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Last update 08 May 2025

GFRA2

Last update 08 May 2025

Basic Info

Synonyms

GDNF family receptor alpha 2, GDNF family receptor alpha-2, GDNF receptor alpha-2

+ [14]

Introduction

Participates in NRTN-induced 'Ser-727' phosphorylation of STAT3. Receptor for neurturin (NRTN), a growth factor that supports the survival of sympathetic neurons (PubMed:10829012, PubMed:29414779, PubMed:31535977, PubMed:9182803). NRTN-binding leads to autophosphorylation and activation of the RET receptor (PubMed:31535977). Also able to mediate GDNF signaling through the RET tyrosine kinase receptor (PubMed:9182803).

Drugs associated with GFRA2

GFRα2/3 inhibitors(Cerevel)

Target

GFRA2 x GFRα3

Mechanism

GFRA2 antagonists [+1]

Active Org.

Cerevel Therapeutics LLC

Originator Org.

Cerevel Therapeutics LLC

Active Indication

Pain [+1]

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with GFRA2

100 Translational Medicine associated with GFRA2

0 Patents (Medical) associated with GFRA2

535

Literatures (Medical) associated with GFRA2

01 Jul 2025·Cancer Letters

Neurturin-induced activation of GFRA2-RET axis potentiates pancreatic cancer glycolysis via phosphorylated hexokinase 2

Article

Author: Yang, Ludi ; Mu, Huiling ; Zhao, Zinan ; Le, Wenjun ; Wang, Yongkun ; Cui, Ran ; Wang, Gaoming ; Chen, Bo ; Liu, Fuguo ; Mutailipu, Muladili ; Jiang, Xiaohua

Pancreatic cancer, characterized by its insidious onset, high invasiveness, resistance to chemotherapy, and a grim prognosis, with a five-year survival rate hovering below 10 %. The identification of novel therapeutic targets addressing tumor progression is therefore critically important. While perineural invasion (PNI) is recognized as a pathological hallmark and key driver of pancreatic cancer progression, its role in metabolic reprogramming of malignant cells has not been fully elucidated. Using integrated metabolomics approaches, we found perineural invasion in pancreatic cancer significantly enhancing glycolytic flux of pancreatic cancer. Our data delineate a neuroendocrine-paracrine signaling axis in which neurturin secreted by neuronal cells binds to the GFRA2 receptor on pancreatic cancer cells, inducing RET kinase recruitment and subsequent heterodimer assembly. This receptor tyrosine kinase complex phosphorylates hexokinase 2 (HK2) at the evolutionarily conserved Ser122 residue, augmenting its hexokinase activity, ultimately driving aerobic glycolysis flux and fueling pancreatic cancer growth. In vivo experiments corroborate our findings, revealing that neurturin blockade effectively halts pancreatic cancer progression and synergizes with RET inhibitors. Our research underscores neurturin as a promising therapeutic target for the treatment of pancreatic cancer.

01 Mar 2025·American Journal of Reproductive Immunology

Finding Potential Drug Targets for Pre‐Eclampsia Using Mendelian Randomisation and Colocalisation Analysis

Article

Author: Zhao, Tingting ; Wu, Chengqian ; Pan, Yingzi ; Ji, Xiaohong ; Xu, Yuexin ; Miao, Jiayan

ABSTRACTIntroductionPre‐eclampsia (PE) is a common complication of pregnancy and there is an urgent need for new drug targets. We performed whole proteome‐wide Mendelian randomisation (MR) and colocalisation analyses to identify potential therapeutic targets for PE.Material and MethodsA two‐sample MR study was conducted using summary‐level statistics of 734 plasma proteins retrieved from large genome‐proteome‐wide association studies. The summary statistics of PE or eclampsia were obtained from the FinnGen consortium. Wald ratio and Inverse variance weighted (IVW) were used to assess the causal association between proteins and PE. Colocalisation analyses were conducted to examine whether the identified proteins and PE shared incidental variants.ResultsGenetically predicted circulating levels of 42 proteins were associated with PE risk after Benjamini‐Hochberg correction. Nineteen of the gene‐predicted proteins showed evidence of increased PE risk (CRELD1, CPA4, AHSG, NFASC, QDPR, NTM, PZP, FAM171B, RTN4R, FLRT2, ADH4, ADM, SPINK5, LGALS4, CKM, SPON2, UROS, CXCL10 and APOBEC3G); 23 proteins reduced the risk of PE (CLIC5, NEO1, SWAP70, KLK8, VWA2, FSTL1, CXCL11, APOB, NPPB, CNTN4, IL12B, ACHE, TCN1, GFRA2, GNMT, HPGDS, DPT, MANBA, SPARCL1, ACE, FUT8, BST1 and ACP1). Bayesian colocalisation indicated that six proteins (VWA2, ACHE, CXCL10, PZP, AHSG and UROS) and PE, which were identified as high evidence of colocalisation with PE.ConclusionsThis study provides evidence of the causal association between genetically predicted 42 proteins associated with PE risk, which might be promising drug targets for PE.

14 Nov 2024·Translational Vision Science & Technology

Potential Drug Targets for Diabetic Retinopathy Identified Through Mendelian Randomization Analysis

Article

Author: Hu, Ziqing ; Wei, Jing ; Wang, Feiyan ; Liu, Huan

PurposeThis study aimed to investigate the causal effect of plasma proteins on diabetic retinopathy (DR) risk and identify potential drug targets for this disease.MethodsTwo-sample Mendelian randomization was performed to explore potential drug targets for DR. A total of 734 proteins were selected as instrumental variables. The Steiger filtering test and colocalization analysis were conducted to determine the causal direction and genetic pleiotropy. Plasma proteins from the decode study were used to validate the findings.ResultsEleven plasma proteins were associated with DR risk. Genetically predicted high levels of CCL3L1 (odds ratio [OR] = 0.582; 95% confidence interval [CI], 0.343-0.986; P = 0.044), PAM (OR = 0.782; 95% CI, 0.652-0.937; P = 0.008), GP1BA (OR = 0.793; 95% CI, 0.632-0.994; P = 0.044), GALNT16 (OR = 0.832; 95% CI, 0.727-0.952; P = 0.008), POGLUT1 (OR = 0.836; 95% CI = 0.703-0.995; P = 0.043), and DKK3 (OR = 0.859; 95% CI, 0.777-0.950; P = 0.003) have the protective effect on DR risk. Genetically predicted high levels of GFRA2 (OR = 1.104; 95% CI, 1.028-1.187; P = 0.007), PATE4 (OR = 1.405; 95% CI, 1.060-1.860; P = 0.018), GSTA1 (OR = 1.464; 95% CI, 1.163-1.842; P = 0.001), SIRPG (OR = 1.600, 95% CI, 1.244-2.057; P = 2.51E-04), and MAPK13 (OR = 1.731; 95% CI, 1.233-2.431; P = 0.002) were associated with an increased risk of DR. However, the colocalization analysis results suggested that SIRPG and GP1BA have a shared causal variant with DR.ConclusionsCCL3L1, PAM, GALNT16, POGLUT1, DKK3, GFRA2, PATE4, GSTA1, and MAPK13 were associated with DR risk and were identified as potential drug targets for DR.Translational RelevanceThe present study has highlighted the role of CCL3L1, PAM, GALNT16, POGLUT1, DKK3, GFRA2, PATE4, GSTA1, and MAPK13 in the development of DR.

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GFRA2

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