BRD2

Chr 6

bromodomain containing 2

Also known as: BRD2-IT1, D6S113E, FSH, FSHRG1, FSRG1, NAT, O27.1.1, RING3

NCBI Gene: 6046ENSG00000204256UniProt: P25440

This gene encodes a transcriptional regulator that belongs to the BET (bromodomains and extra terminal domain) family of proteins. This protein associates with transcription complexes and with acetylated chromatin during mitosis, and it selectively binds to the acetylated lysine-12 residue of histone H4 via its two bromodomains. The gene maps to the major histocompatability complex (MHC) class II region on chromosome 6p21.3, but sequence comparison suggests that the protein is not involved in the immune response. This gene has been implicated in juvenile myoclonic epilepsy, a common form of epilepsy that becomes apparent in adolescence. Multiple alternatively spliced variants have been described for this gene. [provided by RefSeq, Dec 2010]

144
ClinVar variants
5
Pathogenic / LP
1.00
pLI score· haploinsufficient
0
Active trials
Clinical Summary— BRD2
⚡
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.
📋
ClinVar Variants
5 Pathogenic / Likely Pathogenic· 99 VUS of 144 total submissions
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.22LOEUF
pLI 1.000
Z-score 5.05
OE 0.08 (0.04–0.22)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.59Z-score
OE missense 0.92 (0.85–1.00)
417 obs / 452.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.08 (0.04–0.22)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.92 (0.85–1.00)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.44
0≤1.21.6
LoF obs/exp: 3 / 35.5Missense obs/exp: 417 / 452.5Syn Z: -4.45

ClinVar Variant Classifications

144 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic4
Likely Pathogenic1
VUS99
Likely Benign20
Benign20
4
Pathogenic
1
Likely Pathogenic
99
VUS
20
Likely Benign
20
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
4
0
4
Likely Pathogenic
0
0
1
0
1
VUS
0
95
4
0
99
Likely Benign
0
1
5
14
20
Benign
0
5
6
9
20
Total01012023144

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

View in ClinVar →

Protein Context — Lollipop Plot

BRD2 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype

OMIM

No OMIM entries found.

📖
GeneReview available — BRD2
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
BET proteins: Biological functions and therapeutic interventions.
Guo J et al.·Pharmacol Ther
2023Review
Vaccines for measles, mumps, rubella, and varicella in children.
Di Pietrantonj C et al.·Cochrane Database Syst Rev
2021
Synthetic Lethal and Resistance Interactions with BET Bromodomain Inhibitors in Triple-Negative Breast Cancer.
Shu S et al.·Mol Cell
2020
BRD4: New hope in the battle against glioblastoma.
Duan W et al.·Pharmacol Res
2023Review
BET Epigenetic Reader Proteins in Cardiovascular Transcriptional Programs.
Borck PC et al.·Circ Res
2020Review
Prostate cancer-associated SPOP mutations confer resistance to BET inhibitors through stabilization of BRD4.
Dai X et al.·Nat Med
2017
BRD2 bromodomain-mediated regulation of cell state plasticity modulates therapy response in glioblastoma.
Vadla R et al.·Neuro Oncol
2025
Selective inhibition of the BD2 bromodomain of BET proteins in prostate cancer.
Faivre EJ et al.·Nature
2020
BET bromodomain inhibitors: a patent review.
Garnier JM et al.·Expert Opin Ther Pat
2014Review
BRD2 inhibition blocks SARS-CoV-2 infection by reducing transcription of the host cell receptor ACE2.
Samelson AJ et al.·Nat Cell Biol
2022
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools