BEX2

Chr X

brain expressed X-linked 2

Also known as: BEX1, DJ79P11.1

The protein interacts with transcription factor LMO2 in DNA-binding complexes that recognize E-box elements and promotes transcription, while also regulating mitochondrial apoptosis and G1 cell cycle progression through modulation of BCL2 family proteins and cell cycle regulators. Currently, no definitive pediatric neurological phenotypes have been established for pathogenic BEX2 variants, though the gene shows tumor suppressor activity and is expressed in brain tissue. This X-linked gene would follow X-linked inheritance patterns, with the protein showing relatively low constraint to loss-of-function variation.

Summary from RefSeq, UniProt
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0
Active trials
9
Pubs (1 yr)
0
P/LP submissions
P/LP missense
1.27
LOEUF
Multiple*
Mechanism· predicted
Clinical SummaryBEX2
Population Constraint (gnomAD)
Low constraint (pLI 0.10) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.27LOEUF
pLI 0.101
Z-score 1.21
OE 0.41 (0.171.27)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.01Z-score
OE missense 1.00 (0.821.23)
67 obs / 66.7 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.41 (0.171.27)
00.351.4
Missense OE1.00 (0.821.23)
00.61.4
Synonymous OE0.90
01.21.6
LoF obs/exp: 2 / 4.9Missense obs/exp: 67 / 66.7Syn Z: 0.38
DN
0.6936th %ile
GOF
0.84top 5%
LOF
0.2774th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median
DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

BEX2 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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