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URL of this page: https://medlineplus.gov/genetics/gene/sall4/

SALL4 gene

spalt like transcription factor 4

Normal Function

The SALL4 gene is part of a group of genes called the SALL family. These genes provide instructions for making proteins that are essential for the proper formation of tissues and organs before birth. SALL proteins are transcription factors, which means they bind to specific regions of DNA and help control the activity of particular genes.

The exact function of the SALL4 protein remains unclear, although the protein appears to support and maintain embryonic stem cells, which are present during early development and give rise to other types of cells. Studies done in other animals suggest that the SALL4 protein plays a critical role in the developing arms and legs. This protein may also be important for the development of nerves that control eye movement and for the formation of the walls (septa) that divide the heart into separate chambers.

Health Conditions Related to Genetic Changes

Duane-radial ray syndrome

Genetic changes that cause disease are called pathogenic variants. Pathogenic variants in the SALL4 gene can cause Duane-radial ray syndrome, also called Okihiro syndrome. This condition is characterized by abnormalities of the bones in the arms and hands, problems with the eyes and ears, and occasional heart or kidney defects.

Most of the pathogenic variants that cause Duane-radial ray syndrome are considered “loss-of-function variants” because they reduce the activity of the SALL4 protein or decrease the amount of protein that is produced by cells. Some of the pathogenic variants that cause Duane-radial ray syndrome create a premature stop signal in the instructions for making the SALL4 protein. As a result, cells do not produce any functional proteins from one copy of this gene. Researchers are investigating how a reduction in the amount of SALL4 protein disrupts the development of the eyes, arms, hands, and other tissues in people with Duane-radial ray syndrome.

More About This Health Condition

Anophthalmia/Microphthalmia

MedlinePlus Genetics provides information about Anophthalmia/Microphthalmia

More About This Health Condition

Coloboma

MedlinePlus Genetics provides information about Coloboma

More About This Health Condition

Other Names for This Gene

  • HSAL4

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

  • Ajam-Hosseini M, Parvini F, Angaji A. A novel de novo nonsense mutation in SALL4 causing duane radial ray syndrome: a case report and expanding the phenotypic spectrum. BMC Med Genomics. 2023 Feb 24;16(1):33. doi: 10.1186/s12920-023-01467-1. Citation on PubMed
  • Al-Baradie R, Yamada K, St Hilaire C, Chan WM, Andrews C, McIntosh N, Nakano M, Martonyi EJ, Raymond WR, Okumura S, Okihiro MM, Engle EC. Duane radial ray syndrome (Okihiro syndrome) maps to 20q13 and results from mutations in SALL4, a new member of the SAL family. Am J Hum Genet. 2002 Nov;71(5):1195-9. doi: 10.1086/343821. Epub 2002 Oct 22. Citation on PubMed or Free article on PubMed Central
  • Borozdin W, Boehm D, Leipoldt M, Wilhelm C, Reardon W, Clayton-Smith J, Becker K, Muhlendyck H, Winter R, Giray O, Silan F, Kohlhase J. SALL4 deletions are a common cause of Okihiro and acro-renal-ocular syndromes and confirm haploinsufficiency as the pathogenic mechanism. J Med Genet. 2004 Sep;41(9):e113. doi: 10.1136/jmg.2004.019901. No abstract available. Citation on PubMed or Free article on PubMed Central
  • Gao C, Kong NR, Li A, Tatetu H, Ueno S, Yang Y, He J, Yang J, Ma Y, Kao GS, Tenen DG, Chai L. SALL4 is a key transcription regulator in normal human hematopoiesis. Transfusion. 2013 May;53(5):1037-49. doi: 10.1111/j.1537-2995.2012.03888.x. Epub 2012 Aug 31. Citation on PubMed
  • Harvey SA, Logan MP. sall4 acts downstream of tbx5 and is required for pectoral fin outgrowth. Development. 2006 Mar;133(6):1165-73. doi: 10.1242/dev.02259. Citation on PubMed
  • Kohlhase J, Chitayat D, Kotzot D, Ceylaner S, Froster UG, Fuchs S, Montgomery T, Rosler B. SALL4 mutations in Okihiro syndrome (Duane-radial ray syndrome), acro-renal-ocular syndrome, and related disorders. Hum Mutat. 2005 Sep;26(3):176-83. doi: 10.1002/humu.20215. Citation on PubMed
  • Kohlhase J, Heinrich M, Schubert L, Liebers M, Kispert A, Laccone F, Turnpenny P, Winter RM, Reardon W. Okihiro syndrome is caused by SALL4 mutations. Hum Mol Genet. 2002 Nov 1;11(23):2979-87. doi: 10.1093/hmg/11.23.2979. Citation on PubMed
  • Kohlhase J. SALL4-Related Disorders. 2004 Aug 16 [updated 2022 Mar 17]. 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/NBK1373/ Citation on PubMed
  • Koshiba-Takeuchi K, Takeuchi JK, Arruda EP, Kathiriya IS, Mo R, Hui CC, Srivastava D, Bruneau BG. Cooperative and antagonistic interactions between Sall4 and Tbx5 pattern the mouse limb and heart. Nat Genet. 2006 Feb;38(2):175-83. doi: 10.1038/ng1707. Epub 2005 Dec 25. Citation on PubMed
  • Miertus J, Borozdin W, Frecer V, Tonini G, Bertok S, Amoroso A, Miertus S, Kohlhase J. A SALL4 zinc finger missense mutation predicted to result in increased DNA binding affinity is associated with cranial midline defects and mild features of Okihiro syndrome. Hum Genet. 2006 Mar;119(1-2):154-61. doi: 10.1007/s00439-005-0124-7. Epub 2006 Jan 3. Citation on PubMed
  • Paradisi I, Arias S. IVIC syndrome is caused by a c.2607delA mutation in the SALL4 locus. Am J Med Genet A. 2007 Feb 15;143(4):326-32. doi: 10.1002/ajmg.a.31603. Citation on PubMed
  • Sun B, Xu L, Bi W, Ou WB. SALL4 Oncogenic Function in Cancers: Mechanisms and Therapeutic Relevance. Int J Mol Sci. 2022 Feb 12;23(4):2053. doi: 10.3390/ijms23042053. Citation on PubMed
  • Tatetsu H, Kong NR, Chong G, Amabile G, Tenen DG, Chai L. SALL4, the missing link between stem cells, development and cancer. Gene. 2016 Jun 15;584(2):111-9. doi: 10.1016/j.gene.2016.02.019. Epub 2016 Feb 16. Citation on PubMed
  • Terhal P, Rosler B, Kohlhase J. A family with features overlapping Okihiro syndrome, hemifacial microsomia and isolated Duane anomaly caused by a novel SALL4 mutation. Am J Med Genet A. 2006 Feb 1;140(3):222-6. doi: 10.1002/ajmg.a.31060. 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.