Last update 01 Nov 2024

SORCS3

Last update 01 Nov 2024

Basic Info

Synonyms

KIAA1059, SORCS, SORCS3

+ [2]

Introduction-

Drugs associated with SORCS3

WO2024052329

Patent Mining

Target

SORCS3

Mechanism-

Active Org.

University of Helsinki [+1]

Originator Org.

University of Helsinki [+1]

Active Indication

Agoraphobia [+1]

Inactive Indication-

Drug Highest PhaseDiscovery

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with SORCS3

100 Translational Medicine associated with SORCS3

0 Patents (Medical) associated with SORCS3

Literatures (Medical) associated with SORCS3

01 Aug 2024·Cellular Oncology

Identification of a novel gene signature related to prognosis and metastasis in gastric cancer

Article

Author: Artetxe-Zurutuza, Aizpea ; Moreno-Valladares, Manuel ; Moncho-Amor, Veronica ; Otaegi-Ugartemendia, Maddalen ; Elizazu, Joseba ; Carrasco-Garcia, Estefania ; Matheu, Ander

AbstractBackgroundGastric Cancer (GC) presents poor outcome, which is consequence of the high incidence of recurrence and metastasis at early stages. GC patients presenting recurrent or metastatic disease display a median life expectancy of only 8 months. The mechanisms underlying GC progression remain poorly understood.MethodsWe took advantage of public available GC datasets from TCGA using GEPIA, and identified the matched genes among the 100 genes most significantly associated with overall survival (OS) and disease free survival (DFS). Results were confirmed in ACRG cohort and in over 2000 GC cases obtained from several cohorts integrated using our own analysis pipeline. The Kaplan-Meier method and multivariate Cox regression analyses were used for prognostic significance and linear modelling and correlation analyses for association with clinic-pathological parameters and biological hallmarks. In vitro and in vivo functional studies were performed in GC cells with candidate genes and the related molecular pathways were studied by RNA sequencing.ResultsHigh expression of ANKRD6, ITIH3, SORCS3, NPY1R and CCDC178 individually and as a signature was associated with poor prognosis and recurrent disease in GC. Moreover, the expression of ANKRD6 and ITIH3 was significantly higher in metastasis and their levels associated to Epithelial to Mesenchymal Transition (EMT) and stemness markers. In line with this, RNAseq analysis revealed genes involved in EMT differentially expressed in ANKRD6 silencing cells. Finally, ANKRD6 silencing in GC metastatic cells showed impairment in GC tumorigenic and metastatic traits in vitro and in vivo.ConclusionsOur study identified a novel signature involved in GC malignancy and prognosis, and revealed a novel pro-metastatic role of ANKRD6 in GC.

01 May 2024·Neuropsychopharmacology

Dissecting the genetic overlap between severe mental disorders and markers of cellular aging: Identification of pleiotropic genes and druggable targets

Article

Author: Ardau, Raffaella ; Paribello, Pasquale ; Chillotti, Caterina ; Patrinos, George P ; Squassina, Alessio ; Severino, Giovanni ; Manchia, Mirko ; Pisanu, Claudia ; Meloni, Anna ; Congiu, Donatella

Patients with severe mental disorders such as bipolar disorder (BD), schizophrenia (SCZ) and major depressive disorder (MDD) show a substantial reduction in life expectancy, increased incidence of comorbid medical conditions commonly observed with advanced age and alterations of aging hallmarks. While severe mental disorders are heritable, the extent to which genetic predisposition might contribute to accelerated cellular aging is not known. We used bivariate causal mixture models to quantify the trait-specific and shared architecture of mental disorders and 2 aging hallmarks (leukocyte telomere length [LTL] and mitochondrial DNA copy number), and the conjunctional false discovery rate method to detect shared genetic loci. We integrated gene expression data from brain regions from GTEx and used different tools to functionally annotate identified loci and investigate their druggability. Aging hallmarks showed low polygenicity compared with severe mental disorders. We observed a significant negative global genetic correlation between MDD and LTL (r_g = -0.14, p = 6.5E-10), and no significant results for other severe mental disorders or for mtDNA-cn. However, conditional QQ plots and bivariate causal mixture models pointed to significant pleiotropy among all severe mental disorders and aging hallmarks. We identified genetic variants significantly shared between LTL and BD (n = 17), SCZ (n = 55) or MDD (n = 19), or mtDNA-cn and BD (n = 4), SCZ (n = 12) or MDD (n = 1), with mixed direction of effects. The exonic rs7909129 variant in the SORCS3 gene, encoding a member of the retromer complex involved in protein trafficking and intracellular/intercellular signaling, was associated with shorter LTL and increased predisposition to all severe mental disorders. Genetic variants underlying risk of SCZ or MDD and shorter LTL modulate expression of several druggable genes in different brain regions. Genistein, a phytoestrogen with anti-inflammatory and antioxidant effects, was an upstream regulator of 2 genes modulated by variants associated with risk of MDD and shorter LTL. While our results suggest that shared heritability might play a limited role in contributing to accelerated cellular aging in severe mental disorders, we identified shared genetic determinants and prioritized different druggable targets and compounds.

01 Feb 2024·Alzheimer's & Dementia

Whole genome methylation sequencing in blood identifies extensive differential DNA methylation in late‐onset dementia due to Alzheimer's disease

Article

Author: Keleş, Sündüz ; Bergmann, Phillip E. ; Johnson, Sterling C. ; Alisch, Reid S. ; Asthana, Sanjay ; Madrid, Andy ; Breen, Coleman ; Clark, Lindsay R. ; Papale, Ligia A. ; Hogan, Kirk J.

AbstractINTRODUCTIONDNA microarray‐based studies report differentially methylated positions (DMPs) in blood between late‐onset dementia due to Alzheimer's disease (AD) and cognitively unimpaired individuals, but interrogate < 4% of the genome.METHODSWe used whole genome methylation sequencing (WGMS) to quantify DNA methylation levels at 25,409,826 CpG loci in 281 blood samples from 108 AD and 173 cognitively unimpaired individuals.RESULTSWGMS identified 28,038 DMPs throughout the human methylome, including 2707 differentially methylated genes (e.g., SORCS3, GABA, and PICALM) encoding proteins in biological pathways relevant to AD such as synaptic membrane, cation channel complex, and glutamatergic synapse. One hundred seventy‐three differentially methylated blood‐specific enhancers interact with the promoters of 95 genes that are differentially expressed in blood from persons with and without AD.DISCUSSIONWGMS identifies differentially methylated CpGs in known and newly detected genes and enhancers in blood from persons with and without AD.Highlights

Whole genome DNA methylation levels were quantified in blood from persons with and without Alzheimer's disease (AD).

Twenty‐eight thousand thirty‐eight differentially methylated positions (DMPs) were identified.

Two thousand seven hundred seven genes comprise DMPs.

Forty‐eight of 75 independent genetic risk loci for AD have DMPs.

One thousand five hundred sixty‐eight blood‐specific enhancers comprise DMPs, 173 of which interact with the promoters of 95 genes that are differentially expressed in blood from persons with and without AD.

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SORCS3

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