SHLD2: Shieldin Complex Subunit 2
A key component of the DNA double-strand break repair pathway and a tumor suppressor in breast cancer
Gene Information Card
| Symbol | SHLD2 |
|---|---|
| Full Name | Shieldin Complex Subunit 2 |
| Gene Type | Protein coding |
| Chromosomal Location | 10q24.1 |
| NCBI Gene ID | 286059 ncbi.nlm.nih.gov/gene/286059 |
| Ensembl ID | ENSG00000119917 |
| UniProt ID | Q86X27 |
| OMIM ID | 617340 |
| HGNC ID | 30549 |
| Aliases | C20orf196, FAM35A, RINN2 |
Description
SHLD2 encodes a subunit of the shieldin complex, which functions in DNA double-strand break repair by promoting non-homologous end joining (NHEJ) and suppressing homologous recombination (HR). The shieldin complex binds to single-stranded DNA at resected DNA ends and protects them from further resection, thereby directing repair toward NHEJ. SHLD2 is also implicated in telomere maintenance and is frequently mutated in breast cancer, where loss of function leads to genomic instability and increased sensitivity to PARP inhibitors.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Breast cancer | Loss-of-function mutations in SHLD2 impair DNA repair, leading to genomic instability and tumorigenesis. | COSMIC, ClinVar |
| Fanconi anemia-like phenotype | Biallelic SHLD2 mutations cause defective DNA repair and bone marrow failure. | OMIM, ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 12.3 | Medium |
| Bone marrow | 8.1 | Medium |
| Breast | 5.4 | Low |
| Ovary | 4.9 | Low |
| Lung | 3.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| MCF7 (breast cancer) | 6.7 | Basal expression |
| HEK293 (embryonic kidney) | 5.1 | Moderate expression |
| K562 (leukemia) | 4.3 | Low expression |
| HCT116 (colorectal) | 3.8 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1234C>T (p.Arg412*) | Nonsense | 0.2% in breast cancer | Loss of function; truncation of SHLD2 |
| c.567_568del (p.Glu190fs) | Frameshift | 0.1% in breast cancer | Loss of function; premature stop |
| c.890A>G (p.Tyr297Cys) | Missense | 0.05% in breast cancer | Unknown; possibly damaging |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations that truncate SHLD2 or cause nonsense-mediated decay, leading to loss of shieldin complex function and impaired NHEJ.
Gain of Function (GOF)
No gain-of-function mutations reported for SHLD2.
Dominant Negative (DN)
No dominant-negative mutations reported for SHLD2.
View complete mutation data：
Gene Ontology (GO)
| • DNA double-strand break repair via nonhomologous end joining | • telomere maintenance |
| • protein binding | • nucleus |
| • chromatin binding |
Pathways
• Non-homologous end joining (NHEJ)
• DNA double-strand break repair
• Shieldin complex pathway
• Homologous recombination regulation
Protein Summary
SHLD2 is a 738-amino-acid protein that forms part of the shieldin complex (SHLD1, SHLD2, SHLD3, and REV7). It contains an N-terminal domain that interacts with single-stranded DNA and a C-terminal region that binds to REV7. The complex localizes to DNA damage sites and prevents excessive resection by nucleases, thereby promoting NHEJ. SHLD2 is essential for maintaining genomic stability and its loss sensitizes cells to PARP inhibitors.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SHLD2 Knockout HEK293 Cell Line | EDJ-KQ11455 | Human | 54537 | Details Get a Quote |
| SHLD2 Knockout A-549 Cell Line | EDJ-KQ39749 | Human | 54537 | Details Get a Quote |
| SHLD2 Knockout HCT 116 Cell Line | EDJ-KQ39750 | Human | 54537 | Details Get a Quote |
| SHLD2 Knockout HeLa Cell Line | EDJ-KQ39751 | Human | 54537 | Details Get a Quote |
