Ask about this productRelated genes to: RABEP1 antibody
- Gene:
- RABEP1 NIH gene
- Name:
- rabaptin, RAB GTPase binding effector protein 1
- Previous symbol:
- -
- Synonyms:
- neurocrescin, RAB5EP, RABPT5, rabaptin-5
- Chromosome:
- 17p13.2
- Locus Type:
- gene with protein product
- Date approved:
- 2003-07-14
- Date modifiied:
- 2014-11-19
Related products to: RABEP1 antibody
Related articles to: RABEP1 antibody
- Genome-wide studies in late-onset Alzheimer's disease (LOAD) have uncovered many risk loci, yet identifying the causal genes and clarifying how these genetic signals connect to molecular and cellular mechanisms relevant to AD pathogenesis remains challenging. - Source: PubMed
Publication date: 2026/03/30
Waghmare Swapnil GKrishna Meera MMaccoux Emily CFranitza Ariel LLink Brian AE Lezi - Neutrophils are the first responders of our innate immune system, crucial for defense against various infections. The intricate regulation of neutrophil migration is essential for neutrophil function. However, a complete mechanistic understanding is missing. We previously performed a miRNA overexpression screen and identified miR-190 as a potent suppressor of neutrophil migration in zebrafish. Through a second round of small-scale screening using neutrophil-specific knockouts of putative miR-190 targets, we identified that rabep1 (encoding Rabaptin, RAB GTPase binding effector protein 1) is essential for neutrophil motility and chemotaxis in zebrafish. Re-expressing full-length Rabaptin, but not its truncation lacking the Rab4/Rab5 binding domain, rescued cell motility in the knockout. Knocking down RABEP1 in differentiated human leukemia (dHL-60) cells consistently reduced cell motility. RABAPTIN-deficient dHL-60 cells are defective with fast recycling, yet maintain a normal Rab5 GTP level. The RABAPTIN-deficient cells displayed reduced PAK phosphorylation and decreased F-actin levels, yet still appropriately polarized upon chemokine stimulation. Overexpression of dominant-negative Rab4 or Rab5 has a similar inhibitory effect on neutrophil migration. Our data suggest that RABAPTIN drives endosomal recycling, Rac activation, and leading-edge actin polymerization, providing significant insights into the role of the endocytic pathway in neutrophil motility. - Source: PubMed
Kim Daniel HSyahirah RamizahZheng ConwyDing ChangHsu Alan YPikes TylerLiang ZhaolunLiu ShengLi LinlinBao XiaopingUmulis DavidWan JunDeng Qing - Molecular quantitative trait locus (QTL) studies increasingly profile chromatin accessibility, histone modifications, DNA methylation, RNA modifications such as N6-methyladenosine (m6A), and transcription across multiple cell types using high-throughput sequencing, generating dense base-pair-resolved measurements. The conventional approach of testing each variant against each molecular feature independently suffers from severe multiple testing burden and ignores linkage disequilibrium and spatial correlation. Existing fine-mapping methods only partially address these challenges and are sub-optimal for analyzing such datasets: multivariate approaches such as jointly analyze multiple molecular contexts but are designed for a single trait value per context and cannot accommodate thousands of base-resolution measurements per context, while functional approaches such as model spatial structure across thousands of measurements but analyze each context separately. Here, we introduce , which integrates multivariate analysis with wavelet-based functional regression to jointly fine-map thousands of base-resolution traits across multiple cell types. In simulations, identified causal variants and affected molecular features more accurately than , while cannot be applied to this type of data. Applied to single-nucleus chromatin accessibility data from six brain cell types from postmortem aging human brains, substantially increased discovery and resolution, with substantial power gains for cell types with limited samples. Multi-cell-type analysis revealed extensive sharing of regulatory effects on chromatin accessibility (caQTL). Importantly, produces Bayesian inference compatible with the framework, enabling systematic multi-omic integration. Applied to Alzheimer's disease loci, we integrated caQTL with expression QTLs, epigenomic QTLs, and GWAS, observing regulatory patterns suggesting complex mechanisms at loci including , , , and . - Source: PubMed
Publication date: 2025/11/28
Liu AnjingDe Jager Philip LBennett David Wang GaoDenault William R P - Molecular QTL studies quantify whether genetic variants affect molecular traits, but non-linear effects including distributional patterns, variance, and interactions provide mechanistic insights beyond mean-level associations. Methods for detecting distributional effects have been developed for eQTL analysis, yet applications have focused on method demonstrations rather than large-scale biological discovery. We comprehensively mapped quantile, variance, and interaction QTLs across 34 data-set from 22 molecular contexts in >2,300 human brain donors, revealing that 48.7% of quantile QTLs (qQTLs) exhibit context-dependent regulation invisible to linear models, with enrichment at phenotypic extremes and in cell-type-specific regulatory elements, chromatin accessibility regions, and long-range chromosomal contacts. qQTL variants explained additional trait heritability beyond linear QTLs for brain-related traits. At Alzheimer's disease (AD) risk loci, qQTL analysis revealed complex regulatory architecture including variance effects at , lower-quantile-specific effects at partially explained by ε4 interactions, and coordinated epigenetic regulation at loci harboring //. Quantile-based transcriptome-wide association studies identified 34 AD risk genes and additional aging-related genes beyond standard TWAS, with enrichment in immune regulation and telomere maintenance pathways where distributional effects may reflect threshold-dependent mechanisms. Our non-linear QTL atlas and qTWAS resource enable characterization of context-dependent regulatory effects in complex disease genetics. - Source: PubMed
Publication date: 2025/12/01
Liu AnjingJiang RoulanLi RuixiCao XueweiQi ZiningFeng RuSun HaoFujita MasashiComandante-Lou NatachaLakhani Chirag MEmpawi JennyKnowles David AZhang XiaolingDey Kushal KDe Jager PhilipBennett David Wang TianyingWang Gao - Greater than a hundred genetic risk factors for Alzheimer’s disease (AD) have been identified by genome-wide association studies (GWAS), many of which are primarily expressed in microglia. However, the pathogenic role for most of them remains unclear. We sought to assess at scale how AD GWAS hits influence human microglial inflammatory responses. Thus, we conducted CRISPR inhibition (CRISPRi) screens of 119 AD GWAS hits in hiPSC-derived microglia (iMGLs), with reactive oxygen species (ROS) produced in response to the viral mimic poly(I:C) as a readout. Top hits that either decreased or increased ROS in response to poly(I:C) when knocked down were then interrogated in CROP-seq experiments, where CRISPRi was combined with single cell RNA-sequencing (scRNA-seq). These analyses identified 9 unique microglial clusters, including a poly(I:C)-driven inflammatory cluster (2). Emerging evidence supports a pathogenic role of viral infections in AD and our scRNA-seq showed significant overlap with AD-relevant microglial clusters. Knockdown (KD) of two hit genes, and , which lead to high levels of ROS in the presence of poly(I:C), increased the proportion of inflammatory cluster 2 cells and led to functionally related changes in gene expression. In addition, KD of reduced the proportion of iMGLs in the disease-associated microglia (DAM) cluster under all conditions, suggesting that may modulate the DAM response. In contrast, KD of hit genes, or which led to low levels of ROS in the presence of poly(I:C), did not significantly affect the proportion of cells in inflammatory cluster 2 but rather shaped the inflammatory response. This included upregulation of a poly(I:C)-independent HLA inflammatory cluster (6) by INPP5D KD under all conditions. Despite or being involved in disparate biological processes, their perturbation led to similar changes in gene expression, which included changes in genes related to metabolism such as oxidative phosphorylation, suggesting a shared conversion point by which AD GWAS hits affect cell state. Overall, our data begin to elucidate the functional roles played by various AD GWAS hits, including how they regulate and shape inflammatory responses such as those observed in AD. - Source: PubMed
Publication date: 2025/12/03
Cardona Christopher LWei LaiKim JoonwonAngeles EllenSingh GunjandeepChen ShiyePatel RonakIfediora NkechimeCanoll PeterTeich Andrew FHargus GunnarChavez AlejandroSproul Andrew A