更新于：2024-11-01

HERC2

更新于：2024-11-01

基本信息

别名

D15F37S1、E3 ubiquitin-protein ligase HERC2、HECT and RLD domain containing E3 ubiquitin protein ligase 2

+ [5]

简介

E3 ubiquitin-protein ligase that regulates ubiquitin-dependent retention of repair proteins on damaged chromosomes. Recruited to sites of DNA damage in response to ionizing radiation (IR) and facilitates the assembly of UBE2N and RNF8 promoting DNA damage-induced formation of 'Lys-63'-linked ubiquitin chains. Acts as a mediator of binding specificity between UBE2N and RNF8. Involved in the maintenance of RNF168 levels. E3 ubiquitin-protein ligase that promotes the ubiquitination and proteasomal degradation of XPA which influences the circadian oscillation of DNA excision repair activity. By controlling the steady-state expression of the IGF1R receptor, indirectly regulates the insulin-like growth factor receptor signaling pathway (PubMed:26692333). Modulates also iron metabolism by regulating the basal turnover of FBXL5 (PubMed:24778179).

关联

项与 HERC2 相关的药物

HERC 2-TriKE

靶点

FcRIII x HERC2 x IL-15Rα

作用机制

FcRIII激动剂 [+2]

在研机构

GT Biopharma, Inc.

原研机构

GT Biopharma, Inc.

在研适应症

实体瘤

非在研适应症-

最高研发阶段药物发现

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 HERC2 相关的临床结果

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100 项与 HERC2 相关的转化医学

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0 项与 HERC2 相关的专利（医药）

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230

项与 HERC2 相关的文献（医药）

2025-01-01·American Journal of Ophthalmology

Heritability and Genetic Factors of Astigmatism and Corneal Curvature: A Systematic Review and Meta-analysis

Review

作者: Young, Alvin L. ; Yam, Jason C ; Zhang, Xiu Juan ; Kam, Ka Wai ; Tham, Clement C. ; Tham, Clement C ; Pang, Chi Pui ; Chen, Li Jia ; Shing, Erica ; Young, Alvin L ; Yam, Jason C. ; Zaabaar, Ebenezer

PURPOSETo systematically review and meta-analyze all reported heritability studies of refractive astigmatism (RA), corneal astigmatism (CA) and corneal curvature (CC), and evaluate the existing genetic associations of RA, CA and CC.DESIGNSystematic review and meta-analysis (PROSPERO ID: CRD42023447370).METHODSStudies that reported the heritability and genetic associations of RA, CA and/or CC were identified from PubMed, Web of Science and EMBASE (from inception to October 1, 2023). Newcastle-Ottawa Scale criteria was used to assess the risk of bias. Meta-analyses of heritability were conducted using random-effects model for mean difference. All current genetic associations were catalogued according to level of statistical significance.RESULTSPooled heritabilities were moderate for RA (h² = 0.46, 95% CI: 0.27-0.65), CA (h² = 0.48, 95% CI: 0.38-0.58) and CC (h² = 0.64, 95% CI: 0.53-0.76). Subgroup analyses revealed significant differences between analysis methods (CA: P < .01; CC: P = .03) and populations (CA: P < .01; CC: P < .01) in both CA and CC, and between age groups in CA (P < .01). Totally 50 single-nucleotide polymorphisms (SNPs) in 10 genes have been reported with overlapping associations with RA, CA, and/or CC, with BMP3, FMNL2, HERC2, PROX1-AS1, and ZC3H11B associated with RA and CA, FBN1, NHSL1, and PDGFRA with CA and CC, TRAF3IP1 with RA and CC, and CASC15 with RA, CA, and CC.CONCLUSIONSThis study confirms moderate heritabilities of RA, CA and CC. Through evaluating overlapping SNPs or genes between these three phenotypes, we prioritized 50 SNPs in 10 genes as candidate variants for further validation. These findings highlight the complex genetic architecture of astigmatism and indicate shared and distinct genetic markers for different astigmatism-related corneal parameters. Future studies in different populations and functional studies evaluating the roles of the involved genes in astigmatism are warranted.

2024-09-04·G3: Genes, Genomes, Genetics

PAX3 haploinsufficiency in Maine Coon cats with dominant blue eyes and hearing loss resembling the human Waardenburg syndrome

Article

作者: Letko, Anna ; Rudd Garces, Gabriela ; Leeb, Tosso ; Schmidt, Martin J ; Schirl, Katja ; Lühken, Gesine ; Abitbol, Marie ; Lyons, Leslie A ; Farke, Daniela

AbstractThis study investigated the dominant blue eyes (DBE) trait linked to hearing impairment and variable white spotting in Maine Coon cats. Fifty-eight animals descending from 2 different DBE lineages, the Dutch and the Topaz lines, were sampled. They comprised 48 cats from the Dutch bloodline, including 9 green-eyed and 31 blue-eyed cats, with some individuals exhibiting signs of deafness, and 8 stillborn kittens. Samples from the Topaz lineage included 10 blue-eyed animals. A brainstem auditory evoked response test revealed a reduced to absent response to auditory stimuli and absent physiological waveforms in all of the 8 examined DBE animals. We sequenced the genome of 2 affected cats from the Dutch line and searched for variants in 19 candidate genes for the human Waardenburg syndrome and pigmentary disorders. This search yielded 9 private protein-changing candidate variants in the genes PAX3, EDN3, KIT, OCA2, SLC24A5, HERC2, and TYRP1. The genotype–phenotype cosegregation was observed for the PAX3 variant within all animals from the Dutch lineage. The mutant allele was absent from 461 control genomes and 241 additionally genotyped green-eyed Maine Coons. We considered the PAX3 variant as the most plausible candidate—a heterozygous nonsense single base pair substitution in exon 6 of PAX3 (NC_051841.1:g.205,787,310G>A, XM_019838731.3:c.937C>T, XP_019694290.1:p.Gln313*), predicted to result in a premature stop codon. PAX3 variants cause auditory–pigmentary syndrome in humans, horses, and mice. Together with the comparative data from other species, our findings strongly suggest PAX3:c.937C>T (OMIA:001688-9685) as the most likely candidate variant for the DBE, deafness, and minimal white spotting in the Maine Coon Dutch line. Finally, we propose the designation of DBERE (Rociri Elvis Dominant Blue Eyes) allele in the domestic cat.

2024-09-01·Ophthalmology

Survival in Patients with Uveal Melanoma Is Linked to Genetic Variation at HERC2 Single Nucleotide Polymorphism rs12913832

Article

作者: Jager, Martine J ; de Knijff, Peter ; Luyten, Gregorius P.M. ; Gelmi, Maria Chiara ; Jager, Martine J. ; te Raa, Marije ; de Leeuw, Rick H. ; Heijmans, Bastiaan T ; Wierenga, Annemijn P A ; Luyten, Gregorius P M ; Versluis, Mieke ; Heijmans, Bastiaan T. ; de Leeuw, Rick H ; Te Raa, Marije ; Wierenga, Annemijn P.A. ; Houtzagers, Laurien E ; Houtzagers, Laurien E.

PURPOSEUveal melanoma (UM) is a rare disease, with the highest incidence in people with fair skin and light eyes. Eye color is largely genetically determined and is defined by a set of single nucleotide polymorphisms (SNPs). We set out to determine whether we could identify a SNP related to prognosis.DESIGNWe sequenced DNA from peripheral blood mononuclear cells of 392 patients with UM and obtained the genotype of 6 common eye color-related SNPs. Clinical and histopathologic tumor characteristics, tumor chromosome status, and patient survival were compared among patients with different genotypes.PARTICIPANTSThree hundred ninety-two patients who underwent enucleation for UM at the Leiden University Medical Center, Leiden, The Netherlands.METHODSWe isolated DNA from peripheral blood leukocytes of 392 patients with UM and performed sequencing, using 6 eye color SNPs from the HIrisPlex-S assay (Erasmus MC, Walsh lab). The genotypes extracted from the sequencing data were uploaded onto the HIrisPlexwebtool (https://hirisplex.erasmusmc.nl/) for eye color prediction. We tested the association of eye color SNPs with tumor characteristics and chromosome aberrations using Pearson's chi-square test and the Mann-Whitney U test and evaluated survival with Kaplan-Meier curves with the log-rank test and Cox regression.MAIN OUTCOME MEASURESUveal melanoma-related survival.RESULTSOf 392 patients with analyzable genotype data, 307 patients (78%) were assigned blue eyes, 74 patients (19%) were assigned brown eyes, and 11 patients (3%) could not be assigned to either blue or brown. Patients with a genetically blue eye color showed worse survival (P = 0.04). This was related to 1 genotype: patients with the G/G genotype of rs12913832 (HERC2), which codes for blue eye color showed a worse prognosis (P = 0.017) and more often had high-risk tumors (monosomy of chromosome 3; P = 0.04) than in patients with an A/G or A/A genotype.CONCLUSIONSThe G/G genotype of rs12913832 (HERC2), which is related to blue eye color, not only is a genetic factor related to the risk of UM develop, but also is linked to a worse prognosis because of an association with a higher risk of a high-risk UM developing (carrying monosomy of chromosome 3).FINANCIAL DISCLOSURE(S)The author(s) have no proprietary or commercial interest in any materials discussed in this article.