Reviewed December 2009
What is the official name of the SALL4 gene?
The official name of this gene is “spalt-like transcription factor 4.”
SALL4 is the gene's official symbol. The SALL4 gene is also known by other names, listed below.
What is the normal function of the SALL4 gene?
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.
How are changes in the SALL4 gene related to health conditions?
- Duane-radial ray syndrome - caused by mutations in the SALL4 gene
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.
- other disorders - caused by mutations in the SALL4 gene
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. 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.
Where is the SALL4 gene located?
Cytogenetic Location: 20q13.2
Molecular Location on chromosome 20: base pairs 50,400,550 to 50,419,058
The SALL4 gene is located on the long (q) arm of chromosome 20 at position 13.2.
More precisely, the SALL4 gene is located from base pair 50,400,550 to base pair 50,419,058 on chromosome 20.
See How do geneticists indicate the location of a gene? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genelocation) in the Handbook.
Where can I find additional information about SALL4?
You and your healthcare professional may find the following resources about SALL4 helpful.
- Gene Reviews - Clinical summary (http://www.ncbi.nlm.nih.gov/books/NBK1373/)
Genetic Testing Registry - Repository of genetic test information
- GTR: Genetic tests for SALL4 (http://www.ncbi.nlm.nih.gov/gtr/tests/?term=57167%5Bgeneid%5D)
You may also be interested in these resources, which are designed for genetics professionals and researchers.
- PubMed - Recent literature (http://www.ncbi.nlm.nih.gov/pubmed?term=((SALL4%5BTIAB%5D)%20OR%20(sal-like%204%5BTIAB%5D))%20AND%20((Genes%5BMH%5D)%20OR%20(Genetic%20Phenomena%5BMH%5D))%20AND%20english%5Bla%5D%20AND%20human%5Bmh%5D%20AND%20%22last%203600%20days%22%5Bdp%5D)
OMIM - Genetic disorder catalog
- IVIC SYNDROME (http://omim.org/entry/147750)
- SAL-LIKE 4 (http://omim.org/entry/607343)
Research Resources - Tools for researchers
- Atlas of Genetics and Cytogenetics in Oncology and Haematology (http://atlasgeneticsoncology.org/Genes/GC_SALL4.html)
- GeneCards (http://www.genecards.org/cgi-bin/carddisp.pl?id_type=entrezgene&id=57167)
- HUGO Gene Nomenclature Committee (http://www.genenames.org/data/hgnc_data.php?hgnc_id=15924)
- NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/57167)
What other names do people use for the SALL4 gene or gene products?
- sal (Drosophila)-like 4
- sal-like 4
- sal-like 4 (Drosophila)
- Zinc finger protein SALL4
See How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.
What glossary definitions help with understanding SALL4?
extraocular muscles ;
You may find definitions for these and many other terms in the Genetics Home Reference
- 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. Epub 2002 Oct 22. (http://www.ncbi.nlm.nih.gov/pubmed/12395297?dopt=Abstract)
- Borozdin W, Boehm D, Leipoldt M, Wilhelm C, Reardon W, Clayton-Smith J, Becker K, Mühlendyck 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. (http://www.ncbi.nlm.nih.gov/pubmed/15342710?dopt=Abstract)
- Gene Review: SALL4-Related Disorders (http://www.ncbi.nlm.nih.gov/books/NBK1373/)
- Harvey SA, Logan MP. sall4 acts downstream of tbx5 and is required for pectoral fin outgrowth. Development. 2006 Mar;133(6):1165-73. (http://www.ncbi.nlm.nih.gov/pubmed/16501170?dopt=Abstract)
- Kohlhase J, Chitayat D, Kotzot D, Ceylaner S, Froster UG, Fuchs S, Montgomery T, Rösler 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. (http://www.ncbi.nlm.nih.gov/pubmed/16086360?dopt=Abstract)
- 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. (http://www.ncbi.nlm.nih.gov/pubmed/12393809?dopt=Abstract)
- 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. Epub 2005 Dec 25. (http://www.ncbi.nlm.nih.gov/pubmed/16380715?dopt=Abstract)
- 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. Epub 2006 Jan 3. (http://www.ncbi.nlm.nih.gov/pubmed/16402211?dopt=Abstract)
- NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/57167)
- 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. (http://www.ncbi.nlm.nih.gov/pubmed/17256792?dopt=Abstract)
- Terhal P, Rösler 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. (http://www.ncbi.nlm.nih.gov/pubmed/16411190?dopt=Abstract)
The resources on this site should not be used as a substitute for
professional medical care or advice. Users seeking information about
a personal genetic disease, syndrome, or condition should consult with a qualified
See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.