BEST1 Gene - Bestrophin 1
Calcium-activated chloride channel and retinal pigment epithelium marker
Gene Information Card
| Symbol | BEST1 |
|---|---|
| Full Name | Bestrophin 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 11q12.3 |
| NCBI Gene ID | 7439 ncbi.nlm.nih.gov/gene/7439 |
| Ensembl ID | ENSG00000167995 |
| UniProt ID | O76090 |
| OMIM ID | 607854 |
| HGNC ID | 1270 |
| Aliases | VMD2, BMD, RP50, TU15B |
Description
BEST1 encodes bestrophin 1, a transmembrane protein that functions as a calcium-activated chloride channel primarily expressed in the retinal pigment epithelium (RPE). It plays a critical role in ion transport and maintaining RPE homeostasis. Mutations in BEST1 cause several inherited retinal dystrophies, including Best vitelliform macular dystrophy (BVMD), adult-onset vitelliform macular dystrophy (AVMD), and autosomal recessive bestrophinopathy (ARB).
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Best vitelliform macular dystrophy (BVMD) | Dominant-negative or gain-of-function mutations impair chloride channel activity, leading to lipofuscin accumulation in RPE | ClinVar, OMIM |
| Adult-onset vitelliform macular dystrophy (AVMD) | Missense mutations reduce channel conductance, causing delayed photoreceptor degeneration | ClinVar, OMIM |
| Autosomal recessive bestrophinopathy (ARB) | Biallelic loss-of-function mutations abolish channel activity, resulting in severe RPE dysfunction | ClinVar, OMIM |
| Retinitis pigmentosa 50 (RP50) | Rare missense variants disrupt protein folding and trafficking, leading to photoreceptor death | ClinVar, OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Retina | 32.5 | High |
| Retinal pigment epithelium | 45.1 | High |
| Brain (cerebellum) | 2.3 | Low |
| Heart | 1.1 | Low |
| Liver | 0.5 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| ARPE-19 (RPE cell line) | 38.7 | High expression |
| HEK293 | 0.8 | Low expression |
| HeLa | 0.3 | Not detected |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.652C>T (p.Arg218Cys) | Missense | Common | Dominant-negative; reduced chloride conductance |
| c.422G>A (p.Arg141His) | Missense | Frequent | Gain-of-function; altered channel gating |
| c.2T>C (p.Met1Thr) | Start loss | Rare | Loss-of-function; no protein production |
| c.1003G>A (p.Gly335Arg) | Missense | Rare | Dominant-negative; impaired trafficking |
Mutation functional classification
Loss of Function (LOF)
Biallelic loss-of-function mutations (e.g., start loss, nonsense) cause autosomal recessive bestrophinopathy (ARB) with complete loss of chloride channel activity.
Gain of Function (GOF)
Some missense mutations (e.g., p.Arg141His) increase channel open probability, leading to altered ion homeostasis and dominant BVMD.
Dominant Negative (DN)
Common missense mutations (e.g., p.Arg218Cys) exert dominant-negative effects by disrupting multimeric channel assembly, reducing overall chloride conductance.
View complete mutation data：
Gene Ontology (GO)
| • calcium-activated chloride channel activity (GO:0005227) | • integral component of membrane (GO:0016021) |
| • plasma membrane (GO:0005886) | • ion transport (GO:0006811) |
| • locomotory behavior (GO:0007626) | • visual perception (GO:0007601) |
Pathways
• Calcium signaling pathway (Reactome: R-HSA-4086400)
• Ion channel transport (Reactome: R-HSA-983712)
Protein Summary
Bestrophin 1 is a 585-amino acid transmembrane protein with four to six membrane-spanning domains. It forms pentameric calcium-activated chloride channels in the basolateral membrane of RPE cells. The protein regulates ion flux, fluid transport, and pH homeostasis essential for photoreceptor support. Mutations disrupt channel function, leading to lipofuscin accumulation and retinal degeneration.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| BEST1 Knockout HEK293 Cell Line | EDJ-KQ6007 | Human | 7439 | Details Get a Quote |
| BEST1 Knockout A-549 Cell Line | EDJ-KQ29614 | Human | 7439 | Details Get a Quote |
| BEST1 Knockout HCT 116 Cell Line | EDJ-KQ29615 | Human | 7439 | Details Get a Quote |
| BEST1 Knockout HeLa Cell Line | EDJ-KQ29616 | Human | 7439 | Details Get a Quote |
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