Ask about this productRelated genes to: HGSNAT antibody
- Gene:
- HGSNAT NIH gene
- Name:
- heparan-alpha-glucosaminide N-acetyltransferase
- Previous symbol:
- TMEM76
- Synonyms:
- FLJ32731, HGNAT
- Chromosome:
- 8p11.21-p11.1
- Locus Type:
- gene with protein product
- Date approved:
- 2005-09-23
- Date modifiied:
- 2018-11-16
Related products to: HGSNAT antibody
Related articles to: HGSNAT antibody
- Sialic acid O-acetylation is implicated in the modulation of sialoglycan recognition and ganglioside biology. The sugar modification is catalyzed by CASD1, a Golgi membrane protein that encompasses a luminal catalytic domain and a multipass transmembrane domain. The mechanism of how acetyl-CoA is provided to the Golgi remains poorly understood. Here, we show that the acetyl-CoA transporter SLC33A1 provides acetyl-CoA to the luminal domain of CASD1 and that patient-derived SLC33A1 variants linked to inherited neurodevelopmental and neurodegenerative disorders impair ganglioside 9-O-acetylation. Under conditions that enable the formation of 7,9-di-O-acetylated sialoglycans, genetic inactivation of SLC33A1 impaired di-O-acetylation, but unexpectedly, still enabled mono-O-acetylation. Structure prediction and site-directed mutagenesis revealed a second active site in CASD1 that shares striking similarities with the catalytic acetyl-CoA binding transmembrane tunnel of the lysosomal acetyltransferase HGSNAT. Together, our data provide strong evidence that CASD1 has dual functionalities and catalyzes 7,9-di-O-acetylation through SLC33A1-dependent luminal acetylation and SLC33A1-independent transmembrane acetylation. - Source: PubMed
Publication date: 2026/04/01
Albers MalenaBosse LydiaSchröter LarissaJunemann Anna-Maria TRossdam CharlotteHartmann MaikeGrove MelanieLitfin ThomasEgger Anna-SophiaKwiatkowski MarcelThedieck KathrinZocher GeorgBuettner Falk F RMalde Alpeshkumar Kvon Itzstein MarkMühlenhoff Martina - Inherited retinal dystrophies (IRDs) are a genetically diverse group of vision loss disorders with over 360 implicated genes. However, 30-50% of cases remain unresolved after panel-based clinical testing and may benefit from exome or genome sequencing for a genetic diagnosis. To manage the extensive and analytically demanding datasets generated by genome sequencing, we developed ReDGAP (Retinal Degeneration Genome Analysis Pipeline), a phenotype-guided, semi-automated genome analysis pipeline that integrates clinical phenotyping with flexible variant scoring to prioritize variants of interest ( https://github.com/vincentlab-la/ReDGAP ). The pipeline supports the joint analysis of multiple variant classes, using an evidence-weighted scoring system informed by in silico predictors. Validation in eleven previously solved IRD cases achieved a 100% re-identification rate. Application to five unsolved cases yielded diagnoses in four (80%), including intronic variants in CRB1 and HGSNAT, a tandem duplication in OAT, and a 5'UTR deletion affecting a retina-specific promoter of RPGRIP1. Functional validation confirmed transcript-level disruptions in three variants, while computational analysis demonstrated regulatory impact in the fourth. Integrating phenotypic data with broad variant analysis offers a tailored model for improving IRD diagnostics, enabling timely molecular diagnoses and informing eligibility for emerging gene-targeted therapies. This positions ReDGAP as a tailored, clinically relevant model for investigating rare diseases within the evolving landscape of precision health. - Source: PubMed
Publication date: 2026/03/28
Ahmed LaylaTavares ErikaLi Janice MinAhmed KashifMehta MaanikEileen ChristabelAh-Sen GenevieveOsman RahmaGreen-Sanderson KitDvaladze AnnaNimmo GraemeDeshwar Ashish RPaton TaraCasallo GuillermoMarshall Christian RHeon EliseVincent Ajoy - Mucopolysaccharidosis type IIIC (MPS IIIC) is a rare lysosomal storage disorder caused by biallelic pathogenic variants in the HGSNAT gene, encoding heparan-α-glucosaminide N-acetyltransferase. Deficient enzymatic activity leads to heparan sulfate accumulation, resulting in progressive central nervous system involvement and multisystem disease. Clinical features typically include developmental delay, intellectual disability, behavioral disturbances, coarse facial features, hypertrichosis, and hearing loss. This report describes the oldest documented siblings with MPS IIIC: a male diagnosed at 46 years (currently 50 years) and his sister diagnosed at 38 years (currently 42 years). Both presented with bilateral sensorineural hearing loss, retinitis pigmentosa, intellectual disability, mildly coarse facial features, and hypertrichosis. Molecular analysis identified two novel HGSNAT variants: c.1205T>C; p.(Leu402Pro) and c.1565C>A; p.(Thr522Lys). Functional studies demonstrated markedly reduced heparan-α-glucosaminide N-acetyltransferase activity and elevated urinary heparan sulfate excretion, providing biochemical evidence supporting variant pathogenicity and confirming the diagnosis. These cases expand both the phenotypic and genotypic spectrum of MPS IIIC and underscore the importance of considering this disorder in adults with multisystem involvement. Functional characterization proved essential for establishing a definitive diagnosis when molecular findings alone were inconclusive. - Source: PubMed
Publication date: 2026/03/25
Yu OwenMoore ChristineCarratu KevinWongkittichote ParithHong XinyingFrigeni Marta - Lysosomal dysfunction is central to Parkinson's disease pathogenesis, with as the strongest established genetic risk factor. Numerous other genes involved in lysosomal sphingolipid, glycosphingolipid and ceramide metabolism have been proposed as contributors to Parkinson's disease, underscoring the need for comprehensive genetic analyses across these pathways. We analysed rare variants (minor allele frequency < 0.01) across 36 lysosomal genes (excluding ) in 8,267 individuals with Parkinson's disease and 68,208 controls, including a subset of 793 early-onset Parkinson's disease (≤50 years) cases. Targeted sequencing was performed in four cohorts at McGill University (3,456 Parkinson's disease patients and 2,664 controls) and results were combined with whole-genome sequencing data from the UK Biobank (2,848 cases, 62,451 controls), and from the Accelerating Medicines Partnership - Parkinson's Disease (1,963 cases, 3,093 controls). We analysed the association of rare variants in these genes with Parkinson's disease using Sequence Kernel Association Test-Optimal (SKAT-O) across variant classes (all rare variants, nonsynonymous, loss-of-function and predicted damaging variants with a Combined Annotation Dependent Depletion (CADD) score >20), with meta-analysis across cohorts. We additionally performed per-domain analyses for variants in gene segments encoding functional domains. False discovery rate correction was applied. Meta-analysis identified a significant association between rare variants in and Parkinson's disease (Pfdr=0.04). Several additional lysosomal genes showed nominal associations (P<0.05), including and . Domain-based analyses identified a strong enrichment of nonsynonymous variants within the beta-acetyl-hexosaminidase-like domain of HEXA (P = 8.0 × 10), although this signal did not survive correction for multiple testing (Pfdr=0.154). In early-onset Parkinson's disease, domain-based analyses revealed significant associations in (Pfdr=7.3×10) and (Pfdr=0.03). Together, these results provide genetic evidence that rare variants across multiple lysosomal pathways, particularly those related to sialylation, ganglioside metabolism, ceramide biology, and lysosomal proteolysis, may contribute to Parkinson's disease susceptibility beyond , highlighting biologically coherent pathways for future replication and functional investigation. - Source: PubMed
Publication date: 2026/02/18
Senkevich KonstantinParlar Sitki CemChantereault CloeLiu LangYu EricRudakou UladzislauAhmad JamilRuskey Jennifer AAsayesh FarnazSpiegelman DanWaters CherylMonchi OuryDauvilliers YvesDupré NicolasGreenbaum LiorHassin-Baer SharonMiliukhina IrinaTimofeeva AllaEmelyanov AntonPchelina SofyaAlcalay Roy NGan-Or Ziv - Mucopolysaccharidosis type IIIC (MPS IIIC) is a rare lysosomal storage disorder caused by pathogenic variants in the HGSNAT gene. Data from large patient cohorts remain scarce, particularly in Latin America. - Source: PubMed
Publication date: 2025/12/26
Montenegro Yorran Hardman AraújoAlves Maria Fernanda AnteroSantos-Lopes Simone Silva DosSouza Carolina Fischinger Moura dePoswar Fabiano de OliveiraBrusius-Facchin Ana CarolinaBender-Pasetto FernandaMichelin-Tirelli KristianeSebastião Fernanda MedeirosTrapp Franciele BarbosaRibeiro Erlane MarquesMedeiros Paula Frassinetti Vasconcelos deKim Chong AeEmbiraçu Emilia KatianeRiegel-Giugliani MariluceBaldo GuilhermeGiugliani Roberto