ArticleHuman mutation2011
Molecular defects in human carbamoy phosphate synthetase I: mutational spectrum, diagnostic and protein structure considerations.
Article in Human mutation, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers, 1 of them a synthesis that pooled it.
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Who cites it
38 citing papers in PubMed, 1 synthesis or guideline pooled it, 79 citations in OpenAlex.
- Trans-ethnic kidney function association study reveals putative causal genes and effects on kidney-specific disease aetiologies.Nature communications · 2019Pooled it
- CPS1: a multipurpose mitochondrial enzyme, bile protein, acute liver injury biomarker, and cytokine.Gut · 2026Review
- Post-meal loss of consciousness in an adult patient with carbamoyl phosphate synthetase 1 deficiency and two newly identified heterozygous variants: a case report.BMC neurology · 2026Article
- Review
- Use of an oversized AAV8 vector for CPS1 deficiency results in long-term survival and ammonia control.Molecular therapy. Nucleic acids · 2025Article
- Carbamoly-phosphate synthetase 1 (CPS1) deficiency: A tertiary center retrospective cohort study and literature review.Molecular genetics and metabolism reports · 2024Article
- Datamining approaches for examining the low prevalence of N-acetylglutamate synthase deficiency and understanding transcriptional regulation of urea cycle genes.Journal of inherited metabolic disease · 2024Article
- Fast and deep phosphoproteome analysis with the Orbitrap Astral mass spectrometer.Nature communications · 2024Article
- Genetic variants affecting mitochondrial function provide further insights for kidney disease.BMC genomics · 2024Article
- Long-term follow-up of children with carbamoyl phosphate synthase 1 deficiency detected in newborn screening.Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2023Article
- Clinical and genetic analysis of a case of late onset carbamoyl phosphate synthase I deficiency caused by CPS1 mutation and literature review.BMC medical genomics · 2023Review
- Novel compound heterozygote variants: c.4193_4206delinsG (p.Leu1398Argfs*25), c.793C > A (p.Pro265Thr), in the CPS1 gene (NM_001875.4) causing late onset carbamoyl phosphate synthetase 1 deficiency-Lessons learned.Molecular genetics and metabolism reports · 2022Article
- O-GlcNAcylation enhances CPS1 catalytic efficiency for ammonia and promotes ureagenesis.Nature communications · 2022Article
- Novel pathogenic variant (c.2947C > T) of the carbamoyl phosphate synthetase 1 gene in neonatal-onset deficiency.Frontiers in neuroscience · 2022Article
- A deep intronic variant is a common cause of OTC deficiency in individuals with previously negative genetic testing.Molecular genetics and metabolism reports · 2021Article
- A Case of Carbamazepine-Induced Aggravation of Self-Limited Epilepsy with Centrotemporal Spikes Epilepsy and Valproate-Induced Hyperammonemic Encephalopathy in a Child with Heterozygous Gene Variant of Carbomoyl Phosphatase Synthetase Deficiency.Case reports in neurological medicine · 2021Article
- Split AAV-Mediated Gene Therapy Restores Ureagenesis in a Murine Model of Carbamoyl Phosphate Synthetase 1 Deficiency.Molecular therapy : the journal of the American Society of Gene Therapy · 2020Article
- Molecular, biochemical, and clinical analyses of five patients with carbamoyl phosphate synthetase 1 deficiency.Journal of clinical laboratory analysis · 2020Article
- Improvement of diagnostic yield in carbamoylphosphate synthetase 1 (JIMD reports · 2020Article
- Mitochondrial Enzymes of the Urea Cycle Cluster at the Inner Mitochondrial Membrane.Frontiers in physiology · 2020Article
Corrections and comments
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Authors and funding
15 authors at 5 institutions in 4 countries.
Funding
Abstract
Deficiency of carbamoyl phosphate synthetase I (CPSI) results in hyperammonemia ranging from neonatally lethal to environmentally induced adult-onset disease. Over 24 years, analysis of tissue and DNA samples from 205 unrelated individuals diagnosed with CPSI deficiency (CPSID) detected 192 unique CPS1 gene changes, of which 130 are reported here for the first time. Pooled with the already reported mutations, they constitute a total of 222 changes, including 136 missense, 15 nonsense, 50 changes of other types resulting in enzyme truncation, and 21 other changes causing in-frame alterations. Only ∼10% of the mutations recur in unrelated families, predominantly affecting CpG dinucleotides, further complicating the diagnosis because of the "private" nature of such mutations. Missense changes are unevenly distributed along the gene, highlighting the existence of CPSI regions having greater functional importance than other regions. We exploit the crystal structure of the CPSI allosteric domain to rationalize the effects of mutations affecting it. Comparative modeling is used to create a structural model for the remainder of the enzyme. Missense changes are found to directly correlate, respectively, with the one-residue evolutionary importance and inversely correlate with solvent accessibility of the mutated residue. This is the first large-scale report of CPS1 mutations spanning a wide variety of molecular defects highlighting important regions in this protein.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.