cps1  (Proteintech)

Journal: Disease Models & Mechanisms

Article Title: A hypomorphic model of CPS1 deficiency for investigating the effects of hyperammonemia on the developing nervous system

doi: 10.1242/dmm.052303

Figure Lengend Snippet: The Asn674Ile CPS1 variant is in the bicarbonate phosphorylation region and converts a polar uncharged amino acid to one that is nonpolar and hydrophobic. (A) The domain composition is noted and the amino acid location is identified by the numerals. The mutation is in the C-terminal moiety with bicarbonate phosphorylation, the first two steps in the production of carbamoyl phosphate by phosphorylation of bicarbonate by ATP to produce carboxyphosphate followed by attack by NH 3 to yield carbamate [adapted from under the terms of the CC-BY 4.0 license]. (B) Cartoon representation and enlargement (inset) of the ligand-bound human CPS1 protein (PDB ID, 5DOU; ) transparency set to 50%. (Note that colors of the domain correspond with those used in A.) Asn674 is highlighted in red sticks. ADP in the bicarbonate phosphorylation domain is shown in red, orange, yellow and blue sticks. K + and Mg 2+ ions are shown in purple and green spheres, respectively. Catalytic residues around ADP are shown in light green lines. The yellow dashed line indicates the distance between the center of the Asn674 residue and the center of ADP in angstroms.

Article Snippet: Following PBS washes, host-conjugated secondary antibodies were incubated at RT for 2 h [goat anti-rabbit Alexa Fluor 594 against CPS1 antibody (Thermo Fisher Scientific, A-11012, used at 1:500), goat anti-mouse Alexa Fluor 488 against glutamine synthetase antibody (Thermo Fisher Scientific, A-11001, used at 1:500) and PureBlu DAPI (Bio-Rad, 1351303, used at 1:500)].

Techniques: Variant Assay, Phospho-proteomics, Mutagenesis, Residue

Journal: Disease Models & Mechanisms

Article Title: A hypomorphic model of CPS1 deficiency for investigating the effects of hyperammonemia on the developing nervous system

doi: 10.1242/dmm.052303

Figure Lengend Snippet: Cps1 hypomorphic mouse models demonstrate normal liver enzymes while having elevated ammonia and altered response to ammonia loading and carglumic acid administration. (A,B) Values for the liver transaminases alanine aminotransferase and aspartate aminotransferase from plasma of both Cps1 N674I/N674I and Cps1 0/N674I hypomorphic mouse models were similar to wild-type values. (C) Plasma ammonia has a step-wise increase based on the Cps1 mutation, with wild type< Cps1 N674I/N674I < Cps1 0/N674I : 31.00±10.99 µm/l, 46.90±14.35 µm/l and 84.10±35.26 µm/l, respectively. (D) Ammonium challenging with 5 mmol/kg demonstrates a step-wise increase in plasma ammonia based on genotype at 20 min after administration and declines close to baseline at 60 min ( n =10 per group). (E) Behavioral testing was performed 15 min after administration. (F) When a higher dose of ammonium is administered (7.5 mmol/kg), greater differences are detected between the hypomorphic and wild-type mice. (G) Behavioral scores were similar between groups reflective of the effect of high blood ammonia levels on the central nervous system. (H) Carglumic acid in drinking water led to a decline in plasma ammonia in wild-type mice but did not in the hypomorphic mice. n =4-5 per group for A,B, n =10 per group for D-F, n =6 per group for G,H, and n =5-6 per group for I. Data presented as mean±s.d. ns, not significant; * P <0.05, ** P <0.01 (A-G, one-way ANOVA with Dunnett's T3 multiple comparison test; H, paired two-tailed t -test).

Article Snippet: Following PBS washes, host-conjugated secondary antibodies were incubated at RT for 2 h [goat anti-rabbit Alexa Fluor 594 against CPS1 antibody (Thermo Fisher Scientific, A-11012, used at 1:500), goat anti-mouse Alexa Fluor 488 against glutamine synthetase antibody (Thermo Fisher Scientific, A-11001, used at 1:500) and PureBlu DAPI (Bio-Rad, 1351303, used at 1:500)].

Techniques: Clinical Proteomics, Mutagenesis, Comparison, Two Tailed Test

Journal: Disease Models & Mechanisms

Article Title: A hypomorphic model of CPS1 deficiency for investigating the effects of hyperammonemia on the developing nervous system

doi: 10.1242/dmm.052303

Figure Lengend Snippet: Cps1 hypomorphic models demonstrate increased Nags expression and reduced Cps1 protein and enzyme activity, while ureagenesis is maintained. (A) Fold change in hepatic Cps1 RNA expression comparing genotypes was performed normalized to Cps1 wild-type mice (at 1). (B) Fold change in hepatic Nags RNA expression was determined comparing genotypes normalized to Nags wild-type mice (at 1). (C) Representative western blot images from different mouse genotypes examining hepatic Cps1 expression with β-actin loading control (each lane represents a different mouse). (D) Quantitation of western blot of Cps1 protein levels between genotypes demonstrating markedly reduced protein in the hypomorphic mice. (E,F) Representative Cps1 liver immunostaining of the different mouse genotypes (Cps1 in red, glutamine synthetase in green) (E), with average fluorescence intensity per group represented (F). (G) Cps1 enzyme activity was determined from each genotype, showing marked reduction in the hypomorphic mouse livers. (H) [ 15 N]urea enrichment is decreased in the compound heterozygote, while [ 15 N]citrulline enrichment is decreased in both the homozygous mutant and the compound heterozygote. [ 15 N]glutamine is increased in the compound heterozygote. n =10 per group for A,B,D,G; n =8 per group for H; n =3 mice per group for E,F with ROI as n =5 (see ). ns, not significant; * P <0.05, *** P <0.001, **** P <0.0001 (A,B,F,G,H, one-way ANOVA with Dunnett's T3 multiple comparison test; D, ordinary one-way ANOVA Tukey's multiple comparison test). AUC, area under the curve; CIT, citrulline; F, female; GLN, glutamine; M, male; WT, wild type. Scale bars: 1 mm.

Article Snippet: Following PBS washes, host-conjugated secondary antibodies were incubated at RT for 2 h [goat anti-rabbit Alexa Fluor 594 against CPS1 antibody (Thermo Fisher Scientific, A-11012, used at 1:500), goat anti-mouse Alexa Fluor 488 against glutamine synthetase antibody (Thermo Fisher Scientific, A-11001, used at 1:500) and PureBlu DAPI (Bio-Rad, 1351303, used at 1:500)].

Techniques: Expressing, Activity Assay, RNA Expression, Western Blot, Control, Quantitation Assay, Immunostaining, Fluorescence, Mutagenesis, Comparison

Journal: Disease Models & Mechanisms

Article Title: A hypomorphic model of CPS1 deficiency for investigating the effects of hyperammonemia on the developing nervous system

doi: 10.1242/dmm.052303

Figure Lengend Snippet: Behavioral testing of hypomorphic compound heterozygote receiving standard mouse chow reveals an anxiety-like phenotype. Behavioral phenotype testing was performed on adult mice of each genotype ( n =12-17 per group). (A) Novel object recognition testing revealed there was an absence of statistically significant differences between wild-type (black circles), Cps1 N674I/N674I (blue squares) and Cps1 0/N674I (red triangles) mice. (B) In open field testing, measurement of entry to the center was reduced with increasing loss of Cps1. (C) Quantitative measurement of distance traveled was similarly reduced with increasing Cps1 loss. Together, B and C suggest an anxiety-like behavior. (D-F) Light/dark transition testing further suggested anxiety-like behavior: number of entries to the lighted area (D), total amount of time spent in the light side (E) and average speed in the light (F) was reduced for the compound heterozygote. ns, not significant; * P <0.05, ** P <0.01, *** P <0.001, **** P <0.0001 (A-F, one-way ANOVA with Dunnett's T3 multiple comparison test).

Article Snippet: Following PBS washes, host-conjugated secondary antibodies were incubated at RT for 2 h [goat anti-rabbit Alexa Fluor 594 against CPS1 antibody (Thermo Fisher Scientific, A-11012, used at 1:500), goat anti-mouse Alexa Fluor 488 against glutamine synthetase antibody (Thermo Fisher Scientific, A-11001, used at 1:500) and PureBlu DAPI (Bio-Rad, 1351303, used at 1:500)].

Techniques: Comparison

Journal: Disease Models & Mechanisms

Article Title: A hypomorphic model of CPS1 deficiency for investigating the effects of hyperammonemia on the developing nervous system

doi: 10.1242/dmm.052303

Figure Lengend Snippet: Conditioned fear testing of hypomorphic compound heterozygote receiving high-protein chow further confirms an anxiety-like phenotype. Behavioral phenotype testing was performed on adult mice of each genotype ( n =12-17 per group). In fear conditioning studies of contextual memory in which sexes were combined for analysis, there was evidence of increased freezing in the compound heterozygote. (A) At baseline, freezing was increased in Cps1 compound heterozygote mice. (B) During acquisition, there were no differences during the acquisition (i.e. shock) intertrial intervals (ITIs), demonstrating that mice were freezing following shocks. The only difference was in the final minute of the third ITI as the compound heterozygote demonstrated increased freezing. (C,D) However, upon re-exposure to context 24 h later, total freezing (C) and freezing across the whole session (D) were increased in the compound heterozygote compared to homozygous mutant and wild-type controls, demonstrating that the compound heterozygous mice had stronger contextual fear conditioning memory, consistent with an anxiety-like phenotype. ns, not significant; * P <0.05, ** P <0.01 (A,C, ordinary one-way ANOVA with Tukey's multiple comparison test; B,D, two-way ANOVA with mixed effects analysis).

Article Snippet: Following PBS washes, host-conjugated secondary antibodies were incubated at RT for 2 h [goat anti-rabbit Alexa Fluor 594 against CPS1 antibody (Thermo Fisher Scientific, A-11012, used at 1:500), goat anti-mouse Alexa Fluor 488 against glutamine synthetase antibody (Thermo Fisher Scientific, A-11001, used at 1:500) and PureBlu DAPI (Bio-Rad, 1351303, used at 1:500)].

Techniques: Mutagenesis, Comparison

Journal: Disease Models & Mechanisms

Article Title: A hypomorphic model of CPS1 deficiency for investigating the effects of hyperammonemia on the developing nervous system

doi: 10.1242/dmm.052303

Figure Lengend Snippet: CRISPR design showing the endogenous exon 18 of Cps1 and genetic development of Asn674Ile Cps1 hypomorphic mouse model. (A) Pink AAT is the N codon, green C is the silent mutation target to ablate the protospacer adjacent motif (PAM), red cut site shows the cleavage point. The dark green is the gRNA protospacer, light green is the PAM. The sequence of the single-stranded oligodeoxynucleotide repair template shows the 5′ homology arm (blue), 3′ homology arm (red), the introduction of ATT (N>I) and the silent mutation (green). (B) Chromatogram alignment between the identified founder (top) and the wild-type control (bottom). Bottom sequence report shows a 96% contribution of homology-directed repair allele (Ans674Ile) per inference of CRISPR edits (ICE) analysis output. (C) Chromatogram alignment from N1 animals of the potential off-target from chr1:155673955-155673977, showing the region as intact and without off-target indels.

Article Snippet: Following PBS washes, host-conjugated secondary antibodies were incubated at RT for 2 h [goat anti-rabbit Alexa Fluor 594 against CPS1 antibody (Thermo Fisher Scientific, A-11012, used at 1:500), goat anti-mouse Alexa Fluor 488 against glutamine synthetase antibody (Thermo Fisher Scientific, A-11001, used at 1:500) and PureBlu DAPI (Bio-Rad, 1351303, used at 1:500)].

Techniques: CRISPR, Mutagenesis, Sequencing, Control

Journal: iScience

Article Title: APE1 promotes lung adenocarcinoma through G4-mediated transcriptional reprogramming of urea cycle metabolism

doi: 10.1016/j.isci.2025.112275

Figure Lengend Snippet: CPS1 restoration alleviates DNA damage and proliferation defects of APE1 -/- LUAD (A) Kaplan-Meier curves showing overall survival of CPS1 -high (the highest 25%) or CPS1 -low (the remaining 75%) LUAD patients classified based on CPS1 mRNA levels. The source data is accessible through GEPIA. (B) Western blot analysis of CPS1 and γH2AX in wildtype ( APE1 +/+ ), APE1 knockout ( APE1 −/− ) and APE1 knockout with the restoration of CPS1 ( APE1 −/− + CPS1) A549 cells. ACTB was detected as a loading control. (C) Representative immunofluorescence images of A549 cells with the indicated genotypes stained with anti-γH2AX (green) and DAPI (blue) from two independent experiments. Scale bar indicates 20 μm. (D) Percentage of cells with greater than 10 γH2AX foci in APE1 +/+ and APE1 −/− A549 cells with or without restoration of CPS1. Five representative images for APE +/+ and ten representative images for APE1 −/− or APE1 −/− + CPS1 group form two independent experiments were counted, respectively. (E) Cell growth curves of APE1 −/− A549 cells with or without restoration of CPS1. (F) Effect of supplementing uridine and thymidine (UT) or adenosine (A) on cell proliferation rate in APE1 −/− A549 cells. Data in (E) and (F) presented as mean ± SEM from three biological replicates. The data in (B) and (E) are derived from two independent CRISPR clones. Statistical significance was assessed using two-sided log rank test (A), two-tailed unpaired Student’s t test (D), or two-way ANOVA (E and F). ns, not significant.

Article Snippet: Biotin-labeled CPS1 G4 oligonucleotide (5′-[Biotin] TTG TCC GGG TGG GTT AAG GGC CCT G-3′), CPS1 MUT oligonucleotide (5′-[Biotin] TTG TCC GAG TGA GTT AAG AGC CCT G-3′), ARG2 G4 oligonucleotide (5′-[Biotin] GGG GGA CCG GGA GGC GAG GAG AGG ATG GG-3′), ARG2 MUT oligonucleotide (5′-[Biotin] GGA GTA CCG TGA GAC GAG TAG AGT ATG AG-3′) and MYC G4 oligonucleotide (5′-[Biotin] TGA GGG TGG GTA GGG TGG GTA-3′) were synthesized by Sangon Biotech.

Techniques: Western Blot, Knock-Out, Control, Immunofluorescence, Staining, Derivative Assay, CRISPR, Clone Assay, Two Tailed Test

Journal: iScience

Article Title: APE1 promotes lung adenocarcinoma through G4-mediated transcriptional reprogramming of urea cycle metabolism

doi: 10.1016/j.isci.2025.112275

Figure Lengend Snippet: APE1 knockout hinders the presence of G4 structures in the CPS1 and ARG2 promoters (A) Promoter sequences of CPS1 (top) and ARG2 (bottom) identified by G4Hunter using a window of 20 nucleotides and a threshold of 1.25 with their corresponding score on both forward and reverse strands. The shaded boxes indicate the G4-forming sequences used in Figure 5 . (B) Genome browser representation of G4 structures and Observed-G4s (OGs) at the promoters of CPS1 (top) and ARG2 (bottom) in human cells. Data of G4P ChIP-Seq and G4-seq are from GSE133379 and GSE63874, respectively. (C) Reduced G4 signals in A549 cells upon APE1 deletion. Plot profile (top) and heatmaps (bottom) showing enrichment of G4 (RPGC, reads per genome coverage) in APE1 +/+ and APE1 −/− A549 cells. The signal is plotted in a 6 kb window flanking the transcriptional start sites (TSS). (D) Genome browser representation of G4 structures, H3K4me3 and chromatin accessibility at the promoters of CPS1 (top) and ARG2 (bottom). The shaded boxes highlight G4 structures co-occurring in the promoter regions enriched in H3K4me3.

Article Snippet: Biotin-labeled CPS1 G4 oligonucleotide (5′-[Biotin] TTG TCC GGG TGG GTT AAG GGC CCT G-3′), CPS1 MUT oligonucleotide (5′-[Biotin] TTG TCC GAG TGA GTT AAG AGC CCT G-3′), ARG2 G4 oligonucleotide (5′-[Biotin] GGG GGA CCG GGA GGC GAG GAG AGG ATG GG-3′), ARG2 MUT oligonucleotide (5′-[Biotin] GGA GTA CCG TGA GAC GAG TAG AGT ATG AG-3′) and MYC G4 oligonucleotide (5′-[Biotin] TGA GGG TGG GTA GGG TGG GTA-3′) were synthesized by Sangon Biotech.

Techniques: Knock-Out, ChIP-sequencing

Journal: iScience

Article Title: APE1 promotes lung adenocarcinoma through G4-mediated transcriptional reprogramming of urea cycle metabolism

doi: 10.1016/j.isci.2025.112275

Figure Lengend Snippet: APE1 regulates the transcription of CPS1 and ARG2 by facilitating G4 structure formation (A) BG4 CUT&Tag sequencing profiles for the G4 edited sites at the promoters of CPS1 (upper) or ARG2 (bottom) and the STAT3 control site. (B) RT-qPCR analysis of CPS1 in CPS1 MUT (top) and ARG2 in ARG2 MUT (bottom) A549 cells. “MUT” denotes that the G4 sequence in the promoter of the respective genes was mutated by gene editing. (C) RT-qPCR analysis of CPS1 in CPS1 MYC G4 (top) and ARG2 in ARG2 MYC G4 (bottom) A549 cells. “MYC G4” denotes that the native G4 sequence in the promoter of the respective genes was replaced by MYC G4 sequence. (D) RT-qPCR analysis of CPS1 and ARG2 in APE1 +/+ and APE1 −/− A549 cells treated with G4-stabilizing ligand PDS (5 mM) for 2 h. (E) RT-qPCR analysis of CPS1 and ARG2 in APE1 −/− A549 cells with restoration of either APE1 WT or N212A mutant. (F) RT-qPCR analysis of CPS1 and ARG2 in APE1 +/+ and APE1 −/− A549 cells treated with OGG1 inhibitor TH5487 (5 μM) for 2 h. (G) The proliferation of APE1 +/+ and APE1 −/− A549 cells treated with OGG1 inhibitor TH5487 for 24 h. Cells were counted using the CCK8 assay. The expression levels were normalized to GAPDH , and then compared to the untreated APE1 +/+ control, which was set to 1.0. Data in (B–G) are presented as mean ± SEM from three (G) or four (B–F) biological replicates. The data presented in (B–D) and (F and G) are derived from four independent CRISPR clones. Statistical significance was assessed using two-tailed unpaired Student’s t test. ns, not significant.

Article Snippet: Biotin-labeled CPS1 G4 oligonucleotide (5′-[Biotin] TTG TCC GGG TGG GTT AAG GGC CCT G-3′), CPS1 MUT oligonucleotide (5′-[Biotin] TTG TCC GAG TGA GTT AAG AGC CCT G-3′), ARG2 G4 oligonucleotide (5′-[Biotin] GGG GGA CCG GGA GGC GAG GAG AGG ATG GG-3′), ARG2 MUT oligonucleotide (5′-[Biotin] GGA GTA CCG TGA GAC GAG TAG AGT ATG AG-3′) and MYC G4 oligonucleotide (5′-[Biotin] TGA GGG TGG GTA GGG TGG GTA-3′) were synthesized by Sangon Biotech.

Techniques: Sequencing, Control, Quantitative RT-PCR, Mutagenesis, CCK-8 Assay, Expressing, Derivative Assay, CRISPR, Clone Assay, Two Tailed Test

Journal: iScience

Article Title: APE1 promotes lung adenocarcinoma through G4-mediated transcriptional reprogramming of urea cycle metabolism

doi: 10.1016/j.isci.2025.112275

Figure Lengend Snippet: APE1 shows strong binding affinity to G4 structures in CPS1 and ARG2 promoters (A and B) Schematic diagram of G4, non-G4 (control) regions and G4-mutated sequences at the CPS1 (A) and ARG2 (B) promoters. The underlined sequences denote G4-forming oligo containing the G4 motif or non-G4-forming oligo in which G residues are substituted with A (Mut, in blue). The location and length of each DNA fragment amplified in the real-time ChIP-PCR experiments ( Figure 5 E) are indicated. Arrows represent the positions of the primers. Red letters indicate the positions critical for G4 formation. TSS, transcription start site. (C) Binding curves illustrating the association and dissociation of recombinant APE1 protein to the immobilized, biotinylated ssDNA oligonucleotide containing the CPS1 (left) and ARG2 (right) G4 by biolayer interferometry (BLI) analysis. Apparent KD for the most abundant population is indicated. (D) BLI assay for non-G4-forming (MUT) oligonucleotides of CPS1 (left) and ARG2 (right). (E) Enrichment of APE1 on the CPS1 (left) and ARG2 (right) promoters in knock-in A549 cells with HA-tagged APE1 (HA-APE1 WT ) and in APE1 −/− expressing transgenic FLAG-tagged APE1 N212A (FLAG-APE1 N212A ). ChIP-qPCR was performed, with control regions located within the gene body lacking G4-forming ability ( Figure 5 A). Data are presented as mean ± SEM from four biological replicates. Statistical significance was assessed using two-tailed unpaired Student’s t test (E). ns, not significant.

Article Snippet: Biotin-labeled CPS1 G4 oligonucleotide (5′-[Biotin] TTG TCC GGG TGG GTT AAG GGC CCT G-3′), CPS1 MUT oligonucleotide (5′-[Biotin] TTG TCC GAG TGA GTT AAG AGC CCT G-3′), ARG2 G4 oligonucleotide (5′-[Biotin] GGG GGA CCG GGA GGC GAG GAG AGG ATG GG-3′), ARG2 MUT oligonucleotide (5′-[Biotin] GGA GTA CCG TGA GAC GAG TAG AGT ATG AG-3′) and MYC G4 oligonucleotide (5′-[Biotin] TGA GGG TGG GTA GGG TGG GTA-3′) were synthesized by Sangon Biotech.

Techniques: Binding Assay, Control, Amplification, Recombinant, Knock-In, Expressing, Transgenic Assay, ChIP-qPCR, Two Tailed Test

Journal: iScience

Article Title: APE1 promotes lung adenocarcinoma through G4-mediated transcriptional reprogramming of urea cycle metabolism

doi: 10.1016/j.isci.2025.112275

Figure Lengend Snippet:

Article Snippet: Biotin-labeled CPS1 G4 oligonucleotide (5′-[Biotin] TTG TCC GGG TGG GTT AAG GGC CCT G-3′), CPS1 MUT oligonucleotide (5′-[Biotin] TTG TCC GAG TGA GTT AAG AGC CCT G-3′), ARG2 G4 oligonucleotide (5′-[Biotin] GGG GGA CCG GGA GGC GAG GAG AGG ATG GG-3′), ARG2 MUT oligonucleotide (5′-[Biotin] GGA GTA CCG TGA GAC GAG TAG AGT ATG AG-3′) and MYC G4 oligonucleotide (5′-[Biotin] TGA GGG TGG GTA GGG TGG GTA-3′) were synthesized by Sangon Biotech.

Techniques: Virus, Recombinant, Purification, Cell Counting, Protein Extraction, Genome Wide, Binding Assay, Next-Generation Sequencing, CRISPR, Software

Journal: Molecular Genetics and Metabolism Reports

Article Title: Identification of novel variants in carbamoyl phosphate synthetase 1 gene and comparative pathogenicity assessments of CPS1 missense variants following ACMG/AMP-ClinGen recommendation for computational tools

doi: 10.1016/j.ymgmr.2025.101208

Figure Lengend Snippet: Sanger sequencing of patients with CPS1 variants. A. P1 has three heterozygous variants of c.1927 A > G (p.Asn643Asp), c.2375 T > G (p.Met792Arg) and c.3443 T > A (p.Met1148Lys). B. P2 has two heterozygous variants of c.3784C > T (p.Arg1262Ter), c.3734 T > A (p.Leu1245His). The red arrows refer corresponding variants.

Article Snippet: In this study, we presented the detailed laboratory features and genetic analysis of two patients with heterozygous variants of CPS1, c.1927 A > G (p.Asn643Asp), c.2375 T > G (p.Met792Arg), c.3443 T > A (p.Met1148Lys) in patient 1; c.3784C > T (p.Arg1262Ter), c.3734 T > A (p.Leu1245His) in patient 2, respectively. c.1927 A > G (p.Asn643Asp) and c.2375 T > G (p.Met792Arg) are novel out of 5 variants and classified as variants of uncertain significance (VUS) under the guidelines of ACMG/AMP-ClinGen.

Techniques: Sequencing

Journal: Molecular Genetics and Metabolism Reports

Article Title: Identification of novel variants in carbamoyl phosphate synthetase 1 gene and comparative pathogenicity assessments of CPS1 missense variants following ACMG/AMP-ClinGen recommendation for computational tools

doi: 10.1016/j.ymgmr.2025.101208

Figure Lengend Snippet: Free energy changes of CPS1 missense variants.

Article Snippet: In this study, we presented the detailed laboratory features and genetic analysis of two patients with heterozygous variants of CPS1, c.1927 A > G (p.Asn643Asp), c.2375 T > G (p.Met792Arg), c.3443 T > A (p.Met1148Lys) in patient 1; c.3784C > T (p.Arg1262Ter), c.3734 T > A (p.Leu1245His) in patient 2, respectively. c.1927 A > G (p.Asn643Asp) and c.2375 T > G (p.Met792Arg) are novel out of 5 variants and classified as variants of uncertain significance (VUS) under the guidelines of ACMG/AMP-ClinGen.

Techniques:

Journal: Molecular Genetics and Metabolism Reports

Article Title: Identification of novel variants in carbamoyl phosphate synthetase 1 gene and comparative pathogenicity assessments of CPS1 missense variants following ACMG/AMP-ClinGen recommendation for computational tools

doi: 10.1016/j.ymgmr.2025.101208

Figure Lengend Snippet: Flexibility changes of CPS1 missense variants.

Article Snippet: In this study, we presented the detailed laboratory features and genetic analysis of two patients with heterozygous variants of CPS1, c.1927 A > G (p.Asn643Asp), c.2375 T > G (p.Met792Arg), c.3443 T > A (p.Met1148Lys) in patient 1; c.3784C > T (p.Arg1262Ter), c.3734 T > A (p.Leu1245His) in patient 2, respectively. c.1927 A > G (p.Asn643Asp) and c.2375 T > G (p.Met792Arg) are novel out of 5 variants and classified as variants of uncertain significance (VUS) under the guidelines of ACMG/AMP-ClinGen.

Techniques:

Journal: Molecular Genetics and Metabolism Reports

Article Title: Identification of novel variants in carbamoyl phosphate synthetase 1 gene and comparative pathogenicity assessments of CPS1 missense variants following ACMG/AMP-ClinGen recommendation for computational tools

doi: 10.1016/j.ymgmr.2025.101208

Figure Lengend Snippet: Genotypic features and in silico investigations of CPS1 missense variants and Comparative evaluation of pathogenicity interpretation of CPS1 variants before and after PP3/BP4 criteria updating.

Article Snippet: In this study, we presented the detailed laboratory features and genetic analysis of two patients with heterozygous variants of CPS1, c.1927 A > G (p.Asn643Asp), c.2375 T > G (p.Met792Arg), c.3443 T > A (p.Met1148Lys) in patient 1; c.3784C > T (p.Arg1262Ter), c.3734 T > A (p.Leu1245His) in patient 2, respectively. c.1927 A > G (p.Asn643Asp) and c.2375 T > G (p.Met792Arg) are novel out of 5 variants and classified as variants of uncertain significance (VUS) under the guidelines of ACMG/AMP-ClinGen.

Techniques: In Silico, Variant Assay

Journal: Molecular Genetics and Metabolism Reports

Article Title: Identification of novel variants in carbamoyl phosphate synthetase 1 gene and comparative pathogenicity assessments of CPS1 missense variants following ACMG/AMP-ClinGen recommendation for computational tools

doi: 10.1016/j.ymgmr.2025.101208

Figure Lengend Snippet: Pathogenicity interpretation of CPS1 variants.

Article Snippet: In this study, we presented the detailed laboratory features and genetic analysis of two patients with heterozygous variants of CPS1, c.1927 A > G (p.Asn643Asp), c.2375 T > G (p.Met792Arg), c.3443 T > A (p.Met1148Lys) in patient 1; c.3784C > T (p.Arg1262Ter), c.3734 T > A (p.Leu1245His) in patient 2, respectively. c.1927 A > G (p.Asn643Asp) and c.2375 T > G (p.Met792Arg) are novel out of 5 variants and classified as variants of uncertain significance (VUS) under the guidelines of ACMG/AMP-ClinGen.

Techniques: Variant Assay

Journal: Molecular Genetics and Metabolism Reports

Article Title: Identification of novel variants in carbamoyl phosphate synthetase 1 gene and comparative pathogenicity assessments of CPS1 missense variants following ACMG/AMP-ClinGen recommendation for computational tools

doi: 10.1016/j.ymgmr.2025.101208

Figure Lengend Snippet: Distribution and flow changes of CPS1 pathogenicity classification in ClinVar. A. Left: 95.12 % (312 variants) are classified as VUS, 4.57 % (15 variants) are classified as LP and 0.3 % (1 variant) are classified as B in ClinVar Database before PP3 criterion application; Right: 89.63 % (294 variants) are classified as VUS, 9.45 % (31 variants) are classified as LP and 0.61 % (2 variants) are classified as P and 0.3 % (1 variant) are classified as B in ClinVar Database after PP3 criterion application. B. Reported variants group; Left: 67.57 % (25 variants) are classified as VUS and 32.43 % (12 variants) are classified as LP before PP3 criterion application; Right: 18.92 % (7 variants) are classified as VUS, 75.68 % (28 variants) are classified as LP and 5.41 % (2 variants) are classified as P after PP3 criterion application. C. Unreported variants group; Left: 98.63 % (287 variants) are classified as VUS, 1.03 % (3 variants) are classified as LP and 0.34 % (1 variants) are classified as B before PP3 criterion application; Right: 98.63 % (287 variants) are classified as VUS, 1.03 % (3 variants) are classified as LP and 0.34 % (1 variants) are classified as B after PP3 criterion application.

Article Snippet: In this study, we presented the detailed laboratory features and genetic analysis of two patients with heterozygous variants of CPS1, c.1927 A > G (p.Asn643Asp), c.2375 T > G (p.Met792Arg), c.3443 T > A (p.Met1148Lys) in patient 1; c.3784C > T (p.Arg1262Ter), c.3734 T > A (p.Leu1245His) in patient 2, respectively. c.1927 A > G (p.Asn643Asp) and c.2375 T > G (p.Met792Arg) are novel out of 5 variants and classified as variants of uncertain significance (VUS) under the guidelines of ACMG/AMP-ClinGen.

Techniques: Variant Assay