BRD4

Chr 19AD

bromodomain containing 4

Also known as: CAP, CDLS6, FSHRG4, HUNK1, HUNKI, MCAP

NCBI Gene: 23476ENSG00000141867UniProt: O60885OMIM: 608749

The protein encoded by this gene is homologous to the murine protein MCAP, which associates with chromosomes during mitosis, and to the human RING3 protein, a serine/threonine kinase. Each of these proteins contains two bromodomains, a conserved sequence motif which may be involved in chromatin targeting. This gene has been implicated as the chromosome 19 target of translocation t(15;19)(q13;p13.1), which defines an upper respiratory tract carcinoma in young people. Two alternatively spliced transcript variants have been described. [provided by RefSeq, Jul 2008]

GeneReviewsOMIMResearchGenerating clinical summary…
LOFmechanismADLOEUF 0.051 OMIM phenotype
Clinical Summary— BRD4
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Gene-Disease Validity (ClinGen)
syndromic intellectual disability · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
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ClinVar Variants
35 unique Pathogenic / Likely Pathogenic· 412 VUS of 969 total submissions
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
Explore recent and relevant literature in Research Assistant →
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GeneReview available — BRD4
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
LoF Constraint?
0.05LOEUF
pLI 1.000
Z-score 7.27
OE 0.00 (0.00–0.05)
Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint?
3.59Z-score
OE missense 0.64 (0.60–0.69)
519 obs / 805.3 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?
LoF OE?0.00 (0.00–0.05)
0≤0.351.4
Missense OE?0.64 (0.60–0.69)
0≤0.61.4
Synonymous OE?1.25
0≤1.21.6
LoF obs/exp: 0 / 61.5Missense obs/exp: 519 / 805.3Syn Z: -3.62
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongBRD4-related Cornelia de Lange-like syndromeLOFAD

This gene — mechanism propensity

DN
0.17100th %ile
GOF
0.2398th %ile
LOF
0.88top 5%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · 83% of P/LP variants are LoF · LOEUF 0.05

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

969 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic16
Likely Pathogenic19
VUS412
Likely Benign409
Benign73
Conflicting16
16
Pathogenic
19
Likely Pathogenic
412
VUS
409
Likely Benign
73
Benign
16
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
14
0
2
0
16
Likely Pathogenic
15
4
0
0
19
VUS
3
374
31
4
412
Likely Benign
0
22
115
272
409
Benign
0
9
42
22
73
Conflicting
—16
Total32409190298945

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

View in ClinVar →

12 pathogenic / likely-pathogenic (of 21) ClinVar copy-number / structural variants overlap BRD4 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →

Protein Context — Lollipop Plot

BRD4 · protein map & ClinVar variants

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

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients