URL of this page: https://medlineplus.gov/genetics/gene/smc1a/

SMC1A gene

structural maintenance of chromosomes 1A

Normal Function

The SMC1A gene provides instructions for making a protein that is part of the structural maintenance of chromosomes (SMC) family. Within the nucleus, SMC proteins help regulate the structure and organization of chromosomes.

The protein produced from the SMC1A gene helps control chromosomes during cell division. Before cells divide, they must copy all of their chromosomes. The copied DNA from each chromosome is arranged into two identical structures, called sister chromatids, which are attached to one another during the early stages of cell division. The SMC1A protein is part of a protein group called the cohesin complex that holds the sister chromatids together.

Researchers believe that the SMC1A protein, as a structural component of the cohesin complex, also plays important roles in stabilizing cells' genetic information, repairing damaged DNA, and regulating the activity of certain genes that are essential for normal development.

Health Conditions Related to Genetic Changes

Cornelia de Lange syndrome

Variants (also called mutations) in the SMC1A gene have been identified in people with Cornelia de Lange syndrome, a developmental disorder that affects many parts of the body. Researchers estimate that variants in this gene account for about 5 percent of all cases of this condition.

Most of the SMC1A gene variants that cause Cornelia de Lange syndrome change single protein building blocks (amino acids) in the SMC1A protein. These variants alter the structure and function of the protein, which likely interferes with the activity of the cohesin complex and impairs its ability to regulate genes that are critical for normal development. Although researchers do not fully understand how these changes cause Cornelia de Lange syndrome, they suspect that altered gene regulation probably underlies many of the developmental problems characteristic of the condition.

Studies suggest that variants in the SMC1A gene tend to cause a form of Cornelia de Lange syndrome with relatively mild features. Compared to variants in the NIPBL gene, which are the most common known cause of the disorder, SMC1A gene variants often cause less significant delays in development and growth and are less likely to cause major birth defects.

More About This Health Condition

Other disorders

Variants in the SMC1A gene have also been identified in infants with a form of X-linked epilepsy. (X-linked refers to the fact that the SMC1A gene is on the X chromosome, one of the two sex chromosomes.) This condition, called developmental and epileptic encephalopathy-85 with or without midline brain defects (or DEE85), appears to affect only females. Affected individuals develop severe, recurrent seizures (epilepsy) by age 2 and have intellectual and developmental impairments. These individuals can also have distinctive facial features.

Most of the SMC1A gene variants that cause DEE85 result in an abnormally short blueprint for making protein. As a result, the blueprint is likely broken down, preventing SMC1A protein production. The gene variants that cause DEE85 severely reduce or eliminate SMC1A protein function in cells. A loss of SMC1A protein function likely interferes with the activity of the cohesin complex and impairs its ability to regulate genes that are critical for normal development. Although researchers do not fully understand how these changes cause DEE85, they suspect that altered gene regulation probably underlies many of the developmental problems characteristic of the condition. It is thought that variants that result in little or no SMC1A protein function cause the more severe signs and symptoms of DEE85, and variants that result in a partially functional version of the protein cause Cornelia de Lange syndrome.

Other Names for This Gene

  • DXS423E
  • KIAA0178
  • segregation of mitotic chromosomes 1
  • SMC1
  • SMC1-alpha
  • SMC1A_HUMAN
  • SMC1L1
  • SMCB

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

  • Baranano KW, Kimball A, Fong SL, Egense AS, Hudon C, Kline AD. Further Characterization of SMC1A Loss of Function Epilepsy Distinct From Cornelia de Lange Syndrome. J Child Neurol. 2022 Apr;37(5):390-396. doi: 10.1177/08830738221081244. Epub 2022 Mar 3. Citation on PubMed
  • Borck G, Zarhrate M, Bonnefont JP, Munnich A, Cormier-Daire V, Colleaux L. Incidence and clinical features of X-linked Cornelia de Lange syndrome due to SMC1L1 mutations. Hum Mutat. 2007 Feb;28(2):205-6. doi: 10.1002/humu.9478. Citation on PubMed
  • Deardorff MA, Kaur M, Yaeger D, Rampuria A, Korolev S, Pie J, Gil-Rodriguez C, Arnedo M, Loeys B, Kline AD, Wilson M, Lillquist K, Siu V, Ramos FJ, Musio A, Jackson LS, Dorsett D, Krantz ID. Mutations in cohesin complex members SMC3 and SMC1A cause a mild variant of cornelia de Lange syndrome with predominant mental retardation. Am J Hum Genet. 2007 Mar;80(3):485-94. doi: 10.1086/511888. Epub 2007 Jan 17. Citation on PubMed or Free article on PubMed Central
  • Deardorff MA, Noon SE, Krantz ID. Cornelia de Lange Syndrome. 2005 Sep 16 [updated 2020 Oct 15]. In: Adam MP, Everman DB, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews(R) [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2022. Available from http://www.ncbi.nlm.nih.gov/books/NBK1104/ Citation on PubMed
  • Gervasini C, Russo S, Cereda A, Parenti I, Masciadri M, Azzollini J, Melis D, Aravena T, Doray B, Ferrarini A, Garavelli L, Selicorni A, Larizza L. Cornelia de Lange individuals with new and recurrent SMC1A mutations enhance delineation of mutation repertoire and phenotypic spectrum. Am J Med Genet A. 2013 Nov;161A(11):2909-19. doi: 10.1002/ajmg.a.36252. Epub 2013 Oct 2. Citation on PubMed
  • Liu J, Feldman R, Zhang Z, Deardorff MA, Haverfield EV, Kaur M, Li JR, Clark D, Kline AD, Waggoner DJ, Das S, Jackson LG, Krantz ID. SMC1A expression and mechanism of pathogenicity in probands with X-Linked Cornelia de Lange syndrome. Hum Mutat. 2009 Nov;30(11):1535-42. doi: 10.1002/humu.21095. Citation on PubMed or Free article on PubMed Central
  • Mannini L, Cucco F, Quarantotti V, Krantz ID, Musio A. Mutation spectrum and genotype-phenotype correlation in Cornelia de Lange syndrome. Hum Mutat. 2013 Dec;34(12):1589-96. doi: 10.1002/humu.22430. Epub 2013 Sep 16. Citation on PubMed or Free article on PubMed Central
  • Mannini L, Liu J, Krantz ID, Musio A. Spectrum and consequences of SMC1A mutations: the unexpected involvement of a core component of cohesin in human disease. Hum Mutat. 2010 Jan;31(1):5-10. doi: 10.1002/humu.21129. Citation on PubMed or Free article on PubMed Central
  • Musio A, Selicorni A, Focarelli ML, Gervasini C, Milani D, Russo S, Vezzoni P, Larizza L. X-linked Cornelia de Lange syndrome owing to SMC1L1 mutations. Nat Genet. 2006 May;38(5):528-30. doi: 10.1038/ng1779. Epub 2006 Apr 9. Citation on PubMed
  • Revenkova E, Focarelli ML, Susani L, Paulis M, Bassi MT, Mannini L, Frattini A, Delia D, Krantz I, Vezzoni P, Jessberger R, Musio A. Cornelia de Lange syndrome mutations in SMC1A or SMC3 affect binding to DNA. Hum Mol Genet. 2009 Feb 1;18(3):418-27. doi: 10.1093/hmg/ddn369. Epub 2008 Nov 7. Citation on PubMed or Free article on PubMed Central

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.