CTNNA2

Last update 08 May 2025

Basic Info

Synonyms

Alpha N-catenin, Alpha-catenin-related protein, CAP-R

+ [5]

Introduction

May function as a linker between cadherin adhesion receptors and the cytoskeleton to regulate cell-cell adhesion and differentiation in the nervous system (By similarity). Required for proper regulation of cortical neuronal migration and neurite growth (PubMed:30013181). It acts as a negative regulator of Arp2/3 complex activity and Arp2/3-mediated actin polymerization (PubMed:30013181). It thereby suppresses excessive actin branching which would impair neurite growth and stability (PubMed:30013181). Regulates morphological plasticity of synapses and cerebellar and hippocampal lamination during development. Functions in the control of startle modulation (By similarity).

100 Clinical Results associated with CTNNA2

100 Translational Medicine associated with CTNNA2

0 Patents (Medical) associated with CTNNA2

337

Literatures (Medical) associated with CTNNA2

01 Apr 2025·European Journal of Medical Genetics

Seven loci associated with schizophrenia and bipolar I disorder in selected southern African population groups

Article

Author: Schneider, Sue-Rica ; Pretorius, Paul Janus ; Rebello, Renate ; Cason, Errol Duncan ; Spies, Johannes Jacobus

Two major psychiatric disorders, schizophrenia and bipolar I disorder, are regarded as distinct disorder entities; however, they share intricate connections through characteristic overlap and underlying genetic aetiology, challenging the traditional dichotomy. This convergence emerged as an essential area of investigation in understanding the genetic determinants of schizophrenia and bipolar I disorder. Moreover, psychiatric genetic research has revealed demographic disparities, with South African population groups notably underrepresented. Therefore, this preliminary targeted candidate gene association study of 20 single nucleotide polymorphisms implicated in schizophrenia and bipolar I disorder aimed to investigate association and overlap. Candidate loci for schizophrenia and bipolar I disorder were selected through an exploratory Illumina® Infinium PsychArray-24 analysis combined with literature and database searches. Genotyping of the selected loci was performed with the Agena Bioscience MassARRAY® platform on 96 cases (58 schizophrenia and 38 bipolar I disorder patients) and 44 controls of Afrikaner, Sotho, and Tswana descent. Association analysis was performed by comparing and combining population and phenotype groups. Significant (p < 0.05) loci in the ADAMTSL1, CACNA1B, CACNA1C, CDH13, CTNNA2, RBFOX1, and TRIO genes were identified as possible susceptibility factors, and differences were observed with the association between population and phenotype groups. Through further pathway analysis, the calcium and cadherin-catenin pathways were identified as possible role players in the aetiology of schizophrenia and bipolar I disorder. The study represented an essential step towards understanding the genetic contribution towards schizophrenia and bipolar I disorder in distinct population groups and has the potential to contribute towards the knowledge base and inform future research efforts.

01 Feb 2025·Journal of Affective Disorders

Methylome-wide association study of adolescent depressive episode with psychotic symptoms and childhood trauma

Article

Author: Sun, Yumeng ; Shen, Yuan ; Lin, Yuchen ; Lin, Ling ; Li, Huiyan ; Xue, Zhenpeng ; Liu, Jianbo ; Xu, Jianchang ; Liang, Nana ; Lu, Jianping

BACKGROUNDEmerging evidence suggests that DNA methylation is crucial in the mental disorder pathophysiology. The current study attempted to identify the dysregulation of DNA methylation patterns in adolescent patients suffering from depressive episodes (DE) while considering the impact of various subtypes, including psychotic symptoms and a history of childhood trauma.METHODSThe study included 67 patients with DE and 30 healthy controls (HCs) subjects. Severe depressive episode (SDE) patients were grouped according to psychotic symptoms, such as SDE with vs. SDE without psychotic symptoms (cases 29 vs. 21). The Childhood Trauma Questionnaire-Short Form helped assess childhood trauma among all patients. Thus, all the patients were divided into adolescent DE experiencing ≥ two trauma types vs. experiencing ≤ one trauma type (cases, 50 vs. 17). Methylome-wide analysis was conducted on peripheral blood to identify methylation differences in CpG sites for three comparisons: DE vs. HCs, SDE patients with vs. without psychotic symptoms, and DE patients having 0-1 type of childhood trauma vs. those having ≥two types of childhood trauma.RESULTSAdolescent DE patients demonstrated a predominant trend of lower methylation levels than HCs, with 259 hypermethylated and 3956 hypomethylated sites. Differentially hypomethylated sites involve related genes such as FKBP5, BDNF, NR3C1, GABRB3, SHANK1, SLC38A1, SLC6A18, CHRNB1, CTNNA2, CTTNBP2, etc. All these genes could be involved in DE pathogenesis. Significant DNA methylation differences could be observed in SDE subgroups with and without psychotic symptoms (e.g., genes like DTNB, CNTN1, CTNNA2), along with those DE patients having 0-1 type of childhood trauma compared to those with ≥2 types (e.g., VWA3B, SYT10, SDK2, CAMSAP3). Many significant methylated sites were associated with genes involved in brain development, highlighting the potential pathophysiological mechanisms linked with DE and its subtypes, such as psychotic symptoms and childhood trauma.CONCLUSIONOur findings suggest that differential DNA methylation is associated with the pathophysiology of DE, as well as the presence of psychotic symptoms and a history of childhood trauma. These blood-based methylation patterns may serve as biomarkers for DE and shed light on underlying mechanisms across these subtypes.

01 Jan 2025·JAMA Oncology

The Phase 3 EXTENTORCH Randomized Clinical Trial

Article

Author: Zhang, Guojun ; Li, Min ; Han, Zhigang ; Yang, Runxiang ; Chen, Gongyan ; Gu, Kangsheng ; Zhang, Wei ; Hu, Sheng ; Zhou, Min ; Wang, Rui ; Yu, Wenbo ; Wang, Jianfang ; Li, Yinyin ; Zhang, Xiqin ; Gu, Shanshan ; Li, Chong ; Xia, Bing ; Wang, Ye ; Jin, Faguang ; Yi, Tienan ; Yu, Jianjun ; Sun, Yilan ; Huang, Xiaoping ; Liu, Yunpeng ; Zhou, Caicun ; Chen, Shaoshui ; Fang, Jian ; Bao, Yongxing ; Luo, Xianming ; Li, Yan ; Huang, Jianan ; Ding, Cuimin ; Cheng, Ying ; Jiang, Liyan ; Chen, Yongxing ; Pan, Yueyin ; Xu, Kai ; Fu, Xiuhua ; Zhang, Zhihong ; Yang, Hong ; Fan, Qingxia ; Huang, Cheng ; Wu, Huita ; Wu, Lin ; Zhao, Yanqiu ; Wang, Baocheng ; Wang, Donglin ; Lv, Dongqing ; Zhang, Mingjun ; Hu, Jie ; Liu, Laiyu ; Li, Manxiang ; Zhang, Simo ; Zheng, Wei-E. ; Bi, Minghong

ImportancePatients with extensive-stage small cell lung cancer (ES-SCLC) have poor prognoses and unmet medical needs.ObjectiveTo evaluate the efficacy and safety of toripalimab plus etoposide and platinum-based chemotherapy (EP) vs placebo plus EP as a first-line treatment for patients with ES-SCLC.Design, Setting, and ParticipantsThis multicenter, double-blind, placebo-controlled phase 3 randomized clinical trial (EXTENTORCH study) enrolled patients from September 26, 2019, to May 20, 2021, and was conducted at 49 sites in China. Eligible patients had histologically or cytologically confirmed ES-SCLC without previous systemic antitumor therapy for ES-SCLC. Data were analyzed between May 6, 2023, and June 1, 2024.InterventionsPatients were randomized (1:1) to receive toripalimab, 240 mg, or placebo plus EP every 3 weeks for up to 4 to 6 cycles, followed by maintenance with toripalimab or placebo until disease progression, intolerable toxic effects, or up to 2 years of treatment.Main Outcomes and MeasuresThe primary end points were investigator-assessed progression-free survival (PFS) and overall survival (OS). Whole-exome sequencing results identified correlative biomarkers for clinical efficacy.ResultsAmong 595 screened patients, 442 eligible patients were randomized (median [range] age, 63 [30-77] years; 366 [82.8%] male); 223 patients were randomized to toripalimab plus EP, and 219 to placebo plus EP. By April 20, 2023, the median (range) survival follow-up was 13.7 (0.0-42.7) months. Compared with placebo, toripalimab improved investigator-assessed PFS (hazard ratio [HR], 0.67 [95% CI, 0.54-0.82]; P &lt; .001), and significantly reduced the risk of death (HR, 0.80 [95% CI, 0.65-0.98]; P = .03). The median OS was 14.6 (95% CI, 12.9-16.6) months in the toripalimab group vs 13.3 (95% CI, 11.8-14.4) months in the placebo group. Whole-exome sequencing results from 300 patients identified low intratumor heterogeneity, HLA-A11+ HLA-B62− haplotype, wild-type KMT2D and COL4A4, or sequence variations in CTNNA2 or SCN4A correlated with favorable PFS and OS in the toripalimab group. No new safety signals were observed. Grade 3 or higher treatment-emergent adverse event incidence was similar between the toripalimab and placebo safety set groups (199 of 222 patients [89.6%] vs 193 of 216 patients [89.4%], respectively).Conclusions and RelevanceIn this phase 3 randomized clinical trial, adding toripalimab to first-line chemotherapy demonstrated significant improvements in PFS and OS for patients with ES-SCLC. The treatment exhibited an acceptable safety profile, supporting this combination regimen as a new treatment option for patients with ES-SCLC.Trial RegistrationClinicalTrials.gov Identifier: NCT04012606

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CTNNA2

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