SYNJ1

Last update 08 May 2025

Basic Info

Synonyms

inositol polyphosphate-5-phosphatase G, INPP5G, KIAA0910

+ [6]

Introduction

Phosphatase that acts on various phosphoinositides, including phosphatidylinositol 4-phosphate, phosphatidylinositol (4,5)-bisphosphate and phosphatidylinositol (3,4,5)-trisphosphate (PubMed:23804563, PubMed:27435091). Has a role in clathrin-mediated endocytosis (By similarity). Hydrolyzes PIP2 bound to actin regulatory proteins resulting in the rearrangement of actin filaments downstream of tyrosine kinase and ASH/GRB2 (By similarity).

100 Clinical Results associated with SYNJ1

100 Translational Medicine associated with SYNJ1

0 Patents (Medical) associated with SYNJ1

334

Literatures (Medical) associated with SYNJ1

01 Mar 2025·JCO Precision Oncology

Comprehensive Molecular and Genomic Analysis of NCI-MATCH Subprotocol Y: Capivasertib in Patients With an AKT1 E17K –Mutated Tumor

Article

Author: Gross, Jacob ; Bu, Xiangning ; Wang, Victoria ; McShane, Lisa M. ; Harris, Lyndsay N. ; Maican, Cayden ; McCourt, Carolyn K. ; Guan, Ping ; Lahey, Matthew T. ; O'Dwyer, Peter J. ; Patton, David ; Kalinsky, Kevin

PURPOSE NCI-MATCH (EAY131) is a precision medicine trial using genomic testing to allocate patients with advanced malignancies to targeted treatments. Arm Y evaluated capivasertib, a pan AKT inhibitor, in patients with an AKT1 E17K –mutated tumor. Here, we report on the translational objectives of the study, a molecular and genomic analysis of specimens to identify potential biomarkers of response or resistance to capivasertib. METHODS Eligible patients had AKT1 E17K –mutated metastatic tumors that progressed with standard treatment and received capivasertib 480 mg orally twice daily for 4 days on and 3 days off weekly in 28-day cycles. The primary end point was objective response rate (ORR). We performed whole-exome sequencing, RNA sequencing, and gene set and pathway enrichment analysis on 25 pretreatment tissue samples and evaluated findings in responders (complete response [CR], n = 0, and partial response, n = 9) and nonresponders (stable disease, n = 13, and progressive disease, n = 3). RESULTS The ORR was 28.6% (10 of 35) in the reported primary trial and 36% (9 of 25) in this translational cohort. Mutations in the TP53 gene were more frequent in responders, whereas the PI3K/AKT/mTOR pathway genes TYRO3 , SYNJ1 , and CDIPT were significantly altered in nonresponders. DNA repair, p53, E2F, and Wnt-beta catenin pathways were enriched in the responder group. Unsupervised clustering of gene expression identified five genes, ANKRD30A , SUSD4 , TTC6 , POTEJ , and POTEI , that were significantly higher in responders and lower in nonresponders. In addition, EGFR expression was significantly increased in nonresponders. CONCLUSION In patients with AKT1 E17K –mutated tumors, capivasertib achieved a clinically significant ORR. TP53 mutations appear to be associated with response, whereas certain additional PI3K/AKT/mTOR pathway mutations and EGFR overexpression appear to be associated with nonresponse to capivasertib. Further investigation of predictive biomarkers is warranted.

10 Feb 2025·Journal of Cancer

Identification of a Lactate Accumulation Model to Explain the Heterogeneity in Prognosis, Immune Landscape, and Tumor Environment for HNSCC patients

Article

Author: Xiao, Xiang ; Wang, Tingting ; Jin, Yi ; Yu, Tingjie ; Xiang, Jiayu ; Zhou, Yonghong ; Huang, Siwei

Head and neck squamous cell carcinoma (HNSCC) is one of the most frequent cancers with a high mortality rate. Lactate accumulation, a hallmark of cancer, has received extensive attention, but its role in HNSCC remains underexplored. Therefore, we identified 33 prognostic genes related to lactate accumulation. By consensus clustering, we separated all HNSCC samples into cluster_A or cluster_B and explored the difference of clinicopathological characteristics and genomics landscape. Next, we performed LASSO analysis and RSF to calculate the lactate-related gene score (LRGS) and constructed a risk model with high accuracy for predicting survival, as estimated by ROC, nomogram, and calibration curve. Then, through OncoPredict algorithm and TCIA, we filter the suitable drugs, especially immunology with diverse LRGS. GSEA analysis showed that the DEGs of LRGS were enriched in activation of immune response and positive regulation of immune response. Moreover, we developed a tumor-infiltrating immune-related lncRNA signature (TILSig) through a combination of 115 immune cell lines from 16 GEO datasets and DealGPL570. Subsequently, we identified the 9 tumor-infiltrating immune-related lncRNAs and calculated the TIL_score. The correlations among these tumor-infiltrating immune-related lncRNAs, hub lactate-related genes and LRGS levels were visualized. According to validation using multiple datasets including TCGA, GSE65858, GSE41613, GSE27020, and the IMvigor 210 database, CARS2, NFU1, and SYNJ1 were identified as hub genes. In light of a comprehensive pan-cancer study, we analyzed these genes to detect the potential clinical value. In conclusion, the constructed LRGS provides important insights for subsequent mechanistic research and can guide clinicians in proposing therapeutic strategies for HNSCC patients.

01 Jan 2025·Journal of Inherited Metabolic Disease

Spermidine Recovers the Autophagy Defects Underlying the Pathophysiology of Cell Trafficking Disorders

Article

Author: Oyarzábal, Alfonso ; Darling, Alejandra ; García‐Cazorla, Àngels ; Illescas, Sofía ; Gimeno‐Agud, Helena ; Díaz‐Osorio, Yaiza ; Ramos, Jose Miguel ; Mari‐Vico, Rosanna

ABSTRACTCell trafficking alterations are a growing group of disorders and one of the largest categories of Inherited Metabolic Diseases. They have complex and variable clinical presentation. Regarding neurological manifestations they can present a wide repertoire of symptoms ranging from neurodevelopmental to neurodegnerative disorders. The study of monogenic cell trafficking diseases draws an scenario to understanding this complex group of disorders and to find new therapeutic avenues. Within their pathophysiology, alterations in autophagy outstand as a targetable mechanism of disease, ammended to be modulated through different strategies. In this work we have studied the pathophysiology of two cell trafficking disorders due to mutations in SYNJ1 and NBAS genes. Specifically, we have assesed the autophagic flux in primary fibroblast cultures of the patients and gender/age‐matched controls and whether it could be address with a therapeutic purpose. The results have shaped autophagy as one of the hallmarks of the disease. Moreover, we tested in vitro the effect of spermidine, a natural polyamine that acts as an autopagy inductor. Due to the positive results, its efficacy was evaluated later on the patients as well, in a series of n‐of‐1 clinical trials, achieving improvement in some clinical aspects related to motricity and cognition. Defining autophagy alterations as a common feature in the pathophysiology of cell trafficking disorders is a great step towards their treatment, as it represents a potential actionable target for the personalized treatement of these disorders.

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SYNJ1

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