BEX4

Chr X

brain expressed X-linked 4

ENSG00000102409 UniProt: Q9NWD9 OMIM: 300692

The BEX4 protein regulates microtubule deacetylation by modulating SIRT2 deacetylase activity and acts as a pseudosubstrate for the CRL2(FEM1B) complex, participating in cell cycle progression and genomic stability. Mutations cause X-linked intellectual disability with variable additional features including seizures and developmental delays. This follows X-linked inheritance, affecting primarily males with carrier females potentially showing mild symptoms.

OMIM ResearchSummary from RefSeq, UniProt

May play a role in microtubule deacetylation by negatively regulating the SIRT2 deacetylase activity toward alpha-tubulin and thereby participate in the control of cell cycle progression and genomic stability (PubMed:27512957). In absence of reductive stress, acts as a pseudosubstrate for the CRL2(FEM1B) complex: associates with FEM1B via zinc, thereby preventing association between FEM1B and its substrates (By similarity)

OMIM ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.82

LOEUF

—

Mechanism

Some data sources returned errors (1)

ncbi: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.82LOEUF

pLI 0.672

Z-score 1.77

OE 0.00 (0.00–0.82)

Moderately constrained

Typical tolerance to LoF variation

Missense Constraint?

0.24Z-score

OE missense 0.90 (0.71–1.16)

44 obs / 48.7 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.00 (0.00–0.82)

0≤0.351.4

Missense OE?0.90 (0.71–1.16)

0≤0.61.4

Synonymous OE?1.09

0≤1.21.6

LoF obs/exp: 0 / 3.6Missense obs/exp: 44 / 48.7Syn Z: -0.30

Background carrier burden — how many people carry a rare variant somewhere in BEX4?

gnomAD v4 · ~732k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 580

115 rare PASS variants

Rare truncating (LoF)

1 in 28,000

5 rare PASS variants

Rare synonymous (reference)

1 in 1,600

39 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for BEX4. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~561k	1 in 650	1 in 16,000
South Asian	~36k	1 in 870	≈ 1 in 29,000
Remaining (unassigned)	~31k	1 in 610	none seen
European (Finnish)	~27k	1 in 4,400	≈ 1 in 25,000
Admixed American	~23k	1 in 930	none seen
African / African American	~21k	1 in 1,500	none seen
East Asian	~20k	1 in 840	none seen
Ashkenazi Jewish	~13k	≈ 1 in 6,200	none seen
Middle Eastern	~2,758	≈ 1 in 1,300	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 1 coding exons well covered in gnomAD exomes and genomes.? see exons ↓