Ask about this productRelated genes to: POGZ Blocking Peptide
- Gene:
- POGZ NIH gene
- Name:
- pogo transposable element derived with ZNF domain
- Previous symbol:
- -
- Synonyms:
- KIAA0461, ZNF635m, ZNF280E
- Chromosome:
- 1q21.3
- Locus Type:
- gene with protein product
- Date approved:
- 2002-08-29
- Date modifiied:
- 2017-03-30
Related products to: POGZ Blocking Peptide
Related articles to: POGZ Blocking Peptide
- One of the seminal discoveries from genetic studies of autism spectrum disorder and related neurodevelopmental disorders (NDDs) has been that loss-of-function (LoF) mutations in genes that impact transcriptional regulation confer substantial liability to NDDs. Haploinsufficiency of the epigenetic regulator POGZ represents one of the strongest such associations; however, little is known about the mechanisms by which POGZ LoF alters early neuronal development. Here, we created an allelic series of CRISPR-engineered human induced pluripotent stem cell (hiPSC) clones harboring mono- and bi-allelic POGZ deletions. In hiPSC-derived neural stem cells (NSCs) and Neurogenin-2-induced neurons (iNs), POGZ LoF altered the expression of genes associated with synaptic and intracellular signaling and extracellular matrix organization. Our multiomics profiling also showed altered footprinting of critical transcription factors (e.g., activator protein 1 complexes) that were enriched at promoters of differentially expressed genes associated with synaptic function. To further interrogate the shared molecular changes associated with NDDs, we compared our results to deletions of the transcription factor MEF2C and the sodium channel gene SCN2A that we generated in these same isogenic iNs. These analyses revealed strong enrichment of extracellular matrix and intracellular signaling disruption associated with POGZ and MEF2C deletion, whereas POGZ and SCN2A haploinsufficiency exhibited shared transcriptional effects on gene modules enriched for NDD-associated genes with opposing regulatory effects. Notably, we also observed alterations to synaptic firing rate and neurite extension with bi-allelic deletions. These shared molecular consequences suggest key points of convergence that connect gene regulation to neuronal function in the etiology of neurodevelopmental pathologies. - Source: PubMed
Publication date: 2026/07/10
Moyses-Oliveira MarianaLiu YatingErdin SerkanGao DadiBhavsar RiyaMohajeri KianaO'Keefe KathrynBoone Philip MXavier GabrielaLiao CalwingLi AiqunYadav RachitaSalani MonicaLucente DianeCurrall Benjaminde Esch Celine E FTai Derek J CRuderfer DouglasBrennand Kristen JGusella James FTalkowski Michael E - White-Sutton syndrome (WHSUS; OMIM 616364) is a rare neurodevelopmental disorder caused by pathogenic variants in the gene and characterized by developmental delay, intellectual disability, speech impairment, autism spectrum features, and dysmorphic traits. Although most reported cases are sporadic, inherited forms are exceptionally rare. We describe a familial case of WHSUS involving an affected mother and two children carrying a heterozygous nonsense variant, highlighting marked intra-familial phenotypic variability and expanding the clinical spectrum of the disorder. Clinical evaluation included multidisciplinary assessments. Genetic testing was performed using clinical exome sequencing (CES) with a virtual neurodevelopmental disorder (NDD) gene panel, followed by Sanger confirmation and segregation analysis in family members. The POGZ transcript reference NM_015100.3 was used for variant nomenclature and verified with the Mutalyzer tool. CNV detection from NGS data was performed using the Alissa CNV caller (Agilent) and visualized via IGV; the Xp11.22 microduplication was confirmed by chromosomal microarray (aCGH) and parental segregation analyses. CES identified the heterozygous pathogenic variant c.1522C>T (p.Arg508*) in the female proband (III), an infant presenting with global developmental delay, hypotonia, speech impairment, gait abnormalities, and characteristic dysmorphic features. Segregation analysis demonstrated maternal inheritance and confirmed the presence of the variant in her affected brother (III), who also carries a de novo 1.79 kb microduplication at Xp11.22, while the maternal grandparents tested negative, indicating a de novo origin in the mother. The mother exhibited an attenuated phenotype, including mild neuropsychiatric and gastrointestinal manifestations. The variant is predicted to undergo nonsense-mediated decay (NMD), consistent with a moderate clinical presentation; however, experimental validation was not performed. This report documents a rare familial occurrence of WHSUS with highly variable expressivity. Our findings broaden the phenotypic and molecular characterization of -related disorders and emphasize the importance of comprehensive segregation studies and early genomic diagnosis. While experimental data link POGZ deficiency to DNA repair defects, no longitudinal clinical studies have demonstrated increased cancer risk in WHSUS; therefore, formal malignancy screening guidelines cannot be established at present, and this issue deserves future study in larger cohorts or registries. - Source: PubMed
Publication date: 2026/06/21
Chetta MassimilianoLattarulo SimoneStasi MicheleKrylovska YevheniiaLastella PatriziaResta NicolettaPalumbo OrazioPalumbo PietroBukvic Nenad - Autism Spectrum Disorder (ASD) is a complex neurodevelopmental disorder with substantial genetic heterogeneity. While coding variants have been extensively studied, non-coding regulatory variants-which constitute approximately 99% of the human genome-remain largely underexplored. Their functional impact, particularly at the single-cell level and in organoid models, requires further characterization to better understand how these variants contribute to ASD pathogenesis. - Source: PubMed
Publication date: 2026/06/05
Dominguez-Alonso SaraCarballo-Pacoret PTrotta Jr PaulGonzalez-Peñas JParellada MArango CCarracedo ARodriguez-Fontenla C - Alternative splicing generates extraordinary transcriptomic complexity in the human brain, yet the full-length isoform landscape across human cortical cell types remains uncharted. Combining fluorescence-activated nuclei sorting with long- and short-read RNA sequencing, we generated isoform-resolved transcriptomes for five major lineages of the adult human prefrontal and orbitofrontal cortex: GABAergic neurons, glutamatergic neurons, oligodendrocytes, astrocytes, and microglia. We cataloged over 220,000 full-length isoforms, ~35-56% previously unannotated; novel transcripts were longer, more exon-rich, and predominantly protein-coding. Contrary to the neuron-centric view of cortical complexity, glial lineages, particularly oligodendrocytes and microglia, emerged as the most isoform-diverse populations in the cortex. Differential transcript usage and dominant isoform switching defined cell identity, with ~59-62% of differentially regulated transcripts absent from current annotations. Critically, pathogenic variants were enriched >2-fold at novel splice boundaries within disease genes including , , and , establishing isoform selection as a primary axis of cortical identity and exposing a layer of pathogenic variation invisible to canonical gene annotations. - Source: PubMed
Publication date: 2026/05/27
Yang AndySantos Miguel Rodriguez de LosKozlenkov AlexeyVadukapuram RamuHurd YasminDracheva StellaHumphrey JackBreen Michael S - What is already known about this topic? ◦. Variants of the POGZ gene cause an autosomal dominant neurodevelopmental syndrome, White–Sutton syndrome (WSS). ◦. To date, the majority of reported WSS cases have been diagnosed postnatally in individuals presenting with neurodevelopmental abnormalities. Only two prenatal cases have been documented in the literature. What does this study add? ◦. Our report reinforces microcephaly as a recurrent and potentially characteristic prenatal imaging feature of WSS. ◦. We first report fetal craniofacial anomalies, including micrognathia and auricular dysmorphism, as novel prenatal indicators suggestive of WSS. - Source: PubMed
Publication date: 2026/06/04
Liu PingLuo Hong-YuLi Dong-Zhi