BEX3

Chr X

brain expressed X-linked 3

Also known as: Bex, DXS6984E, HGR74, Hero20, NADE, NGFRAP1

The BEX3 protein functions as a signaling adapter molecule in neuronal apoptosis pathways, particularly in nerve growth factor receptor-mediated cell death and zinc-triggered neuronal death, and acts as a pseudosubstrate regulator of the CRL2(FEM1B) ubiquitin ligase complex. Mutations in BEX3 cause X-linked intellectual disability with seizures and behavioral abnormalities. This X-linked condition primarily affects males, with females typically being unaffected carriers.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
3
Pubs (1 yr)
0
P/LP submissions
P/LP missense
0.96
LOEUF
DN
Mechanism· predicted
Clinical SummaryBEX3
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.62) — some intolerance to loss-of-function variants.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.96LOEUF
pLI 0.621
Z-score 1.63
OE 0.00 (0.000.96)
Moderately constrained

Typical tolerance to LoF variation

Missense Constraint
1.00Z-score
OE missense 0.59 (0.440.81)
28 obs / 47.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.00 (0.000.96)
00.351.4
Missense OE0.59 (0.440.81)
00.61.4
Synonymous OE1.26
01.21.6
LoF obs/exp: 0 / 3.1Missense obs/exp: 28 / 47.2Syn Z: -0.76
DN
0.6357th %ile
GOF
0.6247th %ile
LOF
0.4037th %ile

The highest-scoring mechanism for this gene is dominant-negative.

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

BEX3 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →