CASTOR1
protein-codingcytosolic arginine sensor for mTORC1 subunit 1
Gene summary
Enables several functions, including arginine binding activity; identical protein binding activity; and protein sequestering activity. Involved in cellular response to L-arginine; cellular response to amino acid starvation; and regulation of TORC1 signaling. Located in GATOR2 complex and cytosol. [provided by Alliance of Genome Resources, Jul 2025]
- GATSL3
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~4.5 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 CASTOR1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001037666.3. 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 | 1 | 1 | ||||
| missense | 45 | 1 | 46 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 3 | 3 | ||||
| Total | 0 | 0 | 49 | 1 | 0 | 50 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001032755.1 | 9 | MANE Select | |
| Ensembl | ENSP00000384183.4 | 9 | MANE Select | |
| Ensembl | ENSP00000385868.3 | 8 | Standard | |
| Ensembl | ENSP00000385868.3 | 8 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- regulation of intracellular signal transduction
- cellular response to L-arginine
- negative regulation of TORC1 signaling
Molecular Function
- protein binding
- arginine binding
- identical protein binding
Cellular Component
- cytosol
- GATOR2 complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000407689
- Coding exons
- 9
- Length
- 4511
- Individuals with no LoFs
- 125041
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 58
- Defined
- 125099
- p
- 0.000232
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.59 | 140 | 204 | 0.686 | 0.0000123 | 2099 |
| Missense (PolyPhen) | 42 | 70.597 | 0.59492 | 757 | ||
| Synonymous | 0.912 | 81 | 92.1 | 0.879 | 0.00000640 | 682 |
| Loss of Function | 2.24 | 5 | 14.1 | 0.355 | 6.02e-7 | 162 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00034 | 0.00025 | rare |
| Latino/Admixed American | 0.00042 | 0.00041 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00017 | 0.00017 | rare |
| Finnish | 0.00025 | 0.00019 | rare |
| European (Non-Finnish) | 0.00030 | 0.00025 | rare |
| South Asian | 0.00019 | 0.00016 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Functions as an intracellular arginine sensor within the amino acid-sensing branch of the TORC1 signaling pathway. As a homodimer or a heterodimer with CASTOR2, binds and inhibits the GATOR subcomplex GATOR2 and thereby mTORC1. Binding of arginine to CASTOR1 allosterically disrupts the interaction of CASTOR1- containing dimers with GATOR2 which can in turn activate mTORC1 and the TORC1 signaling pathway. {ECO:0000269|PubMed:26972053, ECO:0000269|PubMed:27487210}.;
Intolerance Scores
- RVIS EVS
- -0.21
- RVIS percentile EVS
- 38.58
Essentials
- Essential (gene trap)
- N