Affinage

GGCT

Gamma-glutamylcyclotransferase · UniProt O75223

Length
188 aa
Mass
21.0 kDa
Annotated
2026-04-28
100 papers in source corpus 16 papers cited in narrative 16 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

GGCT is a homodimeric gamma-glutamyl cyclotransferase that catalyzes the conversion of gamma-glutamyl dipeptides to 5-oxoproline (pyroglutamic acid) and free amino acids via a Glu98-dependent acid/base mechanism, thereby participating in glutathione homeostasis and cellular redox regulation (PMID:18515354, PMID:34409610). In mice, GGCT is dispensable for normal development but essential for red blood cell antioxidant defense and lifespan, as Ggct deletion causes progressive anemia with elevated ROS and depleted GSH/cysteine in erythrocytes (PMID:34409610); GGCT also functions as a critical downstream effector of oncogenic Ras, sustaining transformed cell proliferation by buffering ROS through the GSH pathway (PMID:31400748). Transcriptionally activated by NF-Y (via CCAAT box elements) and directly by Myc (promoter binding), GGCT promotes cancer cell proliferation, EMT-driven invasion, and ferroptosis resistance through interactions with MRPL9 and stabilization of RPS15A, which suppresses p53 and maintains SLC7A11-dependent GSH synthesis (PMID:21883928, PMID:38924236, PMID:36233293, PMID:40044122). Its enzymatic product pyroglutamic acid can additionally drive protein aggregation in drug-resistant glioblastoma, linking GGCT catalytic output to proteostatic stress (PMID:39949960).

Mechanistic history

Synthesis pass · year-by-year structured walk · 10 steps
  1. 2007 Medium

    Before any mechanistic characterization, GGCT (C7orf24) was shown to promote cancer cell proliferation—establishing it as a functionally relevant gene in tumor biology but without any known enzymatic activity or pathway placement.

    Evidence siRNA knockdown in bladder cancer cells and stable overexpression in NIH3T3 with proliferation readouts

    PMID:21136669

    Open questions at the time
    • No enzymatic activity known
    • Mechanism of proliferative effect unknown
    • No in vivo validation
  2. 2008 High

    The molecular identity of GGCT was established: it is a gamma-glutamyl cyclotransferase with a novel homodimeric fold, and Glu98 was identified as the catalytic residue essential for its acid/base mechanism—providing the first biochemical framework for this protein.

    Evidence Recombinant enzyme assay, X-ray crystallography at 1.7 Å, and E98A/E98Q site-directed mutagenesis

    PMID:18515354

    Open questions at the time
    • Physiological substrates in vivo not defined
    • No connection to GSH metabolism yet established
    • No structural basis for inhibitor design
  3. 2011 High

    Transcriptional regulation of GGCT was elucidated: NF-Y drives basal transcription through CCAAT boxes in the TATA-less promoter, and GGCT expression oscillates during the cell cycle, linking its expression to proliferative programs.

    Evidence Luciferase reporters with deletion/mutation constructs, EMSA, ChIP for NF-Y, siRNA knockdown of NF-YB

    PMID:21883928

    Open questions at the time
    • Whether cell-cycle oscillation is functionally required unknown
    • Other transcription factors not yet identified
    • Post-translational regulation unexplored
  4. 2016 Medium

    GGCT's pro-proliferative role was extended to gastric cancer, where knockdown caused G2/M arrest and apoptosis, and N-glutaryl-L-alanine was identified as a potent active-site inhibitor, providing a pharmacological tool.

    Evidence shRNA knockdown with cell cycle/apoptosis flow cytometry; in vitro enzyme inhibition assay with recombinant GGCT

    PMID:27373633 PMID:27905872

    Open questions at the time
    • Whether enzymatic activity is required for proliferative effects unknown
    • No in vivo inhibitor testing
    • Mechanism connecting enzymatic product to cell cycle not defined
  5. 2019 High

    GGCT was placed as a downstream effector of oncogenic Ras, required for Ras-driven transformation and lung tumorigenesis in vivo, while being dispensable for normal development—establishing a specific oncogenic context for GGCT function through GSH-ROS regulation.

    Evidence LSL-KrasG12D mouse model, Ggct knockout mice, siRNA, proliferation/transformation assays, ROS/GSH measurements

    PMID:31400748

    Open questions at the time
    • How Ras signaling upregulates GGCT not defined
    • Whether GGCT is required for other oncogene-driven cancers unknown
    • Tissue-specific requirements not mapped
  6. 2020 Medium

    GGCT was connected to the EMT program: knockdown in colorectal cancer cells reduced N-cadherin, Vimentin, and Snail expression and suppressed migration/invasion, identifying a downstream pathway by which GGCT promotes metastatic behavior.

    Evidence GGCT knockdown with Western blot and qRT-PCR for EMT markers, Transwell migration/invasion assays

    PMID:32724344

    Open questions at the time
    • Whether EMT regulation is direct or secondary to metabolic changes unknown
    • No in vivo metastasis model
    • Upstream signals connecting GGCT to EMT transcription factors not identified
  7. 2021 High

    A physiological role for GGCT was established in vivo: Ggct-null mice develop splenomegaly and progressive anemia due to elevated ROS, decreased GSH and cysteine in RBCs, and shortened erythrocyte lifespan—demonstrating that GGCT is essential for red cell redox homeostasis.

    Evidence Ggct knockout mouse, RBC lifespan assay, ROS measurement, GSH/cysteine quantification, H2O2 sensitivity assay

    PMID:34409610

    Open questions at the time
    • Mechanism by which GGCT maintains cysteine supply not fully resolved
    • Whether other hematopoietic lineages are affected unknown
    • Compensatory pathways (e.g., 5-oxoprolinase) not characterized
  8. 2022 Medium

    Direct protein-protein interactions of GGCT were identified in thyroid cancer: GGCT binds and stabilizes CD44 and separately interacts with MRPL9 to activate MAPK/ERK signaling, connecting GGCT to non-enzymatic signaling functions.

    Evidence Co-immunoprecipitation, immunofluorescence co-localization, shRNA knockdown with MAPK/ERK readout, xenograft models

    PMID:35213720 PMID:36233293

    Open questions at the time
    • Whether GGCT enzymatic activity is needed for these protein interactions unknown
    • Reciprocal validation of CD44 interaction limited
    • How MRPL9 interaction activates ERK mechanistically unclear
  9. 2024 Medium

    Three advances converged: Myc was identified as a direct transcriptional activator of GGCT (promoter binding confirmed by ChIP); GGCT was shown to stabilize RPS15A, suppressing p53 and maintaining SLC7A11-dependent GSH synthesis to inhibit ferroptosis; and a GGCT/REST/miR-34a-5p positive feedback loop was discovered in glioma—placing GGCT at the intersection of oncogenic transcription, ferroptosis resistance, and feedback-controlled self-amplification.

    Evidence ChIP and CRISPR deletion of Myc binding site with tumorigenesis assay; Co-IP + LC-MS/MS for RPS15A with p53/SLC7A11/ferroptosis readouts; RNA-seq and dual-luciferase reporter for REST/miR-34a-5p loop with rescue experiments

    PMID:38924236 PMID:39128259 PMID:40044122

    Open questions at the time
    • Whether Myc-driven GGCT transcription is context-dependent beyond osteosarcoma unknown
    • RPS15A stabilization mechanism (direct binding vs. indirect) not fully resolved
    • REST feedback loop not validated outside glioma
  10. 2025 Medium

    A novel non-canonical function was uncovered: GGCT-derived pyroglutamic acid directly binds aggregating proteins and drives protein aggregation in drug-resistant glioblastoma, linking GGCT catalytic output to proteostatic collapse rather than solely to GSH metabolism.

    Evidence Genetic and pharmacological GGCT inhibition (Pro-GA), protein aggregation assays, oxidative stress measurement, patient tumor immunostaining

    PMID:39949960

    Open questions at the time
    • Structural basis for pyroglutamic acid–protein interaction not determined
    • Whether this aggregation mechanism operates in non-glioblastoma contexts unknown
    • Single lab finding not yet independently confirmed

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include whether GGCT's enzymatic activity versus its protein-protein interactions are independently required for its oncogenic functions, the structural basis of its non-enzymatic partner interactions, and how GGCT coordinates GSH homeostasis with ferroptosis resistance across different tissue contexts.
  • Separation-of-function mutants (enzymatic vs. scaffolding) have not been generated
  • No structural model for GGCT-MRPL9 or GGCT-RPS15A complexes
  • In vivo relevance of pyroglutamic acid-driven aggregation beyond glioblastoma untested

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016787 hydrolase activity 2 GO:0140096 catalytic activity, acting on a protein 2
Localization
GO:0005829 cytosol 2
Pathway
R-HSA-1430728 Metabolism 3 R-HSA-162582 Signal Transduction 2 R-HSA-1640170 Cell Cycle 2 R-HSA-5357801 Programmed Cell Death 2
Partners
CD44MRPL9NFYBRPS15A

Evidence

Reading pass · 16 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2008 C7orf24 (GGCT) was identified as gamma-glutamyl cyclotransferase, catalyzing the formation of 5-oxoproline (pyroglutamic acid) from gamma-glutamyl dipeptides. Crystal structure at 1.7 Å resolution revealed a homodimeric enzyme with a novel fold ('BtrG-like'). Active-site mutagenesis showed that Glu98 acts as a general acid/base in the catalytic mechanism; E98A and E98Q mutations completely inactivate the enzyme without altering the overall fold. Enzyme activity assay (recombinant protein), X-ray crystallography (1.7 Å), site-directed mutagenesis (E98A, E98Q) The Journal of biological chemistry High 18515354
2019 GGCT was identified as a downstream effector of oncogenic Ras. GGCT is required for oncogenic Ras-induced primary mouse cell proliferation and transformation, and for in vivo lung cancer formation in the LSL-KrasG12D mouse model. GGCT deficiency is compatible with normal mouse development. GGCT regulates a glutathione (GSH)-reactive oxygen species (ROS) metabolic pathway that alleviates oncogenic stress. LSL-KrasG12D mouse model (genetic), siRNA knockdown, cell proliferation/transformation assays, in vivo lung cancer model iScience High 31400748
2021 Ggct deletion in mice leads to splenomegaly and progressive anaemia due to elevated oxidative damage and shortened red blood cell (RBC) lifespan. Ggct-/- RBCs show increased ROS and are more sensitive to H2O2-induced damage. GSH and its precursor L-cysteine are decreased in Ggct-/- RBCs, establishing a critical role for Ggct in RBC redox balance and lifespan maintenance through regulation of GSH metabolism. Ggct knockout mouse model, RBC lifespan assay, ROS measurement, GSH/cysteine quantification, H2O2 sensitivity assay British journal of haematology High 34409610
2007 C7orf24 (GGCT) protein expression promotes cancer cell proliferation. Knockdown by siRNA significantly inhibited proliferation of bladder cancer cell lines, and stable overexpression in NIH3T3 cells increased growth rate, establishing a role for GGCT in cell proliferation. siRNA knockdown (MTT assay), stable retroviral overexpression (growth rate assay) Proteomics. Clinical applications Medium 21136669
2011 NF-Y transcription factor binds to three proximal CCAAT boxes in the TATA-less C7orf24 (GGCT) promoter to drive basal transcription. NF-YB depletion significantly reduces C7orf24 mRNA and protein. C7orf24 expression oscillates during the cell cycle, consistent with NF-Y-mediated cell-cycle-coupled transcription. Luciferase reporter assay (5'-deleted and site-directed mutant constructs), EMSA, ChIP assay, siRNA knockdown of NF-YB The FEBS journal High 21883928
2011 GGCT (C7orf24) knockdown by siRNA in osteosarcoma cell lines inhibited cell growth, enhanced cell clustering, inhibited cell motility and invasion. Gene ontology analysis of expression changes implicated cell adhesion and protein transport pathways downstream of GGCT. siRNA knockdown, proliferation assay, motility/invasion assay, genome-wide gene expression profiling Anticancer research Medium 21508379
2016 GGCT knockdown in gastric cancer cells (MGC80-3 and AGS) inhibited cell proliferation, reduced colony formation, caused G2/M cell cycle arrest, and induced apoptosis, establishing a role for GGCT in gastric cancer cell cycle progression and survival. Lentiviral shRNA knockdown, MTT assay, colony formation assay, flow cytometry (cell cycle and apoptosis analysis) BMC biochemistry Medium 27905872
2020 GGCT promotes colorectal cancer cell migration and invasion through regulation of epithelial-mesenchymal transition (EMT), modulating EMT-associated genes including N-cadherin, Vimentin, Snail1, and Snail2. GGCT knockdown, migration/invasion assays, EMT marker expression (Western blot, qRT-PCR) Oncology letters Medium 32724344
2022 GGCT interacts with and stabilizes CD44 protein in papillary thyroid cancer (PTC) cells. miR-205-5p binds the 3'-UTR of GGCT mRNA (confirmed by dual-luciferase reporter and RNA pulldown) to suppress GGCT, thereby downregulating CD44. GGCT knockdown inhibited growth and metastasis in vitro and in vivo and reduced mesenchymal markers. Co-immunoprecipitation, dual-luciferase reporter assay, RNA-RNA pulldown, siRNA knockdown, xenograft mouse model Endocrinology Medium 35213720
2022 GGCT physically interacts with MRPL9 (mitochondrial ribosomal protein L9) in papillary thyroid cancer cells, as shown by immunofluorescence co-localization and co-immunoprecipitation. Knockdown of either GGCT or MRPL9 inhibits the MAPK/ERK signaling pathway, suppresses cell proliferation and migration in vitro, and inhibits xenograft tumor growth and lung metastasis in vivo. Immunofluorescence, co-immunoprecipitation, shRNA knockdown, MAPK/ERK pathway analysis, xenograft mouse model International journal of molecular sciences Medium 36233293
2024 GGCT promotes the protein stability of RPS15A in papillary thyroid cancer cells, as shown by co-immunoprecipitation followed by LC-MS/MS. RPS15A stabilization by GGCT suppresses p53 expression, which in turn maintains SLC7A11 expression, thereby sustaining GSH synthesis and inhibiting ferroptosis. GGCT knockdown promotes ferroptosis (increased MDA and ROS, decreased GSH). miR-205-5p targets the 3'-UTR of GGCT to suppress this pathway. Co-immunoprecipitation + LC-MS/MS, Western blot (p53, SLC7A11, RPS15A), ROS/MDA/GSH measurement, xenograft assay, miRNA 3'-UTR reporter Cancer science Medium 40044122
2025 GGCT-derived pyroglutamic acid (its enzymatic byproduct) can bind aggregating proteins and drive protein aggregation. Genetic and pharmacological inhibition of GGCT prevents protein aggregation in drug-resistant glioblastoma cells and reduces oxidative stress. GGCT expression is elevated upon drug resistance and is associated with increased mitochondrial function. Genetic GGCT knockdown, pharmacological GGCT inhibition (Pro-GA), protein aggregation assays, oxidative stress measurement, patient tumor immunostaining iScience Medium 39949960
2024 Myc directly upregulates Ggct transcription by binding to the Ggct promoter. Deletion of the Myc binding site in the Ggct promoter by genome editing attenuates the tumorigenic potential of p53-deficient osteosarcoma cells. Ggct deletion suppresses p53-deficient osteosarcomagenesis in mice. ChIP (Myc binding to Ggct promoter), genome editing (CRISPR deletion of Myc binding site), Ggct conditional knockout mouse model, tumorigenesis assay Cancer science High 38924236
2016 Eighteen N-acyl-L-alanine analogues were tested as GGCT inhibitors using recombinant human GGCT protein. N-glutaryl-L-alanine was identified as the most potent inhibitor, providing insight into the active-site substrate requirements of human GGCT. In vitro enzyme inhibition assay with recombinant human GGCT protein Chemical & pharmaceutical bulletin Medium 27373633
2009 C7orf24 (GGCT) mRNA is expressed in multiple rat tissues, with highest levels in liver (hepatocytes) and kidney (renal tubules), as determined by quantitative RT-PCR and in situ hybridization histochemistry, suggesting important metabolic roles in these organs. RT-PCR, quantitative RT-PCR, in situ hybridization histochemistry The journal of histochemistry and cytochemistry Low 19687470
2024 In glioma cells, GGCT downregulates REST expression, and REST in turn suppresses miR-34a-5p, which targets the 3'-UTR of GGCT to inhibit GGCT expression, forming a positive feedback loop (GGCT/REST/miR-34a-5p). REST overexpression rescued the inhibitory effects of GGCT knockdown on proliferation, invasion, and xenograft tumor formation. RNA-seq, RT-qPCR, Western blot, dual luciferase reporter assay, in vitro and in vivo rescue experiments (REST overexpression) Translational oncology Medium 39128259

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2019 Long-read sequencing identifies GGC repeat expansions in NOTCH2NLC associated with neuronal intranuclear inclusion disease. Nature genetics 394 31332381
1995 The CAG and GGC microsatellites of the androgen receptor gene are in linkage disequilibrium in men with prostate cancer. Cancer research 369 7728763
2020 Expansion of GGC repeat in the human-specific NOTCH2NLC gene is associated with essential tremor. Brain : a journal of neurology 162 31819945
2010 Variant CCG and GGC repeats within the CTG expansion dramatically modify mutational dynamics and likely contribute toward unusual symptoms in some myotonic dystrophy type 1 patients. Human molecular genetics 132 20080938
2021 Translation of GGC repeat expansions into a toxic polyglycine protein in NIID defines a novel class of human genetic disorders: The polyG diseases. Neuron 123 33887199
2020 Expansion of GGC Repeat in GIPC1 Is Associated with Oculopharyngodistal Myopathy. American journal of human genetics 116 32413282
2008 The identification and structural characterization of C7orf24 as gamma-glutamyl cyclotransferase. An essential enzyme in the gamma-glutamyl cycle. The Journal of biological chemistry 110 18515354
2021 The GGC repeat expansion in NOTCH2NLC is associated with oculopharyngodistal myopathy type 3. Brain : a journal of neurology 108 33693509
2005 Effect of GGC (glycine) repeat length polymorphism in the human androgen receptor on androgen action. The Prostate 87 15389799
2018 GGC Repeat Expansion and Exon 1 Methylation of XYLT1 Is a Common Pathogenic Variant in Baratela-Scott Syndrome. American journal of human genetics 81 30554721
2004 Androgen receptor gene CAG and GGC repeat lengths in idiopathic male infertility. Molecular human reproduction 79 15044606
2002 Absence of association between a polymorphic GGC repeat in the 5' untranslated region of the reelin gene and autism. Molecular psychiatry 73 12192627
1996 Solution structures of the individual single strands of the fragile X DNA triplets (GCC)n.(GGC)n. Nucleic acids research 70 8604324
2020 Identification of GGC repeat expansion in the NOTCH2NLC gene in amyotrophic lateral sclerosis. Neurology 68 32989102
2001 Extent of linkage disequilibrium between the androgen receptor gene CAG and GGC repeats in human populations: implications for prostate cancer risk. Human genetics 68 11702204
2001 CAG and GGC repeat polymorphisms in the androgen receptor gene and breast cancer susceptibility in BRCA1/2 carriers and non-carriers. British journal of cancer 66 11437399
2002 Polymorphic GGC repeats in the androgen receptor gene are associated with hereditary and sporadic prostate cancer risk. Human genetics 64 11935317
2021 Upstream open reading frame with NOTCH2NLC GGC expansion generates polyglycine aggregates and disrupts nucleocytoplasmic transport: implications for polyglycine diseases. Acta neuropathologica 58 34694469
1997 Specificity and kinetics of interstrand and intrastrand bifunctional alkylation by nitrogen mustards at a G-G-C sequence. Nucleic acids research 57 9092631
2010 Proteomic profiling of mammary carcinomas identifies C7orf24, a gamma-glutamyl cyclotransferase, as a potential cancer biomarker. Journal of proteome research 55 20527979
2003 Androgen receptor (CAG)n and (GGC)n polymorphisms and breast cancer risk in a population-based case-control study of young women. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 55 12582022
2019 The Precursor to Glutathione (GSH), γ-Glutamylcysteine (GGC), Can Ameliorate Oxidative Damage and Neuroinflammation Induced by Aβ40 Oligomers in Human Astrocytes. Frontiers in aging neuroscience 50 31440155
1993 Phylogenetic distribution and genetic mapping of a (GGC)n microsatellite from rice (Oryza sativa L.). Plant molecular biology 50 8448360
2007 A novel tumor-related protein, C7orf24, identified by proteome differential display of bladder urothelial carcinoma. Proteomics. Clinical applications 49 21136669
2005 Androgen receptor gene CAG and GGC repeat lengths in cryptorchidism. European journal of endocrinology 48 15757859
2021 The Phenotypes and Mechanisms of NOTCH2NLC-Related GGC Repeat Expansion Disorders: a Comprehensive Review. Molecular neurobiology 42 34718964
2024 Adaptive Long-Read Sequencing Reveals GGC Repeat Expansion in ZFHX3 Associated with Spinocerebellar Ataxia Type 4. Movement disorders : official journal of the Movement Disorder Society 39 38197134
2022 Expression of expanded GGC repeats within NOTCH2NLC causes behavioral deficits and neurodegeneration in a mouse model of neuronal intranuclear inclusion disease. Science advances 38 36417528
2009 Bases in the anticodon loop of tRNA(Ala)(GGC) prevent misreading. Nature structural & molecular biology 37 19305404
1996 In vitro expansion of GGC:GCC repeats: identification of the preferred strand of expansion. Nucleic acids research 35 8759019
2005 Androgen receptor CAG and GGC polymorphisms in Mediterraneans: repeat dynamics and population relationships. Journal of human genetics 34 16365681
2011 Involvement of cancer biomarker C7orf24 in the growth of human osteosarcoma. Anticancer research 30 21508379
2012 Prevention of tumor growth by needle-free jet injection of anti-C7orf24 siRNA. Cancer gene therapy 29 22653386
2022 GGC Repeat Expansion of RILPL1 is Associated with Oculopharyngodistal Myopathy. Annals of neurology 28 35700120
2024 A GGC-repeat expansion in ZFHX3 encoding polyglycine causes spinocerebellar ataxia type 4 and impairs autophagy. Nature genetics 27 38684900
2020 Low Prevalence of NOTCH2NLC GGC Repeat Expansion in White Patients with Movement Disorders. Movement disorders : official journal of the Movement Disorder Society 26 33026126
2013 Have androgen receptor gene CAG and GGC repeat polymorphisms an effect on sperm motility in infertile men? Andrologia 26 23725463
2003 Esophageal cancer risk in relation to GGC and CAG trinucleotide repeat lengths in the androgen receptor gene. International journal of cancer 26 12925954
2008 Polymorphic CAG and GGC repeat lengths in the androgen receptor gene and prostate cancer risk: analysis of a Brazilian population. Cancer investigation 25 18181049
2021 GGC Repeat Expansion in the NOTCH2NLC Gene Is Associated With a Phenotype of Predominant Motor-Sensory and Autonomic Neuropathy. Frontiers in genetics 24 34306035
2022 MiR-205-5p/GGCT Attenuates Growth and Metastasis of Papillary Thyroid Cancer by Regulating CD44. Endocrinology 23 35213720
2016 Knockdown of GGCT inhibits cell proliferation and induces late apoptosis in human gastric cancer. BMC biochemistry 23 27905872
2023 GGC repeat expansion in NOTCH2NLC induces dysfunction in ribosome biogenesis and translation. Brain : a journal of neurology 22 36825461
2006 Testosterone levels in relation to oral contraceptive use and the androgen receptor CAG and GGC length polymorphisms in healthy young women. Human reproduction (Oxford, England) 21 16920725
2022 Interaction of MRPL9 and GGCT Promotes Cell Proliferation and Migration by Activating the MAPK/ERK Pathway in Papillary Thyroid Cancer. International journal of molecular sciences 19 36233293
1990 Fibrinogen Baltimore I: polymerization defect associated with a gamma 292Gly----Val (GGC----GTC) mutation. Blood 19 2257302
2020 GGCT promotes colorectal cancer migration and invasion via epithelial-mesenchymal transition. Oncology letters 18 32724344
1999 Interaction of an alpha(+)-thalassemia deletion with either a highly unstable alpha-globin variant (alpha2, codon 59, GGC-->GAC) or a nondeletional alpha-thalassemia mutation (AATAAA-->AATAAG): comparison of phenotypes illustrating "dominant" alpha-thalassemia. Hemoglobin 18 10569721
2024 Spinocerebellar ataxia type 4 is caused by a GGC expansion in the ZFHX3 gene and is associated with prominent dysautonomia and motor neuron signs. Journal of internal medicine 16 38973251
2018 Structure and Dynamics of DNA and RNA Double Helices Obtained from the CCG and GGC Trinucleotide Repeats. The journal of physical chemistry. B 16 29617130
2019 Ras Downstream Effector GGCT Alleviates Oncogenic Stress. iScience 15 31400748
2005 GGC and StuI polymorphism on the androgen receptor gene in endometrial cancer patients. Biochemical and biophysical research communications 15 15721279
2003 Origin of Hb A2' (Hb B2) [delta16(A13)Gly --> Arg (GGC --> CGC)]. Hemoglobin 14 12779272
2024 Review of Phenotypic Heterogeneity of Neuronal Intranuclear Inclusion Disease and NOTCH2NLC-Related GGC Repeat Expansion Disorders. Neurology. Genetics 13 38586597
2022 NOTCH2NLC expanded GGC repeats in patients with cerebral small vessel disease. Stroke and vascular neurology 13 36207023
2023 NOTCH2NLC GGC repeat expansion causes retinal pathology with intranuclear inclusions throughout the retina and causes visual impairment. Acta neuropathologica communications 12 37131242
2021 Ggct (γ-glutamyl cyclotransferase) plays an important role in erythrocyte antioxidant defense and red blood cell survival. British journal of haematology 12 34409610
2021 Natural selection at the RASGEF1C (GGC) repeat in human and divergent genotypes in late-onset neurocognitive disorder. Scientific reports 12 34584172
2020 Novel Antioxidant Therapy with the Immediate Precursor to Glutathione, γ-Glutamylcysteine (GGC), Ameliorates LPS-Induced Cellular Stress in In Vitro 3D-Differentiated Airway Model from Primary Cystic Fibrosis Human Bronchial Cells. Antioxidants (Basel, Switzerland) 12 33266084
2016 Studies on human eRF3-PABP interaction reveal the influence of eRF3a N-terminal glycin repeat on eRF3-PABP binding affinity and the lower affinity of eRF3a 12-GGC allele involved in cancer susceptibility. RNA biology 12 26818177
2011 Multiple NF-Y-binding CCAAT boxes are essential for transcriptional regulation of the human C7orf24 gene, a novel tumor-associated gene. The FEBS journal 12 21883928
2012 Androgen receptor GGC polymorphism and testosterone levels associated with high risk of prostate cancer and benign prostatic hyperplasia. Molecular biology reports 11 23184046
2003 A missense mutation (GGC[435Gly]-->AGC[Ser]) in exon 8 of the CYP11B2 gene inherited in Japanese patients with congenital hypoaldosteronism. Hormone research 11 14614232
2024 Prevalence and Characterization of NOTCH2NLC GGC Repeat Expansions in Koreans: From a Hospital Cohort Analysis to a Population-Wide Study. Neurology. Genetics 10 38779172
2023 Expression of expanded GGC repeats within NOTCH2NLC causes cardiac dysfunction in mouse models. Cell & bioscience 10 37644522
2018 Association between androgen receptor polymorphic CAG and GGC repeat lengths and cryptorchidism: A meta-analysis of case-control studies. Journal of pediatric urology 10 29914823
2016 Synthesis and GGCT Inhibitory Activity of N-Glutaryl-L-alanine Analogues. Chemical & pharmaceutical bulletin 10 27373633
1987 Hybridization between a repeated region of herpes simplex virus type 1 DNA containing the sequence [GGC]n and heterodisperse cellular DNA and RNA. Virus research 10 2436393
2024 Neuronal Intranuclear Inclusion Disease with NOTCH2NLC GGC Repeat Expansion: A Systematic Review and Challenges of Phenotypic Characterization. Aging and disease 9 38377026
2010 A novel missense mutation, GGC(Arg454) --> TGC(Cys), of CYP11B1 gene identified in a Chinese family with steroid 11beta-hydroxylase deficiency. Chinese medical journal 9 20529578
2007 Association of tri-nucleotide (CAG and GGC) repeat polymorphism of androgen receptor gene in Taiwanese women with refractory or remission rheumatoid arthritis. Clinical rheumatology 9 17431729
1994 Hb Fannin-Lubbock in five Spanish families is characterized by two mutations: beta 111 GTC-->CTC (Val-->Leu) and beta 119 GGC-->GAC (Gly-->Asp). Hemoglobin 9 7852084
2023 NOTCH2NLC GGC Repeat Expansion in Patients With Vascular Leukoencephalopathy. Stroke 8 36942588
2017 A polymorphic GGC repeat in the NPAS2 gene and its association with melanoma. Experimental biology and medicine (Maywood, N.J.) 8 28799406
2002 Linkage disequilibrium between the androgen receptor gene CAG and GGC repeats in the African-American population. Current urology reports 8 12084187
2025 GGC repeat expansions in NOTCH2NLC cause uN2CpolyG cerebral amyloid angiopathy. Brain : a journal of neurology 7 39167540
2024 Genome-wide identification and analysis of the GGCT gene family in wheat. BMC genomics 7 38177998
2023 Intermediate-Length GGC Repeat Expansion in NOTCH2NLC Was Identified in Chinese Patients with Amyotrophic Lateral Sclerosis. Brain sciences 7 36672065
2020 No genetic evidence for the involvement of GGC repeat expansions of the NOTCH2NLC gene in Chinese patients with multiple system atrophy. Neurobiology of aging 7 32768149
2009 The mRNA distribution of C7orf24, a gamma-glutamyl cyclotransferase, in rat tissues. The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society 7 19687470
2025 Oxidative stress induced protein aggregation via GGCT produced pyroglutamic acid in drug resistant glioblastoma. iScience 6 39949960
2025 Polyglycine-mediated aggregation of FAM98B disrupts tRNA processing in GGC repeat disorders. Science (New York, N.Y.) 6 40674500
2024 NOTCH2NLC GGC intermediate repeat with serine induces hypermyelination and early Parkinson's disease-like phenotypes in mice. Molecular neurodegeneration 6 39609868
2023 GGC expansions in NOTCH2NLC contribute to Parkinson disease and dopaminergic neuron degeneration. European journal of neurology 6 37975799
2022 Patients with biallelic GGC repeat expansions in NOTCH2NLC exhibiting a typical neuronal intranuclear inclusion disease phenotype. Genomics 6 36041634
2006 Absence of association of a polymorphic GGC repeat at the 5' untranslated region of the reelin gene with schizophrenia. Psychiatry research 6 16556465
2001 Mutagenicity of a single 1-nitropyrene-DNA adduct N-(deoxyguanosin-8-yl)-1-aminopyrene in Escherichia coli located in a GGC sequence. Mutagenesis 6 11682635
2001 Modelling studies on neurodegenerative disease-causing triplet repeat sequences d(GGC/GCC)n and d(CAG/CTG)n. Journal of biosciences 6 11807295
2024 The GGCT and REST positive feedback loop promotes tumor growth in Glioma. Translational oncology 5 39128259
2022 GGC repeat expansions in NOTCH2NLC causing a phenotype of lower motor neuron syndrome. Journal of neurology 5 35366689
2019 The effect of GGC and CAG repeat polymorphisms on the androgen receptor gene in response to finasteride therapy in men with androgenetic alopecia. Journal of research in medical sciences : the official journal of Isfahan University of Medical Sciences 5 31949455
2016 Influence of Androgen Receptor Gene CAG and GGC Polymorphisms on Male Sexual Function: A Cross-Sectional Study. International journal of endocrinology 5 28243253
1996 HMG box proteins interact with multiple tandemly repeated (GCC)n (GGC)m DNA sequences. Journal of biomolecular structure & dynamics 5 8913860
2025 GGCT Inhibits Ferroptosis in PTC Cells by Upregulating p53 Through RPS15A. Cancer science 4 40044122
2024 Novel islands of GGC and GCC repeats coincide with human evolution. Gene 4 38262548
2024 Myc upregulates Ggct, γ-glutamylcyclotransferase to promote development of p53-deficient osteosarcoma. Cancer science 4 38924236
2016 Androgen receptor GGC repeat might be more involved than CAG repeat in the regulation of the metabolic profile in men. Internal and emergency medicine 4 27251588
2012 Modulation of oxidative stress by γ-glutamylcysteine (GGC) and conjugated linoleic acid (CLA) isomer mixture in human umbilical vein endothelial cells. Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association 4 22490668
1997 delta-Thalassemic phenotype due to two "novel" delta-globin gene mutations: CD11[GTC-->GGC (A8)-HbA2-Pylos] and CD 85[TTT-->TCT(F1)-HbA2-Etolia]. Human mutation 4 9101295
1990 The restriction enzyme EheI (GGC/GCC) is sensitive to CpG methylation. Nucleic acids research 4 2362829