BEST1 bestrophin 1 [Homo sapiens (human)] - Gene

Summary

Official Symbol: BEST1provided by HGNC
Official Full Name: bestrophin 1provided by HGNC
Primary source: HGNC:HGNC:12703
See related: Ensembl:ENSG00000167995 MIM:607854; AllianceGenome:HGNC:12703
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: ARB; BMD; BEST; RP50; VMD2; TU15B; Best1V1Delta2
Summary: This gene encodes a member of the bestrophin gene family. This small gene family is characterized by proteins with a highly conserved N-terminus with four to six transmembrane domains. Bestrophins may form chloride ion channels or may regulate voltage-gated L-type calcium-ion channels. Bestrophins are generally believed to form calcium-activated chloride-ion channels in epithelial cells but they have also been shown to be highly permeable to bicarbonate ion transport in retinal tissue. Mutations in this gene are responsible for juvenile-onset vitelliform macular dystrophy (VMD2), also known as Best macular dystrophy, in addition to adult-onset vitelliform macular dystrophy (AVMD) and other retinopathies. Alternative splicing results in multiple variants encoding distinct isoforms.[provided by RefSeq, Nov 2008]
Expression: Broad expression in brain (RPKM 5.3), appendix (RPKM 3.0) and 23 other tissues See more
Orthologs: mouse all
NEW: Try the new Gene table
Try the new Transcript table

Genomic context

Location:: 11q12.3

Exon count:: 13

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	11	NC_000011.10 (61949821..61965515)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	11	NC_060935.1 (61938644..61954340)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	11	NC_000011.9 (61717293..61732987)

Chromosome 11 - NC_000011.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

Go to the top of the page Help

Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

Go to the top of the page Help

See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

Go to the top of the page Help

GeneRIFs: Gene References Into Functions

What's a GeneRIF?

The Retinal Phenotype Associated with the p.Pro101Thr BEST1 Variant.
Title: The Retinal Phenotype Associated with the p.Pro101Thr BEST1 Variant.
Typical best vitelliform dystrophy secondary to biallelic variants in BEST1.
Title: Typical best vitelliform dystrophy secondary to biallelic variants in BEST1.
Comprehensive Genetic Analysis Unraveled the Missing Heritability and a Founder Variant of BEST1 in a Chinese Cohort With Autosomal Recessive Bestrophinopathy.
Title: Comprehensive Genetic Analysis Unraveled the Missing Heritability and a Founder Variant of BEST1 in a Chinese Cohort With Autosomal Recessive Bestrophinopathy.
A novel compound heterozygous BEST1 gene mutation in two siblings causing autosomal recessive bestrophinopathy.
Title: A novel compound heterozygous BEST1 gene mutation in two siblings causing autosomal recessive bestrophinopathy.
Photoreceptor function and structure in retinal degenerations caused by biallelic BEST1 mutations.
Title: Photoreceptor function and structure in retinal degenerations caused by biallelic BEST1 mutations.
BEST1 novel mutation causes Bestrophinopathies in six families with distinct phenotypic diversity.
Title: BEST1 novel mutation causes Bestrophinopathies in six families with distinct phenotypic diversity.
Genetic and clinical features of BEST1-associated retinopathy based on 59 Chinese families and database comparisons.
Title: Genetic and clinical features of BEST1-associated retinopathy based on 59 Chinese families and database comparisons.
Impaired Bestrophin Channel Activity in an iPSC-RPE Model of Best Vitelliform Macular Dystrophy (BVMD) from an Early Onset Patient Carrying the P77S Dominant Mutation.
Title: Impaired Bestrophin Channel Activity in an iPSC-RPE Model of Best Vitelliform Macular Dystrophy (BVMD) from an Early Onset Patient Carrying the P77S Dominant Mutation.
Self-organization and surface properties of hBest1 in models of biological membranes.
Title: Self-organization and surface properties of hBest1 in models of biological membranes.
Clinical reassessments and whole-exome sequencing uncover novel BEST1 mutation associated with bestrophinopathy phenotype.
Title: Clinical reassessments and whole-exome sequencing uncover novel BEST1 mutation associated with bestrophinopathy phenotype.

Submit: New GeneRIF Correction See all GeneRIFs (154)

Phenotypes

Go to the top of the page Help

Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Autosomal dominant vitreoretinochoroidopathy MedGen: C3888099 OMIM: 193220 GeneReviews: Bestrophinopathies	Compare labs
Autosomal recessive bestrophinopathy MedGen: C3888198 OMIM: 611809 GeneReviews: Bestrophinopathies	Compare labs
Retinitis pigmentosa 50 MedGen: C2750789 OMIM: 613194 GeneReviews: Nonsyndromic Retinitis Pigmentosa Overview	Compare labs
Vitelliform macular dystrophy 2 MedGen: C2745945 OMIM: 153700 GeneReviews: Bestrophinopathies	Compare labs

EBI GWAS Catalog

Description
Genetic loci associated with plasma phospholipid n-3 fatty acids: a meta-analysis of genome-wide association studies from the CHARGE Consortium. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study of circulating estradiol, testosterone, and sex hormone-binding globulin in postmenopausal women. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study of plasma N6 polyunsaturated fatty acids within the cohorts for heart and aging research in genomic epidemiology consortium. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

Go to the top of the page Help

See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

Go to the top of the page Help

Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

Go to the top of the page Help

Markers

D11S3983 (e-PCR)
- UniSTS:17680

STS-L20941 (e-PCR)
- UniSTS:21529

D1S2060E (e-PCR)
- UniSTS:151601

D11S3430 (e-PCR)
- UniSTS:152671

D10S16 (e-PCR)
- UniSTS:155756

D1S1425 (e-PCR)
- UniSTS:149621

WI-15952 (e-PCR)
- UniSTS:65431

D8S467 (e-PCR)
- UniSTS:80311

L29953 (e-PCR)
- UniSTS:52164

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables bicarbonate channel activity	IDA Inferred from Direct Assay more info	PubMed
enables bicarbonate transmembrane transporter activity	TAS Traceable Author Statement more info
contributes_to chloride channel activity	IDA Inferred from Direct Assay more info	PubMed
enables chloride channel activity	IDA Inferred from Direct Assay more info	PubMed
enables identical protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables intracellularly calcium-gated chloride channel activity	IDA Inferred from Direct Assay more info	PubMed
enables intracellularly calcium-gated chloride channel activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables intracellularly calcium-gated chloride channel activity	TAS Traceable Author Statement more info
enables ligand-gated channel activity	ISS Inferred from Sequence or Structural Similarity more info

Process	Evidence Code	Pubs
involved_in bicarbonate transport	IEA Inferred from Electronic Annotation more info
involved_in chloride transmembrane transport	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within chloride transport	IDA Inferred from Direct Assay more info	PubMed
involved_in detection of light stimulus involved in visual perception	IEA Inferred from Electronic Annotation more info
involved_in gamma-aminobutyric acid secretion, neurotransmission	ISS Inferred from Sequence or Structural Similarity more info
involved_in glutamate secretion	ISS Inferred from Sequence or Structural Similarity more info
involved_in monoatomic ion transmembrane transport	TAS Traceable Author Statement more info
involved_in protein complex oligomerization	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of calcium ion transport	IEA Inferred from Electronic Annotation more info
involved_in regulation of synaptic plasticity	ISS Inferred from Sequence or Structural Similarity more info
involved_in transepithelial chloride transport	IDA Inferred from Direct Assay more info	PubMed
involved_in visual perception	TAS Traceable Author Statement more info	PubMed

Component	Evidence Code	Pubs
located_in basal plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in basolateral plasma membrane	IDA Inferred from Direct Assay more info	PubMed
part_of chloride channel complex	IDA Inferred from Direct Assay more info	PubMed
located_in cytosol	TAS Traceable Author Statement more info	PubMed
located_in membrane	TAS Traceable Author Statement more info	PubMed
located_in membrane microdomain	ISS Inferred from Sequence or Structural Similarity more info
located_in plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	TAS Traceable Author Statement more info
located_in presynapse	IEA Inferred from Electronic Annotation more info

General protein information

Go to the top of the page Help

Preferred Names: bestrophin-1

Names: Best disease; vitelliform macular dystrophy protein 2

NCBI Reference Sequences (RefSeq)

Go to the top of the page Help

NEW Try the new Transcript table

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_009033.1 RefSeqGene

Range

5468..19578

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001139443.2 → NP_001132915.1 bestrophin-1 isoform 2

See identical proteins and their annotated locations for NP_001132915.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) encodes the longest isoform (2).

Source sequence(s)

AF057169, AP003733, BC015220, BC041664

Consensus CDS

CCDS44623.1

UniProtKB/TrEMBL

J7LCD9

Related

ENSP00000399709.2, ENST00000449131.6

Conserved Domains (1) summary

pfam01062
Location:16 → 255

Bestrophin; Bestrophin, RFP-TM, chloride channel
NM_001300786.2 → NP_001287715.1 bestrophin-1 isoform 3

See identical proteins and their annotated locations for NP_001287715.1

Status: REVIEWED

Description

Transcript Variant: This variant (3) lacks an alternate in-frame exon and differs in the 3' UTR and coding sequence compared to variant 2. The resulting isoform (3) lacks an alternate internal segment and has a shorter and distinct C-terminus compared to isoform 2.

Source sequence(s)

AP003733, BC015220

UniProtKB/TrEMBL

A0A0S2Z4M4, J7LCD9

Conserved Domains (1) summary

pfam01062
Location:16 → 231

Bestrophin; Bestrophin, RFP-TM, chloride channel
NM_001300787.2 → NP_001287716.1 bestrophin-1 isoform 4

See identical proteins and their annotated locations for NP_001287716.1

Status: REVIEWED

Description

Transcript Variant: This variant (4) differs in the 3' UTR and coding sequence compared to variant 2. The resulting isoform (4) has a shorter and distinct C-terminus compared to isoform 2.

Source sequence(s)

AK295998, AP003733, BC015220

UniProtKB/TrEMBL

A0A0S2Z579, J7LCD9

Conserved Domains (1) summary

pfam01062
Location:16 → 256

Bestrophin; RFP-TM, chloride channel
NM_001363591.2 → NP_001350520.1 bestrophin-1 isoform 5

Status: REVIEWED

Source sequence(s)

AP003733

UniProtKB/TrEMBL

J7LCD9

Conserved Domains (1) summary

pfam01062
Location:3 → 210

Bestrophin; RFP-TM, chloride channel
NM_001363592.1 → NP_001350521.1 bestrophin-1 isoform 6

Status: REVIEWED

Source sequence(s)

AK289681, AP003733

Consensus CDS

CCDS86208.1

UniProtKB/TrEMBL

A0A0C4DGE9, B7Z336

Related

ENSP00000432681.1, ENST00000524926.5

Conserved Domains (1) summary

pfam01062
Location:9 → 291

Bestrophin; Bestrophin, RFP-TM, chloride channel
NM_001363593.2 → NP_001350522.1 bestrophin-1 isoform 7

Status: REVIEWED

Source sequence(s)

AP003733

UniProtKB/TrEMBL

B7Z5C9
NM_004183.4 → NP_004174.1 bestrophin-1 isoform 1

See identical proteins and their annotated locations for NP_004174.1

Status: REVIEWED

Description

Transcript Variant: This variant (1) differs in the 5' UTR and coding sequence and in the 3' UTR and coding sequence compared to variant 2. The resulting isoform (1) is longer at the N-terminus and has a shorter and distinct C-terminus compared to isoform 2.

Source sequence(s)

AF057169, BC015220

Consensus CDS

CCDS31580.1

UniProtKB/Swiss-Prot

A8K0W6, B7Z3J8, B7Z736, O75904, O76090, Q53YQ9, Q8IUR9, Q8IZ80

UniProtKB/TrEMBL

J7LCD9

Related

ENSP00000367282.4, ENST00000378043.9

Conserved Domains (1) summary

pfam01062
Location:9 → 315

Bestrophin; Bestrophin, RFP-TM, chloride channel

RNA

NR_134580.2 RNA Sequence

Status: REVIEWED

Description

Transcript Variant: This variant (5) contains an alternate exon, uses an alternate internal splice junction, and differs in the 3' end compared to variant 2. This variant is represented as non-coding because the use of the 5'-most expected translational start codon renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).

Source sequence(s)

AF057170, AP003733, BC015220