BEST2

Chr 19

bestrophin 2

Also known as: VMD2L1

NCBI Gene: 54831ENSG00000039987UniProt: Q8NFU1

This gene is a member of the bestrophin gene family of anion channels. Bestrophin genes share a similar gene structure with highly conserved exon-intron boundaries, but with distinct 3' ends. Bestrophins are transmembrane proteins that contain a homologous region rich in aromatic residues, including an invariant arg-phe-pro motif. Mutation in one of the family members (bestrophin 1) is associated with vitelliform macular dystrophy. The bestrophin 2 gene is mainly expressed in the retinal pigment epithelium and colon. [provided by RefSeq, Jul 2008]

109
ClinVar variants
19
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— BEST2
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
19 Pathogenic / Likely Pathogenic· 82 VUS of 109 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.31LOEUF
pLI 0.000
Z-score 0.42
OE 0.91 (0.64–1.31)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.42Z-score
OE missense 0.78 (0.70–0.86)
252 obs / 324.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.91 (0.64–1.31)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.78 (0.70–0.86)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.00
0≤1.21.6
LoF obs/exp: 21 / 23.2Missense obs/exp: 252 / 324.2Syn Z: -0.03

ClinVar Variant Classifications

109 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic17
Likely Pathogenic2
VUS82
Likely Benign5
17
Pathogenic
2
Likely Pathogenic
82
VUS
5
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
17
0
17
Likely Pathogenic
0
0
2
0
2
VUS
0
77
5
0
82
Likely Benign
0
5
0
0
5
Benign
0
0
0
0
0
Total082240106

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

BEST2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
BESTROPHIN 2; BEST2
MIM #607335 · *
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Functional roles of bestrophins in ocular epithelia.
Marmorstein AD et al.·Prog Retin Eye Res
2009Review
Predicting the risk of acute respiratory failure among asthma patients-the A2-BEST2 risk score: a retrospective study.
Qi Y et al.·PeerJ
2023Cohort
Quantification of TFF3 expression from a non-endoscopic device predicts clinically relevant Barrett's oesophagus by machine learning.
Berman AG et al.·EBioMedicine
2022
Use of a Cytosponge biomarker panel to prioritise endoscopic Barrett's oesophagus surveillance: a cross-sectional study followed by a real-world prospective pilot.
Pilonis ND et al.·Lancet Oncol
2022
Risk stratification of Barrett's oesophagus using a non-endoscopic sampling method coupled with a biomarker panel: a cohort study.
Ross-Innes CS et al.·Lancet Gastroenterol Hepatol
2017Cohort
A variant of the Ca2+-activated Cl channel Best3 is expressed in mouse exocrine glands.
Srivastava A et al.·J Membr Biol
2008Functional
Bronchiectasis exacerbation study on azithromycin and amoxycillin-clavulanate for respiratory exacerbations in children (BEST-2): study protocol for a randomized controlled trial.
Chang AB et al.·Trials
2013
[New methods of artificial respiratory ventilation].
Javorka K·Bratisl Lek Listy
1990
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools