TSPAN12
Tetraspanin 12: A key regulator of Norrin/β-catenin signaling in retinal vascular development
Gene Information Card
| Symbol | TSPAN12 |
|---|---|
| Full Name | Tetraspanin 12 |
| Gene Type | Protein coding |
| Chromosomal Location | 7q31.31 |
| NCBI Gene ID | 23554 ncbi.nlm.nih.gov/gene/23554 |
| Ensembl ID | ENSG00000106031 |
| UniProt ID | O95859 |
| OMIM ID | 613138 |
| HGNC ID | 21381 |
| Aliases | NET-2, NET2, TM4SF12 |
Description
TSPAN12 encodes tetraspanin 12, a member of the tetraspanin family of transmembrane proteins. It acts as a critical component of the Norrin/FZD4/LRP5 signaling complex, facilitating β-catenin-dependent transcription in retinal vascular development. Loss-of-function mutations in TSPAN12 cause familial exudative vitreoretinopathy (FEVR), a disorder of retinal angiogenesis.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Familial exudative vitreoretinopathy (FEVR) | Loss-of-function mutations impair Norrin-induced β-catenin signaling, leading to defective retinal vascularization | ClinVar, OMIM |
| Exudative vitreoretinopathy 5 | Autosomal dominant or recessive FEVR caused by TSPAN12 mutations | OMIM #613310 |
| Retinopathy of prematurity (ROP) | Rare variants may contribute to severe ROP phenotype | PubMed studies |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Retina | 12.5 | Medium |
| Lung | 8.3 | Low |
| Kidney | 6.1 | Low |
| Placenta | 5.4 | Low |
| Heart | 4.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| ARPE-19 (retinal pigment epithelium) | 15.2 | Moderate expression |
| HUVEC (umbilical vein endothelial) | 9.8 | Low expression |
| HEK 293 | 7.5 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.2T>C (p.Met1?) | Missense | Rare | Loss of start codon, no protein |
| c.226C>T (p.Arg76*) | Nonsense | Rare | Premature stop, loss of function |
| c.377G>A (p.Arg126His) | Missense | Rare | Impaired Norrin signaling |
| c.533G>A (p.Arg178Gln) | Missense | Rare | Reduced β-catenin activation |
Mutation functional classification
Loss of Function (LOF)
Most TSPAN12 mutations are loss-of-function, disrupting Norrin/FZD4 complex formation and β-catenin signaling.
Gain of Function (GOF)
Not reported.
Dominant Negative (DN)
Some missense mutations may exert dominant-negative effects by interfering with wild-type tetraspanin function.
View complete mutation data：
Gene Ontology (GO)
| • plasma membrane (GO:0005886) | • signal transduction (GO:0007165) |
| • angiogenesis (GO:0001525) | • canonical Wnt signaling pathway (GO:0060070) |
| • positive regulation of transcription by RNA polymerase II (GO:0045944) | • integral component of membrane (GO:0016021) |
Pathways
• Norrin signaling pathway (Reactome: R-HSA-4641262)
• β-catenin/Wnt signaling (KEGG: hsa04310)
Protein Summary
Tetraspanin 12 is a 305-amino acid transmembrane protein with four hydrophobic domains. It localizes to the plasma membrane and interacts with Frizzled-4 (FZD4) and LRP5 to form a receptor complex specific for Norrin (NDP). This complex activates β-catenin/TCF transcriptional programs essential for retinal vascular development. TSPAN12 is not required for canonical Wnt signaling but is indispensable for Norrin-mediated signaling.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| TSPAN12 Knockout HEK293 Cell Line | EDJ-KQ8066 | Human | 23554 | Details Get a Quote |
| TSPAN12 Knockout A-549 Cell Line | EDJ-KQ33887 | Human | 23554 | Details Get a Quote |
| TSPAN12 Knockout HCT 116 Cell Line | EDJ-KQ33888 | Human | 23554 | Details Get a Quote |
| TSPAN12 Knockout HeLa Cell Line | EDJ-KQ33889 | Human | 23554 | Details Get a Quote |
