BEST3
protein-codingbestrophin 3, the group of Bestrophins
Gene summary
BEST3 belongs to the bestrophin family of anion channels, which includes BEST1 (MIM 607854), the gene mutant in vitelliform macular dystrophy (VMD; MIM 153700), and 2 other BEST1-like genes, BEST2 (MIM 607335) and BEST4 (MIM 607336). Bestrophins are transmembrane (TM) proteins that share a homology region containing a high content of aromatic residues, including an invariant arg-phe-pro (RFP) motif. The bestrophin genes share a conserved gene structure, with almost identical sizes of the 8 RFP-TM domain-encoding exons and highly conserved exon-intron boundaries. Each of the 4 bestrophin genes has a unique 3-prime end of variable length (Stohr et al., 2002 [PubMed 12032738]; Tsunenari et al., 2003 [PubMed 12907679]).[supplied by OMIM, Mar 2008]
- VMD2L3
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~56.1 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to BEST3 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_032735.3. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 3 | 3 | ||||
| missense | 86 | 3 | 89 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 86 | 6 | 0 | 92 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_116124.2 | 9 | MANE Select | |
| Ensembl | ENSP00000332413.5 | 9 | MANE Select | |
| RefSeq | NP_001269542.1 | 7 | Standard | |
| RefSeq | NP_001269543.1 | 9 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Stimuli-sensing channels
- Ion channel transport
- Transport of small molecules
Biological Process
- biological_process
- negative regulation of ion transport
- chloride transmembrane transport
Molecular Function
- molecular_function
- chloride channel activity
Cellular Component
- plasma membrane
- chloride channel complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000330891
- Coding exons
- 9
- Length
- 56117
- Individuals with no LoFs
- 125509
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 239
- Defined
- 125748
- p
- 0.000951
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.556 | 337 | 367 | 0.918 | 0.0000193 | 4375 |
| Missense (PolyPhen) | 91 | 104.92 | 0.86734 | 1256 | ||
| Synonymous | -0.0233 | 142 | 142 | 1.00 | 0.00000809 | 1302 |
| Loss of Function | -0.209 | 28 | 26.8 | 1.04 | 0.00000138 | 305 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00033 | 0.00031 | rare |
| Latino/Admixed American | 0.0010 | 0.0010 | notable |
| Ashkenazi Jewish | 0.0065 | 0.0065 | notable |
| East Asian | 0.00061 | 0.00060 | rare |
| Finnish | 0.0010 | 0.0010 | notable |
| European (Non-Finnish) | 0.00055 | 0.00044 | rare |
| South Asian | 0.0016 | 0.0013 | notable |
| Other | 0.0017 | 0.0016 | notable |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Forms calcium-sensitive chloride channels. Permeable to bicarbonate. {ECO:0000269|PubMed:12907679}.;
Recessive Scores
- pRec
- 0.104
Intolerance Scores
- LoFtool
- 0.227
- RVIS EVS
- 0.13
- RVIS percentile EVS
- 63.57
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.482
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |