SMARCAL1 Gene: Structure, Function, and Clinical Significance
A comprehensive guide to the SMARCAL1 gene, its protein product, associated diseases, and mutation landscape.
Gene Information Card
| Symbol | SMARCAL1 |
|---|---|
| Full Name | SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a-like 1 |
| Gene Type | protein-coding |
| Chromosomal Location | 2q35 |
| NCBI Gene ID | 50485 ncbi.nlm.nih.gov/gene/50485 |
| Ensembl ID | ENSG00000138375 |
| UniProt ID | Q9NZC9 |
| OMIM ID | 606622 |
| HGNC ID | 11102 |
| Aliases | HARP, SIOD |
Description
The SMARCAL1 gene encodes a protein that belongs to the SNF2 family of helicase-like proteins. It functions as an annealing helicase that catalyzes the rewinding of single-stranded DNA (ssDNA) into double-stranded DNA (dsDNA) in an ATP-dependent manner. This activity is crucial for maintaining genomic stability during DNA replication and repair, particularly at stalled replication forks. Mutations in SMARCAL1 are associated with Schimke immuno-osseous dysplasia (SIOD), a rare autosomal recessive disorder characterized by spondyloepiphyseal dysplasia, renal failure, and T-cell immunodeficiency.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Schimke immuno-osseous dysplasia (SIOD) | Loss-of-function mutations in SMARCAL1 lead to defective DNA damage response and replication fork stability, causing cellular apoptosis and organ-specific defects. | Multiple mutations identified in SIOD patients; functional studies confirm impaired annealing helicase activity. |
| Focal segmental glomerulosclerosis (FSGS) | SMARCAL1 mutations can cause renal dysfunction, including FSGS, due to podocyte injury from genomic instability. | Case reports and clinical studies in SIOD patients. |
| Immunodeficiency | Defective SMARCAL1 impairs V(D)J recombination and T-cell development, leading to immune deficiency. | Observed in SIOD patients; functional assays show reduced recombination efficiency. |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Kidney | 15.2 | Medium |
| Bone marrow | 10.5 | Medium |
| Thymus | 8.3 | Low |
| Liver | 6.1 | Low |
| Brain | 4.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 12.4 | High expression in embryonic kidney cells |
| HeLa | 9.8 | Moderate expression in cervical cancer cells |
| MCF7 | 7.2 | Low expression in breast cancer cells |
| K562 | 6.5 | Low expression in leukemia cells |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1333C>T (p.Arg445Ter) | Nonsense | Rare (found in SIOD patients) | Premature stop codon leading to truncated protein, loss of function |
| c.2542G>A (p.Glu848Lys) | Missense | Rare (found in SIOD patients) | Disrupts ATPase domain, reducing helicase activity |
| c.1684C>T (p.Arg562Trp) | Missense | Rare (found in SIOD patients) | Affects DNA binding, impairing annealing activity |
| c.2011delA (p.Thr671ProfsTer23) | Frameshift | Rare (found in SIOD patients) | Frameshift leading to truncated protein, loss of function |
Mutation functional classification
Loss of Function (LOF)
Most SMARCAL1 mutations are loss-of-function, leading to reduced or absent annealing helicase activity, causing genomic instability and SIOD.
Gain of Function (GOF)
No gain-of-function mutations have been reported for SMARCAL1.
Dominant Negative (DN)
Some missense mutations may exert a dominant-negative effect by interfering with wild-type protein function, though evidence is limited.
View complete mutation data：
Gene Ontology (GO)
| • DNA annealing helicase activity | • ATP binding |
| • DNA binding | • chromatin binding |
| • DNA repair | • replication fork processing |
| • response to DNA damage stimulus |
Pathways
• DNA replication
• DNA damage response
• Fanconi anemia pathway (related)
• Homologous recombination
Protein Summary
The SMARCAL1 protein is a 954-amino acid annealing helicase that belongs to the SNF2 family. It contains a helicase ATP-binding domain and a helicase C-terminal domain. It functions as a homodimer and binds to replication protein A (RPA) to recognize stalled replication forks. It catalyzes the rewinding of ssDNA into dsDNA, promoting fork regression and restart. This activity is essential for maintaining genomic stability under replication stress. Defects in SMARCAL1 lead to accumulation of DNA damage and apoptosis, particularly in rapidly dividing cells, explaining the clinical features of SIOD.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SMARCAL1 Knockout Huh-7 Cell Line | EDJ-KQ46 | Human | 50485 | Details Get a Quote |
| SMARCAL1 Knockout HEK293 Cell Line | EDJ-KQ2082 | Human | 50485 | Details Get a Quote |
| SMARCAL1 Knockout A-549 Cell Line | EDJ-KQ22171 | Human | 50485 | Details Get a Quote |
| SMARCAL1 Knockout HCT 116 Cell Line | EDJ-KQ22172 | Human | 50485 | Details Get a Quote |
| SMARCAL1 Knockout HeLa Cell Line | EDJ-KQ22173 | Human | 50485 | Details Get a Quote |
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