RIN1: Ras and Rab Interactor 1
A multifunctional signaling protein involved in endocytosis, cell adhesion, and tumor suppression
Gene Information Card
| Symbol | RIN1 |
|---|---|
| Full Name | Ras and Rab Interactor 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 11q13.2 |
| NCBI Gene ID | 9610 ncbi.nlm.nih.gov/gene/9610 |
| Ensembl ID | ENSG00000149131 |
| UniProt ID | Q13671 |
| OMIM ID | 605965 |
| HGNC ID | 9974 |
| Aliases | RIN1, RIN1_HUMAN |
Description
RIN1 (Ras and Rab Interactor 1) encodes a multifunctional cytoplasmic protein that acts as a guanine nucleotide exchange factor (GEF) for Rab5 and as an effector for Ras. It regulates receptor-mediated endocytosis, cell adhesion, and actin cytoskeleton remodeling. RIN1 also interacts with and activates ABL tyrosine kinases, influencing cell migration and growth. The gene is implicated in tumor suppression, with loss or reduced expression observed in several cancers, and mutations have been linked to developmental disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Breast cancer | Reduced RIN1 expression correlates with poor prognosis; loss of RIN1 promotes invasion and metastasis via ABL pathway activation. | PMID: 19029980, COSMIC |
| Colorectal cancer | RIN1 downregulation associated with tumor progression; epigenetic silencing via promoter methylation. | PMID: 21573172, COSMIC |
| Lung cancer | Decreased RIN1 expression linked to aggressive tumor behavior and reduced survival. | PMID: 23233736, COSMIC |
| Developmental disorder (intellectual disability) | Heterozygous missense variants in RIN1 identified in patients with neurodevelopmental phenotypes. | ClinVar, PMID: 31036916 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.3 | Medium |
| Lung | 8.7 | Low |
| Heart | 6.2 | Low |
| Liver | 4.1 | Not detected |
| Kidney | 9.5 | Low |
| Testis | 15.8 | Medium |
| Breast | 7.3 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 10.2 | Embryonic kidney cells |
| HeLa | 8.9 | Cervical cancer cells |
| MCF7 | 6.5 | Breast cancer cells |
| A549 | 5.1 | Lung cancer cells |
| HCT116 | 7.8 | Colorectal cancer cells |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1132C>T (p.Arg378Cys) | Missense | <0.01% | Reduced GEF activity; associated with developmental disorder |
| c.1465G>A (p.Glu489Lys) | Missense | <0.01% | Impaired ABL binding; reported in ClinVar |
| c.174delC (p.Pro59fs) | Frameshift | <0.01% | Loss of function; observed in COSMIC |
| c.1972C>T (p.Arg658Trp) | Missense | <0.01% | Unknown functional effect; rare population variant |
Mutation functional classification
Loss of Function (LOF)
Frameshift and nonsense mutations (e.g., c.174delC) lead to truncated protein and loss of Rab5 GEF activity, contributing to tumor progression.
Gain of Function (GOF)
Not well documented; no clear gain-of-function mutations reported in RIN1.
Dominant Negative (DN)
Missense variants (e.g., p.Arg378Cys) may interfere with wild-type RIN1 function by disrupting Rab5 binding, potentially acting in a dominant-negative manner.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Ras signaling pathway (Reactome: R-HSA-5673001)
• Rab5-mediated endocytosis (Reactome: R-HSA-8876198)
• ABL family kinase signaling (Reactome: R-HSA-912631)
• Regulation of actin dynamics (Reactome: R-HSA-5663222)
Protein Summary
RIN1 is a 783-amino-acid protein (UniProt Q13671) containing an N-terminal VPS9 domain responsible for Rab5 GEF activity, a central Ras-binding domain (RBD), and a C-terminal proline-rich region that interacts with SH3 domains of ABL kinases. It localizes to endosomes and the cytoplasm, promoting Rab5-dependent endocytosis and modulating cell adhesion and migration via ABL activation. RIN1 is considered a tumor suppressor, with loss of expression or function linked to cancer progression.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| RIN1 Knockout HEK293 Cell Line | EDJ-KQ1280 | Human | 9610 | Details Get a Quote |
| RIN1 Knockout A-549 Cell Line | EDJ-KQ19322 | Human | 9610 | Details Get a Quote |
| RIN1 Knockout HCT 116 Cell Line | EDJ-KQ20672 | Human | 9610 | Details Get a Quote |
| RIN1 Knockout HeLa Cell Line | EDJ-KQ20673 | Human | 9610 | Details Get a Quote |
