CASC3: Cancer Susceptibility Candidate 3 (CASC3) Gene
Comprehensive genomic and functional analysis of CASC3, a core component of the exon junction complex (EJC) involved in mRNA splicing, localization, and nonsense-mediated decay (NMD).
Gene Information Card
| Symbol | CASC3 |
|---|---|
| Full Name | Cancer Susceptibility Candidate 3 |
| Gene Type | Protein-coding |
| Chromosomal Location | 17q21.1 |
| NCBI Gene ID | 22794 ncbi.nlm.nih.gov/gene/22794 |
| Ensembl ID | ENSG00000108349 |
| UniProt ID | O15234 |
| OMIM ID | 606504 |
| HGNC ID | 1500 |
| Aliases | MLN51, BTZ |
Description
CASC3 (Cancer Susceptibility Candidate 3) encodes a core component of the exon junction complex (EJC). The EJC is deposited on spliced mRNAs upstream of exon-exon junctions and plays critical roles in mRNA export, subcellular localization, translation enhancement, and nonsense-mediated mRNA decay (NMD). CASC3 interacts with other EJC core proteins (eIF4A3, MAGOH, RBM8A) and is essential for proper gene expression regulation. Overexpression and mutations have been implicated in various cancers, including breast cancer and neuroblastoma.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Breast Cancer | CASC3 overexpression may enhance EJC-dependent mRNA transport and translation of oncogenic transcripts, promoting tumorigenesis. | PMID: 12154099; COSMIC |
| Neuroblastoma | Amplification of the 17q21 region including CASC3 is associated with aggressive neuroblastoma; CASC3 may contribute to oncogenic mRNA processing. | PMID: 15696293; COSMIC |
| Colorectal Cancer | Altered CASC3 expression linked to dysregulated NMD and splicing, potentially affecting tumor suppressor gene expression. | PMID: 23034409; COSMIC |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 22.5 | High |
| Lymph node | 18.3 | High |
| Bone marrow | 15.7 | High |
| Brain | 8.2 | Medium |
| Liver | 6.1 | Medium |
| Heart | 4.5 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa (cervical carcinoma) | 20.1 | High expression; used in EJC studies |
| MCF7 (breast cancer) | 18.7 | Overexpressed relative to normal breast tissue |
| SH-SY5Y (neuroblastoma) | 16.3 | Amplification of 17q21 region |
| HEK293 (embryonic kidney) | 12.4 | Moderate expression; model for NMD studies |
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 start codon; potential loss of function |
| c.112C>T (p.Arg38Trp) | Missense | <0.01% | Unknown significance; reported in COSMIC |
| c.454G>A (p.Glu152Lys) | Missense | <0.01% | Unknown significance; COSMIC |
| Amplification | Copy number gain | ~5% in neuroblastoma | Gain of function; increased CASC3 expression |
Mutation functional classification
Loss of Function (LOF)
Rare missense variants (e.g., p.Met1?) may disrupt protein expression or EJC assembly, potentially impairing NMD and mRNA surveillance.
Gain of Function (GOF)
Gene amplification (17q21) leading to CASC3 overexpression is observed in neuroblastoma and breast cancer, likely enhancing oncogenic mRNA processing.
Dominant Negative (DN)
No dominant-negative mutations currently documented in ClinVar or COSMIC for CASC3.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Nonsense-Mediated Decay (NMD) – Reactome R-HSA-927802
• mRNA Splicing – Major Pathway – Reactome R-HSA-72163
• Transport of Mature mRNA derived from an Intron-Containing Transcript – Reactome R-HSA-159236
Protein Summary
CASC3 (also known as MLN51 or BTZ) is a 703-amino-acid protein that serves as a core scaffold of the exon junction complex (EJC). It contains an N-terminal SEL1L-like domain and a C-terminal region that mediates interactions with eIF4A3, MAGOH, and RBM8A. CASC3 is essential for EJC assembly and function, linking splicing to downstream mRNA export, localization, translation, and NMD. The protein is predominantly nuclear but shuttles to the cytoplasm. Its overexpression in several cancers suggests a role in promoting oncogenic gene expression programs.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CASC3 Knockout HEK293 Cell Line | EDJ-KQ7678 | Human | 22794 | Details Get a Quote |
| CASC3 Knockout HCT 116 Cell Line | EDJ-KQ33032 | Human | 22794 | Details Get a Quote |
| CASC3 Knockout HeLa Cell Line | EDJ-KQ33033 | Human | 22794 | Details Get a Quote |
| CASC3 Knockout A-549 Cell Line | EDJ-KQ31708 | Human | 22794 | Details Get a Quote |
