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Last update 08 May 2025

PTPN22

Last update 08 May 2025

Basic Info

Synonyms

Hematopoietic cell protein-tyrosine phosphatase 70Z-PEP, Lymphoid phosphatase, Lyp

+ [10]

Introduction

Acts as a negative regulator of T-cell receptor (TCR) signaling by direct dephosphorylation of the Src family kinases LCK and FYN, ITAMs of the TCRz/CD3 complex, as well as ZAP70, VAV, VCP and other key signaling molecules (PubMed:16461343, PubMed:18056643). Associates with and probably dephosphorylates CBL. Dephosphorylates LCK at its activating 'Tyr-394' residue (PubMed:21719704). Dephosphorylates ZAP70 at its activating 'Tyr-493' residue (PubMed:16461343). Dephosphorylates the immune system activator SKAP2 (PubMed:21719704). Positively regulates toll-like receptor (TLR)-induced type 1 interferon production (PubMed:23871208). Promotes host antiviral responses mediated by type 1 interferon (By similarity). Regulates NOD2-induced pro-inflammatory cytokine secretion and autophagy (PubMed:23991106). Acts as an activator of NLRP3 inflammasome assembly by mediating dephosphorylation of 'Tyr-861' of NLRP3 (PubMed:27043286). Dephosphorylates phospho-anandamide (p-AEA), an endocannabinoid to anandamide (also called N-arachidonoylethanolamide) (By similarity).

Drugs associated with PTPN22

LTV-1

Target

PTPN22

Mechanism

PTPN22 antagonists

Active Org.-

Originator Org.

Sanford Burnham Prebys Medical Discovery Institute

Active Indication-

Inactive Indication

Autoimmune Diseases

Drug Highest PhasePending

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with PTPN22

100 Translational Medicine associated with PTPN22

0 Patents (Medical) associated with PTPN22

1,290

Literatures (Medical) associated with PTPN22

01 Dec 2025·Immunologic Research

Deciphering autoimmune susceptibility: a meta-analysis of PTPN22 gene variants

Review

Author: Veerabathiran, Ramakrishnan ; Thomas, Sheena Mariam

Autoimmune disorders are intricate conditions where the immune system directs its attack towards the body's tissues. The goal is to perform a thorough meta-analysis focusing on the genetic and epigenetic aspects of autoimmune disorders, specifically examining the role of the PTPN22 gene, particularly the rs2476601 variation, in influencing susceptibility to autoimmune diseases. The study followed PRISMA 2020 guidelines and PROSPERO registration and conducted a comprehensive meta-analysis to explore the association between PTPN22 gene variations and autoimmune disorders. Case-control studies presenting genotype information were included, and quantitative data analysis was performed using MetaGenyo software. The meta-analysis included 43 studies with 20,669 controls and 9,397 cases of autoimmune diseases, focusing on the PTPN22 gene rs2476601 polymorphism. Significant associations were observed between the PTPN22 polymorphisms across multiple genetic models, including allelic, dominant, and recessive models. However, no link was found between the over-dominant model. The obtained p-values were < 0.01 for the allele model (C vs T; OR: 0.63, 95% CI: 0.48-0.81, I² = 92%), 0.03 for the dominant model (CC + CT vs. TT; OR: 0.47, 95% CI: 0.24-0.95, I² = 87%), and < 0.01 for the recessive model (TT vs. CT + CC; OR: 0.61, 95% CI: 0.47-0.79, I² = 89%). However, the over-dominant model (CT vs. CC + TT; OR: 1.68, 95% CI: 1.32-2.15, I² = 86%) did not show a significant p-value (> 0.05). This meta-analysis emphasizes the significant impact of PTPN22 gene variations on autoimmune diseases, suggesting its potential as a biomarker for assessing risk and guiding targeted interventions.

01 Apr 2025·The Journal of Molecular Diagnostics

Biomimetic Digital Twins and Multiomics

Article

Author: Brough, Dalton ; Du, Luke ; Glick, Joe ; Kearns, William G ; Stamoulis, Georgios ; Germain, Chandra ; Kearns, Laura ; Baisch, Lawrence ; Benner, Andrew

The National Academies of Sciences, Engineering, and Medicine issued a report on December 15, 2023, "Foundational Research Gaps and Future Directions for Digital Twins." This described the importance of using biomimetic digital twins and multiomics in research. These were incorporated in the current analysis of patients with rheumatoid arthritis (RA). Exome sequencing, genotype-phenotype ranking, and biomimetic digital twin analysis were used to identify five pathogenic and one likely pathogenic DNA variants in patient samples analyzed, which were absent from controls. The variants identified in these genes, P2RX7, HTRA2, PTPN22, FLG, CD46, and EIF4G1, play a role in the development of RA. Additionally, 3172 variants of unknown clinical significance (VUSs) were identified in patient samples, which were absent from controls. All VUSs appeared to be associated with RA. Hidden or dark data were identified from six genes. These genes, often found in patient samples, included HIF1A, HLA-DOA, PTGER3, HIPK3, TGFBR3, and HIF1A-AS3. VUSs identified in genes HIF1A, HLA-DOA, PTGER3, and HIPK3 were directly related to the pathogenesis of RA, whereas VUSs identified in genes TGFBR3 and HIF1A-AS3 were indirectly related. The current results suggest that biomimetic digital twins and multiomics can provide further insight into the development of RA. This may also potentially help with the process of reclassifying VUSs. The reclassification of VUSs will play a critical role in complex molecular diagnostics and drug development.

01 Apr 2025·Biomaterials

LIFU-unlocked endogenous H2S generation for enhancing atherosclerosis-specific gas-enzymatic therapy

Article

Author: Jiang, Weixi ; Li, Pan ; Du, Chier ; Cheng, Chen ; Zhou, Zhiyi ; Ren, Jianli ; Wang, Jingxue ; Xu, Min ; Ran, Haitao ; Wang, Xiaoting ; An, Hongjin ; Guo, Xun ; Hou, Shengzhe ; Wang, Zhigang ; Qiu, Xiaoling

Atherosclerotic plaques, which are characterized by endothelial oxidative stress, lipid metabolism disorders and persistent inflammation, can induce serious cardiovascular diseases. However, the pharmacotherapies currently used to treat atherosclerosis (AS), such as lipid-lowering and antithrombotic drugs, can regulate only a single pathological feature of AS, and there is still a dearth of integrated platforms for the multifaceted regulation of AS progression. Herein, we developed a synergistic combination of endogenous H₂S gas therapy with a multienzyme-like nanozyme (named ^LyP-1Lip@HS) for the treatment of AS. The high affinity of the LyP-1 peptide for macrophages and foam cells within plaques allows ^LyP-1Lip@HS to actively target atherosclerotic lesions. After cavitation was induced by low-intensity focused ultrasound (LIFU), the lipid membrane of ^LyP-1Lip@HS was disrupted, thereby "unlocking" the enzyme-like activity of hollow mesoporous Prussian blue (HMPB) and facilitating the release of the endogenous H₂S donor S-allyl-L-cysteine (SAC). Notably, H₂S endogenously generated by enzymatic catalysis plays multiple roles, upregulating the ATP-binding cassette transporter A1 in foam cells to increase lipid efflux and promote the conversion of M1 macrophages to M2 macrophages. Moreover, the high level of reactive oxygen species in the inflammatory microenvironment of the plaque was mitigated. Overall, ^LyP-1Lip@HS provides a specific and controlled treatment to prevent oxidative stress, inflammation and lipid metabolism disorders, making it a candidate for AS treatment.

News (Medical) associated with PTPN22

24 Apr 2025

·www.prnewswire.com

TEDCO's Maryland Innovation Initiative Announces FY2025 Technology Assessment Awards

Over $1 million awarded to 7 university projects COLUMBIA, Md., April 24, 2025 /PRNewswire/ -- TEDCO, Maryland's economic engine for technology companies, announced the next round of Maryland Innovation Initiative (MII)'s Technology Assessment awards, marking a significant milestone in promoting the commercialization of groundbreaking research from Maryland's prestigious academic research institutions. The Technology Assessment award is a nine-month project that builds on strong preliminary data that demonstrates the technology's utility for specific commercial applications beyond basic research. TEDCO MII Team Maryland Innovation Initiative (PRNewsfoto/TEDCO) Over $1 million awarded to 7 university projects in Maryland Post this "The Technology Assessment phase of our program provides non-dilutive funding to advance technologies with commercial potential," said Abi Kulshreshtha, MII's executive director. "In this award cycle, the Maryland Innovation Initiative staff and technical reviewers selected seven projects from a competitive pool of applicants, which altogether received grants totaling more than $1 million to advance innovations ranging from new cancer therapeutics to inclusive AI-driven education technology solutions." The seven awardees are below: Heather Ames: Cell-HKer/siRaf, a promising therapeutic for Solid Tumors; University of Maryland, Baltimore Kevin Aroom: The Baby Gro Pro Smartscale: improving early diagnosis of medical problems and rare diseases; University of Maryland, College Park Steven Bernstein: Development of a novel optic nerve-stem cell therapy for glaucoma prevention and treatment; University of Maryland, Baltimore Won Jin Ho: Targeting PTPN22 for cancer immunotherapy; Johns Hopkins University Melanie Killen: Utilizing natural language processing technology for creating inclusive classrooms resubmission; University of Maryland, College Park Yuxing Li: Development and evaluation of a C. difficile-specific endolysin and dual therapy for C. difficile infection; University of Maryland, Baltimore Venkataramana Sidhaye: Development of a novel inhaled gene therapy, based on HAPLN1 transgene expression, for treating COPD; Johns Hopkins University Startup companies joining TEDCO's MII portfolio have access to a variety of TEDCO resources including mentor opportunities. A complete list of funded companies can be found on the MII webpage (here). MII's Funding Opportunities The MII program, administered by TEDCO, was created as a collaboration between the State of Maryland and five leading academic research institutions—Johns Hopkins University, Morgan State University, University of Maryland, Baltimore, University of Maryland, Baltimore County, and University of Maryland, College Park— that aims to leverage each institution's strengths to transition promising technologies into the commercial sector. "MII continues to bring innovation from lab to market," said Renée Winsky, chair of the MII Board of Directors. "Since inception, it has supported the creation of nearly 400 jobs, created or supported more than 190 startups, and invested over $58 million in the Maryland innovation ecosystem and we look forward to continuing this progress." MII has also expanded its reach to include two additional comprehensive universities, Frostburg State University and Bowie State University, along with the creation of the Baltimore Innovation Initiative (BII). All of these pilot programs aim to foster a more equitable innovation and entrepreneurial ecosystem across Maryland. For more information, visit the MII webpage. About TEDCO TEDCO, the Maryland Technology Development Corporation, enhances economic empowerment growth through the fostering of an inclusive entrepreneurial innovation ecosystem. TEDCO identifies, invests in, and helps grow technology and life science-based companies in Maryland. Learn more at . Media Contact Tammi Thomas, Chief Development & Marketing Officer, TEDCO, [email protected] Rachael Kalinyak, Associate Director, Marketing & Communications, TEDCO, [email protected] SOURCE TEDCO WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

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PTPN22

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