RIN2 Gene - RIN2 Protein - RIN2 Function
Comprehensive biomedical resource for RIN2 (Ras and Rab Interactor 2): genomic data, expression, mutations, and associated diseases.
Gene Information Card
| Symbol | RIN2 |
|---|---|
| Full Name | Ras and Rab Interactor 2 |
| Gene Type | Protein coding |
| Chromosomal Location | 20p11.23 |
| NCBI Gene ID | 54453 ncbi.nlm.nih.gov/gene/54453 |
| Ensembl ID | ENSG00000101204 |
| UniProt ID | Q8WYP3 |
| OMIM ID | 610222 |
| HGNC ID | 18750 |
| Aliases | RIN2, RIN2L, RIN2 variant, Ras interaction protein 2 |
Description
RIN2 (Ras and Rab Interactor 2) encodes a protein that functions as a guanine nucleotide exchange factor (GEF) for Rab5 and Rab31, regulating endocytic trafficking and membrane dynamics. It is involved in cell adhesion, migration, and receptor recycling. Mutations in RIN2 cause MACS syndrome (macrocephaly, alopecia, cutis laxa, and scoliosis), a rare autosomal recessive disorder.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| MACS syndrome (macrocephaly, alopecia, cutis laxa, scoliosis) | Loss-of-function mutations in RIN2 impair Rab5/Rab31-mediated endosomal trafficking, leading to defective extracellular matrix remodeling and connective tissue abnormalities. | OMIM #613075; ClinVar; multiple case reports (e.g., Basel-Vanagaite et al., 2009) |
| Cutis laxa with macrocephaly | Similar mechanism as MACS syndrome; RIN2 deficiency disrupts dermal fibroblast function and collagen homeostasis. | OMIM; literature review |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Skin | 12.5 | Medium |
| Lung | 8.3 | Medium |
| Heart | 6.1 | Low |
| Brain | 4.2 | Low |
| Liver | 3.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Fibroblasts (dermal) | 15.2 | High expression; relevant to MACS syndrome |
| HeLa | 9.8 | Moderate expression |
| HEK293 | 7.5 | Moderate expression |
| K562 | 2.1 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.841C>T (p.Arg281*) | Nonsense | Rare | Loss of function; premature stop codon leading to nonsense-mediated decay |
| c.1123delG (p.Ala375Profs*13) | Frameshift deletion | Rare | Loss of function; truncated protein |
| c.1570C>T (p.Arg524Trp) | Missense | Rare | Likely loss of function; disrupts GEF activity |
Mutation functional classification
Loss of Function (LOF)
Most reported RIN2 mutations are loss-of-function (nonsense, frameshift, splice-site), leading to reduced or absent protein expression and impaired Rab5/Rab31 activation.
Gain of Function (GOF)
No gain-of-function mutations have been reported for RIN2.
Dominant Negative (DN)
No dominant-negative mutations have been described; MACS syndrome is autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Rab5-mediated endocytosis (Reactome: R-HSA-8856828)
• Endosomal trafficking (Reactome: R-HSA-5653656)
Protein Summary
The RIN2 protein (UniProt Q8WYP3) is a 960-amino-acid cytoplasmic protein containing a VPS9 domain that confers GEF activity toward Rab5 and Rab31. It localizes to early endosomes and regulates endocytic vesicle fusion, receptor recycling, and cell migration. RIN2 is widely expressed, with highest levels in skin fibroblasts, consistent with its role in connective tissue homeostasis.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| RIN2 Knockout HEK293 Cell Line | EDJ-KQ3078 | Human | 54453 | Details Get a Quote |
| RIN2 Knockout A-549 Cell Line | EDJ-KQ24369 | Human | 54453 | Details Get a Quote |
| RIN2 Knockout HeLa Cell Line | EDJ-KQ24370 | Human | 54453 | Details Get a Quote |
| RIN2 Knockout HCT 116 Cell Line | EDJ-KQ73354 | Human | 54453 | Details Get a Quote |
