Ask about this productRelated genes to: SHARPIN antibody
- Gene:
- SHARPIN NIH gene
- Name:
- SHANK associated RH domain interactor
- Previous symbol:
- -
- Synonyms:
- DKFZP434N1923, SIPL1
- Chromosome:
- 8q24.3
- Locus Type:
- gene with protein product
- Date approved:
- 2005-08-09
- Date modifiied:
- 2016-11-01
Related products to: SHARPIN antibody
Related articles to: SHARPIN antibody
- Alzheimer's disease and related dementias (ADRD) and Parkinson's disease and related disorders (PDRD) have substantial genetic contributions, yet the role of rare damaging coding variants remains incompletely characterized at population scale. We performed gene-based burden testing of rare loss-of-function and deleterious missense variants using whole-genome sequencing data from large population biobanks combined with disease-specific sequencing cohorts, leveraging proxy phenotypes to maximize statistical power for late-onset neurodegenerative diseases. We confirmed rare variant burden in established ADRD genes () and PDRD genes (). We additionally identified novel associations in ADRD () and PDRD (). The strongest signal was observed for , where damaging variants clustered within domains mediating interactions with Rab GTPases and retromer components. Our results demonstrate the power of population-scale sequencing combined with proxy phenotypes to identify rare coding risk genes for neurodegenerative diseases. - Source: PubMed
Publication date: 2026/03/04
Le Guen YannPeña-Tauber AndrésPulgrossi Rafael CatoiaPark JunyoungOrias HoldenGreicius Michael D - Systemic autoinflammatory diseases (SAID) with inborn errors of cell death (IECD) are caused by overactivation of programmed cell death (PCD). However, the pathogenesis by which PCD leads to autoinflammation remains unclear. Here, we identified IECD patients carrying compound heterozygous RIPK1 variants K377E/R390G with autoinflammatory manifestations. Mechanistically, K377E and R390G mutations suppress NF-κB signaling and activate RIPK1 to promote cell death. CD8 T cells of the patients displayed overactivated RIPK1 and excessive cell death, leading to an elevated CD4/CD8 ratio, which could also be detected in patients with cleavage-resistant mutation of RIPK1 or SHARPIN deficiency. We show that the increased cell death of CD8 T cells promotes TNF and IFN-γ secretion to activate monocytes/macrophages, which triggers overproduction of proinflammatory cytokines. In addition, disruption of the communication between T cells and monocytes/macrophages through pharmacologic blockade of TNF and IFN attenuates proinflammatory cytokine production in macrophages and relieves all the symptoms in patients. This study further clarifies the mechanism for a group of IECD with SAID. Increased CD4/CD8 ratio and augmented RIPK1 activation in T cells provide potentially additional criteria for diagnosis of RIPK1-dependent IECD and a combination of TNF/JAK inhibitor could be an effective therapy for the diagnosed patients. - Source: PubMed
Publication date: 2026/03/11
Dai JialinJin TaijieSu GaixiuHan XuWang JunLiu ChenluZheng WenjieZhang QiuyeZhang RanranKuehn Hye SunYang JunGuo LiZhang DanLi MingXu YingjieYue TongWen MinZhu JiaKang MinLai JianmingWu FeifeiWang ShihaoZhang JiahuiAksentijevich IvonaRosenzweig Sergio DLee Pui YYuan JunyingYu XiaominZhou Qing - The cerebrospinal fluid (CSF) proteome offers a direct readout of central nervous system (CNS) biology but its genetic architecture remains incompletely defined. We conducted the largest single-site CSF genome-wide association study (GWAS) to date, analysing 7,092 SomaScan proteins in 1,259 individuals. Using a covariate-adjusted model including proteomic PCs and disease status, we identified 1,971 genome-wide significant pQTLs (954 cis, 971 trans), 1,409 of which replicated in an independent CSF dataset. We discovered 264 previously unreported loci, replicated 511 associations, refined 80 known loci, and 265 proxy-based associations. Using a previously published reproducibility framework, we show that robust discovery concentrates in reliable measurements, underscoring the importance of rigorous quality control. Enrichment analyses revealed immune/complement and extracellular matrix biology. Mendelian randomization prioritised causal proteins: PILRA, TREM2, IL34, CR2, SHARPIN and ERBB1 (Alzheimer's disease); BST1 and GPNMB (Parkinson's disease); STX6 (Creutzfeldt Jacobs disease); and ATXN3 and B4GALNT1 (Amyotrophic lateral sclerosis), providing a scalable framework for orthogonal target validation in neurodegeneration. - Source: PubMed
Publication date: 2026/02/22
Puerta RaquelGarcía-González Pablode Rojas ItziarCapdevila-Bayo MariaOlivé ClàudiaMuñoz-Morales ÁlvaroBayón-Buján PaulaValenzuela AlejandroYang ChengranTimsina JigyashaLiu MenghanChakkarai SathyaseelanSotolongo-Grau OscarCalm BertaMiguel AndreaSolivar AriadnaMontrreal LauraMartínez MartaKhan AsifZhao FeiyangTantinyà NatàliaRosende-Roca MaitéeAlegret MontserratMoreno-Grau SoniaFernández Maria VictoriaMarquié MartaValero SergiCavazos Jose EnriqueSanz PilarMontalban XavierTàrraga LluisSmets BartBoada MercèSeshadri SudhaSargurupremraj MuralidharanCruchaga CarlosCano AmandaCabrera-Socorro AlfredoRuiz Agustín - Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, and fatal interstitial lung disease which affects 3 million people worldwide. Our previous study confirmed that isoforskolin (ISOF) can improve the status of the mouse with pulmonary fibrosis (PF). This study aimed to explore the effect of ISOF on linear ubiquitin chain assembly complex (LUBAC) in the cell model of PF induced by transforming growth factor-β1 (TGF-β1). - Source: PubMed
Publication date: 2026/01/26
He BifengHe HuilinLi LingyuLiu XiaofeiWen YiqiongHua ShuSun Shibo - Surgical services were poorly prepared for the COVID-19 pandemic, leading to widescale disruption to elective activity. This study aimed to identify actionable priorities to strengthen pandemic preparedness of surgical and hospital systems. - Source: PubMed
Publication date: 2026/01/29