BEST3 bestrophin 3 [Homo sapiens (human)] - Gene

Summary

Official Symbol: BEST3provided by HGNC
Official Full Name: bestrophin 3provided by HGNC
Primary source: HGNC:HGNC:17105
See related: Ensembl:ENSG00000127325 MIM:607337; AllianceGenome:HGNC:17105
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: VMD2L3
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]
Expression: Biased expression in brain (RPKM 1.2), testis (RPKM 0.5) and 4 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 12q15

Exon count:: 15

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	12	NC_000012.12 (69643508..69699303, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	12	NC_060936.1 (69622438..69684535, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	12	NC_000012.11 (70037288..70093083, complement)

Chromosome 12 - NC_000012.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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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

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

whole-exome sequencing implicates a rare non-synonymous single-nucleotide variants of BEST3 as a candidate for mandibular prognathism in the Japanese pedigree.
Title: Whole-exome sequencing in a Japanese pedigree implicates a rare non-synonymous single-nucleotide variant in BEST3 as a candidate for mandibular prognathism.
results demonstrated that Best-3 is an endogenous inhibitor of NF-kappaB signaling pathway in endothelial cells, suggesting that forced Best-3 expression may be a novel approach for the treatment of vascular inflammatory diseases.
Title: Bestrophin 3 ameliorates TNFα-induced inflammation by inhibiting NF-κB activation in endothelial cells.
Results provide evidence that the bestrophins are expressed in pancreatic duct cells and, more specifically, that hBest1 plays a role in the calcium activated chloride channels found in these cells.
Title: Bestrophin expression and function in the human pancreatic duct cell line, CFPAC-1.
These results suggest that an auto-inhibitory mechanism in C termini of bestrophin 3 may be universal among bestrophins investigated in the study.
Title: Activation of bestrophin Cl- channels is regulated by C-terminal domains.
identified three novel VMD2-related human genes demonstrating a high degree of conservation in their respective RFP-TM domains [VMD2L1, VMD2L2, VMD2L3]
Title: Three novel human VMD2-like genes are members of the evolutionary highly conserved RFP-TM family.

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Phenotypes

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

Review eQTL and phenotype association data in this region using PheGenI

EBI GWAS Catalog

Description
Genome-wide meta-analyses of nonsyndromic cleft lip with or without cleft palate identify six new risk loci. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

G32926 (e-PCR)
- UniSTS:117504

RH120549 (e-PCR)
- UniSTS:133714

RH102802 (e-PCR)
- UniSTS:97136

RH44642 (e-PCR)
- UniSTS:41146

RH44577 (e-PCR)
- UniSTS:30912

SHGC-33073 (e-PCR)
- UniSTS:30913

RH93788 (e-PCR)
- UniSTS:85444

A009W40 (e-PCR)
- UniSTS:69581

SHGC-34028 (e-PCR)
- UniSTS:44766

D12S1816 (e-PCR)
- UniSTS:25335

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables intracellularly calcium-gated chloride channel activity	IDA Inferred from Direct Assay more info	PubMed
enables ligand-gated monoatomic anion channel activity	ISS Inferred from Sequence or Structural Similarity more info
enables metal ion binding	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in chloride transmembrane transport	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of monoatomic ion transport	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
part_of chloride channel complex	IEA Inferred from Electronic Annotation more info
located_in plasma membrane	ISS Inferred from Sequence or Structural Similarity more info

General protein information

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Preferred Names: bestrophin-3

Names: vitelliform macular dystrophy 2-like 3; vitelliform macular dystrophy 2-like protein 3

NCBI Reference Sequences (RefSeq)

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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.

mRNA and Protein(s)

NM_001282613.2 → NP_001269542.1 bestrophin-3 isoform 3

See identical proteins and their annotated locations for NP_001269542.1

Status: VALIDATED

Description

Transcript Variant: This variant (3) differs in the 5' UTR, lacks a portion of the 5' coding region, and uses a downstream in-frame start codon, compared to variant 1. The encoded isoform (3) is shorter at the N-terminus, compared to isoform 1.

Source sequence(s)

BC028087, BC151138, DA767581

Consensus CDS

CCDS61192.1

UniProtKB/Swiss-Prot

Q8N1M1

Related

ENSP00000449548.1, ENST00000553096.5

Conserved Domains (1) summary

pfam01062
Location:3 → 210

Bestrophin; RFP-TM, chloride channel
NM_001282614.2 → NP_001269543.1 bestrophin-3 isoform 4

See identical proteins and their annotated locations for NP_001269543.1

Status: VALIDATED

Description

Transcript Variant: This variant (4) contains an alternate 3' terminal exon and it thus differs in the 3' coding region and 3' UTR, compared to variant 1. The encoded isoform (4) has a distinct and shorter C-terminus, compared to isoform 1.

Source sequence(s)

AF440758, AY515706, BX374313

Consensus CDS

CCDS61193.1

UniProtKB/Swiss-Prot

Q8N1M1

Related

ENSP00000329064.4, ENST00000331471.8

Conserved Domains (1) summary

pfam01062
Location:8 → 315

Bestrophin; Bestrophin, RFP-TM, chloride channel
NM_001282615.2 → NP_001269544.1 bestrophin-3 isoform 5

See identical proteins and their annotated locations for NP_001269544.1

Status: VALIDATED

Description

Transcript Variant: This variant (5) lacks a portion of the 5' UTR and 5' coding region, uses a downstream in-frame start codon, and lacks several 3' exons but includes an alternate 3' terminal exon, compared to variant 1. The encoded isoform (5) is shorter at the N-terminus, has a distinct C-terminus and is significantly shorter than isoform 1. Both variants 5 and 6 encode isoform 5.

Source sequence(s)

AC025263, BC006440

Consensus CDS

CCDS73496.1

UniProtKB/Swiss-Prot

Q8N1M1

Related

ENSP00000266661.4, ENST00000266661.8

Conserved Domains (1) summary

cl01544
Location:3 → 67

Bestrophin; RFP-TM, chloride channel
NM_001282616.2 → NP_001269545.1 bestrophin-3 isoform 5

See identical proteins and their annotated locations for NP_001269545.1

Status: VALIDATED

Description

Transcript Variant: This variant (6) lacks a portion of the 5' UTR and 5' coding region, uses a downstream in-frame start codon, and lacks several 3' exons but includes an alternate 3' terminal exon, compared to variant 1. The encoded isoform (5) is shorter at the N-terminus, has a distinct C-terminus and is significantly shorter than isoform 1. Both variants 5 and 6 encode isoform 5.

Source sequence(s)

AC025263, BC006440, BP225850

Consensus CDS

CCDS73496.1

UniProtKB/Swiss-Prot

Q8N1M1

Related

ENSP00000449377.1, ENST00000551160.5

Conserved Domains (1) summary

cl01544
Location:3 → 67

Bestrophin; RFP-TM, chloride channel
NM_032735.3 → NP_116124.2 bestrophin-3 isoform 1

See identical proteins and their annotated locations for NP_116124.2

Status: VALIDATED

Description

Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1).

Source sequence(s)

AC025263, AK096459, BC028087

Consensus CDS

CCDS8992.2

UniProtKB/Swiss-Prot

B5MDI8, F8VVZ2, Q53YQ7, Q8N1M1, Q8N356, Q8NFT9, Q9BR80

Related

ENSP00000332413.5, ENST00000330891.10

Conserved Domains (1) summary

pfam01062
Location:8 → 315

Bestrophin; Bestrophin, RFP-TM, chloride channel
NM_152439.4 → NP_689652.2 bestrophin-3 isoform 2

Status: VALIDATED

Description

Transcript Variant: This variant (2) differs in the 5' UTR, lacks a portion of the 5' coding region, uses a downstream in-frame start codon, and lacks an in-frame exon in the central coding region, compared to variant 1. The encoded isoform (2) is shorter at the N-terminus, compared to isoform 1.

Source sequence(s)

AK096459, BC028087, BF739974

Consensus CDS

CCDS41810.1

UniProtKB/Swiss-Prot

Q8N1M1

Related

ENSP00000433213.1, ENST00000488961.5

Conserved Domains (1) summary

cl01544
Location:5 → 102

Bestrophin; Bestrophin, RFP-TM, chloride channel

RNA

NR_104220.2 RNA Sequence

Status: VALIDATED

Description

Transcript Variant: This variant (7) consists of two exons that variant 1 lacks, but it shares its 5' exon with variant 2 and its 3' exon with variants 5 and 6. This variant is represented as non-coding because it lacks an in-frame ORF that is likely to be translated.

Source sequence(s)

AC025263, BC006440, BC028087, BF739974