BRPF1

Chr 3AD

bromodomain and PHD finger containing 1

Also known as: BR140, IDDDFP

NCBI Gene: 7862ENSG00000156983UniProt: P55201

This gene encodes a bromodomain, PHD finger and chromo/Tudor-related Pro-Trp-Trp-Pro (PWWP) domain containing protein. The encoded protein is a component of the MOZ/MORF histone acetyltransferase complexes which function as a transcriptional regulators. This protein binds to the catalytic MYST domains of the MOZ and MORF proteins and may play a role in stimulating acetyltransferase and transcriptional activity of the complex. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

Primary Disease Associations & Inheritance

Intellectual developmental disorder with dysmorphic facies and ptosisMIM #617333
AD
290
ClinVar variants
39
Pathogenic / LP
1.00
pLI score· haploinsufficient
0
Active trials
Clinical Summary— BRPF1
🧬
Gene-Disease Validity (ClinGen)
syndromic complex neurodevelopmental disorder · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
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
39 Pathogenic / Likely Pathogenic· 195 VUS of 290 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
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.
0.18LOEUF
pLI 1.000
Z-score 6.17
OE 0.08 (0.04–0.18)
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.
3.83Z-score
OE missense 0.61 (0.56–0.66)
464 obs / 761.5 exp
Constrained

Highly missense-constrained (top ~0.1%)

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 (0.04–0.18)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.61 (0.56–0.66)
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.1.05
0≤1.21.6
LoF obs/exp: 4 / 52.1Missense obs/exp: 464 / 761.5Syn Z: -0.71

ClinVar Variant Classifications

290 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic28
Likely Pathogenic11
VUS195
Likely Benign51
Benign3
Conflicting2
28
Pathogenic
11
Likely Pathogenic
195
VUS
51
Likely Benign
3
Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
9
0
19
0
28
Likely Pathogenic
7
3
1
0
11
VUS
0
179
16
0
195
Likely Benign
0
26
4
21
51
Benign
0
1
0
2
3
Conflicting
—2
Total162094023290

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

View in ClinVar →

Protein Context — Lollipop Plot

BRPF1 · protein map & ClinVar variants

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

Gene2Phenotype Curations

BRPF1-related syndromic intellectual disability with ptosis

definitive
ADLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Intellectual developmental disorder with dysmorphic facies and ptosis

MIM #617333

Molecular basis of disorder known

Autosomal dominant
📖
GeneReview available — BRPF1
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
The Phenotypic and Genotypic Spectrum of BRPF1-Related Disorder: 29 New Patients and Literature Review.
Colson C et al.·Clin Genet
2025Review
KAT6A and KAT7 Histone Acetyltransferase Complexes Are Molecular Dependencies and Therapeutic Targets in NUP98-Rearranged Acute Myeloid Leukemia.
Michmerhuizen NL et al.·Cancer Discov
2025
Anemia and thrombocytopenia due to a novel BRPF1 variant in a family from Çanakkale with intellectual disability and dysmorphic facies: Case report and review of the literature.
Kose CC et al.·Am J Med Genet A
2023Review
Chromatin-focused genetic and chemical screens identify BRPF1 as a targetable vulnerability in Taxol-resistant triple-negative breast cancer.
Yedier-Bayram O et al.·Exp Mol Med
2025
Essential gene screening identifies the bromodomain-containing protein BRPF1 as a new actionable target for endocrine therapy-resistant breast cancers.
Salvati A et al.·Mol Cancer
2024
Beyond 'speech delay': Expanding the phenotype of BRPF1-related disorder.
Morison LD et al.·Eur J Med Genet
2024
Uncovering the non-histone interactome of the BRPF1 bromodomain using site-specific azide-acetyllysine photochemistry.
Barman S et al.·J Biol Chem
2024
Bromodomain and PHD Finger-Containing Protein 1: From Functions to a Developmental Disorder, Cancer, and Therapeutics.
Razavi A et al.·Results Probl Cell Differ
2025Review
Lysine Acetyltransferase 6 Complexes in Neurodevelopmental Disorders and Different Types of Cancer.
Mousavi N et al.·Results Probl Cell Differ
2025Review
Ocular findings of BRPF1 variants: a case report and literature review.
Mallapragada LSV et al.·J AAPOS
2025Review
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