ptprd

Elevated impulsivity is a key component of attention-deficit hyperactivity disorder (ADHD), bipolar disorder and juvenile myoclonic epilepsy (JME). We performed a genome-wide association, colocalization, polygenic risk score, and pathway analysis of impulsivity in JME (n = 381). Results were followed up with functional characterisation using a drosophila model. We identified genome-wide associated SNPs at 8q13.3 (P = 7.5 × 10-9 ) and 10p11.21 (P = 3...

INTRODUCTION: Chronic graft-versus-host disease (cGVHD) is a debilitating side effect of allogeneic hematopoietic cell transplantation (HCT), affecting the quality of life of patients. We used whole exome sequencing to identify candidate SNPs and complete a multi-marker gene-level analysis using a cohort of cGVHD( +) (N = 16) and cGVHD( -) (N = 66) HCT patients. METHODS: Saliva samples were collected from HCT patients (N = 82) pre-conditioning in a multi-center study from March 2011 to May 2018...

Nonalcoholic fatty liver disease (NAFLD) is common and partially heritable and has no effective treatments. We carried out a genome-wide association study (GWAS) meta-analysis of imaging (n = 66,814) and diagnostic code (3,584 cases versus 621,081 controls) measured NAFLD across diverse ancestries. We identified NAFLD-associated variants at torsin family 1 member B (TOR1B), fat mass and obesity associated (FTO), cordon-bleu WH2 repeat protein like 1 (COBLL1)/growth factor receptor-bound protein 14 (GRB14), insulin receptor (INSR), sterol regulatory element-binding transcription factor 1 (SREBF1) and patatin-like phospholipase domain-containing protein 2 (PNPLA2), as well as validated NAFLD-associated variants at patatin-like phospholipase domain-containing protein 3 (PNPLA3), transmembrane 6 superfamily 2 (TM6SF2), apolipoprotein E (APOE), glucokinase regulator (GCKR), tribbles homolog 1 (TRIB1), glycerol-3-phosphate acyltransferase (GPAM), mitochondrial amidoxime-reducing component 1 (MARC1), microsomal triglyceride transfer protein large subunit (MTTP), alcohol dehydrogenase 1B (ADH1B), transmembrane channel like 4 (TMC4)/membrane-bound O-acyltransferase domain containing 7 (MBOAT7) and receptor-type tyrosine-protein phosphatase δ (PTPRD)...

Receptor protein tyrosine phosphatases (RPTPs) are involved in a broad list of cellular, developmental, and physiological functions. Altering their expression leads to significant changes in protein phosphorylation linked to a growing list of human diseases, including cancers and neurological disorders. In this issue of Genes & Development , Qian and colleagues (pp. XXX-XXX) present the identification of a monoclonal antibody targeting PTPRD extracellular domain-inducing dimerization and inhibition of the phosphatase activities, causing the proteolysis of dimeric PTPRD by a mechanism involving intracellular degradation pathways...

Protein tyrosine phosphatases (PTPs) are critical regulators of signal transduction but have yet to be exploited fully for drug development. Receptor protein tyrosine phosphatase δ (RPTPδ/PTPRD) has been shown to elicit tumor-promoting functions, including elevating SRC activity and promoting metastasis in certain cell contexts. Dimerization has been implicated in the inhibition of receptor protein tyrosine phosphatases (RPTPs). We have generated antibodies targeting PTPRD ectodomains with the goal of manipulating their dimerization status ectopically, thereby regulating intracellular signaling...

While the genetics of MS risk susceptibility are well-described, and recent progress has been made on the genetics of disease severity, the genetics of disease progression remain elusive. We therefore investigated the genetic determinants of MS progression on longitudinal brain MRI: change in brain volume (BV) and change in T2 lesion volume (T2LV), reflecting progressive tissue loss and increasing disease burden, respectively. We performed genome-wide association studies of change in BV (N = 3401) and change in T2LV (N = 3513) across six randomized clinical trials from Biogen and Roche/Genentech: ADVANCE, ASCEND, DECIDE, OPERA I & II, and ORATORIO...

OBJECTIVE: Dopaminergic dysfunction, iron reduction and variations in the PTPRD gene (protein tyrosine phosphatase receptor type delta) may be associated with restless leg syndrome (RLS). Here, we evaluate the effect of pramipexole (PPX) and exercise on genes and proteins associated with RLS and on sleep patterns in spontaneously hypertensive rats (SHR). METHODS: Animals were distributed into 4 groups: 1) Control (CTRL); 2) Exercise (EX); 3) Exercise and pramipexole (EX + PPX); and 4) Pramipexole (PPX)...

Telomeres are terminal DNA regions of chromosomes that prevent chromosomal fusion and degradation during cell division. In cattle, leukocyte telomere length (LTL) is associated with longevity, productive lifespan, and disease susceptibility. However, the genetic basis of LTL in this species is less studied than in humans. In this study, we utilized the whole-genome resequencing data of 239 animals from 17 cattle breeds for computational leukocyte telomere length estimation and subsequent genome-wide association study of LTL...

BACKGROUND: Immune checkpoint inhibitors (ICIs) have become the standard treatment for advanced non-small cell lung cancer (NSCLC). ICIs can provide durable responses and prolong survival for some patients. With the increasing routine of next-generation sequencing (NGS) in clinical practice, it is essential to integrate prognostic factors to establish novel nomograms to improve clinical prediction ability in NSCLC with ICIs treatment. METHODS: Clinical information, response data, and genome data of advanced NSCLC treated ICIs were obtained from cBioPortal...

Adipokines play a significant role in cardiometabolic diseases. Asprosin, a newly discovered adipokine, was first identified as a glucose-raising protein hormone. Asprosin also stimulates appetite and regulates glucose and lipid metabolism. Its identified receptors so far include Olfr734 and Ptprd. Clinical studies have found that asprosin may be associated with cardiometabolic diseases. Asprosin may have diagnostic and therapeutic potential in obesity, diabetes, metabolic syndrome and atherosclerotic cardiovascular diseases...

OBJECTIVE: PTPRD and PTPRT are phosphatases of the JAK-STAT pathway related to immunotherapy. However, the role and mechanism of PTPRD and PTPRT mutations in multiple cancers remains unclear. METHODS: Clinical data and PTPRD/PTPRT mutation information from 12 cohorts were collected and classified as a discovery cohort and three validation cohorts. The association between PTPRD/PTPRT mutations and immunotherapeutic efficacy was analyzed. Then, the association between PTPRD/PTPRT mutation and immune profiles was analyzed using The Cancer Genome Atlas (TCGA) cohort...

OBJECTIVES: Our aim was to describe the molecular characteristics of Renal Cell Carcinoma (RCC) and develop a small panel of RCC-associated genes from a large panel of cancer-related genes. MATERIALS AND METHODS: Clinical data of 55 patients with RCC diagnosed in four hospitals from September 2021 to August 2022 were collected. Among the 55 patients, 38 were diagnosed with clear cell RCC (ccRCC), and the other 17 were diagnosed with non-clear cell RCC (nccRCC), including 10 cases of papillary renal cell carcinoma, 2 cases of hereditary leiomyomatosis and RCC syndrome (HLRCC), 1 eosinophilic papillary RCC, 1 tubular cystic carcinoma, 1 TFE3 gene fusion RCC, and 2 RCC with sarcomatoid differentiation...

BACKGROUND: More than 75 common variant loci account for only a portion of the heritability for Alzheimer's disease (AD). A more complete understanding of the genetic basis of AD can be deduced by exploring associations with AD-related endophenotypes. METHODS: We conducted genome-wide scans for cognitive domain performance using harmonized and co-calibrated scores derived by confirmatory factor analyses for executive function, language, and memory. We analyzed 103,796 longitudinal observations from 23,066 members of community-based (FHS, ACT, and ROSMAP) and clinic-based (ADRCs and ADNI) cohorts using generalized linear mixed models including terms for SNP, age, SNP × age interaction, sex, education, and five ancestry principal components...

BACKGROUND: We analyzed the somatic mutation distributions as well as pathways associated with liver/lung metastasis of CRC using next-generation sequencing panel. METHODS: We detected the somatic SNV/indel mutations of 1126 tumor-related genes in CRC, liver/lung metastasis of CRC and liver /lung cancer. We combined the MSK and GEO datasets to identified the genes and pathways related to the metastasis of CRC. RESULTS: We identified 174 genes related to liver metastasis of CRC, 78 genes related to lung metastasis of CRC, and 57 genes related to both liver and lung metastasis in two datasets...

The three main types of marginal zone lymphoma (MZL), recognized by the current lymphoma classifications are the extranodal MZL of mucosa-associated lymphoid tissue, the splenic MZL, and the nodal MZL. They share some karyotype lesions (trisomies of chromosomes 3 and 18, deletions at 6q23), and alterations of the nuclear factor kappa B (NFkB) pathway are also common in all of them. However, they differ in the presence of recurrent translocations, mutations affecting the Notch signaling pathway (NOTCH2 and less commonly NOTCH1), the transcription factors Kruppel-like factor 2 (KLF2) or the receptor-type protein tyrosine phosphatase delta (PTPRD)...

Protein Tyrosine Phosphatase receptor type D (PTPRD) is a member of the protein tyrosine phosphatase family that mediates cell adhesion and synaptic specification. Genetic studies have linked Ptprd to several neuropsychiatric phenotypes, including Restless Leg Syndrome (RLS), opioid abuse disorder, and antipsychotic-induced weight gain. Genome-wide association studies (GWAS) of either pediatric obsessive-compulsive traits, or Obsessive-Compulsive Disorder (OCD), have identified loci near PTPRD as genome-wide significant, or strongly suggestive for this trait...

Substance use disorders provide challenges for development of effective medications. Use of abused substances is likely initiated, sustained and "quit" by complex brain and pharmacological mechanisms that have both genetic and environmental determinants. Medical utilities of prescribed stimulants and opioids provide complex challenges for prevention: how can we minimize their contribution to substance use disorders while retaining medical benefits for pain, restless leg syndrome, attention deficit hyperactivity disorder, narcolepsy and other indications...

OBJECTIVES: Insulin resistance is a common risk factor for metabolic syndrome (MetS), leading to type 2 diabetes mellitus and cardiovascular diseases. This study tested the hypothesis that the polygenic variants associated with the risk of insulin resistance (IR) interact with the lifestyles and nutrient intake of participants aged >40 in a large city hospital-based cohort (n = 58 701). METHODS: Polygenic risk score (PRS)-lifestyle interactions were evaluated...

Rare genetic disorders represent some of the most severe and life-limiting conditions that constitute a considerable burden on global healthcare systems and societies. Most individuals affected by rare disorders remain undiagnosed, highlighting the unmet need for improved disease gene discovery and novel variant interpretation. Aberrant (de) phosphorylation can have profound pathological consequences underpinning many disease processes. Numerous phosphatases and associated proteins have been identified as disease genes, with many more likely to have gone undiscovered thus far...

Objective: To investigate the distribution and characteristics of gene mutations in osteosarcoma, and to analyze the frequency and types of detectable mutations, and to identify potential targets for individualized treatment of osteosarcoma. Methods: The fresh tissue or paraffin-embedded tissue samples of 64 cases of osteosarcoma that were surgically resected or biopsied and then subject to next generation sequencing, were collected from Beijing Jishuitan Hospital, China from November 2018 to December 2021...