RIN3: Ras and Rab Interactor 3
A guanine nucleotide exchange factor involved in endocytic trafficking and vesicle-mediated transport, with implications in bone density and cancer.
Gene Information Card
| Symbol | RIN3 |
|---|---|
| Full Name | Ras and Rab Interactor 3 |
| Gene Type | Protein coding |
| Chromosomal Location | 14q32.12 |
| NCBI Gene ID | 79890 ncbi.nlm.nih.gov/gene/79890 |
| Ensembl ID | ENSG00000100842 |
| UniProt ID | Q8TB24 |
| OMIM ID | 610223 |
| HGNC ID | 18752 |
| Aliases | RIN3, Ras and Rab interactor 3 |
Description
RIN3 (Ras and Rab Interactor 3) encodes a protein that functions as a guanine nucleotide exchange factor (GEF) for Rab5 and Rab31, regulating early endocytic trafficking and vesicle-mediated transport. The protein contains a VPS9 domain and interacts with Ras family members. RIN3 is implicated in bone mineral density regulation and has been associated with various cancers through somatic mutations and expression alterations.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Osteoporosis (bone mineral density variation) | RIN3 variants affect endocytic trafficking in osteoclasts, modulating bone resorption. | GWAS studies (PMID: 30598548, 26367794) |
| Breast cancer | Somatic mutations and altered RIN3 expression may influence Rab5-mediated endocytosis of growth factor receptors. | COSMIC database; PMID: 23535729 |
| Lung adenocarcinoma | RIN3 copy number alterations and expression changes observed in tumor samples. | COSMIC database; TCGA analysis |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 5.2 | Low |
| Lung | 8.1 | Medium |
| Breast | 6.4 | Medium |
| Bone marrow | 3.0 | Low |
| Testis | 12.5 | High |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| MCF7 (breast cancer) | 7.8 | Basal expression |
| A549 (lung cancer) | 6.5 | Moderate expression |
| HEK293 (embryonic kidney) | 9.2 | High expression |
| K562 (leukemia) | 4.1 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1552C>T (p.Arg518Trp) | Missense | <0.01% | Unknown functional effect; reported in ClinVar |
| c.2230G>A (p.Val744Met) | Missense | <0.01% | Likely benign; population frequency low |
| c.1015_1016insA (p.Thr339Asnfs*12) | Frameshift | <0.01% | Predicted loss of function; reported in COSMIC |
Mutation functional classification
Loss of Function (LOF)
Frameshift and nonsense mutations in the VPS9 domain are predicted to disrupt Rab GEF activity, impairing endocytic trafficking.
Gain of Function (GOF)
No confirmed gain-of-function mutations reported in RIN3.
Dominant Negative (DN)
Missense mutations in the VPS9 domain may act as dominant-negative by sequestering Rab5 without productive nucleotide exchange.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Endocytosis (Reactome R-HSA-199991)
• Rab5 regulation of early endosome (Reactome R-HSA-8876198)
• Ras signaling pathway (KEGG hsa04014)
Protein Summary
The RIN3 protein (UniProt Q8TB24) is 988 amino acids long and contains an N-terminal VPS9 domain responsible for Rab5 GEF activity, a central Ras association (RA) domain, and a C-terminal proline-rich region. It localizes to early endosomes and regulates endocytic trafficking by activating Rab5. RIN3 also interacts with activated Ras, linking Ras signaling to endocytosis.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| RIN3 Knockout HEK293 Cell Line | EDJ-KQ1120 | Human | 79890 | Details Get a Quote |
| RIN3 Knockout A-549 Cell Line | EDJ-KQ20309 | Human | 79890 | Details Get a Quote |
| RIN3 Knockout HCT 116 Cell Line | EDJ-KQ20310 | Human | 79890 | Details Get a Quote |
| RIN3 Knockout HeLa Cell Line | EDJ-KQ20311 | Human | 79890 | Details Get a Quote |
