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Normal Function
The SMARCAL1 gene provides instructions for producing a protein that interacts with DNA. The SMARCAL1 protein helps when the process of making new copies of DNA, called DNA replication, is blocked by DNA damage. When DNA replication stalls, the SMARCAL1 proteins repair DNA damage by reattaching the two strands of DNA's double helix and allowing replication to proceed.
The SMARCAL1 protein is also thought to influence the activity (expression) of other genes through a couple of different mechanisms. One mechanism is by attaching (binding) to certain regions of DNA and turning specific genes on or turning off. The other mechanism is by binding to chromatin, which is the complex of DNA and protein that packages DNA into chromosomes. Research on the function of similar proteins suggests that the SMARCAL1 protein may be involved in a process known as chromatin remodeling. This occurs by changing (remodeling) the structure of chromatin to alter how tightly DNA is packaged. Chromatin remodeling is one way gene expression is regulated during development. When DNA is tightly packed, gene expression is lower than when DNA is loosely packed.
Health Conditions Related to Genetic Changes
Schimke immuno-osseous dysplasia
Variants (also called mutations) in the SMARCAL1 gene have been found to cause Schimke immuno-osseous dysplasia. This condition is characterized by short stature, kidney disease, and a weakened immune system. The variants associated with Schimke immuno-osseous dysplasia disrupt the usual functions of the SMARCAL1 protein or prevent the production of any functional protein. People who have no functional SMARCAL1 proteins tend to have a more severe form of this disorder than those who have malfunctioning proteins.
Variants in the SMARCAL1 gene disrupt the usual functions of the SMARCAL1 protein or prevent the production of any functional protein. The altered or missing SMARCAL1 protein cannot repair DNA damage, which stalls DNA replication. While the exact mechanisms are unclear, this disruption in DNA replication and the buildup of DNA damage lead to the skeletal, immune system, and other problems in people with Schimke immuno-osseous dysplasia.
More About This Health ConditionOther Names for This Gene
- HARP
- HepA-related protein
- HHARP
- SMAL1_HUMAN
Additional Information & Resources
Tests Listed in the Genetic Testing Registry
Scientific Articles on PubMed
Catalog of Genes and Diseases from OMIM
References
- Bansal R, Hussain S, Chanana UB, Bisht D, Goel I, Muthuswami R. SMARCAL1, the annealing helicase and the transcriptional co-regulator. IUBMB Life. 2020 Oct;72(10):2080-2096. doi: 10.1002/iub.2354. Epub 2020 Aug 5. Citation on PubMed
- Boerkoel CF, Takashima H, John J, Yan J, Stankiewicz P, Rosenbarker L, Andre JL, Bogdanovic R, Burguet A, Cockfield S, Cordeiro I, Frund S, Illies F, Joseph M, Kaitila I, Lama G, Loirat C, McLeod DR, Milford DV, Petty EM, Rodrigo F, Saraiva JM, Schmidt B, Smith GC, Spranger J, Stein A, Thiele H, Tizard J, Weksberg R, Lupski JR, Stockton DW. Mutant chromatin remodeling protein SMARCAL1 causes Schimke immuno-osseous dysplasia. Nat Genet. 2002 Feb;30(2):215-20. doi: 10.1038/ng821. Epub 2002 Jan 22. Citation on PubMed
- Deguchi K, Clewing JM, Elizondo LI, Hirano R, Huang C, Choi K, Sloan EA, Lucke T, Marwedel KM, Powell RD Jr, Santa Cruz K, Willaime-Morawek S, Inoue K, Lou S, Northrop JL, Kanemura Y, van der Kooy D, Okano H, Armstrong DL, Boerkoel CF. Neurologic phenotype of Schimke immuno-osseous dysplasia and neurodevelopmental expression of SMARCAL1. J Neuropathol Exp Neurol. 2008 Jun;67(6):565-77. doi: 10.1097/NEN.0b013e3181772777. Citation on PubMed
- Elizondo LI, Cho KS, Zhang W, Yan J, Huang C, Huang Y, Choi K, Sloan EA, Deguchi K, Lou S, Baradaran-Heravi A, Takashima H, Lucke T, Quiocho FA, Boerkoel CF. Schimke immuno-osseous dysplasia: SMARCAL1 loss-of-function and phenotypic correlation. J Med Genet. 2009 Jan;46(1):49-59. doi: 10.1136/jmg.2008.060095. Epub 2008 Sep 19. Citation on PubMed
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