Affinage

GGCT

Gamma-glutamylcyclotransferase · UniProt O75223

Length
188 aa
Mass
21.0 kDa
Annotated
2026-06-10
100 papers in source corpus 17 papers cited in narrative 17 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

GGCT (C7orf24) is a gamma-glutamyl cyclotransferase that converts gamma-glutamyl dipeptides to 5-oxoproline (pyroglutamic acid) and free amino acids, functioning as a homodimer with a unique BtrG-like fold and Glu98 as its catalytic general acid/base (PMID:18515354). Through this enzymatic activity it governs glutathione (GSH) homeostasis and redox balance: Ggct-null mice develop splenomegaly and progressive haemolytic anaemia, with red blood cells showing elevated ROS, increased H2O2 sensitivity, and depleted GSH and its precursor l-cysteine, establishing GGCT as essential for erythrocyte redox balance and survival (PMID:34409610). The same GSH-ROS regulatory function is co-opted in cancer, where GGCT acts downstream of oncogenic Ras to alleviate oncogenic stress and is required for Ras-driven transformation and lung tumorigenesis (PMID:31400748), and downstream of Myc, which directly binds the Ggct promoter to drive a pro-tumorigenic program in p53-deficient osteosarcoma (PMID:38924236). Across multiple tumour types GGCT knockdown suppresses proliferation, migration, invasion, and survival (PMID:21136669, PMID:21508379, PMID:27905872), and in papillary thyroid cancer it physically interacts with CD44, MRPL9, and RPS15A to stabilize partner proteins and signal through MAPK/ERK and an RPS15A→p53→SLC7A11 axis that confers ferroptosis resistance (PMID:35213720, PMID:36233293, PMID:40044122). Its transcription is TATA-less and CCAAT-dependent, driven by NF-Y binding to proximal CCAAT boxes via the NF-YB subunit, with expression oscillating across the cell cycle (PMID:21883928). Substrate-mimetic active-site inhibitors and the enzymatic byproduct pyroglutamic acid have additionally been linked to protein-aggregation phenotypes in glioblastoma (PMID:27373633, PMID:39949960).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 2007 Medium

    Established that GGCT is functionally required for cancer cell proliferation, motivating mechanistic dissection of an otherwise uncharacterized open reading frame.

    Evidence siRNA knockdown and retroviral overexpression with proliferation assays in cancer cell lines and NIH3T3

    PMID:21136669

    Open questions at the time
    • No molecular mechanism for the proliferative effect
    • Enzymatic identity not yet known
    • Single lab, two phenotypic readouts only
  2. 2008 High

    Defined the molecular identity of C7orf24 as a gamma-glutamyl cyclotransferase and resolved its catalytic mechanism, converting a phenotypic gene into a defined enzyme.

    Evidence Recombinant enzymatic assay, 1.7 Å X-ray crystallography, and active-site mutagenesis (E98A/E98Q)

    PMID:18515354

    Open questions at the time
    • Did not connect enzymatic activity to the cellular proliferative phenotype
    • In vivo physiological substrate spectrum not addressed
    • No link to GSH metabolism established yet
  3. 2009 Medium

    Mapped baseline tissue expression, showing GGCT is broadly expressed with enrichment in metabolically active liver and kidney.

    Evidence RT-PCR, qRT-PCR, and in situ hybridization across rat tissues

    PMID:19687470

    Open questions at the time
    • No functional consequence tied to tissue distribution
    • Subcellular localization not resolved
  4. 2011 High

    Identified the transcriptional control of GGCT, showing NF-Y drives basal expression through proximal CCAAT boxes and couples expression to the cell cycle.

    Evidence Luciferase reporter deletion/mutation, EMSA, ChIP, and NF-YB siRNA in HeLa cells

    PMID:21883928

    Open questions at the time
    • Did not link transcriptional control to oncogenic signalling inputs
    • Cell-cycle oscillation mechanism not detailed
  5. 2011 Medium

    Extended the proliferative requirement to invasive phenotypes, showing GGCT supports growth, motility, and invasion in osteosarcoma.

    Evidence siRNA knockdown with growth/motility/invasion assays and genome-wide expression profiling

    PMID:21508379

    Open questions at the time
    • Implicated adhesion/transport pathways not mechanistically validated
    • No rescue or epistasis
  6. 2012 Medium

    Demonstrated an in vivo requirement for GGCT in tumour growth, supporting therapeutic targeting.

    Evidence Needle-free jet injection of anti-C7orf24 siRNA into lung cancer-bearing mice with tumour volume and IHC readouts

    PMID:22653386

    Open questions at the time
    • No mechanistic pathway tied to the in vivo effect
    • Single delivery model
  7. 2016 Medium

    Refined the cellular phenotype, showing GGCT loss arrests cells at G2/M and triggers apoptosis, and separately defined substrate-mimetic inhibitor requirements.

    Evidence Lentiviral shRNA with flow cytometry in gastric cancer cells; in vitro SAR inhibition assay of 18 N-acyl-L-alanine analogues on recombinant GGCT

    PMID:27373633 PMID:27905872

    Open questions at the time
    • Connection between cell-cycle arrest and enzymatic activity not established
    • Inhibitor potency not tested in cells
  8. 2019 High

    Placed GGCT genetically downstream of oncogenic Ras and tied its function to GSH-ROS metabolism in alleviating oncogenic stress.

    Evidence LSL-KrasG12D mouse model, primary cell transformation, in vivo lung cancer, GSH/ROS measurement, and genetic knockout

    PMID:31400748

    Open questions at the time
    • Molecular link between cyclotransferase activity and GSH pool not fully resolved
    • Did not address non-Ras tumour contexts
  9. 2020 Low

    Linked GGCT to EMT regulation in colorectal cancer, broadening its role in metastatic phenotypes.

    Evidence siRNA knockdown with migration/invasion assays and Western blot of EMT markers

    PMID:32724344

    Open questions at the time
    • No rescue or pathway epistasis
    • Single knockdown approach
    • EMT regulation mechanism unknown
  10. 2021 High

    Defined the essential physiological role of GGCT in erythrocyte redox balance via GSH metabolism, explaining the consequences of its loss in normal tissue.

    Evidence Ggct knockout mouse with blood counts, spleen histology, ROS/H2O2 sensitivity, and GSH/l-cysteine quantification

    PMID:34409610

    Open questions at the time
    • Mechanism linking GGCT cyclotransferase output to GSH precursor levels not fully delineated
    • Other tissues' dependence not characterized
  11. 2022 Medium

    Identified direct protein partners (CD44, MRPL9) and upstream miRNA control, expanding GGCT into a protein-stabilizing scaffold acting through MAPK/ERK.

    Evidence Co-IP, immunofluorescence, dual-luciferase reporter, RNA pull-down, and in vivo xenograft/metastasis models in papillary thyroid cancer

    PMID:35213720 PMID:36233293

    Open questions at the time
    • Whether protein stabilization depends on enzymatic activity unknown
    • Direct binding interface not mapped
    • Single lab
  12. 2024 High

    Established Myc as a direct transcriptional driver of GGCT in tumorigenesis and identified a REST/miR-34a-5p feedback loop, integrating GGCT into oncogenic transcriptional circuits.

    Evidence ChIP and CRISPR deletion of the Myc binding site, Ggct knockout osteosarcoma mouse model; separately siRNA/RNA-seq and reporter assays defining a GGCT/REST/miR-34a-5p loop in glioma

    PMID:38924236 PMID:39128259

    Open questions at the time
    • How GGCT downregulates REST mechanistically unresolved
    • Crosstalk between Myc and NF-Y inputs not addressed
  13. 2025 Medium

    Connected GGCT to ferroptosis resistance through an RPS15A→p53→SLC7A11 axis and linked its enzymatic byproduct pyroglutamic acid to protein aggregation in glioblastoma.

    Evidence Co-IP/LC-MS/MS, GSH/ROS/MDA and ferroptosis assays, reporter assays, and xenografts in PTC; genetic and pharmacological (Pro-GA) GGCT inhibition with aggregation assays and patient samples in GBM

    PMID:39949960 PMID:40044122

    Open questions at the time
    • Mechanism by which RPS15A stabilization activates p53 axis incompletely defined
    • Whether pyroglutamic acid aggregation effect generalizes beyond GBM unknown
    • Single lab per finding

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how GGCT's defined cyclotransferase activity mechanistically connects its protein-stabilizing interactions (CD44, MRPL9, RPS15A) and its scaffold/signalling roles to its core GSH-ROS metabolic function.
  • No structure of GGCT bound to any protein partner
  • Whether partner stabilization requires catalytic activity untested
  • Physiological substrate spectrum in vivo not fully defined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140098 catalytic activity, acting on RNA 2 GO:0016853 isomerase activity 1
Localization
GO:0005829 cytosol 1
Pathway
R-HSA-8953897 Cellular responses to stimuli 3 R-HSA-1430728 Metabolism 2 R-HSA-1643685 Disease 2 R-HSA-74160 Gene expression (Transcription) 2
Partners
CD44MRPL9MYCNF-YBRPS15A

Evidence

Reading pass · 17 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. The crystal structure was solved at 1.7 Å resolution, revealing a homodimer of 20,994-Da subunits with a unique 'BtrG-like' fold. Active-site mutagenesis identified Glu98 as the catalytic general acid/base; mutation of Glu98 to Ala or Gln completely inactivated the enzyme without altering the overall fold. Recombinant protein expression, enzymatic assay, X-ray crystallography (1.7 Å), site-directed mutagenesis (E98A, E98Q) The Journal of biological chemistry High 18515354
2007 C7orf24 (GGCT) knockdown via siRNA in cancer cell lines produced significant antiproliferative effects (MTT assay), and overexpression in NIH3T3 cells increased growth rate, establishing a role for GGCT in cancer cell proliferation. siRNA knockdown, MTT proliferation assay, retroviral overexpression, growth rate assay Proteomics. Clinical applications Medium 21136669
2011 C7orf24 (GGCT) knockdown in osteosarcoma cell lines inhibited cell growth, motility, and invasion. Gene ontology analysis of differentially expressed genes after C7orf24 siRNA treatment implicated cell adhesion and protein transport pathways. siRNA knockdown, growth assay, motility and invasion assays, genome-wide gene expression profiling Anticancer research Medium 21508379
2011 The human C7orf24 (GGCT) promoter is TATA-less and contains five CCAAT boxes. Three proximal CCAAT boxes are essential for basal transcription, and NF-Y (nuclear factor Y) specifically binds all three via its NF-YB subunit, driving C7orf24 transcription. Depletion of NF-YB in HeLa cells significantly reduced C7orf24 mRNA and protein levels. C7orf24 expression oscillates during the cell cycle, consistent with NF-Y-mediated cell cycle regulation. Luciferase reporter assay with 5'-deleted and site-directed mutant constructs, EMSA, chromatin immunoprecipitation (ChIP), NF-YB siRNA knockdown The FEBS journal High 21883928
2012 In vivo knockdown of C7orf24 (GGCT) by needle-free jet injection of anti-C7orf24 siRNA into lung cancer-bearing mice significantly inhibited tumor growth, demonstrating an in vivo requirement for GGCT in tumor proliferation. In vivo siRNA delivery by needle-free jet injection, tumor volume measurement, immunohistochemistry for C7orf24 protein levels in tumor tissue Cancer gene therapy Medium 22653386
2016 GGCT knockdown (lentiviral shRNA) in gastric cancer cells inhibited cell proliferation, reduced colony formation, arrested the cell cycle at G2/M phase, and induced late apoptosis, establishing GGCT as required for gastric cancer cell proliferation and survival. Lentivirus-mediated shRNA knockdown, MTT assay, colony formation assay, flow cytometry (cell cycle and apoptosis) BMC biochemistry Medium 27905872
2016 N-glutaryl-L-alanine was identified as the most potent inhibitor of recombinant human GGCT among 18 N-acyl-L-alanine analogues tested, defining substrate-mimetic inhibitor requirements for the GGCT active site. In vitro inhibition assay with recombinant human GGCT protein, structure-activity relationship analysis of 18 synthetic analogues Chemical & pharmaceutical bulletin Medium 27373633
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 in vivo lung cancer formation in the LSL-KrasG12D mouse model. GGCT regulates a glutathione (GSH)-reactive oxygen species (ROS) metabolic pathway to alleviate oncogenic stress. GGCT deficiency is compatible with normal mouse development. LSL-KrasG12D mouse model, primary mouse cell transformation assays, in vivo lung cancer model, GSH/ROS measurement, genetic knockout iScience High 31400748
2009 C7orf24 (GGCT) mRNA is broadly expressed in rat tissues, with highest levels in liver and kidney (hepatocytes and renal tubules), as determined by RT-PCR, quantitative RT-PCR, and in situ hybridization histochemistry. RT-PCR, quantitative RT-PCR, in situ hybridization histochemistry The journal of histochemistry and cytochemistry Medium 19687470
2020 GGCT knockdown inhibited migration and invasion of colorectal cancer cells and regulated EMT-associated genes (N-cadherin, Vimentin, Snail1, Snail2), placing GGCT upstream of EMT in colorectal cancer. siRNA knockdown, migration and invasion assays, Western blot for EMT markers Oncology letters Low 32724344
2021 Ggct deletion in mice causes splenomegaly and progressive anaemia due to elevated oxidative damage and shortened red blood cell (RBC) lifespan. Ggct-/- RBCs have increased ROS, are more sensitive to H2O2-induced damage, and have decreased glutathione (GSH) and GSH precursor l-cysteine, establishing a critical physiological function for Ggct in RBC redox balance through GSH metabolism. Ggct knockout mouse model, complete blood count, spleen histology, ROS measurement, H2O2 sensitivity assay, GSH and l-cysteine quantification British journal of haematology High 34409610
2022 GGCT interacts physically with CD44 in papillary thyroid cancer (PTC) cells, stabilizing CD44 protein. miR-205-5p binds the 3'-UTR of GGCT (confirmed by dual-luciferase reporter and RNA-RNA pull-down assays) and suppresses GGCT expression, thereby reversing GGCT-driven pro-malignant effects including EMT and CD44 stabilization. Co-immunoprecipitation, dual-luciferase reporter assay, RNA-RNA pull-down, siRNA knockdown, in vitro and in vivo tumor assays Endocrinology Medium 35213720
2022 GGCT physically interacts with MRPL9 (mitochondrial ribosomal protein L9) in PTC cells, as demonstrated by co-immunoprecipitation and immunofluorescence. Knockdown of GGCT or MRPL9 inhibited the MAPK/ERK signaling pathway, suppressed cell proliferation and migration in vitro, and inhibited subcutaneous xenograft growth and lung metastasis in vivo. Co-immunoprecipitation, immunofluorescence, lentiviral knockdown, in vitro proliferation and migration assays, in vivo xenograft and lung metastasis models, Western blot for MAPK/ERK pathway International journal of molecular sciences Medium 36233293
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 attenuated the tumorigenic potential of p53-deficient osteosarcoma cells. Ggct deletion suppressed p53-deficient osteosarcomagenesis in mice, placing GGCT downstream of Myc in a pro-tumorigenic pathway. ChIP (Myc binding to Ggct promoter), CRISPR-Cas9 genome editing of Myc binding site, Ggct knockout mouse model of osteosarcoma, tumorigenic assays Cancer science High 38924236
2025 GGCT-derived pyroglutamic acid (a byproduct of GGCT enzymatic activity) can bind aggregating proteins; genetic and pharmacological inhibition of GGCT prevents protein aggregation in drug-resistant glioblastoma cells. Increased GGCT expression and pyroglutamic acid staining were found in recurrent GBM patient samples. Genetic GGCT inhibition (knockdown), pharmacological GGCT inhibitor (Pro-GA), protein aggregation assays, immunostaining for pyroglutamic acid and GGCT in patient samples iScience Medium 39949960
2025 GGCT interacts with RPS15A by co-immunoprecipitation (confirmed by IP + LC-MS/MS), and promotes RPS15A protein stability. GGCT knockdown inhibited GSH synthesis and promoted ferroptosis in PTC cells by reducing SLC7A11 expression via a RPS15A→p53 axis. miR-205-5p targets the 3'UTR of GGCT to inhibit GGCT-mediated ferroptosis resistance. Co-immunoprecipitation, LC-MS/MS, siRNA knockdown, GSH/ROS/MDA measurements, ferroptosis assays, dual-luciferase reporter assay for miR-205-5p/GGCT 3'UTR, in vivo xenograft tumor formation Cancer science Medium 40044122
2024 GGCT silencing in glioma cells inhibited proliferation, migration, and induced apoptosis. Mechanistically, GGCT downregulated REST expression; REST in turn inhibited miR-34a-5p, which suppresses GGCT via its 3'UTR, forming a GGCT/REST/miR-34a-5p positive feedback loop. In vivo, REST overexpression reversed the repression of xenograft tumor formation induced by GGCT knockdown. siRNA/shRNA knockdown, CCK-8, Transwell, wound healing, flow cytometry, RNA-seq, dual luciferase reporter assay, in vivo xenograft 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 402 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 164 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 133 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 127 33887199
2020 Expansion of GGC Repeat in GIPC1 Is Associated with Oculopharyngodistal Myopathy. American journal of human genetics 118 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 111 18515354
2021 The GGC repeat expansion in NOTCH2NLC is associated with oculopharyngodistal myopathy type 3. Brain : a journal of neurology 110 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 82 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 59 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 52 31440155
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 43 34718964
2022 Expression of expanded GGC repeats within NOTCH2NLC causes behavioral deficits and neurodegeneration in a mouse model of neuronal intranuclear inclusion disease. Science advances 41 36417528
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 40 38197134
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
2024 A GGC-repeat expansion in ZFHX3 encoding polyglycine causes spinocerebellar ataxia type 4 and impairs autophagy. Nature genetics 31 38684900
2022 GGC Repeat Expansion of RILPL1 is Associated with Oculopharyngodistal Myopathy. Annals of neurology 30 35700120
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
2023 GGC repeat expansion in NOTCH2NLC induces dysfunction in ribosome biogenesis and translation. Brain : a journal of neurology 26 36825461
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
2021 GGC Repeat Expansion in the NOTCH2NLC Gene Is Associated With a Phenotype of Predominant Motor-Sensory and Autonomic Neuropathy. Frontiers in genetics 25 34306035
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
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
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) 23 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 20 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
2019 Ras Downstream Effector GGCT Alleviates Oncogenic Stress. iScience 16 31400748
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
2005 GGC and StuI polymorphism on the androgen receptor gene in endometrial cancer patients. Biochemical and biophysical research communications 16 15721279
2024 Review of Phenotypic Heterogeneity of Neuronal Intranuclear Inclusion Disease and NOTCH2NLC-Related GGC Repeat Expansion Disorders. Neurology. Genetics 14 38586597
2003 Origin of Hb A2' (Hb B2) [delta16(A13)Gly --> Arg (GGC --> CGC)]. Hemoglobin 14 12779272
2023 NOTCH2NLC GGC repeat expansion causes retinal pathology with intranuclear inclusions throughout the retina and causes visual impairment. Acta neuropathologica communications 13 37131242
2022 NOTCH2NLC expanded GGC repeats in patients with cerebral small vessel disease. Stroke and vascular neurology 13 36207023
2021 Natural selection at the RASGEF1C (GGC) repeat in human and divergent genotypes in late-onset neurocognitive disorder. Scientific reports 13 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) 13 33266084
2021 Ggct (γ-glutamyl cyclotransferase) plays an important role in erythrocyte antioxidant defense and red blood cell survival. British journal of haematology 12 34409610
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
2024 Prevalence and Characterization of NOTCH2NLC GGC Repeat Expansions in Koreans: From a Hospital Cohort Analysis to a Population-Wide Study. Neurology. Genetics 11 38779172
2016 Synthesis and GGCT Inhibitory Activity of N-Glutaryl-L-alanine Analogues. Chemical & pharmaceutical bulletin 11 27373633
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 Neuronal Intranuclear Inclusion Disease with NOTCH2NLC GGC Repeat Expansion: A Systematic Review and Challenges of Phenotypic Characterization. Aging and disease 10 38377026
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
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
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
2025 Polyglycine-mediated aggregation of FAM98B disrupts tRNA processing in GGC repeat disorders. Science (New York, N.Y.) 8 40674500
2024 Genome-wide identification and analysis of the GGCT gene family in wheat. BMC genomics 8 38177998
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
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
2024 Myc upregulates Ggct, γ-glutamylcyclotransferase to promote development of p53-deficient osteosarcoma. Cancer science 6 38924236
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
2025 GGCT Inhibits Ferroptosis in PTC Cells by Upregulating p53 Through RPS15A. Cancer science 5 40044122
2024 Novel islands of GGC and GCC repeats coincide with human evolution. Gene 5 38262548
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
2024 Dyads of GGC and GCC form hotspot colonies that coincide with the evolution of human and other great apes. BMC genomic data 4 38383300
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
2009 A rare case of alpha-thalassaemia intermedia in a Malay patient double heterozygous for alpha(+)-thalassaemia and a mutation in alpha1 globin gene CD59 (GGC --> GAC). The Medical journal of Malaysia 4 20954559
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

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