BRPF1

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

Basic information

Region (hg38): 3:9731729-9748019

Links

ENSG00000156983 ∙ NCBI:7862 ∙ OMIM:602410 ∙ HGNC:14255 ∙ Uniprot:P55201 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• intellectual developmental disorder with dysmorphic facies and ptosis (Strong), mode of inheritance: AD
• intellectual developmental disorder with dysmorphic facies and ptosis (Strong), mode of inheritance: AD
• intellectual developmental disorder with dysmorphic facies and ptosis (Strong), mode of inheritance: AD
• intellectual developmental disorder with dysmorphic facies and ptosis (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Intellectual disability disorder with dysmorphic facies and ptosis (IDDDFP)	AD	General	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	Craniofacial; Musculoskeletal; Neurologic	27939639; 27939640

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the BRPF1 gene.

• Intellectual developmental disorder with dysmorphic facies and ptosis (23 variants)
• not provided (20 variants)
• Inborn genetic diseases (11 variants)
• BRPF1-related disorder (2 variants)
• Global developmental delay (1 variants)
• Intellectual disability (1 variants)
• Sudden unexplained death in childhood (1 variants)
• See cases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the BRPF1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				33	7	40
missense	2	5	185	25	1	218
nonsense	18	3	1			22
start loss	1	1				2
frameshift	26	11	2			39
inframe indel		1	4			5
splice donor/acceptor (+/-2bp)		4	1			5
splice region			6	1		7
non coding			1		1	2
Total	47	25	194	58	9

Highest pathogenic variant AF is 0.00000657

Variants in BRPF1

This is a list of pathogenic ClinVar variants found in the BRPF1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
3-9734142-T-G		Intellectual developmental disorder with dysmorphic facies and ptosis	Likely pathogenic (May 01, 2020)
3-9734143-G-A			Pathogenic (May 29, 2019)
3-9734150-G-C			Uncertain significance (Jan 02, 2024)
3-9734158-T-C			Likely benign (Feb 01, 2023)
3-9734166-CTT-C		Inborn genetic diseases	Pathogenic (Mar 02, 2023)
3-9734187-C-T		Intellectual developmental disorder with dysmorphic facies and ptosis	Uncertain significance (Dec 19, 2018)
3-9734192-A-G			Uncertain significance (May 12, 2024)
3-9734195-C-T		Inborn genetic diseases	Uncertain significance (Feb 07, 2023)
3-9734203-C-T		Intellectual developmental disorder with dysmorphic facies and ptosis	Benign/Likely benign (Aug 06, 2021)
3-9734207-T-C		Intellectual developmental disorder with dysmorphic facies and ptosis	Likely pathogenic (Jan 01, 2019)
3-9734225-C-T			Pathogenic (Mar 27, 2024)
3-9734229-A-G		Intellectual developmental disorder with dysmorphic facies and ptosis	Uncertain significance (May 21, 2020)
3-9734243-T-TA		Intellectual developmental disorder with dysmorphic facies and ptosis	Pathogenic (Feb 09, 2017)
3-9734262-A-C		BRPF1-related disorder	Uncertain significance (Jul 02, 2024)
3-9734281-C-T			Likely benign (Feb 01, 2025)
3-9734335-G-A		BRPF1-related disorder	Benign (Aug 16, 2018)
3-9734336-C-T		Intellectual developmental disorder with dysmorphic facies and ptosis	Likely benign (Mar 25, 2024)
3-9734337-G-A		BRPF1-related disorder	Uncertain significance (Aug 12, 2024)
3-9734339-C-T			Pathogenic (Aug 13, 2024)
3-9734348-C-G		Inborn genetic diseases	Uncertain significance (Aug 20, 2024)
3-9734348-C-T		Inborn genetic diseases	Likely benign (Apr 23, 2024)
3-9734358-A-G		Intellectual developmental disorder with dysmorphic facies and ptosis	Uncertain significance (Jun 24, 2022)
3-9734367-C-T		Intellectual developmental disorder with dysmorphic facies and ptosis	Uncertain significance (Dec 04, 2018)
3-9734381-G-A		Intellectual developmental disorder with dysmorphic facies and ptosis	Uncertain significance (Dec 27, 2019)
3-9734388-A-T		Inborn genetic diseases	Uncertain significance (Aug 20, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
BRPF1	protein_coding	protein_coding	ENST00000383829	13	16290

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.00000459	125741	0	7	125748	0.0000278

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.83	464	761	0.609	0.0000498	8011
Missense in Polyphen		170	383.36	0.44344		4004
Synonymous	-0.714	307	291	1.05	0.0000177	2387
Loss of Function	6.17	4	52.1	0.0768	0.00000289	589

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000289	0.0000289
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000530	0.0000527
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

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.
• Pathway: Gene expression (Transcription);Generic Transcription Pathway;RNA Polymerase II Transcription;Chromatin modifying enzymes;HATs acetylate histones;Chromatin organization;Regulation of TP53 Activity through Acetylation;Regulation of TP53 Activity;Transcriptional Regulation by TP53 (Consensus)

Recessive Scores

• pRec: 0.123

Intolerance Scores

• loftool: 0.252
• rvis_EVS: -2.26
• rvis_percentile_EVS: 1.27

Haploinsufficiency Scores

• pHI: 0.622
• hipred: Y
• hipred_score: 0.765
• ghis: 0.630

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: K
• gene_indispensability_pred: E
• gene_indispensability_score: 0.837

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Brpf1
• Phenotype: nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); skeleton phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); embryo phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); growth/size/body region phenotype; cellular phenotype; homeostasis/metabolism phenotype

Zebrafish Information Network

• Gene name: brpf1
• Affected structure: hypobranchial 2 cartilage
• Phenotype tag: abnormal
• Phenotype quality: aplastic

Gene ontology

• Biological process: histone H3 acetylation;histone H3-K23 acetylation;positive regulation of transcription, DNA-templated;regulation of signal transduction by p53 class mediator
• Cellular component: nucleus;nucleoplasm;cytoplasm;cytosol;plasma membrane;MOZ/MORF histone acetyltransferase complex
• Molecular function: DNA binding;protein binding;histone acetyltransferase activity (H3-K23 specific);metal ion binding