0.98 | hgnc_dict_v1 |
| gene | ATF4 | “Based on functionality, these TFs were categorized into four groups: (1) progenitor cell TFs (TCF4, POU3F2, NKX2.1, EGR3), (2) stem cell TFs (MYC, SOX2, ASCL1, REST, NR2E1), (3) metabolic reprogramming TFs (HIF1, SREBPs, STATs, SOX9, NRF1, NRF2, p53, FOXO, ATF4, NF-κB), and (4) nuclear TFs (AhR, RXR).” | 0.98 | hgnc_dict_v1 |