| Target Gene | Exon/Isoform | Splicing Effect of TRA2B | Biological Pathway | Disease Association |
|---|---|---|---|---|
| **CHEK1** | Exon 3 / full-length **CHK1** | Promotes exon 3 inclusion and supports production of full-length CHK1; TRA2A/TRA2B depletion reduces productive CHEK1 splicing, lowers CHK1 protein, and increases DNA-damage marker γH2AX (pqac-00000020, pqac-00000021, pqac-00000022) | DNA damage response, chromosome biology, cell viability (pqac-00000021, pqac-00000022) | Genome instability/cell-death phenotypes; aberrant TRA2B isoforms linked to neurodevelopmental disease and cancer-related survival pathways (pqac-00000019, pqac-00000020, pqac-00000022) |
| **LPIN1** | Exon 6; **LPIN1a** vs **LPIN1b** | High TRA2B/SFRS10 promotes exon 6 skipping and favors LPIN1a; reduced TRA2B increases exon 6 inclusion and the lipogenic LPIN1b isoform (pqac-00000030, pqac-00000031) | Hepatic lipogenesis, triglyceride synthesis, VLDL secretion, metabolic regulation (pqac-00000030, pqac-00000031, pqac-00000032) | Obesity, fatty liver/metabolic dysfunction, hypertriglyceridemia (pqac-00000030, pqac-00000031, pqac-00000032) |
| **SMN2** | Exon 7 | Promotes exon 7 inclusion, increasing the productive SMN2 isoform in vitro; effect in vivo appears limited unless strongly overexpressed (pqac-00000018, pqac-00000020) | snRNP/SMN pathway, motor-neuron RNA processing (pqac-00000018, pqac-00000020) | Spinal muscular atrophy (pqac-00000018, pqac-00000020) |
| **RAGE (AGER)** | **esRAGE** vs **mRAGE** splice products | Shifts splicing toward soluble **esRAGE** and away from membrane **mRAGE**; functionally opposes hnRNP A1-driven mRAGE production (pqac-00000020) | AGE/RAGE signaling, inflammatory and neurodegenerative response modulation (pqac-00000020) | Alzheimer’s disease and related neuroinflammatory pathology (pqac-00000018, pqac-00000020) |
| **CD44** | Variant exons **v4/v5** | Promotes inclusion of CD44 v4/v5 exons in a concentration-dependent manner (pqac-00000014, pqac-00000026) | Cell adhesion, migration, invasion, metastatic behavior (pqac-00000014, pqac-00000024, pqac-00000026) | Cancer progression and metastasis, especially breast and other epithelial cancers (pqac-00000014, pqac-00000024, pqac-00000026) |
| **AR / AR-V7** | Cryptic exon **CE3** / **AR-V7** | Enhances CE3 inclusion, promoting AR-V7 synthesis at the expense of full-length AR; depletion reduces AR-V7 and suppresses growth of AR-V7-positive cells (pqac-00000025, pqac-00000027) | Androgen receptor signaling, therapy resistance in advanced prostate cancer (pqac-00000025, pqac-00000027) | Castration-resistant prostate cancer (pqac-00000025, pqac-00000027) |
| **Nasp** | Meiotic exon / **Nasp-T** | Activates inclusion of the conserved meiotic exon producing Nasp-T; target exons often require multiple cooperative TRA2B-binding sites for efficient activation (pqac-00000005, pqac-00000006, pqac-00000010) | Germ-cell development, chromatin/histone handling, meiotic DNA double-strand break monitoring (pqac-00000005, pqac-00000010) | Spermatogenesis and developmental defects when TRA2B-dependent splicing is perturbed (pqac-00000005, pqac-00000036) |
| **MYPT1 (PPP1R12A)** | Smooth-muscle regulatory isoforms | Regulates alternative splicing of MYPT1 isoforms that determine smooth muscle properties/contractility phenotypes (pqac-00000016) | Smooth muscle differentiation and contractility control (pqac-00000016) | Functional relevance to muscle physiology; disease context inferred from smooth-muscle dysfunction rather than a single monogenic disorder in the cited evidence (pqac-00000016) |
| **TRA2A** | Poison exon | Activates TRA2A poison exon inclusion, thereby repressing TRA2A protein output through unproductive splicing/NMD; part of paralog compensation and feedback regulation between Tra2 proteins (pqac-00000013, pqac-00000036) | Splicing-factor homeostasis, paralog cross-regulation, concentration buffering (pqac-00000013, pqac-00000036) | Splicing-network robustness; dysregulation may contribute to broader developmental and disease phenotypes driven by altered TRA2 dosage (pqac-00000013, pqac-00000036) |


*Table: This table summarizes experimentally supported TRA2B-regulated splicing targets, the direction of their splicing regulation, and the biological and disease contexts in which those targets are relevant. It provides a compact map of TRA2B’s best-supported functional outputs across DNA damage response, metabolism, neurobiology, fertility, and cancer.*