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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 involved in the formation of tissues and organs during embryonic development. SALL proteins are transcription factors, which means they attach (bind) to specific regions of DNA and help control the activity of particular genes.

The exact function of the SALL4 protein remains unclear. Based on the functions of similar proteins in other organisms (such as zebrafish and mice), the SALL4 protein appears to play a critical role in the developing limbs. 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

More than 25 mutations in the SALL4 gene have been identified in people with Duane-radial ray syndrome (also known as Okihiro syndrome) or a very similar condition called acro-renal-ocular syndrome. Researchers suspect that Duane-radial ray syndrome and acro-renal-ocular syndrome are part of an overlapping set of syndromes with many possible signs and symptoms.

Most SALL4 gene mutations create a premature stop signal in the instructions for making the SALL4 protein. As a result, cells do not produce any functional protein from one copy of this gene. Researchers are investigating how a reduction in the amount of the SALL4 protein disrupts eye, heart, and limb development in people with Duane-radial ray syndrome and acro-renal-ocular syndrome.

More About This Health Condition

Coloboma

MedlinePlus Genetics provides information about Coloboma

More About This Health Condition

Other disorders

A least one mutation in the SALL4 gene has been found to cause IVIC syndrome, a condition whose signs and symptoms overlap with those of Duane-radial ray syndrome and acro-renal-ocular syndrome (described above). The acronym IVIC stands for Instituto Venezolano de Investigaciones Cientìficas, the center where the condition was first described. Major features of IVIC syndrome include abnormally formed bones in the arms and hands, hearing loss, and problems with eye movement caused by abnormalities of the muscles that surround the eyes (extraocular muscles).

The SALL4 gene mutation responsible for IVIC syndrome creates a premature stop signal in the instructions for making the SALL4 protein. As a result, cells produce an abnormally short version of the protein from one copy of this gene. It is unclear whether this shortened protein is completely nonfunctional or if it retains some of its function as a transcription factor. Researchers are working to determine how this SALL4 gene mutation disrupts early development and leads to the characteristic features of IVIC syndrome.

Other Names for This Gene

  • dJ1112F19.1
  • DRRS
  • HSAL4
  • MGC133050
  • sal (Drosophila)-like 4
  • sal-like 4
  • sal-like 4 (Drosophila)
  • SALL4_HUMAN
  • spalt-like transcription factor 4
  • Zinc finger protein SALL4
  • ZNF797

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

  • 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
  • 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, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews(R) [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2024. 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
  • 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.