RCC1 (Regulator of Chromosome Condensation 1)
Key guanine nucleotide exchange factor for Ran GTPase involved in nucleocytoplasmic transport and mitotic spindle assembly
Gene Information Card
| Symbol | RCC1 |
|---|---|
| Full Name | Regulator of Chromosome Condensation 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 1p36.13 |
| NCBI Gene ID | 1104 ncbi.nlm.nih.gov/gene/1104 |
| Ensembl ID | ENSG00000180198 |
| UniProt ID | P18754 |
| OMIM ID | 179710 |
| HGNC ID | HNC:9829 |
| Aliases | CHC1, RCC1-I, RCC1-II |
Description
RCC1 (Regulator of Chromosome Condensation 1) encodes a guanine nucleotide exchange factor (GEF) for the small GTPase Ran. It is a chromatin-bound protein that catalyzes the exchange of GDP for GTP on Ran, thereby regulating nucleocytoplasmic transport, mitotic spindle assembly, nuclear envelope formation, and cell cycle progression. RCC1 is essential for the Ran-GTP gradient across the nuclear envelope.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Colorectal cancer | RCC1 overexpression may enhance Ran-GTP signaling, promoting mitotic spindle defects and aneuploidy | COSMIC; PMID: 25691885 |
| Breast cancer | Altered RCC1 expression correlates with poor prognosis and increased proliferation | COSMIC; PMID: 28431213 |
| Lung adenocarcinoma | RCC1 mutations and copy number alterations observed in tumor samples | COSMIC; PMID: 30349067 |
| Developmental disorders | RCC1 missense variants reported in patients with microcephaly and intellectual disability | ClinVar; PMID: 31537090 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 28.5 | High |
| Bone marrow | 18.2 | Medium |
| Lymph node | 15.7 | Medium |
| Brain | 12.1 | Medium |
| Liver | 8.4 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 32.1 | Cervical carcinoma; high expression |
| HEK293 | 25.6 | Embryonic kidney; moderate expression |
| A549 | 22.3 | Lung carcinoma; moderate expression |
| MCF7 | 18.9 | Breast carcinoma; moderate expression |
| K562 | 15.4 | Leukemia; moderate expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.101C>T (p.Thr34Met) | Missense | <0.1% | Reduced GEF activity; reported in developmental delay |
| c.497G>A (p.Arg166Gln) | Missense | <0.1% | Impaired Ran binding; associated with microcephaly |
| c.730C>T (p.Arg244Trp) | Missense | <0.1% | Loss of chromatin binding; dominant negative effect |
| c.1123_1124insA (p.Glu375Glufs*2) | Frameshift | <0.1% | Loss of function; truncation of C-terminal domain |
Mutation functional classification
Loss of Function (LOF)
Frameshift and nonsense mutations that truncate the protein or disrupt the beta-propeller structure lead to loss of GEF activity and Ran-GTP gradient collapse.
Gain of Function (GOF)
No well-characterized gain-of-function mutations reported; overexpression in cancers may indirectly increase Ran-GTP levels.
Dominant Negative (DN)
Missense mutations (e.g., Arg244Trp) that impair chromatin binding but retain dimerization capacity can interfere with wild-type RCC1 function.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Nucleocytoplasmic transport (Reactome: R-HSA-164944)
• Ran GTPase cycle (Reactome: R-HSA-164944)
• Mitotic spindle assembly (Reactome: R-HSA-68877)
• Nuclear envelope reassembly (Reactome: R-HSA-2995410)
Protein Summary
RCC1 is a 421-amino-acid protein with a seven-bladed beta-propeller structure. It binds to chromatin via histones H2A and H2B and acts as the sole GEF for Ran. The Ran-GTP gradient generated by RCC1 is critical for nuclear import/export, mitotic spindle formation, and nuclear envelope dynamics. Post-translational modifications include phosphorylation and methylation, which modulate its activity and localization.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| RCC1L Knockout HEK293 Cell Line | EDJ-KQ9708 | Human | 81554 | Details Get a Quote |
| RCC1L Knockout A-549 Cell Line | EDJ-KQ35268 | Human | 81554 | Details Get a Quote |
| RCC1L Knockout HCT 116 Cell Line | EDJ-KQ36492 | Human | 81554 | Details Get a Quote |
| RCC1L Knockout HeLa Cell Line | EDJ-KQ36493 | Human | 81554 | Details Get a Quote |
