GeneBe

BRPF1

protein-coding

bromodomain and PHD finger containing 1, the group of PWWP domain containing|PHD finger proteins|Bromodomain containing

Gene summary

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]

MANE transcript

NM_001003694.2

Inheritance

AD

ClinVar variants

P:120U:331B:112

Top phenotype

Intellectual disability disorder with dysmorphic facies and ptosis (IDDDFP)

gnomAD constraint

pLI —, LoF o/e 0.08

Max pathogenic AF

—

Genomic locus

chr3:9,731,729-9,748,019

External References & Databases

Ensembl (ENSG00000156983)NCBI Gene (7862)OMIM (602410)HGNC:14255GenCCUniProt (P55201)AlphaFoldClinVar (BRPF1)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~16.3 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

syndromic complex neurodevelopmental disorderDEFINITIVE

Inheritance Pattern: AD

Disease ID:MONDO:0800439

Submitter: ClinGen

*BRPF1* was first reported in relation to autosomal dominant syndromic complex neurodevelopmental disorder in 2017 (Mattioli et al., PMID: 27939639; Yan et al., PMID: 27939640). Subsequent evidence was provided by a large case series published in 2024 involving 29 individuals (Colson et al., PMID: 39837771). Phenotypic features reported in affected individuals include intellectual disability, developmental delay, speech and language delay, hypotonia, and behavioral features such as attention deficit-hyperactivity disorder, autistic behaviors, and anxiety. Distinct facial features (e.g., ptosis, blepharophimosis, and broad nasal bridge) were consistently reported. Fourteen variants (frameshift, nonsense, and whole-gene deletions) that have been reported in 22 probands in two publications (PMIDs: 27939639 and 39837771) are included in this curation. More evidence is available in the literature, but the maximum score for genetic evidence (12 points) has been reached. The mechanism of pathogenicity appears to be haploinsufficiency (PMID: 39837771). Splice site variants predicted to result in premature stop codons and variants affecting highly conserved residues further support the gene-disease relationship. This gene-disease relationship is also supported by experimental evidence, including animal and cellular models (PMID: 34485298). In mouse models, hippocampal knockdown of *Brpf1* led to spatial learning deficits and dysregulation of synaptic genes. At the cellular level, knockdown in primary hippocampal neurons impaired excitatory synaptic transmission and led to altered expression of synaptic regulators. In summary, there is definitive evidence supporting the relationship between *BRPF1* and autosomal dominant syndromic complex neurodevelopmental disorder. This has been repeatedly demonstrated in both the research and clinical diagnostic settings, and has been upheld over time. This classification was approved by the ClinGen Intellectual Disability and Autism Gene Curation Expert Panel on April 15, 2025 (SOP Version 11).

intellectual developmental disorder with dysmorphic facies and ptosisSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0015022

Submitter: Ambry Genetics

intellectual developmental disorder with dysmorphic facies and ptosisSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0015022

Submitter: PanelApp Australia

intellectual developmental disorder with dysmorphic facies and ptosisSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0015022

Submitter: Illumina

intellectual developmental disorder with dysmorphic facies and ptosisDEFINITIVE

Inheritance Pattern: AD

Disease ID:MONDO:0015022

Submitter: G2P

intellectual developmental disorder with dysmorphic facies and ptosisSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0015022

Submitter: Labcorp Genetics (formerly Invitae)

intellectual developmental disorder with dysmorphic facies and ptosisDEFINITIVE

Inheritance Pattern: AD

Disease ID:MONDO:0015022

Submitter: Ambry Genetics

Clinical Genomic Database (CGD)

Intellectual disability disorder with dysmorphic facies and ptosis (IDDDFP)AD

Manifestation: Craniofacial; Musculoskeletal; Neurologic

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 27939639; 27939640Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to BRPF1 variants in ClinVar

17 Conditions Cataloged
not providedTotal: 276
Inborn genetic diseasesTotal: 163
Intellectual developmental disorder with dysmorphic facies and ptosisTotal: 119
BRPF1-related disorderTotal: 57
not specifiedTotal: 35
Intellectual disabilityTotal: 7
See casesTotal: 4
Neurodevelopmental disorderTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001003694.2. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
2
clinvar
56
clinvar
5
clinvar
 63
missense
5
clinvar
10
clinvar
322
clinvar
50
clinvar
1
clinvar
 388
nonsense
23
clinvar
11
clinvar
1
clinvar
 35
start loss
2
clinvar
1
clinvar
 3
frameshift
37
clinvar
24
clinvar
2
clinvar
 63
splice donor/acceptor (+/-2bp)
7
clinvar
4
clinvar
 11
Total67533311066563

Highest pathogenic variant AF is 0.000010974509

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 72 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_001003694.2RefSeqNP_001003694.113MANE Select
ENST00000383829.7EnsemblENSP00000373340.213MANE Select
NM_001319049.2RefSeqNP_001305978.112Standard
NM_001319050.2RefSeqNP_001305979.113Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / ModelOrganismObserved Phenotype
brpf1Danio rerio

Structure: hypobranchial 2 cartilage

Quality: aplastic

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • Gene expression (Transcription)
  • Generic Transcription Pathway
  • RNA Polymerase II Transcription
  • Chromatin modifying enzymes
  • HATs acetylate histones

Biological Process

  • histone H3 acetylation
  • histone H3-K23 acetylation
  • positive regulation of transcription, DNA-templated
  • regulation of signal transduction by p53 class mediator

Molecular Function

  • DNA binding
  • protein binding
  • histone acetyltransferase activity (H3-K23 specific)
  • metal ion binding

Cellular Component

  • nucleus
  • nucleoplasm
  • cytoplasm
  • cytosol
  • plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000383829
Coding exons
13
Length
16290
Individuals with no LoFs
125741
Homozygous LoFs
0
Heterozygous LoFs
7
Defined
125748
p
0.0000278
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense3.834647610.6090.00004988011
Missense (PolyPhen)170383.360.443444004
Synonymous-0.7143072911.050.00001772387
Loss of Function6.17452.10.07680.00000289589

Population LoF Frequency

PopulationCAFp-valueStatus
African00.0absent
Latino/Admixed American0.0000290.000029rare
Ashkenazi Jewish00.0absent
East Asian00.0absent
Finnish00.0absent
European (Non-Finnish)0.0000530.000053rare
South Asian00.0absent
Other00.0absent

dbNSFP Gene Annotations

Source: dbNSFP

Function
FUNCTION: Component of the MOZ/MORF complex which has a histone H3 acetyltransferase activity (PubMed:16387653, PubMed:27939640). Preferentially mediates histone H3-K23 acetylation (PubMed:27939640). Positively regulates the transcription of RUNX1 and RUNX2 (PubMed:18794358). {ECO:0000269|PubMed:16387653, ECO:0000269|PubMed:18794358, ECO:0000269|PubMed:27939640}.;
Disease
DISEASE: Intellectual developmental disorder with dysmorphic facies and ptosis (IDDDFP) [MIM:617333]: An autosomal dominant neurodevelopmental disorder characterized by delayed psychomotor development, intellectual disability, delayed language, and facial dysmorphisms, most notably ptosis. Additional features may include poor growth, hypotonia, and seizures. {ECO:0000269|PubMed:27939639, ECO:0000269|PubMed:27939640}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec
0.123

Intolerance Scores

LoFtool
0.252
RVIS EVS
-2.26
RVIS percentile EVS
1.27

Essentials

Essential (CRISPR)
E
Essential (CRISPR2)
S
Essential (gene trap)
K
Indispensability pred.
E
Indispensability score
0.837

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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