CRB2 Gene - Crumbs Cell Polarity Complex Component 2
Essential regulator of apical-basal polarity in epithelial and photoreceptor cells
Gene Information Card
| Symbol | CRB2 |
|---|---|
| Full Name | Crumbs cell polarity complex component 2 |
| Gene Type | Protein coding |
| Chromosomal Location | 9q33.3 |
| NCBI Gene ID | 286204 ncbi.nlm.nih.gov/gene/286204 |
| Ensembl ID | ENSG00000148204 |
| UniProt ID | Q5IJ48 |
| OMIM ID | 609720 |
| HGNC ID | 23488 |
| Aliases | CRB3, MGC26594 |
Description
The CRB2 gene encodes a transmembrane protein that is a component of the Crumbs complex, which is critical for establishing and maintaining apical-basal polarity in epithelial cells and photoreceptor cells. It interacts with PALS1 and PATJ to regulate tight junction formation and cell adhesion. Mutations in CRB2 are associated with kidney diseases such as focal segmental glomerulosclerosis and nephrotic syndrome, as well as retinal degeneration including retinitis pigmentosa.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Focal segmental glomerulosclerosis 9 (FSGS9) | Loss of CRB2 disrupts podocyte polarity and slit diaphragm integrity, leading to proteinuria and glomerular scarring. | OMIM #616220; PMID: 25557784 |
| Nephrotic syndrome type 12 (NPHS12) | Biallelic CRB2 mutations impair podocyte foot process formation and glomerular filtration barrier function. | OMIM #616220; PMID: 25557784 |
| Retinitis pigmentosa (RP) | CRB2 deficiency in photoreceptor cells disrupts outer segment morphogenesis and leads to progressive retinal degeneration. | OMIM #609720; PMID: 26908613 |
| Ventricular septal defect (VSD) | CRB2 mutations may affect cardiac epithelial polarity, contributing to congenital heart defects. | PMID: 26908613 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Kidney | 12.5 | Medium |
| Retina | 8.3 | Medium |
| Brain | 6.1 | Low |
| Heart | 4.8 | Low |
| Liver | 2.3 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 15.2 | High expression in embryonic kidney cells |
| ARPE-19 | 9.7 | Retinal pigment epithelial cell line |
| HepG2 | 3.1 | Low expression in liver carcinoma cells |
| SH-SY5Y | 2.5 | Neuroblastoma cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.2968C>T (p.Arg990*) | Nonsense | Rare | Premature stop codon leading to loss of function |
| c.400C>T (p.Arg134Trp) | Missense | Rare | Disrupts extracellular domain interaction with PALS1 |
| c.1529G>A (p.Arg510Gln) | Missense | Rare | Impairs apical localization and polarity complex assembly |
| c.2150_2151del (p.Leu717Argfs*3) | Frameshift | Rare | Loss of transmembrane and cytoplasmic domains |
Mutation functional classification
Loss of Function (LOF)
Most CRB2 mutations are loss-of-function, leading to haploinsufficiency or complete loss of protein function, disrupting apical-basal polarity in kidney podocytes and retinal photoreceptors.
Gain of Function (GOF)
No gain-of-function mutations have been reported for CRB2.
Dominant Negative (DN)
Some missense mutations (e.g., p.Arg134Trp) may exert dominant-negative effects by interfering with wild-type CRB2 interaction with polarity complex partners.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Apical junction complex (Reactome: R-HSA-420029)
• Cell-cell junction organization (Reactome: R-HSA-421270)
• Tight junction interactions (Reactome: R-HSA-420029)
• Photoreceptor cell maintenance (KEGG: hsa04744)
Protein Summary
CRB2 is a 1285-amino acid transmembrane protein with 19 EGF-like domains and 3 laminin G-like domains in its extracellular region, and a short cytoplasmic tail containing a PDZ-binding motif. It localizes to the apical membrane of epithelial cells and the subapical region of photoreceptor cells, where it forms a complex with PALS1 and PATJ to regulate cell polarity, tight junction formation, and cell adhesion. The protein is essential for kidney podocyte function and retinal photoreceptor morphogenesis.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CRB2 Knockout HEK293 Cell Line | EDJ-KQ1355 | Human | 286204 | Details Get a Quote |
| CRB2 Knockout HeLa Cell Line | EDJ-KQ59549 | Human | 286204 | Details Get a Quote |
| CRB2 Knockout A-549 Cell Line | EDJ-KQ68015 | Human | 286204 | Details Get a Quote |
| CRB2 Knockout HCT 116 Cell Line | EDJ-KQ76394 | Human | 286204 | Details Get a Quote |
