Ask about this productRelated genes to: SLC37A4 antibody
- Gene:
- SLC37A4 NIH gene
- Name:
- solute carrier family 37 member 4
- Previous symbol:
- G6PT1, G6PT2, G6PT3
- Synonyms:
- GSD1b, GSD1c, GSD1d
- Chromosome:
- 11q23.3
- Locus Type:
- gene with protein product
- Date approved:
- 1998-07-15
- Date modifiied:
- 2019-04-23
Related products to: SLC37A4 antibody
Related articles to: SLC37A4 antibody
- Inborn errors of metabolism (IEM) are frequently underdiagnosed in low-resource settings due to limited diagnostic infrastructure. We hypothesized that an integrated clinical-genomic approach could improve diagnosis and management of these conditions. Nineteen Pakistani families with clinically suspected IEM underwent systematic clinical assessment, available biochemical testing, and whole-exome sequencing (WES). Variants were classified according to ACMG/AMP guidelines using evidence from population databases, in silico prediction tools, segregation analysis, and genotype-phenotype correlation. Clinical diagnoses and management strategies were reassessed based on molecular findings. WES provided a molecular diagnosis in 90% (17/19) of families and enabled targeted therapeutic interventions in 70% (13/19). However, clinical outcomes were variable due to advanced disease in some cases and limited follow-up. Seven novel variants were identified in CYP27B1, DYM, MTTP, ALDH3A2, USP53, BRAF, and JAG1, while twelve recurrent mutations were detected in PIGN, GCDH, CLCN7, RNASEH2C, ABCB11, MPV17, IDUA, SMPD1, FBP1, SLC37A4, ACADM, and UGT1A1. Integrating genomic findings with clinical reassessment improved diagnostic precision. An integrated clinical-genomic approach enabled accurate diagnosis of pediatric IEM in resource-limited settings, with particular utility in children with metabolic disorders in a consanguineous population. Identification of both novel and recurrent variants expanded the genotypic and phenotypic spectrum of these disorders and highlighted the clinical utility of genomic diagnostics in optimizing patient care. - Source: PubMed
Publication date: 2026/04/13
Mansoor SumreenaAbid SabeenImran MuhammadMalik Munir IqbalAli QamarHussain ShanawazAli Hafiz AsimMasood YasserChoudhry ShehlaQamar RaheelAzam Maleeha - The human glucose-6-phosphate transporter (G6PT/SLC37A4) mediates the translocation of glucose-6-phosphate (G6P) from the cytoplasm into the endoplasmic reticulum, a process essential for glucose production and the maintenance of blood glucose homeostasis between meals. Dysfunction of G6PT causes glycogen storage disease type Ib (GSD-Ib), a severe metabolic disorder characterized by hypoglycemia, hepatomegaly, and neutropenia. Despite its physiological and clinical significance, the structural basis of G6P recognition and the molecular mechanisms underlying GSD-Ib have remained elusive. Here, we present cryo-electron microscopy structures of human G6PT, revealing a monomer in an outward-open state at 3.1 Å and a homodimeric assembly in a face-to-face topology at 3.3 Å. By combining computational modeling of the G6P-G6PT complexes with functional characterization, we have uncovered the key molecular elements that govern the alternating-access mechanism: an electropositive substrate-binding pocket tailored for phosphorylated sugars; conserved aromatic residues that seal the cytosolic gate; and a dynamic inter-domain salt bridge that regulates the conformational transition. Our work provides fundamental insights into the transport cycle of the organophosphate:phosphate antiporter (OPA) family, offers a framework for interpreting GSD-Ib pathology at the molecular level, and establishes a foundation for advancing the mechanistic understanding of the human SLC37 family. - Source: PubMed
Publication date: 2026/03/30
Zhang WanqinJiao HaizhanXue JingchuanZhou JiaoWang YuyePan QiGuo YutingZhang GeshuHu HongliGuo Xue - Glycogen storage diseases (GSDs) are a group of inherited disorders caused by enzyme or transport protein defects that affect glycogen metabolism, leading to glycogen accumulation in tissues and overlapping clinical symptoms. This study aimed to identify pathogenic genetic variants in Iranian patients suspected of having GSDs and to characterize novel variants. Whole-exome sequencing was performed on 20 patients from consanguineous families, revealing 12 known and three novel pathogenic variants. Novel variants included a homozygous frameshift variant in SLC37A4 in a GSD-Ib patient, a homozygous frameshift variant in GAA in a GSD-II patient, and a homozygous nonsense variant in PHKG2 in a GSD-IXc patient. In silico analyses and structural modelling suggested these variants disrupt protein function, with two variants triggering nonsense-mediated decay and one causing protein truncation. These findings expand the genetic spectrum of GSDs in the Iranian population and highlight the importance of early molecular diagnosis and genetic counselling, especially in consanguineous communities, to improve patient management and prognosis. - Source: PubMed
Publication date: 2026/01/29
Alian FatemehStraub VolkerTöpf AnaSeyedarabi ArefehHashemipour MahinInanlooRahatloo KolsoumSalehi MansoorRostampour Noushin - Glycogen Storage Disease (GSD) Types Ia and Ib are rare metabolic diseases caused by gene variants in and respectively. Although life-threatening fasting hypoglycemia can be controlled by a strict diet, patients often suffer from multiple metabolic abnormalities and severe long-term complications. However, the underlying mechanisms remain incompletely understood, and there is a lack of effective monitoring biomarkers. Therefore, the aims of this study are to investigate the pathological mechanisms of the disease and disease complications in GSD I and identify potential protein biomarkers. - Source: PubMed
Publication date: 2026/02/20
Xiao RuiqiGross-Valle CandelasGerding AlbertThorne Adam MOosterveer Maaike HDerks Terry G Jde Meijer Vincent EHeiner-Fokkema M RebeccaBakker Barbara MWolters Justina C - Human glucose-6-phosphate transporter 1 (G6PT1) is responsible for transporting glucose-6-phosphate (G6P) into the endoplasmic reticulum (ER), a crucial rate-limiting step in both glycogenolysis and gluconeogenesis. Complete and chronic dysfunction of G6PT1 can lead to the severe metabolic disorder GSD1b, whereas moderate and reversible inhibition contributes to diabetes treatment. We determined the structures of human G6PT1 in its apo state and in complex with the substrate G6P, cosubstrate phosphate, and the inhibitor chlorogenic acid (CGA). Captured in both lumen- and cytosol-facing conformations, these structures reveal the specific mechanism of phosphate-coupled G6P transport. In addition, the CGA-bound G6PT1 complex shows that CGA stabilizes the transporter in the cytosol-facing conformation, inhibiting it by competing with substrate binding and preventing conformational transitions, providing previously unreported insights into G6PT1 inhibition. Our findings provide a structural foundation for understanding the mechanisms of substrate recognition, transport, drug inhibition, and the pharmacology of G6PT1, paving the way to the rational design of potential therapeutic agents. - Source: PubMed
Publication date: 2026/01/30
Chen QihaoYuan PuLi RenjieDu XiaoyueYu RileiZhao Yan