SWI/SNF-Related, Matrix-Associated, Actin-Dependent Regulator of Chromatin, Subfamily A-Like Protein 1

Alternative Names

  • SMARCAL1
  • SMARCA-Like Protein 1
  • HepA-Related Protein
  • HARP
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OMIM Number

606622

Gene Map Locus
2q35

Description

The SMARCAL1 gene encodes a protein called HepA-related protein (HARP).  This protein is required for transcriptional regulation, replication, repair, recombination, and covalent modification.  It has helicase and ATPase activities that bind selectively to fork DNA relative to ssDNA or dsDNA and catalyze the rewinding of the stably unwound DNA.  It also rewinds single-stranded DNA bubbles that are stably bound by replication protein A (RPA), and acts throughout the genome to reanneal stably unwound DNA, performing the opposite reaction of many enzymes, such as helicases and polymerases, which unwind DNA. 

Defects in this protein have been associated with Schimke immuno-osseous dysplasia (SIOD) disorder, characterized by spondyloepiphyseal dysplasia, renal dysfunction and T-cell immunodeficiency.

Molecular Genetics

The SMARCAL1 gene was mapped to the long arm of chromosome 2.  It has 16 coding exons spanning approximately 71 kb in the genomic DNA.  The encoded protein comprises 954 amino acids with a molecular mass of 106 kDa.  At least 40 mutations have been found to be associated with Schimke immuno-osseous dysplasia disorder.  These mutations include gene deletions, nonsense, frame shift, splicing and missense mutations.  Patients who have mutations that cause a complete lack of functional SMARCAL1 protein have a more severe form of this disorder than those who have mutations that lead to an active but malfunctioning protein.

Epidemiology in the Arab World

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Other Reports

Saudi Arabia

Taha et al. (2004) described a 5-year-old Saudi boy with Schimke immuno-osseous dysplasia born to first-degree cousins.  A homozygous mutation in exon 6 of the SMARCAL1 gene (1146-1147delAA+IVS6+2delGT) was identified in the affected child.  The mother was heterozygous for the mutation, and the father’s DNA was not available.  This mutation was predicted to destroy the splice donor site and results in a null allele.

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