SHLD3 (Shieldin Complex Subunit 3)
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 | SHLD3 |
|---|---|
| Full Name | Shieldin complex subunit 3 |
| Gene Type | Protein coding |
| Chromosomal Location | 5q35.3 |
| NCBI Gene ID | 100130894 ncbi.nlm.nih.gov/gene/100130894 |
| Ensembl ID | ENSG00000204149 |
| UniProt ID | Q6P9B9 |
| OMIM ID | 618201 |
| HGNC ID | 37247 |
| Aliases | C5orf36, FLJ46321, MGC16384 |
Description
SHLD3 encodes a component of the shieldin complex, which also includes SHLD1, SHLD2, and REV7. This complex functions downstream of 53BP1 and RIF1 to promote non-homologous end joining (NHEJ) during DNA double-strand break repair. SHLD3 is also involved in telomere protection by facilitating the recruitment of the CST complex to telomeres. Loss of SHLD3 impairs NHEJ and leads to increased genomic instability.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Breast cancer | SHLD3 mutations may impair DNA repair, leading to genomic instability and tumorigenesis. | COSMIC; ClinVar |
| Ovarian cancer | Altered SHLD3 expression or function may contribute to defective DNA repair in ovarian tumors. | COSMIC |
| Lung cancer | Somatic mutations in SHLD3 have been identified in lung cancer samples. | COSMIC |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 4.2 | Low |
| Bone marrow | 3.8 | Low |
| Lymph node | 3.5 | Low |
| Spleen | 3.1 | Low |
| Other tissues | <2.0 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 2.5 | Low expression |
| HeLa | 1.8 | Very low |
| K562 | 3.0 | Low |
| MCF7 | 2.2 | Low |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G (p.Met1?) | Missense | <0.01% | Likely loss of function |
| c.100C>T (p.Arg34Trp) | Missense | <0.01% | Unknown significance |
| c.200_201del (p.Glu67fs) | Frameshift | <0.01% | Loss of function |
Mutation functional classification
Loss of Function (LOF)
Frameshift and nonsense mutations in SHLD3 are predicted to cause loss of function, impairing shieldin complex assembly and NHEJ repair.
Gain of Function (GOF)
No gain-of-function mutations have been reported for SHLD3.
Dominant Negative (DN)
No dominant-negative mutations have been characterized for SHLD3.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Non-homologous end joining (NHEJ) - REACTOME R-HSA-5693571
• DNA double-strand break repair - REACTOME R-HSA-5693532
• Telomere maintenance - REACTOME R-HSA-157579
Protein Summary
SHLD3 is a 222-amino acid protein (UniProt Q6P9B9) that localizes to the nucleus. It contains a conserved domain that mediates interaction with SHLD2 and REV7 within the shieldin complex. The protein is essential for the recruitment of the CST complex to telomeres and for promoting NHEJ at DNA breaks. SHLD3 is expressed at low levels in most tissues, with highest expression in testis and bone marrow.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SHLD3 Knockout HEK293 Cell Line | EDJ-KQ11231 | Human | 112441434 | Details Get a Quote |
| SHLD3 Knockout A-549 Cell Line | EDJ-KQ40559 | Human | 112441434 | Details Get a Quote |
| SHLD3 Knockout HCT 116 Cell Line | EDJ-KQ40560 | Human | 112441434 | Details Get a Quote |
| SHLD3 Knockout HeLa Cell Line | EDJ-KQ40561 | Human | 112441434 | Details Get a Quote |
