BEX5

Chr X

brain expressed X-linked 5

Also known as: NGFRAP1L1

The BEX5 protein is predicted to bind signaling receptors and participate in signal transduction within the cytoplasm. This gene shows low constraint against loss-of-function variants (pLI = 0.003, LOEUF = 1.94), suggesting it may tolerate protein-truncating mutations. No well-established human disease associations have been reported for BEX5 mutations.

Summary from RefSeq
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0
Active trials
3
Pubs (1 yr)
0
P/LP submissions
P/LP missense
1.94
LOEUF
Multiple*
Mechanism· predicted
Clinical SummaryBEX5
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — 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
1.94LOEUF
pLI 0.003
Z-score -1.01
OE 1.86 (0.631.94)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.31Z-score
OE missense 0.87 (0.671.13)
39 obs / 44.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE1.86 (0.631.94)
00.351.4
Missense OE0.87 (0.671.13)
00.61.4
Synonymous OE1.01
01.21.6
LoF obs/exp: 3 / 1.6Missense obs/exp: 39 / 44.9Syn Z: -0.02
DN
0.80top 25%
GOF
0.6932th %ile
LOF
0.2871th %ile

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

DNprediction above median
GOFprediction 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

BEX5 · 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.

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Clinical Literature
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