Ask about this productRelated genes to: ADSSL1 antibody
- Gene:
- ADSSL1 NIH gene
- Name:
- adenylosuccinate synthase like 1
- Previous symbol:
- -
- Synonyms:
- FLJ38602
- Chromosome:
- 14q32.33
- Locus Type:
- gene with protein product
- Date approved:
- 2002-12-17
- Date modifiied:
- 2019-03-26
Related products to: ADSSL1 antibody
Related articles to: ADSSL1 antibody
- Muscles use large amounts of ATP during exercise. Three processes are widely recognized as important for maintaining muscle ATP with exercise. They include the phosphagen system, glycolysis, and mitochondrial oxidative phosphorylation. The goal of the current study was to evaluate the role of new purine synthesis in maintaining muscle ATP in individuals with pathogenic variants in adenylosuccinate synthase type 1 (ADSS1), an enzyme involved in muscle ATP synthesis. Muscle energetics were compared in 5 healthy controls and in 3 individuals with ADSS1 myopathy using phosphorus-magnetic resonance spectroscopy (P-MRS) before and after two exercise tasks, one short task that is widely used in muscle physiology and one longer task designed to push ATP use for a longer period. Compared to healthy controls, baseline resting muscle ATP measures were low in the ADSS1 myopathy group. Unlike healthy controls, muscle ATP dropped even with modest exercise in the disease group, and restoration of the energy state was abnormally slow. This rare disorder provides an experiment of nature that suggests synthesis of new purines is a critical fourth process required to maintain muscle ATP during exercise. - Source: PubMed
Publication date: 2026/09/25
Reiter DavidKilic-Berkmen GamzeGudimetla SakethHess Ellen JJinnah H A - Bone fractures in Thoroughbred racehorses are a major welfare problem. Genetic factors contribute to fracture risk. Cell models have previously identified 112 differentially expressed genes in bone-forming osteoblasts derived from horses at high and low genetic risk of fracture. However, 42 of these genes have no published role in bone. In this study, we identified novel roles for a subset of these genes in bone formation. Twenty-six of the 42 genes were expressed in Saos2 cells during basal culture and/or after 21 days of osteogenic culture. Five of these genes (ADSSL1, CABP1, ENO2, SPARCL1 and UCP2) were then stably overexpressed and knocked down, and their effect on osteogenesis was measured. Gene overexpression resulted in significant decreases in Saos2 cell viability and decreased expression of osteogenic genes under basal cell culture, but after 21 days of osteogenic culture there were few significant changes in osteogenic gene expression, collagen deposition or matrix mineralisation. Knockdown of SPARCL1 resulted in total cell death, whereas knockdown of ADSSL1, CABP1, ENO2 and UCP2 resulted in decreased cell viability but limited significant changes in osteogenic gene expression under basal cell culture. However, following osteogenic culture, gene knockdown induced widespread changes in osteogenic gene expression, decreased collagen deposition and increased matrix mineralisation. ADSSL1, CABP1, ENO2 and UCP2 were all expressed at significantly lower levels in osteoblasts from genetically high-risk horses. Taken together, this work demonstrates novel roles for fracture-associated genes in bone formation and matrix mineralisation suggesting these processes may be altered in genetically susceptible horses. - Source: PubMed
Ross Amy CLumsden Ellison SFlood CarolineDudhia JayeshPsifidi AndronikiGuest Deborah J - The incidence of obesity and male infertility continues to rise, and a complex pathophysiological association exists between the two. However, the comorbid molecular mechanisms remain incompletely elucidated. In this study, bioinformatics and machine learning methods were integrated to systematically explore the shared mechanisms of obesity and male infertility, and to predict natural compounds and TCMs with therapeutic potential based on multi-omics data. Datasets of male infertility and obesity were obtained from the GEO database, and 43 intersecting genes were identified through differential expression analysis. Using three machine learning algorithms, including random forest, least absolute shrinkage and selection operator(LASSO) regression, and support vector machine(SVM), five Hub genes(MAP4K4, GPT2, ADSSL1, PAIP2, and GINS3) were screened. The combined diagnostic model achieved an area under the curve(AUC) greater than 0.8, indicating good diagnostic performance. Functional enrichment analysis revealed that these genes are mainly involved in key biological processes such as amino acid metabolism, cell migration, and DNA replication. Immune infiltration analysis showed a significant upregulation of central memory CD4~+ T cells in both diseases, suggesting that chronic immune activation is an important basis for their comorbidity. Single-cell sequencing and pseudotime analyses demonstrated disordered cell differentiation trajectories in the adipose tissue of obese patients and the testicular tissue of infertile patients. Based on the connectivity map(CMap) database, ten natural compounds, including berberine, curcumin, and ginsenosides, were predicted and further validated by molecular docking to have strong binding affinities with the Hub genes. Integration with the traditional Chinese medicine systems pharmacology(TCMSP) platform enabled the construction of a "target-natural compound-herbal medicine" interaction network, identifying 38 corresponding herbal medicines. Property and meridian analysis indicated a predominance of warm nature, sweet flavor, and liver meridian tropism, consistent with the TCM therapeutic principles of "resolving phlegm and dampness, strengthening the spleen, and tonifying the kidney". This study reveals, at the molecular level, the comorbid mechanisms of obesity and male infertility in immune-inflammatory regulation and cell differentiation dysfunction, providing a theoretical basis and potential drug targets for precise TCM intervention in obesity-related male infertility. - Source: PubMed
Gong Zhuo-ZhiFeng Qiu-JianGao Qing-HeWang FuGuo JunLiu Sheng-Jing - ADSS1 myopathy (previously referred to as ADSSL1 myopathy) is a rare autosomal recessive muscle disease caused by mutations in the ADSS1 gene, which encodes an enzyme critical for purine nucleotide synthesis. First characterized in Korean patients in 2016, the disease exhibits phenotypic variability in its clinical presentation. We conducted a retrospective cohort study of 30 patients with genetically confirmed ADSS1 myopathy (18 males and 12 females) at Gangnam Severance Hospital from 2002 to 2024. The patients were classified into proximal-onset (n = 9) and distal-onset (n = 20) groups based on the location of initial muscle weakness, with one patient presenting with isolated hyperCKemia. Clinical assessments, genetic analyses, and muscle MRI were performed on 10 patients to evaluate clinical-radiological correlations. The median age at symptom onset was 8.0 years [Interquartile range (IQR): 7.0-14.0] with a median disease duration of 24.0 years [IQR: 17.0-34.0]. The most common initial symptoms were slow running (66.7%), early fatigue (16.7%), and gait disturbances (10.0%). Facial involvement was observed in 80.0% of the patients and oropharyngeal dysfunction in 56.7%. The median serum creatine kinase level was 214.0 IU/L [IQR: 125.0-394.0]. Genetic analysis revealed five pathogenic ADSS1 variants, with c.781G > A (51.7% of alleles) and c.919del (40.0% of alleles) being the most prevalent. Most patients (73.3%) were compound heterozygous for the two variants. Despite the clinical heterogeneity between the proximal- and distal-onset groups, none of the clinical differences were statistically significant. Muscle MRI revealed a remarkably consistent pattern of preferential involvement of the distal lower limb muscles, particularly the gastrocnemius and soleus muscles, regardless of the initial clinical presentation. This study, which represents the largest Korean ADSS1 myopathy cohort to date, highlights the striking discordance between clinical phenotypes and radiological findings. Although the clinical presentations varied considerably, MRI revealed consistent distal dominant muscle involvement patterns across all patients. This suggests that the underlying pathological process follows a predictable anatomical distribution independent of the initial symptomatic muscle groups. Our findings support the utility of muscle MRI as a valuable diagnostic tool for ADSS1 myopathy and suggest its conceptualization as a unified disease entity with a common pathophysiological mechanism involving selective muscle vulnerability based on metabolic requirements. - Source: PubMed
Publication date: 2026/04/13
Kim Soo-HyunChoi YunjungPark Hyung JunHong Ji-ManChoi Young-Chul - ADSS1 myopathy is an ultrarare congenital myopathy characterized by progressive cardiac and skeletal muscle degeneration with childhood to adolescent onset. This autosomal recessive disease is caused by mutations in the ADSS1 gene, encoding the enzyme adenylosuccinate synthetase (AdSS1). AdSS1 plays a critical role in the adenine nucleotide cycle, which is important for energy metabolism in muscle cells. Enzymatic defects, engendered by loss-of-function mutations in ADSS1, lead to a bottleneck in the adenine nucleotide cycle, causing metabolic dysfunction that ultimately results in progressive muscle weakness, mobility impairment, and respiratory and cardiac dysfunction, often requiring the use of a ventilator. Despite its debilitating nature, there are currently no cures or targeted treatments available, and little research into possible therapeutic strategies has been done. With a limited patient profile encompassing fewer than 200 known patients worldwide, establishing a mouse model for ADSS1 myopathy is critical to understanding its pathogenesis and for developing future therapies. Here, we present and characterize the first mouse model of ADSS1 myopathy-a constitutive Adss1 knockout model-by (1) defining its natural history, (2) exploring its metabolic pathomechanisms, and (3) characterizing its histopathological features. We find that Adss1KO/KO mice have subtle motor deficits and present with histopathological features consistent with patient phenotypes. Overall, we show that despite a relatively mild phenotype, this novel mouse model has quantifiable pathological features that can be used to develop therapies for, and further probe pathophysiology of, ADSS1 myopathy. - Source: PubMed
Kim Morgan EYammine Kathryn MHickey Emily TMatias CatalinaDubosclard Lou CWidrick Jeffrey JBrault Jeffrey JMoghadaszadeh BehzadBeggs Alan H