SPRTN
Spartin, a DNA damage response protein involved in replication fork stability and repair
Gene Information Card
| Symbol | SPRTN |
|---|---|
| Full Name | Spartin |
| Gene Type | Protein coding |
| Chromosomal Location | 1q42.2 |
| NCBI Gene ID | 83932 ncbi.nlm.nih.gov/gene/83932 |
| Ensembl ID | ENSG00000143178 |
| UniProt ID | Q9H0K4 |
| OMIM ID | 615607 |
| HGNC ID | 25458 |
| Aliases | C1orf124, DVC1, PRO4323, SPRTN |
Description
SPRTN encodes spartin, a metalloprotease involved in DNA damage tolerance and replication fork stability. It facilitates the repair of DNA-protein crosslinks and promotes replication fork progression by removing trapped proteins. Mutations in SPRTN cause Ruijs-Aalfs syndrome, characterized by progeroid features and hepatocellular carcinoma predisposition.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Ruijs-Aalfs syndrome | Loss-of-function mutations impair DNA-protein crosslink repair, leading to genomic instability and premature aging | OMIM #615607; ClinVar |
| Hepatocellular carcinoma | SPRTN deficiency promotes replication stress and tumorigenesis in liver | COSMIC; PMID: 28114273 |
| Werner syndrome-like progeria | SPRTN mutations cause accelerated aging features similar to Werner syndrome | OMIM; PMID: 22983593 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 12.5 | Medium |
| Liver | 8.2 | Medium |
| Kidney | 7.1 | Medium |
| Brain | 5.3 | Low |
| Heart | 4.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 10.1 | Liver cancer cell line |
| HeLa | 8.5 | Cervical cancer cell line |
| HEK293 | 7.3 | Embryonic kidney cell line |
| A549 | 6.2 | Lung cancer cell line |
| K562 | 5.0 | Leukemia cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.892C>T (p.Arg298*) | Nonsense | Rare | Loss of function; associated with Ruijs-Aalfs syndrome |
| c.1A>G (p.Met1?) | Start loss | Rare | Loss of function; no protein expression |
| c.1045G>A (p.Gly349Arg) | Missense | Rare | Impaired DNA binding and protease activity |
| c.1333C>T (p.Arg445Trp) | Missense | Rare | Reduced replication fork stability |
Mutation functional classification
Loss of Function (LOF)
Nonsense and start-loss mutations lead to truncated or absent spartin, impairing DNA-protein crosslink repair and causing genomic instability.
Gain of Function (GOF)
No gain-of-function mutations reported.
Dominant Negative (DN)
Missense mutations (e.g., p.Gly349Arg) may act as dominant-negative by interfering with wild-type spartin function in DNA repair.
View complete mutation data：
Gene Ontology (GO)
Pathways
• DNA damage bypass (REACTOME R-HSA-73893)
• Translesion synthesis (REACTOME R-HSA-110313)
• Fanconi anemia pathway (KEGG hsa03460)
Protein Summary
Spartin is a 489-amino acid metalloprotease with a conserved SPRTN domain. It localizes to replication forks and removes trapped DNA-protein crosslinks via its protease activity. It also interacts with ubiquitin and PCNA to regulate translesion synthesis. Loss of spartin leads to replication stress, genomic instability, and predisposition to cancer and premature aging.
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