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URL of this page: https://medlineplus.gov/genetics/gene/rai1/

RAI1 gene

retinoic acid induced 1

Normal Function

The RAI1 gene provides instructions for making a protein that is highly active in nerve cells (neurons) in the brain. The RAI1 protein is a transcription factor, which means that it binds to DNA and helps control the activity (expression) of certain genes.

Studies suggest that the RAI1 protein may play an important role in early brain development. This protein may also help regulate the expression of genes that are involved in daily (circadian) rhythms, such as the sleep-wake cycle. The RAI1 protein also appears to be involved in the development of the bones in the head and face (craniofacial bones).

Health Conditions Related to Genetic Changes

Potocki-Lupski syndrome

The RAI1 gene is located in a region of chromosome 17 that is duplicated in people with Potocki-Lupski syndrome. Having an extra copy of the RAI1 gene is thought to be responsible for many of the major features of Potocki-Lupski syndrome. This condition is characterized by delayed development, intellectual disabilities, sleep disturbances, and behavioral difficulties. In people with Potocki-Lupski syndrome, a small piece of the short (p) arm of chromosome 17 at position p11.2 is duplicated. While the size of the duplications can vary, all of the duplications that are known to cause Potocki-Lupski syndrome contain the RAI1 gene.

Studies suggest that the chromosomal duplication increases the amount of RAI1 protein that is produced, which disrupts the expression of genes that influence circadian rhythms. These changes may account for the sleep disturbances that occur in people with Potocki-Lupski syndrome. Although many of the genes that are regulated by RAI1 have not been identified, too much RAI1 protein may disrupt brain development and contribute to the neurological and behavioral features of this condition. Development of the bones in the head and face may also be affected by excess RAI1 protein, leading to subtle facial differences in people with Potocki-Lupski syndrome.

More About This Health Condition

Smith-Magenis syndrome

Research shows that a partial or total loss of function of the RAI1 gene accounts for most of the signs and symptoms of Smith-Magenis syndrome. The major features of this condition include mild to moderate intellectual disabilities, delayed speech and language skills, distinctive facial features, sleep disturbances, and behavioral problems.

In most people with Smith-Magenis syndrome, the condition results from the deletion of a small piece of chromosome 17 in each cell. In many cases, this chromosome segment, located at 17p11.2, is the same segment that is duplicated in people with Potocki-Lupski syndrome. Occasionally, the deletion is larger or smaller. All of the deletions affect one of the two copies of chromosome 17 in each cell.

All of the deletions that are known to cause Smith-Magenis syndrome contain the RAI1 gene. Studies suggest that the deletion reduces the amount of RAI1 protein in cells, which disrupts the expression of genes involved in circadian rhythms. These changes may account for the sleep disturbances that occur in people with Smith-Magenis syndrome. It is unclear exactly how the loss of one copy of the RAI1 gene leads to all of the features that are associated with this condition.

A small percentage of people with Smith-Magenis syndrome have a variant (also called a mutation) in the RAI1 gene instead of a chromosomal deletion. Although these individuals have many of the major features of the condition, they are less likely than people with a deletion to have short stature, hearing loss, and heart or kidney abnormalities. In people with a deletion, it is likely that the loss of other genes in the deleted region contributes to these additional signs and symptoms.

More About This Health Condition

Yuan-Harel-Lupski syndrome

Having an extra copy of the RAI1 gene in each cell is thought to cause many of the major features of Yuan-Harel-Lupski (YUHAL) syndrome, which is characterized by developmental delays, behavioral problems, and damage to the peripheral nerves. The peripheral nerves connect the brain and spinal cord to muscles and to the cells that detect sensations such as touch, pain, and heat. This condition results from the duplication of a small piece of chromosome 17 in a region designated p12-p11.2. In people with YUHAL syndrome, the duplicated segments can range in size from 3.2 million DNA building blocks (base pairs), also written as 3.2 megabses (Mb), to 19.7 Mb. These duplications affect one of the two copies of chromosome 17 in each cell. 

The duplications that cause YUHAL syndrome all contain the RAI1 gene and a nearby gene called PMP22. The segments may also contain additional genes. Some features of YUHAL syndrome, such as developmental delays, behavioral and sleep problems, and unusual facial features, are similar to those seen in people with Potocki-Lupski syndrome and are likely caused by an extra copy of the RAI1 gene. Other features of YUHAL syndrome, such as muscle weakness and decreased sensitivity to touch and temperature in the lower legs and feet, likely result from an extra copy of the PMP22 gene.

More About This Health Condition

Other Names for This Gene

  • DKFZP434A139
  • KIAA1820
  • MGC12824
  • SMS

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

  • Bi W, Saifi GM, Girirajan S, Shi X, Szomju B, Firth H, Magenis RE, Potocki L, Elsea SH, Lupski JR. RAI1 point mutations, CAG repeat variation, and SNP analysis in non-deletion Smith-Magenis syndrome. Am J Med Genet A. 2006 Nov 15;140(22):2454-63. doi: 10.1002/ajmg.a.31510. Citation on PubMed
  • Bi W, Saifi GM, Shaw CJ, Walz K, Fonseca P, Wilson M, Potocki L, Lupski JR. Mutations of RAI1, a PHD-containing protein, in nondeletion patients with Smith-Magenis syndrome. Hum Genet. 2004 Nov;115(6):515-24. doi: 10.1007/s00439-004-1187-6. Epub 2004 Sep 30. Citation on PubMed
  • Carmona-Mora P, Encina CA, Canales CP, Cao L, Molina J, Kairath P, Young JI, Walz K. Functional and cellular characterization of human Retinoic Acid Induced 1 (RAI1) mutations associated with Smith-Magenis Syndrome. BMC Mol Biol. 2010 Aug 25;11:63. doi: 10.1186/1471-2199-11-63. Citation on PubMed or Free article on PubMed Central
  • Falco M, Amabile S, Acquaviva F. RAI1 gene mutations: mechanisms of Smith-Magenis syndrome. Appl Clin Genet. 2017 Nov 3;10:85-94. doi: 10.2147/TACG.S128455. eCollection 2017. Citation on PubMed
  • Fragoso YD, Stoney PN, Shearer KD, Sementilli A, Nanescu SE, Sementilli P, McCaffery P. Expression in the human brain of retinoic acid induced 1, a protein associated with neurobehavioural disorders. Brain Struct Funct. 2015 Mar;220(2):1195-203. doi: 10.1007/s00429-014-0712-1. Epub 2014 Feb 12. Citation on PubMed
  • Girirajan S, Elsas LJ 2nd, Devriendt K, Elsea SH. RAI1 variations in Smith-Magenis syndrome patients without 17p11.2 deletions. J Med Genet. 2005 Nov;42(11):820-8. doi: 10.1136/jmg.2005.031211. Epub 2005 Mar 23. Citation on PubMed or Free article on PubMed Central
  • Girirajan S, Vlangos CN, Szomju BB, Edelman E, Trevors CD, Dupuis L, Nezarati M, Bunyan DJ, Elsea SH. Genotype-phenotype correlation in Smith-Magenis syndrome: evidence that multiple genes in 17p11.2 contribute to the clinical spectrum. Genet Med. 2006 Jul;8(7):417-27. doi: 10.1097/01.gim.0000228215.32110.89. Citation on PubMed
  • Huang WH, Guenthner CJ, Xu J, Nguyen T, Schwarz LA, Wilkinson AW, Gozani O, Chang HY, Shamloo M, Luo L. Molecular and Neural Functions of Rai1, the Causal Gene for Smith-Magenis Syndrome. Neuron. 2016 Oct 19;92(2):392-406. doi: 10.1016/j.neuron.2016.09.019. Epub 2016 Sep 29. Citation on PubMed or Free article on PubMed Central
  • Mullegama SV, Alaimo JT, Fountain MD, Burns B, Balog AH, Chen L, Elsea SH. RAI1 Overexpression Promotes Altered Circadian Gene Expression and Dyssomnia in Potocki-Lupski Syndrome. J Pediatr Genet. 2017 Sep;6(3):155-164. doi: 10.1055/s-0037-1599147. Epub 2017 Mar 7. Citation on PubMed or Free article on PubMed Central
  • Potocki L, Bi W, Treadwell-Deering D, Carvalho CM, Eifert A, Friedman EM, Glaze D, Krull K, Lee JA, Lewis RA, Mendoza-Londono R, Robbins-Furman P, Shaw C, Shi X, Weissenberger G, Withers M, Yatsenko SA, Zackai EH, Stankiewicz P, Lupski JR. Characterization of Potocki-Lupski syndrome (dup(17)(p11.2p11.2)) and delineation of a dosage-sensitive critical interval that can convey an autism phenotype. Am J Hum Genet. 2007 Apr;80(4):633-49. doi: 10.1086/512864. Epub 2007 Feb 26. Citation on PubMed or Free article on PubMed Central
  • Potocki L, Chen KS, Park SS, Osterholm DE, Withers MA, Kimonis V, Summers AM, Meschino WS, Anyane-Yeboa K, Kashork CD, Shaffer LG, Lupski JR. Molecular mechanism for duplication 17p11.2- the homologous recombination reciprocal of the Smith-Magenis microdeletion. Nat Genet. 2000 Jan;24(1):84-7. doi: 10.1038/71743. Citation on PubMed
  • Potocki L, Neira-Fresneda J, Yuan B. Potocki-Lupski Syndrome. 2017 Aug 24. In: Adam MP, Bick S, Mirzaa GM, Wallace SE, Amemiya A, editors. GeneReviews(R) [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2026. Available from http://www.ncbi.nlm.nih.gov/books/NBK447920/ Citation on PubMed
  • Slager RE, Newton TL, Vlangos CN, Finucane B, Elsea SH. Mutations in RAI1 associated with Smith-Magenis syndrome. Nat Genet. 2003 Apr;33(4):466-8. doi: 10.1038/ng1126. Epub 2003 Mar 24. Citation on PubMed
  • Smith ACM, Berens J, Boyd KE, Brennan C, Gropman A, Haas-Givler B, Vlangos C, Foster R, Franciskovich R, Girirajan S, Raitano Lee N, Taylor C, Turnacioglu SO, Elsea SH. Smith-Magenis Syndrome. 2001 Oct 22 [updated 2026 Apr 2]. In: Adam MP, Bick S, Mirzaa GM, Wallace SE, Amemiya A, editors. GeneReviews(R) [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2026. Available from http://www.ncbi.nlm.nih.gov/books/NBK1310/ Citation on PubMed
  • Williams SR, Zies D, Mullegama SV, Grotewiel MS, Elsea SH. Smith-Magenis syndrome results in disruption of CLOCK gene transcription and reveals an integral role for RAI1 in the maintenance of circadian rhythmicity. Am J Hum Genet. 2012 Jun 8;90(6):941-9. doi: 10.1016/j.ajhg.2012.04.013. Epub 2012 May 10. Citation on PubMed or Free article on PubMed Central
  • Yuan B, Harel T, Gu S, Liu P, Burglen L, Chantot-Bastaraud S, Gelowani V, Beck CR, Carvalho CM, Cheung SW, Coe A, Malan V, Munnich A, Magoulas PL, Potocki L, Lupski JR. Nonrecurrent 17p11.2p12 Rearrangement Events that Result in Two Concomitant Genomic Disorders: The PMP22-RAI1 Contiguous Gene Duplication Syndrome. Am J Hum Genet. 2015 Nov 5;97(5):691-707. doi: 10.1016/j.ajhg.2015.10.003. 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.