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URL of this page: https://medlineplus.gov/genetics/gene/gcm2/

GCM2 gene

glial cells missing transcription factor 2

Normal Function

The GCM2 gene provides instructions for making a protein that is primarily found in the parathyroid glands. These four glands are located in the neck and produce a hormone called parathyroid hormone that regulates the levels of calcium in the blood. The GCM2 protein is needed for the development of the parathyroid glands before birth, and it plays a role in the maintenance of these glands into adulthood.

The GCM2 protein acts as a transcription factor, which means that it binds to specific regions of DNA and helps control the activity of genes. As a transcription factor, it is likely that the GCM2 protein helps produce parathyroid hormone.

Health Conditions Related to Genetic Changes

Familial isolated hyperparathyroidism

Variants (also called mutations) in the GCM2 gene can increase the risk of developing familial isolated hyperparathyroidism, a condition that is characterized by overactive parathyroid glands (hyperparathyroidism). These four glands are located in the neck and release a hormone that helps regulate the levels of calcium in the blood. This regulation is disrupted in people with familial isolated hyperparathyroidism, which can lead to high blood calcium levels (hypercalcemia), kidney stones, thinning of the bones (osteoporosis), nausea, vomiting, high blood pressure (hypertension), weakness, and fatigue.

Most of the GCM2 gene variants that are associated with familial isolated hyperparathyroidism lead to the substitution of one protein building block (amino acid) for another in the GCM2 protein. These changes cause cells to produce an overactive version of the GCM2 protein that likely leads to the overproduction of parathyroid hormone. As a result, more calcium could be released into the blood, causing people to have an increased risk of developing the signs and symptoms of familial isolated hyperparathyroidism.

More About This Health Condition

Other disorders

Variants in the GCM2 gene can also cause isolated hypoparathyroidism, a condition that is characterized by a shortage of parathyroid hormone (hypoparathyroidism). People with isolated hypoparathyroidism often have low levels of calcium in the blood (hypocalemia). Hypocalcemia can cause muscle cramping and other health problems, although many people with this condition have no associated health problems.

Most of the GCM2 gene variants that cause isolated hypoparathyroidism cause cells to produce an altered or abnormally shortened version of the GCM2 protein that does not function properly. As a result, the parathyroid glands produce less parathyroid hormone. Without enough parathyroid hormone, blood levels of calcium are kept low, leading to the signs and symptoms of isolated hypoparathyroidism.

Other Names for This Gene

  • GCMB

Additional Information & Resources

Tests Listed in the Genetic Testing Registry

Scientific Articles on PubMed

Catalog of Genes and Diseases from OMIM

Gene and Variant Databases

References

  • Bowl MR, Mirczuk SM, Grigorieva IV, Piret SE, Cranston T, Southam L, Allgrove J, Bahl S, Brain C, Loughlin J, Mughal Z, Ryan F, Shaw N, Thakker YV, Tiosano D, Nesbit MA, Thakker RV. 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 May 15;19(10):2028-38. doi: 10.1093/hmg/ddq084. Epub 2010 Feb 27. Citation on PubMed
  • Cetani F, Pardi E, Aretini P, Saponaro F, Borsari S, Mazoni L, Apicella M, Civita P, La Ferla M, Caligo MA, Lessi F, Mazzanti CM, Torregossa L, Oppo A, Marcocci C. Whole exome sequencing in familial isolated primary hyperparathyroidism. J Endocrinol Invest. 2020 Feb;43(2):231-245. doi: 10.1007/s40618-019-01107-5. Epub 2019 Sep 5. Citation on PubMed
  • English KA, Lines KE, Thakker RV. Genetics of hereditary forms of primary hyperparathyroidism. Hormones (Athens). 2024 Mar;23(1):3-14. doi: 10.1007/s42000-023-00508-9. Epub 2023 Dec 1. Citation on PubMed
  • Garcia-Castano A, Madariaga L, Gomez-Conde S, Cordo CLR, Lopez-Iglesias M, Garcia-Fernandez Y, Martin A, Gonzalez P, Goicolea I, de Nanclares GP, De la Hoz AB, Aguayo A, de LaPiscina IM, Martinez R, Saso L, Urrutia I, Velasco O, Castano L, Gaztambide S. Five patients with disorders of calcium metabolism presented with GCM2 gene variants. Sci Rep. 2021 Feb 3;11(1):2968. doi: 10.1038/s41598-021-82661-y. Citation on PubMed
  • Guan B, Welch JM, Sapp JC, Ling H, Li Y, Johnston JJ, Kebebew E, Biesecker LG, Simonds WF, Marx SJ, Agarwal SK. GCM2-Activating Mutations in Familial Isolated Hyperparathyroidism. Am J Hum Genet. 2016 Nov 3;99(5):1034-1044. doi: 10.1016/j.ajhg.2016.08.018. Epub 2016 Oct 13. Citation on PubMed
  • Vincze S, Peters NV, Kuo CL, Brown TC, Korah R, Murtha TD, Bellizzi J, Riccardi A, Parham K, Carling T, Costa-Guda J, Arnold A. GCM2 Variants in Familial and Multiglandular Primary Hyperparathyroidism. J Clin Endocrinol Metab. 2022 Apr 19;107(5):e2021-e2026. doi: 10.1210/clinem/dgab929. Citation on PubMed

The information on this site should not be used as a substitute for professional medical care or advice. Contact a health care provider if you have questions about your health.