Ask about this productRelated genes to: PCCB antibody
- Gene:
- PCCB NIH gene
- Name:
- propionyl-CoA carboxylase subunit beta
- Previous symbol:
- -
- Synonyms:
- -
- Chromosome:
- 3q22.3
- Locus Type:
- gene with protein product
- Date approved:
- 1986-01-01
- Date modifiied:
- 2018-04-23
Related products to: PCCB antibody
Related articles to: PCCB antibody
- Propionic acidemia (PA) is an inborn error of metabolism caused by propionyl-CoA carboxylase (PCC) deficiency due to mutations in either or . Without proper management, the disease is associated with high mortality. Even with dietary restriction, patients often develop complications later in life, and the underlying pathological mechanisms remain poorly understood. The liver is the primary organ responsible for propionyl-CoA metabolism, yet the metabolic alterations induced by PCC deficiency in the liver have not been systematically investigated. In this study, we used a hepatocyte model of PA- HepG2 cells-to comprehensively examine metabolic alterations using stable isotope-based metabolic flux analysis. The knockout recapitulated key metabolic features of PA in HepG2 cells. Furthermore, deficiency reduced mitochondrial fatty acid oxidation while increasing glucose oxidation through pyruvate dehydrogenase. In contrast, pyruvate anaplerosis via pyruvate carboxylase was markedly reduced in knockout cells. This reduction in anaplerotic flux impaired the capacity for gluconeogenesis and lipid synthesis, consistent with observations from studies in / (A138T) mice. Additionally, branched-chain keto acid catabolism was reduced in knockout HepG2 cells. Threonine showed minimal metabolic contribution in this model, further supporting the role of propionate as a major source of propionyl-CoA production. Collectively, these findings highlight the metabolic vulnerabilities associated with PCC deficiency and underscore the increased risk of prolonged fasting in patients with PA, particularly those with severe disease. - Source: PubMed
Publication date: 2026/04/15
Lu FangPaiboonrungruang ChorladaHe WentaoXiong ZhaohuiTang PingchuanKasumov TakharChen XiaoxinZhang Guo-Fang - Propionic acidemia is a rare autosomal recessive disorder caused by mutations in the or gene, resulting in deficient propionyl-CoA carboxylase activity. We identified a unique homozygous deep-intronic variant, NM_000282.4:c.1285-1358C>G, in an individual with neonate-onset propionic acidemia. Fibroblasts from this individual expressed only mRNA containing an 84-bp pseudoexon, which is present at low levels in healthy controls, leading to the loss of PCCA and PCCB proteins and severely reduced propionyl-CoA carboxylase activity. Transfection of fibroblasts with chemically synthesized antisense oligonucleotides (ASOs) designed to skip the pseudoexon restored productive splicing, rescued PCCA protein expression, and markedly increased propionyl-CoA carboxylase activity above wild-type levels. The efficacy of the ASOs was further evaluated in fibroblasts from 7 additional individuals with propionic acidemia carrying mutations in or . ASO treatment successfully restored enzymatic activity, particularly in fibroblast lines, with residual activity exceeding 1% of normal. These findings suggest that ASO-mediated splicing correction targeting the 84-bp pseudoexon can restore mRNA, protein, and enzymatic function in individuals with deep intronic mutations, as well as in other individuals with propionic acidemia, indicating the feasibility of ASO therapy as a molecular treatment strategy for a subset of individuals with propionic acidemia. - Source: PubMed
Publication date: 2026/04/02
Totsune ErikoWada YoichiMikami-Saito YasukoArai-Ichinoi NatsukoSaijo NaoyaTakayama JunMaeda YasuhiroNakajima YokoOhara OsamuKure ShigeoKikuchi Atsuo - Propionic acidemia (PA) is conditioned by a deficiency of propionyl-CoA carboxylase, whose subunits are coded by the and genes. In the Mexican population, little is known about the clinical presentation of PA and the underlying genotypic and spectrum. PA is not currently assessed in the mandatory Mexican newborn screening (NBS) program. We aimed to characterize the clinical and genotypic spectrum in 51 Mexican patients with PA seen at a national reference center in Mexico. Most of the patients (92.1%) showed an early symptom onset (mean 21 days of life), delayed diagnosis (mean 5.1 months of life), considerable diagnostic odyssey (mean 4.4 months), and a high early mortality rate (66.7%). Feeding difficulties, hyperammonemia, and metabolic acidosis predominated as early PA signs occurring within the first month of life. At the last follow-up, 60% ( = 18/30) of patients exhibited profound intellectual and motor impairment. Next-generation sequencing revealed that 46.66% ( = 14/30) of cases were -related and 53.3% ( = 16/30) were -related. We identified four clinically relevant novel variants in [c.-10_105 + 11del, p.(Gly226Arg), c.1643 + 3 A > G, p.(Ser245*)] and one in [p.(Met463Arg)]. Protein in silico modeling of the p.(Gly226Arg) and p.(Met463Arg) variants predicted structural disturbances supporting their pathogenicity. The c.2041-1G > T [rs1367867218] and c.1309G > A or p.(Gly437Ser) [rs1349202366] variants were the most frequent pathogenic ones in ( = 5/28 alleles, 17.9%) and ( = 7/32 alleles, 21.9%), respectively. Predominance of neonatal onset, severe neurological sequelae, and high mortality rate emphasize that PA should be considered for inclusion in the Mexican NBS program. Until PA screening is routinely performed at birth in Mexico, efforts are needed to increase pediatricians' awareness of the clinical picture, to support early detection and prompt management. - Source: PubMed
Publication date: 2026/04/15
Vela-Amieva MAlcántara-Ortigoza M AGuillén-López SLópez-Mejía LGonzález-Del Ángel AReyna-Fabián MFernández-Hernández LLópez-Velázquez GabrielMancera-Hernández DEnríquez-Flores SIbarra-González IFernández-Lainez C - Relapse remains the leading cause of treatment failure in pediatric and young adult patients with relapsed/refractory B-cell acute lymphoblastic leukemia (r/r B-ALL) undergoing chimeric antigen receptor T-cell (CAR-T) therapy. While prognostic factors for relapse have been identified, further refinement is needed. We conducted a single-center retrospective study of 69 patients treated with Tisagenlecleucel, to evaluate the prognostic impact of TP53 alterations (TP53), including mutations and/or deletions. Among 49 patients with available samples, 17 (34.7%) had TP53. These patients showed significantly lower remission rates (68.8% vs. 93.8%, p = 0.033) and worse event-free survival (EFS) and overall survival (OS), independent of genetic risk group. Median EFS was 3.8 months (95% CI: 1.2-NE) for TP53 versus 50.9 months (95% CI: 23.9-NE) for TP53 wild-type (TP53). Three-year EFS and OS were 33.1% (95% CI: 16.4%-66.6%) and 37.2% (95% CI: 19.4%-71.4%) for TP53, compared to 56.2% and 81.2% for TP53 (p = 0.0069 and p = 0.0010, respectively). These findings identify TP53 alterations as a strong adverse prognostic factor in patients with r/r B-ALL treated with CAR-T therapy. Screening for TP53 may guide risk-adapted strategies, including early consolidation with hematopoietic stem cell transplantation or alternative therapies. - Source: PubMed
Publication date: 2026/04/04
Alonso-Saladrigues AnnaEsperanza-Cebollada ElenaVicente-Garcés ClaraPerez-Jaume SaraSánchez-Sierra NazaretRicharte-Franqués MercèCatalà AlbertCrespo-Carrasco AlbaDapena José-LuisCuatrecasas Capdevila EstherFaura Morros AnnaRuiz-Cobo Maria AArqués LauraConde Cuevas NuriaAndreu SandraIsola IgnacioJordan IolandaGarcía-Rey EnricLlanos CristinaMarsal JúliaCelis VerónicaCamós MireiaTorrebadell MontserratVega-García NereaRives Susana - Aneuploidy is a hallmark of cancer but often reduces cellular fitness. In childhood B cell acute lymphoblastic leukemia (cB-ALL), hyperdiploidy is the most common cytogenetic abnormality and arises in utero from early hematopoietic stem/progenitor cells (HSPCs), yet its impact on early hematopoiesis remains unclear. We model two proposed routes to hyperdiploidy, chromosome mis-segregation and cytokinesis failure, by transiently exposing human fetal liver-derived HSPCs to reversine or cytochalasin D. Induced hyperdiploidy impaired fitness and delayed differentiation in vitro, causing hyperdiploid cells to be rapidly outcompeted by euploid counterparts. Nonetheless, hyperdiploid cells engrafted immunodeficient mice, where rare clones persisted long term and acquired non-random chromosomal gains frequently observed in cB-ALL. Despite this persistence, they did not initiate leukemia. These findings support a two-step model in which hyperdiploid fetal clones require additional perinatal/postnatal events for malignant transformation. Our work establishes a valuable human model for studying early aneuploidy-driven events in childhood leukemia. - Source: PubMed
Publication date: 2026/03/27
Thampi NamithaCalvo CristinaRodríguez-Cortez VirginiaMartínez-Moreno AlbaRoca-Ho HeleiaVinyoles MeritxellBueno ClaraEspinosa-Aroca LadyPablo-Fontecha VerónicaCamps Jordide la Fuente-González AnaPuente Xose SSolé FrancescFoijer FlorisMenéndez PabloMolina Oscar