CASC3
protein-codingCASC3 exon junction complex subunit, the group of MicroRNA protein coding host genes|Exon junction complex
Gene summary
The product of this gene is a core component of the exon junction complex (EJC), a protein complex that is deposited on spliced mRNAs at exon-exon junctions and functions in nonsense-mediated mRNA decay (NMD). The encoded protein binds RNA and interacts with two other EJC core components. It is predominantly located in the cytoplasm, but shuttles into the nucleus where it localizes to nuclear speckles. [provided by RefSeq, Jul 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~31.9 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to CASC3 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_007359.5. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 2 | 1 | 3 | |||
| missense | 84 | 3 | 87 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 5 | 5 | ||||
| Total | 0 | 0 | 91 | 4 | 0 | 95 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_031385.2 | 13 | MANE Select | |
| Ensembl | ENSP00000264645.6 | 13 | MANE Select | |
| Ensembl | ENSP00000462713.1 | 5 | Standard | |
| Ensembl | ENSP00000464626.1 | 3 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- mRNA surveillance pathway - Homo sapiens (human)
- RNA transport - Homo sapiens (human)
- Gene expression (Transcription)
- RNA Polymerase II Transcription
- Metabolism of RNA
Biological Process
- nuclear-transcribed mRNA catabolic process, nonsense-mediated decay
- mRNA splicing, via spliceosome
- RNA export from nucleus
- mRNA export from nucleus
- regulation of translation
Molecular Function
- RNA binding
- protein binding
- enzyme binding
- ubiquitin protein ligase binding
- identical protein binding
Cellular Component
- nucleoplasm
- cytosol
- cytoplasmic stress granule
- nuclear speck
- dendrite
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000264645
- Coding exons
- 13
- Length
- 31866
- Individuals with no LoFs
- 125737
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 11
- Defined
- 125748
- p
- 0.0000437
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.32 | 339 | 414 | 0.818 | 0.0000231 | 4507 |
| Missense (PolyPhen) | 116 | 166.86 | 0.6952 | 1736 | ||
| Synonymous | 0.548 | 140 | 148 | 0.943 | 0.00000756 | 1475 |
| Loss of Function | 4.52 | 8 | 38.1 | 0.210 | 0.00000239 | 389 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0.000047 | 0.000046 | rare |
| European (Non-Finnish) | 0.000089 | 0.000088 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Core component of the splicing-dependent multiprotein exon junction complex (EJC) deposited at splice junctions on mRNAs. The EJC is a dynamic structure consisting of core proteins and several peripheral nuclear and cytoplasmic associated factors that join the complex only transiently either during EJC assembly or during subsequent mRNA metabolism. The EJC marks the position of the exon-exon junction in the mature mRNA for the gene expression machinery and the core components remain bound to spliced mRNAs throughout all stages of mRNA metabolism thereby influencing downstream processes including nuclear mRNA export, subcellular mRNA localization, translation efficiency and nonsense-mediated mRNA decay (NMD). Stimulates the ATPase and RNA- helicase activities of EIF4A3. Plays a role in the stress response by participating in cytoplasmic stress granules assembly and by favoring cell recovery following stress. Component of the dendritic ribonucleoprotein particles (RNPs) in hippocampal neurons. May play a role in mRNA transport. Binds spliced mRNA in sequence-independent manner, 20-24 nucleotides upstream of mRNA exon-exon junctions. Binds poly(G) and poly(U) RNA homopolymer. {ECO:0000269|PubMed:17375189, ECO:0000269|PubMed:17652158}.;
Recessive Scores
- pRec
- 0.111
Intolerance Scores
- LoFtool
- 0.0981
- RVIS EVS
- -0.89
- RVIS percentile EVS
- 10.37
Essentials
- Essential (CRISPR)
- E
- Essential (CRISPR2)
- S
- Essential (gene trap)
- E
- Indispensability pred.
- N
- Indispensability score
- 0.307
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |