Affinage

GCM2

Chorion-specific transcription factor GCMb · UniProt O75603

Length
506 aa
Mass
56.6 kDa
Annotated
2026-06-10
54 papers in source corpus 23 papers cited in narrative 23 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

GCM2 (GCMB) is a parathyroid-specific zinc-finger transcription factor that governs the differentiation, survival, and maintenance of parathyroid cells (PMID:17382312, PMID:30677043). During development its expression is confined to the parathyroid domain of the third pharyngeal pouch before any morphological distinction, marking the parathyroid lineage (PMID:11335122), and is spatially restricted to caudal pouches by Shh signaling (PMID:21349263) and activated directly by GATA3, which binds a double-GATA motif in the GCMB promoter and lies immediately upstream in the parathyroid transcriptional cascade (PMID:20484821). GCM2 is not required for initial specification but for differentiation and survival: in its absence the parathyroid domain forms but undergoes programmed cell death and fails to sustain PTH and CaSR expression (PMID:17382312), and conditional ablation in adults causes progressive loss of parathyroid proliferation, increased cell death, and gland shrinkage, establishing an ongoing requirement for gland maintenance (PMID:30677043). Mechanistically, GCM2 binds GCM response elements through its GCM DNA-binding domain to directly transactivate both CASR promoters (PMID:18712808) and the PTH promoter, the latter requiring synergistic association with MafB, itself a downstream GCM2 target (PMID:20558332, PMID:21713993). Its activity is structurally partitioned into transactivation domains and a regulatory inhibitory region that also controls protein stability (PMID:10671510), including a C-terminal conserved inhibitory domain (CCID) whose disruption elevates transcriptional activity (PMID:27745835). Genetically, loss-of-function mutations that abolish nuclear localization, DNA binding, or transactivation cause autosomal recessive or dominant-negative hypoparathyroidism (PMID:11602629, PMID:15728199, PMID:20190276, PMID:20463099), whereas gain-of-function CCID variants increase activity and drive familial hyperparathyroidism (PMID:27745835, PMID:35038313). Epigenetic silencing by promoter hypermethylation reduces GCM2 in sporadic parathyroid adenomas (PMID:34077544), and activating variants are linked to galectin-3 induction, a parathyroid carcinoma marker (PMID:41025096).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 2000 High

    Established the modular architecture of GCM2, defining two transactivation domains and an inhibitory region that simultaneously limits transactivation and destabilizes the protein, linking protein stability to transcriptional output.

    Evidence Deletion-construct structure-function analysis, transactivation assays, and pulse-chase half-life measurements in tissue culture

    PMID:10671510

    Open questions at the time
    • Does not identify which residues mediate inhibition
    • No in vivo confirmation of the stability-activity link
  2. 2001 Medium

    Showed that Gcm2 expression demarcates the parathyroid domain of the pharyngeal pouch before any morphological distinction, identifying it as the earliest parathyroid lineage marker.

    Evidence In situ hybridization across mouse developmental stages

    PMID:11335122

    Open questions at the time
    • Expression marks but does not prove functional requirement
    • Upstream activators not defined here
  3. 2001 Medium

    Linked GCMB to human disease by demonstrating that a homozygous loss-of-function deletion causes familial isolated hypoparathyroidism, establishing it as required for parathyroid gland formation.

    Evidence Genetic mapping and mutation identification with haplotype analysis in a human kindred

    PMID:11602629

    Open questions at the time
    • Single family
    • Molecular consequence of the deletion not functionally dissected
  4. 2003 High

    Used genetic epistasis to prove that GCM2-dependent parathyroid output drives the skeletal pathology of CaSR deficiency, separating PTH-mediated bone effects from direct renal CaSR function.

    Evidence Gcm2-/-;CasR-/- double-knockout mice with skeletal and serum biochemistry analysis

    PMID:12671052

    Open questions at the time
    • Does not address GCM2 function outside the parathyroid-CaSR axis
  5. 2005 Medium

    Demonstrated that the GCM DNA-binding domain is required for transactivation independently of DNA binding, by characterizing a G63S mutant that retains DNA binding yet loses activity.

    Evidence Subcellular localization, transactivation, and stability assays on a disease mutant in transfected cells

    PMID:15728199

    Open questions at the time
    • Coactivator interface not identified
    • Single mutant
  6. 2007 High

    Defined GCM2's developmental role as differentiation/survival rather than specification, showing the parathyroid domain forms but dies by apoptosis and fails to sustain PTH/CaSR/CCL21 in its absence.

    Evidence Gcm2 null mouse analysis with apoptosis assays and marker-gene epistasis

    PMID:17382312

    Open questions at the time
    • Direct transcriptional targets not defined in this study
    • Mechanism of cell death not resolved
  7. 2008 Medium

    Identified direct downstream transactivation targets and dominant-negative disease alleles, showing frameshift CCID-region and missense mutants either inhibit wild-type activity or reduce nuclear expression and activity.

    Evidence Mutational analysis with Western blot, nuclear localization, and luciferase reporter assays in fibroblast/HEK293 cells

    PMID:18182452 PMID:18583467

    Open questions at the time
    • Distinguishing loss-of-function from dominant-negative requires the gene target context
    • Single-lab functional assays
  8. 2009 High

    Established CASR as a direct GCM2 target by mapping functional GCM response elements in both CASR promoters and showing a disease mutant exerts a dominant-negative block.

    Evidence Promoter-reporter mutagenesis and oligonucleotide precipitation assays

    PMID:18712808

    Open questions at the time
    • Endogenous occupancy in parathyroid cells not shown here
    • Cofactor requirements not addressed
  9. 2010 High

    Positioned GATA3 directly upstream of GCMB in the parathyroid transcriptional cascade through binding and activation of the GCMB promoter, and identified MafB as a required synergistic partner for PTH activation downstream of GCM2.

    Evidence EMSA, luciferase, ChIP, Gata3 knockout mice; Co-IP and PTH promoter reporter with gcm2-null analysis

    PMID:20484821 PMID:20558332 PMID:21713993

    Open questions at the time
    • Structural basis of GCM2-MafB synergy unknown
    • Full cofactor complex not defined
  10. 2010 High

    Resolved the genotype-mechanism relationship for hypoparathyroidism alleles by mapping mutations to discrete steps — nuclear import, DNA binding, or transactivation — supported by structural modeling of the DNA-binding interface.

    Evidence Localization, EMSA, luciferase assays, and 3D modeling across multiple recessive and dominant mutants

    PMID:20190276 PMID:20463099

    Open questions at the time
    • Models not validated by experimental structure
    • In vivo consequences of individual alleles untested
  11. 2012 Medium

    Refined mutation classification by showing a DNA-binding-domain mutant (C106R) loses DNA binding and activity without inhibiting wild-type, distinguishing simple loss-of-function from dominant-negative alleles.

    Evidence EMSA, luciferase, microscopy, and homology modeling

    PMID:22066718

    Open questions at the time
    • Single mutant
    • No structural validation
  12. 2014 Medium

    Confirmed additional C-terminal loss-of-function alleles in hypoparathyroidism patients through reduced transactivation, extending the allelic spectrum.

    Evidence NGS, luciferase transactivation assay, and droplet digital PCR

    PMID:25137426

    Open questions at the time
    • Mechanistic step affected not isolated
    • Single lab
  13. 2016 High

    Identified the C-terminal conserved inhibitory domain (CCID) and showed recurrent CCID missense variants act as gain-of-function alleles increasing transcriptional activity, defining a proto-oncogenic mechanism in parathyroid cells.

    Evidence Exome sequencing, deletion mapping, and gain-of-function luciferase reporter assays in multiple kindreds

    PMID:27745835

    Open questions at the time
    • How CCID normally restrains activity at the molecular level unresolved
    • Link to tumorigenesis correlative
  14. 2019 High

    Demonstrated a continued requirement for GCM2 in the adult gland by showing conditional ablation causes loss of proliferation, increased death, gland shrinkage, and reduced PTH/Ca, extending its role beyond development to maintenance.

    Evidence Tamoxifen-inducible conditional knockout mice with Ki-67, TUNEL, serum biochemistry, and RT-PCR

    PMID:30677043

    Open questions at the time
    • Direct maintenance targets not identified
    • Proliferation versus survival contributions not separated
  15. 2021 Medium

    Revealed epigenetic silencing of GCM2 via promoter hypermethylation and H3K9me3 as a mechanism in sporadic parathyroid adenomas, reversible by demethylation.

    Evidence RT-qPCR, IHC, bisulfite sequencing, ChIP-qPCR, and pharmacological demethylation in PTH-C1 cells

    PMID:34077544

    Open questions at the time
    • Causal contribution to tumorigenesis not proven
    • Single lab
  16. 2022 Medium

    Extended the genotype-function map by confirming a recessive DNA-binding-defective allele (R67C) and additional activating CCID variants that enhance PTH promoter stimulation, reinforcing the loss/gain dichotomy underlying hypo- versus hyperparathyroidism.

    Evidence Luciferase reporter, oligonucleotide pull-down, and structural modeling; reciprocal ectopic-expression transgenic mice for cell-context dependence

    PMID:35038313 PMID:35941210

    Open questions at the time
    • Permissive cofactor landscape that confers context dependence not defined
    • Single-lab functional assays
  17. 2025 Medium

    Linked GCM2 transcriptional activation to a parathyroid carcinoma marker by showing activating variants induce galectin-3 (Lgals3) in mouse and human parathyroid tissue.

    Evidence Spatial transcriptomics on knock-in mice with immunohistochemistry of human samples carrying activating variants

    PMID:41025096

    Open questions at the time
    • Whether Lgals3 is a direct GCM2 target unknown
    • Functional role of galectin-3 in transformation not tested

Open questions

Synthesis pass · forward-looking unresolved questions
  • The composition of the GCM2 transcriptional complex and the molecular mechanism by which the CCID restrains activity and how its disruption drives proliferation remain undefined.
  • No experimental structure of GCM2-DNA or GCM2-MafB complexes
  • Mechanism connecting CCID gain-of-function to parathyroid proliferation unresolved
  • Full set of direct GCM2 target genes beyond CASR/PTH unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 6 GO:0003677 DNA binding 5
Localization
GO:0005634 nucleus 4
Pathway
R-HSA-1266738 Developmental Biology 4 R-HSA-74160 Gene expression (Transcription) 4 R-HSA-1643685 Disease 3
Partners
GATA3MAFB

Evidence

Reading pass · 23 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2000 Mouse GCMb (mGCMb) contains two separate transactivation domains: one carboxyl-terminally adjacent to the DNA-binding domain and a second within the extreme carboxyl terminus. An inhibitory region unique to mGCMb, located between the two transactivation domains, suppresses both transactivation domains. This inhibitory domain also shortens protein half-life (~4x shorter than mGCMa) when transferred into mGCMa, establishing a direct link between protein stability and transactivation potential. Structure-function analysis with deletion constructs, transactivation assays in tissue culture, pulse-chase experiments The Journal of biological chemistry High 10671510
2001 Gcm2 is expressed specifically in the developing second and third pharyngeal pouches at E9.5 and is confined to a small domain of the third pouch endoderm by E10.5, marking the parathyroid-specific domain before morphological distinctions are present. Foxn1 (thymus marker) does not appear until E11.25, after the common primordium forms, establishing that Gcm2 expression precedes and demarcates the parathyroid domain of the third pharyngeal pouch. In situ hybridization / expression analysis during mouse embryogenesis Mechanisms of development Medium 11335122
2001 Homozygous loss-of-function mutation in GCMB (large intragenic deletion) impairs normal parathyroid gland embryology and causes familial isolated hypoparathyroidism in humans, establishing GCMB as required for parathyroid gland development. Genetic mapping, PCR-based mutation identification, microsatellite haplotype analysis in human kindred The Journal of clinical investigation Medium 11602629
2007 Gcm2 is not required for initial specification or patterning of the parathyroid domain in the third pharyngeal pouch, but is required for the differentiation and subsequent survival of parathyroid precursor cells. In Gcm2-/- mice, the parathyroid-specific domain forms normally but undergoes programmed cell death between E12 and E12.5. Gcm2-/- parathyroid domains fail to express PTH, CasR, and CCL21 (though initiation of CasR and CCL21 expression occurs). Marker gene epistasis placed Gcm2 downstream of known transcription and signaling pathways for parathyroid/thymus organogenesis. Gcm2 null mouse analysis, RNA and protein localization, apoptosis assays, marker gene expression epistasis Developmental biology High 17382312
2009 GCM2 directly transactivates both promoters (P1 and P2) of the calcium-sensing receptor (CASR) gene. GCM response elements within CASR P1 (-451 to -441) and CASR P2 (-166 to -156) were identified as functional binding sites. A dominantly inherited GCM2 mutant (from autosomal dominant hypoparathyroidism family) exerted a dominant-negative effect on wild-type GCM2 transactivation of CASR promoters, completely abolishing CASR promoter activation. Mutated promoter-reporter (luciferase) studies, oligonucleotide precipitation assays, transfection studies Human mutation High 18712808
2008 Two novel heterozygous frameshift mutations in the last GCMB exon (c.1389delT and c.1399delC) cause autosomal dominant hypoparathyroidism via a dominant-negative mechanism. Both mutant GCMB proteins are well expressed and show dose-dependent inhibition of wild-type GCMB transactivation capacity in luciferase reporter assays. Mutational analysis, Western blot, luciferase reporter assay in DF-1 fibroblasts The Journal of clinical endocrinology and metabolism Medium 18583467
2008 Two previously reported GCM2 missense mutations (R47L and G63S) showed decreased nuclear expression and markedly reduced transactivational activity (5–20% of normal) when expressed in HEK293 cells, whereas six other variant GCM2 proteins (G203S, I227V, Y282D, N315D, Q330L, M354V) had normal size, nuclear localization, and transactivational function. Transient transfection in HEK293 cells, nuclear localization assay, transactivation assay The Journal of clinical endocrinology and metabolism Medium 18182452
2005 A G63S missense mutation in the GCM domain (DNA-binding domain) of GCMB causes loss of GCMB transactivation function despite normal subcellular localization, protein stability, and DNA-binding specificity, establishing that the GCM domain is required for transactivation independently of DNA binding. Functional studies in transfected cells: subcellular localization, transactivation assay, protein stability assessment The Journal of clinical endocrinology and metabolism Medium 15728199
2010 GATA3 binds specifically to a functional double-GATA motif within the GCMB promoter and directly activates GCMB transcription, placing GATA3 upstream of GCM2/GCMB in a transcriptional cascade required for parathyroid progenitor cell differentiation and survival. Gata3-/- embryos have no Gcm2 expression by E11.5, and Gata3+/- embryos have fewer Gcm2-expressing cells. Electrophoretic mobility shift assay (EMSA), luciferase reporter assay, chromatin immunoprecipitation (ChIP), Gata3 knockout mouse analysis The Journal of clinical investigation High 20484821
2010 Four GCMB mutations causing autosomal recessive hypoparathyroidism were functionally characterized: R39X failed to localize to the nucleus; R47L and R110W lost DNA-binding ability (by EMSA); I298fsX307 had reduced transactivational ability. 3D modeling of the GCMB DNA-binding domain revealed that R110 is important for structural integrity of helix 2 in the GCMB/DNA binding interface. Subcellular localization studies, EMSA, luciferase reporter assays, 3D structural modeling Human molecular genetics High 20190276
2010 GCMB binds to the PTH gene 5'-promoter (-390/-383 bp) and positively regulates PTH transcription in a parathyroid-derived cell line (PT-r) that endogenously expresses PTH. 1,25(OH)2D3 and high extracellular calcium (via CaSR) exerted inhibitory effects on PTH gene expression in the same system. Luciferase promoter reporter assay, ChIP or binding assays in PT-r parathyroid-derived cell line Bone Medium 20558332
2011 MafB associates with Gcm2 to synergistically activate PTH expression. Gcm2 alone does not stimulate the PTH gene promoter, but the Gcm2-MafB interaction is required for PTH transcription. MafB expression in parathyroid cells is lost in gcm2-null mice, placing MafB downstream of Gcm2 in the parathyroid developmental hierarchy. Co-immunoprecipitation/association assay, PTH promoter-reporter assay, gcm2 null mouse analysis Journal of bone and mineral research Medium 21713993
2010 The GCMB N502H missense mutation retains normal nuclear localization and DNA binding but causes reduced gene transactivation. Cotransfection of wild-type with N502H mutant does not increase luciferase activity, demonstrating a dominant-negative effect consistent with autosomal dominant inheritance. Fluorescence microscopy (nuclear localization), EMSA, luciferase reporter assay in COS7 cells The Journal of clinical endocrinology and metabolism Medium 20463099
2012 The GCMB C106R mutation in the putative DNA-binding domain abolishes interaction with the GCM consensus DNA recognition motif (by EMSA) and reduces transactivation in luciferase assays. However, the C106R mutant does not reduce the activity of co-transfected wild-type GCMB, distinguishing it from dominant-negative mutants. Homology modeling predicts C106R disrupts the DNA-binding interface. EMSA, luciferase reporter assay, fluorescence microscopy, homology modeling Clinical endocrinology Medium 22066718
2016 Deletion analyses of GCM2 identified a small C-terminal conserved inhibitory domain (CCID). Two recurrent missense variants in the CCID (p.L379Q and p.Y394S) act as gain-of-function mutations that increase GCM2 transcriptional activity in reporter assays, establishing the CCID as a regulatory domain whose disruption constitutes a proto-oncogenic mechanism in parathyroid cells. Exome sequencing, deletion analysis, luciferase reporter assay for GCM2 transcriptional activity American journal of human genetics High 27745835
2019 Conditional knockout of Gcm2 in adult mice (tamoxifen-inducible) leads to progressive loss of parathyroid cell proliferation, increased cell death, shrinkage of parathyroid glands, and decreased CaSR- and PTH-expressing cells with reduced serum PTH and Ca levels by 7 months post-induction, establishing that Gcm2 is required for maintenance and proliferation of parathyroid cells in adults. Conditional (tamoxifen-inducible Cre) knockout mice, Ki-67 proliferation staining, TUNEL apoptosis assay, serum biochemistry, RT-PCR for Casr and Pth PloS one High 30677043
2022 A novel homozygous GCM2 p.R67C mutation fails to stimulate transcriptional activity in luciferase assay and loses the ability to bind the consensus GCM recognition sequence (by oligonucleotide pull-down assay and in silico structural modeling), causing hypoparathyroidism. Novel heterozygous CCID variants (p.I383M, p.T386S, and p.Y394S) exert significantly enhanced in vitro transcriptional activity including increased stimulation of the PTH promoter, consistent with FIHP. Luciferase reporter assay, oligonucleotide pull-down assay, in silico structural modeling, Sanger sequencing European journal of endocrinology Medium 35038313
2003 Genetic ablation of Gcm2 (parathyroid agenesis) in CasR-deficient mice rescued perinatal lethality, corrected severe hyperparathyroidism, and healed abnormal bone/cartilage mineralization, demonstrating that rickets and osteomalacia in CasR-deficient mice result from severe hyperparathyroidism rather than a direct skeletal function of CasR. Concomitant Gcm2 and CasR deficiency did not rescue hypocalciuria, indicating direct CasR regulation of renal calcium excretion independent of parathyroid glands. Genetic epistasis by intercrossing Gcm2-/- and CasR-/- mice, skeletal phenotype analysis, serum biochemistry The Journal of clinical investigation High 12671052
2014 Novel GCM2 mutations R367Tfs*15 and T370M, identified by targeted next-generation sequencing, reduce target gene transactivation in functional studies, confirming their loss-of-function nature in hypoparathyroidism patients. Next-generation sequencing, luciferase transactivation assay, droplet digital PCR for deletion confirmation The Journal of clinical endocrinology and metabolism Medium 25137426
2021 GCM2 promoter hypermethylation and gain of H3K9me3 histone methylation are associated with reduced GCM2 mRNA and protein expression in sporadic parathyroid adenomas. Treatment of PTH-C1 cells with the demethylating agent 5-aza-2'-deoxycytidine (DAC) restored GCM2 transcription and decreased DNMT1 protein expression, establishing epigenetic silencing of GCM2 via DNA methylation as a mechanism in parathyroid tumorigenesis. RT-qPCR, immunohistochemistry, bisulfite sequencing, ChIP-qPCR, pharmacological demethylation in PTH-C1 cells The Journal of clinical endocrinology and metabolism Medium 34077544
2011 Shh signaling restricts Gcm2 expression in pharyngeal epithelium to caudal pouches: high Shh signaling in anterior pouches suppresses Gcm2, while low/absent Shh in caudal pouches permits Gcm2 expression. Blocking Shh signaling at later stages induces ectopic Gcm2 expression in anterior pharyngeal epithelium that goes on to express parathyroid markers. Shh pathway inhibition in chick and mouse embryos, Gcm2 expression analysis by in situ hybridization Developmental biology Medium 21349263
2022 Ectopic expression of Gcm2 in thymic epithelium (in the presence or absence of Foxn1) does not activate a parathyroid-specific expression programme, and co-expression of Foxn1 in parathyroid epithelium fails to impose thymopoietic capacity, establishing that Gcm2 and Foxn1 transcription factor activities are cell-context dependent and require permissive transcription factor landscapes. Transgenic mouse models with ectopic transcription factor expression, organ fate analysis Scientific reports Medium 35941210
2025 Spatial transcriptomic analysis of parathyroid glands from Gcm2+/Y392S (activating variant) knock-in mice revealed increased Lgals3 (galectin-3) transcript levels compared to wild-type parathyroid cells. Galectin-3 protein was detected in human parathyroid samples from patients with germline heterozygous activating GCM2 variants (p.Y394S and p.L379Q), linking GCM2 transcriptional activation to a marker of parathyroid carcinoma. 10x Genomics Visium spatial transcriptomics on FFPE tissue, knock-in mouse model, immunohistochemistry of human samples JBMR plus Medium 41025096

Source papers

Stage 0 corpus · 54 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2001 Gcm2 and Foxn1 mark early parathyroid- and thymus-specific domains in the developing third pharyngeal pouch. Mechanisms of development 188 11335122
2002 gcm2 promotes glial cell differentiation and is required with glial cells missing for macrophage development in Drosophila. Developmental biology 138 12167411
2001 Familial isolated hypoparathyroidism caused by a mutation in the gene for the transcription factor GCMB. The Journal of clinical investigation 132 11602629
2003 Rescue of the skeletal phenotype in CasR-deficient mice by transfer onto the Gcm2 null background. The Journal of clinical investigation 126 12671052
2005 glial cells missing and gcm2 cell autonomously regulate both glial and neuronal development in the visual system of Drosophila. Neuron 113 16242405
2016 GCM2-Activating Mutations in Familial Isolated Hyperparathyroidism. American journal of human genetics 93 27745835
2007 Gcm2 is required for the differentiation and survival of parathyroid precursor cells in the parathyroid/thymus primordia. Developmental biology 91 17382312
2010 Gata3-deficient mice develop parathyroid abnormalities due to dysregulation of the parathyroid-specific transcription factor Gcm2. The Journal of clinical investigation 85 20484821
2009 Glial cells missing-2 (GCM2) transactivates the calcium-sensing receptor gene: effect of a dominant-negative GCM2 mutant associated with autosomal dominant hypoparathyroidism. Human mutation 56 18712808
2008 Dominant-negative GCMB mutations cause an autosomal dominant form of hypoparathyroidism. The Journal of clinical endocrinology and metabolism 54 18583467
2004 Zebrafish gcm2 is required for gill filament budding from pharyngeal ectoderm. Developmental biology 52 15581882
2005 GCMB mutation in familial isolated hypoparathyroidism with residual secretion of parathyroid hormone. The Journal of clinical endocrinology and metabolism 50 15728199
2011 MafB interacts with Gcm2 and regulates parathyroid hormone expression and parathyroid development. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 47 21713993
2000 Protein stability and domain topology determine the transcriptional activity of the mammalian glial cells missing homolog, GCMb. The Journal of biological chemistry 44 10671510
2008 Analysis of the GCM2 gene in isolated hypoparathyroidism: a molecular and biochemical study. The Journal of clinical endocrinology and metabolism 36 18182452
2019 Gcm2 regulates the maintenance of parathyroid cells in adult mice. PloS one 34 30677043
2004 GCMB gene, a master regulator of parathyroid gland development, expression, and regulation in hyperparathyroidism. Surgery 32 15657585
2002 Underexpression of Gcm2, a master regulatory gene of parathyroid gland development, in adenomas of primary hyperparathyroidism. Clinical endocrinology 32 12354132
2010 Identification and characterization of novel parathyroid-specific transcription factor Glial Cells Missing Homolog B (GCMB) mutations in eight families with autosomal recessive hypoparathyroidism. Human molecular genetics 31 20190276
2004 Zebrafish gcmb is required for pharyngeal cartilage formation. Mechanisms of development 31 15327784
2019 Analysis of Activating GCM2 Sequence Variants in Sporadic Parathyroid Adenomas. The Journal of clinical endocrinology and metabolism 29 30624640
2017 Familial isolated primary hyperparathyroidism associated with germline GCM2 mutations is more aggressive and has a lesser rate of biochemical cure. Surgery 28 29108698
2010 A missense glial cells missing homolog B (GCMB) mutation, Asn502His, causes autosomal dominant hypoparathyroidism. The Journal of clinical endocrinology and metabolism 28 20463099
1999 GCMB, a second human homolog of the fly glide/gcm gene. Cytogenetics and cell genetics 28 10343099
2017 Ethnicity of Patients With Germline GCM2-Activating Variants and Primary Hyperparathyroidism. Journal of the Endocrine Society 27 29264504
2011 Shh signalling restricts the expression of Gcm2 and controls the position of the developing parathyroids. Developmental biology 25 21349263
2011 Study of parathyroid transcription factor Gcm2 expression in parathyroid lesions. The American journal of surgical pathology 24 21164298
2009 Presence and significance of a R110W mutation in the DNA-binding domain of GCM2 gene in patients with isolated hypoparathyroidism and their family members. European journal of endocrinology 23 19940031
2004 Expression of GCMB by intrathymic parathyroid hormone-secreting adenomas indicates their parathyroid cell origin. The Journal of clinical endocrinology and metabolism 21 14715818
2014 Comprehensive next-generation sequencing analyses of hypoparathyroidism: identification of novel GCM2 mutations. The Journal of clinical endocrinology and metabolism 20 25137426
2022 Novel Glial Cells Missing-2 (GCM2) variants in parathyroid disorders. European journal of endocrinology 17 35038313
2021 Automatic Detection of the Circulating Cell-Free Methylated DNA Pattern of GCM2, ITPRIPL1 and CCDC181 for Detection of Early Breast Cancer and Surgical Treatment Response. Cancers 17 33803633
2011 Mutational analysis of GCMB, a parathyroid-specific transcription factor, in parathyroid adenoma of primary hyperparathyroidism. The Journal of endocrinology 17 21642377
2014 Increased prevalence of the GCM2 polymorphism, Y282D, in primary hyperparathyroidism: analysis of three Italian cohorts. The Journal of clinical endocrinology and metabolism 16 25279501
2020 Germline GCM2 Mutation Screening in Chinese Primary Hyperparathyroidism Patients. Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists 15 33471711
2022 GCM2 Variants in Familial and Multiglandular Primary Hyperparathyroidism. The Journal of clinical endocrinology and metabolism 14 34967908
2012 Identification and characterization of C106R, a novel mutation in the DNA-binding domain of GCMB, in a family with autosomal-dominant hypoparathyroidism. Clinical endocrinology 14 22066718
2010 Involvement of GCMB in the transcriptional regulation of the human parathyroid hormone gene in a parathyroid-derived cell line PT-r: effects of calcium and 1,25(OH)2D3. Bone 14 20558332
2020 Should the GCM2 gene be tested when screening for familial primary hyperparathyroidism? European journal of endocrinology 13 31671402
2012 A novel mutation in the GCM2 gene causing severe congenital isolated hypoparathyroidism. Journal of pediatric endocrinology & metabolism : JPEM 13 23155703
2021 Five patients with disorders of calcium metabolism presented with GCM2 gene variants. Scientific reports 11 33536578
2017 Specifying the molecular pattern of sporadic parathyroid tumorigenesis-The Y282D variant of the GCM2 gene. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 10 28609842
2014 Generation of mice encoding a conditional null allele of Gcm2. Transgenic research 10 24736975
2006 A common structural mechanism underlying GCMB mutations that cause hypoparathyroidism. Medical hypotheses 7 16697534
2023 Variant Tyr 394Ser in the GCM2 Gene Is Rare in a Cohort of Ashkenazi Jews With Primary Hyperparathyroidism. Journal of the Endocrine Society 6 37362385
2021 GCM2 Silencing in Parathyroid Adenoma Is Associated With Promoter Hypermethylation and Gain of Methylation on Histone 3. The Journal of clinical endocrinology and metabolism 6 34077544
2023 GCM2 p.Tyr394Ser variant in Ashkenazi Israeli patients with suspected familial isolated hyperparathyroidism. Frontiers in endocrinology 5 38130397
2023 A Knock-In Mouse Model of the Gcm2 Variant p.Y392S Develops Normal Parathyroid Glands. Journal of the Endocrine Society 3 37885910
2022 Limits to in vivo fate changes of epithelia in thymus and parathyroid by ectopic expression of transcription factors Gcm2 and Foxn1. Scientific reports 3 35941210
2024 Three Siblings With Familial Isolated Hypoparathyroidism: A Diagnostic Journey From CASR to Novel GCM2 Variant. JCEM case reports 2 39439810
2025 A novel heterozygous frameshift pathogenic variant in GCM2 gene causing isolated hypoparathyroidism: a case report. Frontiers in endocrinology 0 40655406
2025 Monitoring breast cancer progression through circulating methylated GCM2 and TMEM240 detection. Clinical epigenetics 0 40691650
2025 Spatial transcriptomic analysis of mouse parathyroid gland cells expressing an activating variant of Gcm2. JBMR plus 0 41025096
2025 Evolution and expression of glial cells missing (GCM1 and GCM2) in monotremes suggest an ancient role in reproduction. Open biology 0 41537828

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