SHLD1: Shieldin Complex Subunit 1
A key component of the shieldin complex involved in DNA double-strand break repair by non-homologous end joining (NHEJ) and telomere protection.
Gene Information Card
| Symbol | SHLD1 |
|---|---|
| Full Name | Shieldin Complex Subunit 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 20p12.3 |
| NCBI Gene ID | 283579 ncbi.nlm.nih.gov/gene/283579 |
| Ensembl ID | ENSG00000125869 |
| UniProt ID | Q8N6M3 |
| OMIM ID | 618208 |
| HGNC ID | 26440 |
| Aliases | C20orf94, RINN3, bA163M19.1 |
Description
SHLD1 encodes a subunit of the shieldin complex, which also includes SHLD2, SHLD3, and REV7. This complex plays a critical role in DNA double-strand break repair by promoting non-homologous end joining (NHEJ) and suppressing homologous recombination. SHLD1 is also involved in telomere protection by regulating telomeric end protection and preventing aberrant telomere fusions. Mutations in SHLD1 are associated with genomic instability and cancer predisposition.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Breast cancer | Loss of SHLD1 impairs NHEJ, leading to genomic instability and increased risk of tumorigenesis. | PMID: 30449621 |
| Ovarian cancer | SHLD1 deficiency sensitizes cells to PARP inhibitors by disrupting DNA repair. | PMID: 30449622 |
| Fanconi anemia-like phenotype | Biallelic SHLD1 mutations cause defective DNA repair and chromosomal instability. | PMID: 31548637 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 12.5 | Medium |
| Bone marrow | 8.3 | Low |
| Lymph node | 7.1 | Low |
| Brain | 4.2 | Low |
| Liver | 3.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 15.2 | Cervical cancer cell line |
| K562 | 10.1 | Leukemia cell line |
| HEK293 | 9.5 | Embryonic kidney cell line |
| MCF7 | 7.8 | Breast cancer cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G (p.Met1?) | Missense | Rare | Loss of start codon, likely loss of function |
| c.325C>T (p.Arg109*) | Nonsense | Rare | Premature stop, loss of function |
| c.502_503del (p.Leu168fs) | Frameshift | Rare | Frameshift, loss of function |
Mutation functional classification
Loss of Function (LOF)
Most SHLD1 mutations are loss-of-function, impairing shieldin complex assembly and NHEJ repair.
Gain of Function (GOF)
No gain-of-function mutations reported.
Dominant Negative (DN)
No dominant-negative mutations reported.
View complete mutation data：
Gene Ontology (GO)
| • DNA double-strand break repair via nonhomologous end joining (GO:0006303) | • telomere maintenance (GO:0000723) |
| • protein binding (GO:0005515) | • nucleus (GO:0005634) |
Pathways
• Non-homologous end joining (NHEJ) (Reactome R-HSA-5693571)
• Shieldin complex-mediated DNA repair (Reactome R-HSA-5693572)
• Telomere maintenance (Reactome R-HSA-157579)
Protein Summary
SHLD1 is a 366-amino acid protein that localizes to the nucleus and forms part of the shieldin complex. It contains a conserved domain that interacts with SHLD2 and REV7. The protein is essential for DNA double-strand break repair via NHEJ, particularly at dysfunctional telomeres. SHLD1 deficiency leads to increased sensitivity to DNA-damaging agents and PARP inhibitors.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SHLD1 Knockout HEK293 Cell Line | EDJ-KQ10544 | Human | 149840 | Details Get a Quote |
| SHLD1 Knockout A-549 Cell Line | EDJ-KQ39307 | Human | 149840 | Details Get a Quote |
| SHLD1 Knockout HCT 116 Cell Line | EDJ-KQ39308 | Human | 149840 | Details Get a Quote |
| SHLD1 Knockout HeLa Cell Line | EDJ-KQ39309 | Human | 149840 | Details Get a Quote |
