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Last update 08 May 2025

GBP4

Last update 08 May 2025

Basic Info

Synonyms

GBP-4, GBP4, GTP-binding protein 4

+ [4]

Introduction

Interferon (IFN)-inducible GTPase that plays important roles in innate immunity against a diverse range of bacterial, viral and protozoan pathogens (By similarity). Negatively regulates the antiviral response by inhibiting activation of IRF7 transcription factor (By similarity).

Drugs associated with GBP4

WO2024192163

Patent Mining

Target

GBP4

Mechanism-

Active Org.

The Regents of the University of California [+1]

Originator Org.

The Regents of the University of California [+2]

Active Indication

Infectious Diseases [+2]

Inactive Indication-

Drug Highest PhaseDiscovery

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with GBP4

100 Translational Medicine associated with GBP4

0 Patents (Medical) associated with GBP4

Literatures (Medical) associated with GBP4

01 Feb 2025·Liver International

Genetic Variants of GBP4: Reduced Risks for Drug‐Induced Acute Liver Failure in Non‐Finnish European Population

Article

Author: Liao, Tsung‐Jen ; Andrade, Raúl J. ; Chen, Minjun ; Xia, Menghang ; Lee, William M. ; Lucena, M. Isabel ; Rule, Jody A. ; Aithal, Guruprasad P. ; Huang, Ruili ; Hayashi, Paul ; Rakela, Jorge ; Pan, Bohun

ABSTRACTBackground and AimsAcute liver failure (ALF) is a serious condition, typically in individuals without prior liver disease. Drug‐induced ALF (DIALF) constitutes a major portion of ALF cases. Our research aimed to identify potential genetic predispositions to DIALF.MethodsWe analysed the potential genetic variants associated with DIALF using the whole exome sequencing data from 75 cases, including 40 non‐Finnish European cases in the pilot study. Chi‐square tests were performed for case–control analysis against the 1000 genomes project as the control. A replication study of 44 DIALF cases that included 24 non‐Finnish Europeans was conducted to validate candidate variants. The association between clinical phenotype and genotypes was analysed using one‐way analysis of variance.ResultsEight variants (rs561037, rs561042, rs608339, rs655260, rs1142886, rs1142888, rs1142889 and rs1142890) in the guanylate binding protein 4 (GBP4) were significantly associated with DIALF in non‐Finnish Europeans in the pilot study and confirmed in the replication study. Rs561037 and rs561042 were highly significant with the lowest allele frequencies in both pilot and replication studies. An association was also found between these variants and milder clinical outcomes, indicated by lower peak levels of ALT, AST and higher Karnofsky performance scores.ConclusionOur study identified eight GBP4 missense variants linked to a lower risk of DIALF in the non‐Finnish European population. The GBP4 protein, activated by interferon‐gamma, plays a critical role in innate immunity. These findings suggest that GBP4 variants might influence immune and inflammatory responses in DIALF, though further studies are needed to elucidate the underlying mechanisms.

01 Aug 2024·Animal genetics

Whole-genome resequencing deciphers patterns of genetic diversity, phylogeny, and evolutionary dynamics in Kashmir cattle.

Article

Author: Wang, Fuwen ; Lei, Chuzhao ; Xiang, Weixuan ; Kuthu, Zulfiqar Hussan ; Ahmed, Zulfiqar ; Xu, Dequan ; Nawaz, Mohsin

AbstractKashmir cattle, which were kept by local pastoralists for centuries, are exceptionally resilient and adaptive to harsh environments. Despite its significance, the genomic characteristics of this cattle breed remain elusive. This study utilized whole genome sequences of Kashmir cattle (n = 20; newly sequenced) alongside published whole genomes of 32 distinct breeds and seven core cattle populations (n = 135). The analysis identified ~25.87 million biallelic single nucleotide polymorphisms in Kashmir cattle, predominantly in intergenic and intron regions. Population structure analyses revealed distinct clustering patterns of Kashmir cattle with proximity to the South Asian, African and Chinese indicine cattle populations. Genetic diversity analysis of Kashmir cattle demonstrated lower inbreeding and greater nucleotide diversity than analyzed global breeds. Homozygosity runs indicated less consanguineous mating in Kashmir cattle compared with European taurine breeds. Furthermore, six selection sweep detection methods were used within Kashmir cattle and other cattle populations to identify genes associated with vital traits, including immunity (BOLA‐DQA5, BOLA‐DQB, TNFAIP8L, FCRL4, AOAH, HIF1AN, FBXL3, MPEG1, CDC40, etc.), reproduction (GOLGA4, BRWD1, OSBP2, LEO1 ADCY5, etc.), growth (ADPRHL1, NRG2, TCF12, TMOD4, GBP4, IGF2, RSPO3, SCD, etc.), milk composition (MRPS30 and CSF1) and high‐altitude adaptation (EDNRA, ITPR2, AGBL4 and SCG3). These findings provide essential genetic insights into the characteristics and establish the foundation for the scientific conservation and utilization of Kashmir cattle breed.

04 Jun 2024·Cancer Research

Whole-Genome DNA Methylation Profiling of Intrahepatic Cholangiocarcinoma Reveals Prognostic Subtypes with Distinct Biological Drivers

Article

Author: Zeng, Yong ; Jiang, Hanyu ; Huang, Jiwei ; Peng, Jiajie ; Liao, Haotian ; Li, Jiaxin ; Wang, Haichuan ; Chen, Lu ; Yuan, Kefei ; Lin, Youpei ; Liao, Mingheng ; Chen, Xing ; Wu, Zhenru

AbstractIntrahepatic cholangiocarcinoma (iCCA) is the second most prevalent primary liver cancer. Although the genetic characterization of iCCA has led to targeted therapies for treating tumors with FGFR2 alterations and IDH1/2 mutations, only a limited number of patients can benefit from these strategies. Epigenomic profiles have emerged as potential diagnostic and prognostic biomarkers for improving the treatment of cancers. In this study, we conducted whole-genome bisulfite sequencing on 331 iCCAs integrated with genetic, transcriptomic, and proteomic analyses, demonstrating the existence of four DNA methylation subtypes of iCCAs (S1–S4) that exhibited unique postoperative clinical outcomes. The S1 group was an IDH1/2 mutation–specific subtype with moderate survival. The S2 subtype was characterized by the lowest methylation level and the highest mutational burden among the four subtypes and displayed upregulation of a gene-expression pattern associated with cell cycle/DNA replication. The S3 group was distinguished by high interpatient heterogeneity of tumor immunity, a gene-expression pattern associated with carbohydrate metabolism, and an enrichment of KRAS alterations. Patients with the S2 and S3 subtypes had the shortest survival among the four subtypes. Tumors in the S4 subtype, which had the best prognosis, showed global methylation levels comparable to normal controls, increased FGFR2 fusions/BAP1 mutations, and the highest copy-number variant burdens. Further integrative and functional analyses identified GBP4 demethylation, which is highly prevalent in the S2 and S3 groups, as an epigenetic oncogenic factor that regulates iCCA proliferation, migration, and invasion. Together, this study identifies prognostic methylome alterations and epigenetic drivers in iCCA.Significance:Characterization of the DNA methylome of intrahepatic cholangiocarcinoma integrated with genomic, transcriptomic, and proteomic analyses uncovers molecular mechanisms affected by genome-wide DNA methylation alterations, providing a resource for identifying potential therapeutic targets.

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GBP4

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