Gene Symbol: GCMB
Description: glial cells missing homolog 2
Alias: GCMB, HRPT4, hGCMb, chorion-specific transcription factor GCMb, GCM motif protein 2, glial cells missing 2, glial cells missing homolog b, glide/gcm protein homolog
Species: human
Products:     GCMB

Top Publications

  1. Kammerer M, Pirola B, Giglio S, Giangrande A. GCMB, a second human homolog of the fly glide/gcm gene. Cytogenet Cell Genet. 1999;84:43-7 pubmed
    ..Here we identify GCMB, which encodes a human protein homologous to the fly glial promoting factor glial cell deficient/glial cell missing ..
  2. Maret A, Ding C, Kornfield S, Levine M. Analysis of the GCM2 gene in isolated hypoparathyroidism: a molecular and biochemical study. J Clin Endocrinol Metab. 2008;93:1426-32 pubmed publisher
    ..Although GCM2 mutations appear to be an uncommon cause of IH, the wide variety of GCM2 polymorphisms suggests that variant alleles may have a role in determining parathyroid function. ..
  3. Yi H, Eom Y, Park I, Lee S, Hong S, Juppner H, et al. Identification and characterization of C106R, a novel mutation in the DNA-binding domain of GCMB, in a family with autosomal-dominant hypoparathyroidism. Clin Endocrinol (Oxf). 2012;76:625-33 pubmed publisher
    Glial cells missing B (GCMB) is a transcription factor that is expressed in the parathyroid hormone (PTH)-secreting cells of the parathyroid glands. Several mutations in GCMB have been reported to cause hypoparathyroidism (HP)...
  4. Tomar N, Bora H, Singh R, Gupta N, Kaur P, Chauhan S, et al. Presence and significance of a R110W mutation in the DNA-binding domain of GCM2 gene in patients with isolated hypoparathyroidism and their family members. Eur J Endocrinol. 2010;162:407-21 pubmed publisher
    b>Glial cells missing 2 (GCM2) gene encodes a parathyroid-specific transcription factor. We assessed GCM2 gene sequence in patients with isolated hypoparathyroidism (IH). Case-control study...
  5. Kumai Y, Kwong R, Perry S. A role for transcription factor glial cell missing 2 in Ca2+ homeostasis in zebrafish, Danio rerio. Pflugers Arch. 2015;467:753-65 pubmed publisher
    ..Overexpression of gcm2 mRNA resulted in a significant increase in the numbers of ecac-expressing ionocytes and Ca(2+) uptake. These observations reveal a critical role for gcm2 in Ca(2+) homeostasis in zebrafish larvae. ..
  6. Peissig K, Condie B, Manley N. Embryology of the Parathyroid Glands. Endocrinol Metab Clin North Am. 2018;47:733-742 pubmed publisher
    ..Therefore, understanding the normal development of the parathyroid will provide insight into the origins of parathyroid disorders. ..
  7. Lu M, Kjellin H, Fotouhi O, Lee L, Nilsson I, Haglund F, et al. Molecular profiles of oxyphilic and chief cell parathyroid adenoma. Mol Cell Endocrinol. 2018;470:84-95 pubmed publisher
    ..Chief and oxyphilic cell parathyroid adenomas have partly overlapping but also distinct molecular profiles. The calmodulin-eEF2K, TR4 and p53 pathways may be involved in the tumor development. ..
  8. Eyal O, Oren A, Jüppner H, Somech R, De Bellis A, MANNSTADT M, et al. Hypoparathyroidism and central diabetes insipidus: in search of the link. Eur J Pediatr. 2014;173:1731-4 pubmed publisher
    ..genes for isolated hypoparathyroidism encoding calcium-sensing receptor, parathyroid hormone, and glial cells missing homolog B did not reveal any mutations...
  9. Trayer V, Séjourné N, Gay S, Thermes V. Evidence for two distinct waves of epidermal ionocyte differentiation during medaka embryonic development. Dev Dyn. 2015;244:888-902 pubmed publisher
    ..This model opens the way for new studies related to epidermal development, plasticity and osmoregulation ontogeny. ..

More Information


  1. Chojnowski J, Masuda K, Trau H, Thomas K, Capecchi M, Manley N. Multiple roles for HOXA3 in regulating thymus and parathyroid differentiation and morphogenesis in mouse. Development. 2014;141:3697-708 pubmed publisher
    ..These data show that Hoxa3 has multiple complex and tissue-specific functions during patterning, differentiation and morphogenesis of the thymus and parathyroids. ..
  2. Verdelli C, Forno I, Morotti A, Creo P, Guarnieri V, Scillitani A, et al. The aberrantly expressed miR-372 partly impairs sensitivity to apoptosis in parathyroid tumor cells. Endocr Relat Cancer. 2018;25:761-771 pubmed publisher
    ..In conclusion, miR-372 is a novel mechanism exploited by a subset of parathyroid tumor cells to partially decrease sensitivity to apoptosis, to increase PTH synthesis and to deregulate Wnt signaling. ..
  3. Kwong R, Perry S. An Essential Role for Parathyroid Hormone in Gill Formation and Differentiation of Ion-Transporting Cells in Developing Zebrafish. Endocrinology. 2015;156:2384-94 pubmed publisher
    ..Taken together, the results of the present study reveal critical roles for PTH1 in promoting the differentiation of epidermal stem cells into mature ionocytes and cartilage formation during development. ..
  4. Naveh Many T, Silver J. Transcription factors that determine parathyroid development power PTH expression. Kidney Int. 2018;93:7-9 pubmed publisher
    ..PTH gene expression is determined by transcriptional and posttranscriptional mechanisms. The study by Morito et al. demonstrates that MafB contributes to the stimulation of the parathyroid by hypocalcemia and uremia. ..
  5. El Lakis M, Nockel P, Gaitanidis A, Guan B, Agarwal S, Welch J, et al. Probability of Positive Genetic Testing Results in Patients with Family History of Primary Hyperparathyroidism. J Am Coll Surg. 2018;226:933-938 pubmed publisher
  6. Li D, Streeten E, Chan A, Lwin W, Tian L, Pellegrino da Silva R, et al. Exome Sequencing Reveals Mutations in AIRE as a Cause of Isolated Hypoparathyroidism. J Clin Endocrinol Metab. 2017;102:1726-1733 pubmed publisher
    ..The presence of antibodies to interferon-α provides a highly sensitive indicator for loss of AIRE function and represents a useful marker for isolated HYPO due to AIRE mutations. ..
  7. Figueiredo M, Silva J, Santos A, Proa V, Alcobia I, Zilhão R, et al. Notch and Hedgehog in the thymus/parathyroid common primordium: Crosstalk in organ formation. Dev Biol. 2016;418:268-82 pubmed publisher
    ..This study offers novel evidence on the role of Notch signalling in T/PT common primordium development, in an Hh-dependent manner. ..
  8. Chiu Y, Chen H. GATA3 inhibits GCM1 activity and trophoblast cell invasion. Sci Rep. 2016;6:21630 pubmed publisher
    ..This study uncovered a new GATA3 function in placenta as a negative regulator of GCM1 activity and trophoblastic invasion. ..
  9. Pillar N, Pleniceanu O, Fang M, Ziv L, Lahav E, Botchan S, et al. A rare variant in the FHL1 gene associated with X-linked recessive hypoparathyroidism. Hum Genet. 2017;136:835-845 pubmed publisher
    ..Altogether, our data suggest that FHL1 is a novel regulator of calcium homeostasis and implicate it as the causative gene for X-linked recessive hypoparathyroidism. ..
  10. Xi X, Lu L, Zhuge C, Chen X, Zhai Y, Cheng J, et al. The hypoparathyroidism-associated mutation in Drosophila Gcm compromises protein stability and glial cell formation. Sci Rep. 2017;7:39856 pubmed publisher
    ..Finally, overexpression of either wild-type human Gcmb (hGcmb) or hGcmb carrying the conserved hypoparathyroidism mutation only slightly affects gliogenesis, indicating ..
  11. Li Y, Wang O, Quan T, Xia W, Jiang Y, Li M, et al. [A genomic study of adult-onset idiopathic hypoparathyroidism in Chinese by targeted next-generation sequencing]. Zhonghua Nei Ke Za Zhi. 2016;55:604-8 pubmed publisher
    ..A novel homozygosis mutation of GCMB gene[c.130G>A (p.G44S)]was identified which was predicted to be deleterious by PolyPhen2...
  12. Lin C, Hu H, Hwang P. Cortisol regulates sodium homeostasis by stimulating the transcription of sodium-chloride transporter (NCC) in zebrafish (Danio rerio). Mol Cell Endocrinol. 2016;422:93-102 pubmed publisher
    ..Taken together, cortisol and GR appear to regulate Na(+) absorption through stimulating ncc expression and the differentiation of ncc-expressing ionocytes, providing new insights into the actions of cortisol on Na(+) uptake. ..
  13. Doyle D, Kirwin S, Sol Church K, Levine M. A novel mutation in the GCM2 gene causing severe congenital isolated hypoparathyroidism. J Pediatr Endocrinol Metab. 2012;25:741-6 pubmed
    ..Informative genetic markers could not exclude identity by descent for the mutant alleles. Gcm2 protein was not detected after transfection, suggesting that complete lack of Gcm2 action accounts for severe hypoparathyroidism. ..
  14. Canaff L, Zhou X, Mosesova I, Cole D, Hendy G. Glial cells missing-2 (GCM2) transactivates the calcium-sensing receptor gene: effect of a dominant-negative GCM2 mutant associated with autosomal dominant hypoparathyroidism. Hum Mutat. 2009;30:85-92 pubmed publisher
    ..In addition, we show that the transactivation of the CASR promoter-reporter constructs by wild-type GCM2 is completely abolished in the presence of the dominant-negative mutant GCM2. ..
  15. El Lakis M, Nockel P, Guan B, Agarwal S, Welch J, Simonds W, et al. Familial isolated primary hyperparathyroidism associated with germline GCM2 mutations is more aggressive and has a lesser rate of biochemical cure. Surgery. 2018;163:31-34 pubmed publisher
    ..Knowledge of these clinical characteristics could optimize the surgical management of GCM2-associated familial isolated hyperparathyroidism. ..
  16. Verdelli C, Avagliano L, Guarnieri V, Cetani F, Ferrero S, Vicentini L, et al. Expression, function, and regulation of the embryonic transcription factor TBX1 in parathyroid tumors. Lab Invest. 2017;97:1488-1499 pubmed publisher
    ..In conclusion, TBX1 is expressed in adult parathyroid cells and deregulated in parathyroid tumors, where TBX1 deficiency may potentially contribute to the low proliferative nature of parathyroid tumors. ..
  17. Bain V, Gordon J, O Neil J, Ramos I, Richie E, Manley N. Tissue-specific roles for sonic hedgehog signaling in establishing thymus and parathyroid organ fate. Development. 2016;143:4027-4037 pubmed
    ..These data support a model in which SHH signaling plays both positive and negative roles in patterning and organogenesis of the thymus and parathyroids. ..
  18. Park S, Eom Y, Choi B, Yi H, Yu S, Lee K, et al. Genetic and clinical characteristics of korean patients with isolated hypoparathyroidism: from the Korean hypopara registry study. J Korean Med Sci. 2013;28:1489-95 pubmed publisher
    ..All coding exons and exon-intron borders of GCMB, CASR, and prepro-PTH were sequenced using PCR-amplified DNA...
  19. Nonaka D. Study of parathyroid transcription factor Gcm2 expression in parathyroid lesions. Am J Surg Pathol. 2011;35:145-51 pubmed publisher
    b>Glial cells missing 2 (Gcm2) is a master regulatory gene of parathyroid gland development, and it is exclusively expressed in the parathyroid gland. Diagnostic application of anti-Gcm2 antibody has not been reported yet...
  20. Maret A, Bourdeau I, Ding C, Kadkol S, Westra W, Levine M. Expression of GCMB by intrathymic parathyroid hormone-secreting adenomas indicates their parathyroid cell origin. J Clin Endocrinol Metab. 2004;89:8-12 pubmed
    GCMA and GCMB are related transcription factors that are critically important for embryological development of the placenta and parathyroid glands, respectively...
  21. Mirczuk S, Bowl M, Nesbit M, Cranston T, Fratter C, Allgrove J, et al. A missense glial cells missing homolog B (GCMB) mutation, Asn502His, causes autosomal dominant hypoparathyroidism. J Clin Endocrinol Metab. 2010;95:3512-6 pubmed publisher
    Glial cells missing B (GCMB), the mammalian homolog of the Drosophila GCM gene, encodes a 506-amino-acid parathyroid-specific transcription factor...
  22. Morito N, Yoh K, Usui T, Oishi H, Ojima M, Fujita A, et al. Transcription factor MafB may play an important role in secondary hyperparathyroidism. Kidney Int. 2018;93:54-68 pubmed publisher
    ..Thus, MafB appears to play an important role in secondary hyperparathyroidism by regulation of parathyroid hormone and cyclin D2 expression. Hence, MafB may represent a new therapeutic target in secondary hyperparathyroidism. ..
  23. Marchiori E, Pelizzo M, Herten M, Townsend D, Rubello D, Boschin I. Specifying the molecular pattern of sporadic parathyroid tumorigenesis-The Y282D variant of the GCM2 gene. Biomed Pharmacother. 2017;92:843-848 pubmed publisher
  24. MANNSTADT M, Holick E, Zhao W, Juppner H. Mutational analysis of GCMB, a parathyroid-specific transcription factor, in parathyroid adenoma of primary hyperparathyroidism. J Endocrinol. 2011;210:165-71 pubmed publisher
    ..b>GCMB is a parathyroid-specific transcription factor, which causes hypoparathyroidism when inactivated on both parental ..
  25. Bowl M, Mirczuk S, Grigorieva I, Piret S, Cranston T, Southam L, et al. Identification and characterization of novel parathyroid-specific transcription factor Glial Cells Missing Homolog B (GCMB) mutations in eight families with autosomal recessive hypoparathyroidism. Hum Mol Genet. 2010;19:2028-38 pubmed publisher
    b>GCMB is a member of the small transcription factor family GCM (glial cells missing), which are important regulators of development, present in vertebrates and some invertebrates...
  26. Correa P, Akerstrom G, Westin G. Underexpression of Gcm2, a master regulatory gene of parathyroid gland development, in adenomas of primary hyperparathyroidism. Clin Endocrinol (Oxf). 2002;57:501-5 pubmed
    ..We speculate that a proper expression level of the Gcm2 transcription factor could be important for maintaining a fully differentiated state of the parathyroid cell. ..
  27. Baumber L, Tufarelli C, Patel S, King P, Johnson C, Maher E, et al. Identification of a novel mutation disrupting the DNA binding activity of GCM2 in autosomal recessive familial isolated hypoparathyroidism. J Med Genet. 2005;42:443-8 pubmed
  28. Thomée C, Schubert S, Parma J, Le P, Hashemolhosseini S, Wegner M, et al. GCMB mutation in familial isolated hypoparathyroidism with residual secretion of parathyroid hormone. J Clin Endocrinol Metab. 2005;90:2487-92 pubmed
    ..gene have been reported in occasional cases, and a mutation of the parathyroid-specific transcription factor GCMB gene has been reported in one familial case...
  29. Mitsui T, Narumi S, Inokuchi M, Nagasaki K, Nakazawa M, Sasaki G, et al. Comprehensive next-generation sequencing analyses of hypoparathyroidism: identification of novel GCM2 mutations. J Clin Endocrinol Metab. 2014;99:E2421-8 pubmed publisher
    ..Using comprehensive NGS analyses, we identified the genetic defect in 35% of HP patients in our cohort and discovered novel GCM2 mutations including submicroscopic deletion that was undetectable by aCGH. ..
  30. Mizobuchi M, Ritter C, Krits I, Slatopolsky E, Sicard G, Brown A. Calcium-sensing receptor expression is regulated by glial cells missing-2 in human parathyroid cells. J Bone Miner Res. 2009;24:1173-9 pubmed publisher
    ..05) by Gcm2 silencing. Exon 1A-containing transcripts from promoter 1 were expressed at very low levels in the cultures. These results indicate that one function of Gcm2 is to maintain high levels of CaR expression in parathyroid cells. ..
  31. Kebebew E, Peng M, Wong M, Ginzinger D, Duh Q, Clark O. GCMB gene, a master regulator of parathyroid gland development, expression, and regulation in hyperparathyroidism. Surgery. 2004;136:1261-6 pubmed
    The glial cell missing gene, GCMB , encodes a transcription factor, which is a master regulator of parathyroid development. We postulated that the GCMB gene might play a role in parathyroid tumorigenesis in hyperparathyroidism...
  32. Kanemura Y, Hiraga S, Arita N, Ohnishi T, Izumoto S, Mori K, et al. Isolation and expression analysis of a novel human homologue of the Drosophila glial cells missing (gcm) gene. FEBS Lett. 1999;442:151-6 pubmed
    A novel human homologue (GCMB) of the Drosophila glial cells missing gene (dGCM) was isolated using RACE. GCMB contained a gcm motif sequence and a nuclear targeting sequence similar to that of dGCM and mouse GCMb...
  33. Marx S, Lourenço D. Familial Hyperparathyroidism - Disorders of Growth and Secretion in Hormone-Secretory Tissue. Horm Metab Res. 2017;49:805-815 pubmed publisher
    ..These differences underlie major differences in clinical expression...
  34. Kawahara M, Iwasaki Y, Sakaguchi K, Taguchi T, Nishiyama M, Nigawara T, et al. 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. 2010;47:534-41 pubmed publisher
    ..Using the cells, we investigated the transcriptional regulation of human PTH gene. We found that GCMB binds to the PTH gene 5'-promoter (-390/-383 bp) and positively regulates its transcription...
  35. Cinque L, Sparaneo A, Penta L, Mencarelli A, Rogaia D, Esposito S, et al. Autosomal Dominant PTH Gene Signal Sequence Mutation in a Family With Familial Isolated Hypoparathyroidism. J Clin Endocrinol Metab. 2017;102:3961-3969 pubmed publisher
    ..An accurate genetic diagnosis in such hypoparathyroid patients is critical for appropriate treatment and genetic counseling. ..
  36. Han S, Tsunekage Y, Kataoka K. Gata3 cooperates with Gcm2 and MafB to activate parathyroid hormone gene expression by interacting with SP1. Mol Cell Endocrinol. 2015;411:113-20 pubmed publisher
    ..These results suggest that Gata3 is a critical regulator of PTH gene expression. ..
  37. D Agruma L, Coco M, Guarnieri V, Battista C, Canaff L, Salcuni A, et al. Increased prevalence of the GCM2 polymorphism, Y282D, in primary hyperparathyroidism: analysis of three Italian cohorts. J Clin Endocrinol Metab. 2014;99:E2794-8 pubmed publisher
    ..05). The higher frequency of GCM2 282D in PHPT and enhanced transcriptional activity of this variant supports the notion that it could contribute causally to parathyroid tumorigenesis. ..
  38. MANNSTADT M, Bertrand G, Muresan M, Weryha G, LeHeup B, Pulusani S, et al. Dominant-negative GCMB mutations cause an autosomal dominant form of hypoparathyroidism. J Clin Endocrinol Metab. 2008;93:3568-76 pubmed publisher
    ..Furthermore, homozygous mutations in glial cells missing B (GCMB) have been implicated in autosomal recessive HP (AR-HP)...
  39. Guan B, Welch J, Sapp J, Ling H, Li Y, Johnston J, et al. GCM2-Activating Mutations in Familial Isolated Hyperparathyroidism. Am J Hum Genet. 2016;99:1034-1044 pubmed publisher
    ..Our results demonstrate that germline-activating mutations affecting the CCID of GCM2 can cause FIHP. ..
  40. He C, Kraft P, Chen C, Buring J, Pare G, Hankinson S, et al. Genome-wide association studies identify loci associated with age at menarche and age at natural menopause. Nat Genet. 2009;41:724-8 pubmed publisher
    ..42 (in or near the gene BRSK1), 5q35.2 (in or near genes UIMC1 and HK3) and 6p24.2 (in the gene SYCP2L). These newly identified loci might expand understanding of the biological pathways regulating these two traits. ..