BRPF1

Chr 3AD

bromodomain and PHD finger containing 1

Also known as: BR140, IDDDFP

The protein is a component of MOZ/MORF histone acetyltransferase complexes that regulate transcription by binding to catalytic MYST domains and stimulating acetyltransferase activity. Loss-of-function mutations cause autosomal dominant intellectual developmental disorder with dysmorphic facies and ptosis. The gene is highly intolerant to loss-of-function variants, indicating haploinsufficiency as the pathogenic mechanism.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
LOFmechanismADLOEUF 0.181 OMIM phenotype
Clinical SummaryBRPF1
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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.
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GeneReview available — BRPF1
Authoritative clinical overview · Recommended first read
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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Dual constrained — LoF & missense intolerant
LoF Constraint
0.18LOEUF
pLI 1.000
Z-score 6.17
OE 0.08 (0.040.18)
Highly constrained

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

Missense Constraint
3.83Z-score
OE missense 0.61 (0.560.66)
464 obs / 761.5 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios
LoF OE0.08 (0.040.18)
00.351.4
Missense OE0.61 (0.560.66)
00.61.4
Synonymous OE1.05
01.21.6
LoF obs/exp: 4 / 52.1Missense obs/exp: 464 / 761.5Syn Z: -0.71
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveBRPF1-related syndromic intellectual disability with ptosisLOFAD
DN
0.2698th %ile
GOF
0.2795th %ile
LOF
0.81top 5%

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

LOFprediction above median · 1 literature citation · LOEUF 0.18

Literature Evidence

LOFBrpf1 Haploinsufficiency Impairs Dendritic Arborization and Spine Formation, Leading to Cognitive DeficitsPMID:31213987

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

0 submitted variants 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.

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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Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC