H3-3B

H3.3 histone B, the group of H3 histones

Basic information

Region (hg38): 17:75776433-75785893

Previous symbols: [ "H3F3B" ]

Links

ENSG00000132475 ∙ NCBI:3021 ∙ OMIM:601058 ∙ HGNC:4765 ∙ Uniprot:P84243 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Bryant-Li-Bhoj neurodevelopmental syndrome 2	AD	Audiologic/Otolaryngologic	Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	Audiologic/Otolaryngologic; Craniofacial; Musculoskeletal; Neurologic; Ophthalmologic	33268356; 34876591

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the H3-3B gene.

• not provided (11 variants)
• Bryant-Li-Bhoj neurodevelopmental syndrome 2 (8 variants)
• Inborn genetic diseases (3 variants)
• Short stature;Global developmental delay;Delayed speech and language development;Intellectual disability;Brain imaging abnormality (1 variants)
• H3-3B-related condition (1 variants)
• Short stature;Global developmental delay;Brain imaging abnormality;Intellectual disability;Delayed speech and language development (1 variants)
• Hemiparkinsonism-hemiatrophy syndrome (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the H3-3B 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			1			1
missense	2	7	3			12
nonsense						0
start loss			1			1
frameshift						0
inframe indel			1			1
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding					2	2
Total	2	7	6	0	2

Variants in H3-3B

This is a list of pathogenic ClinVar variants found in the H3-3B region.

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

Position	Type	Phenotype	Significance	ClinVar
17-75776919-C-T			Benign (Jul 13, 2018)
17-75778594-CTT-C		Intellectual disability;Delayed speech and language development;Short stature;Brain imaging abnormality;Global developmental delay	Likely pathogenic (Jul 15, 2021)
17-75778629-T-C		Bryant-Li-Bhoj neurodevelopmental syndrome 2 • H3-3B-related disorder	Pathogenic/Likely pathogenic (Jun 26, 2023)
17-75778630-G-T		Bryant-Li-Bhoj neurodevelopmental syndrome 2	Likely pathogenic (May 22, 2023)
17-75778641-G-C		Bryant-Li-Bhoj neurodevelopmental syndrome 2	Pathogenic (Feb 02, 2022)
17-75778652-G-T		Hemiparkinsonism-hemiatrophy syndrome	Uncertain significance (Nov 16, 2020)
17-75778678-G-C		Bryant-Li-Bhoj neurodevelopmental syndrome 2	Uncertain significance (Sep 28, 2023)
17-75778796-G-A			Benign (Sep 04, 2019)
17-75778883-C-T			Uncertain significance (Oct 18, 2021)
17-75778937-A-T		Intellectual disability;Delayed speech and language development;Short stature;Brain imaging abnormality;Global developmental delay • Bryant-Li-Bhoj neurodevelopmental syndrome 2	Pathogenic/Likely pathogenic (Feb 02, 2022)
17-75779056-T-C		Inborn genetic diseases	Conflicting classifications of pathogenicity (Mar 10, 2023)
17-75779072-C-T			Pathogenic (Apr 18, 2022)
17-75779077-G-A			Likely pathogenic (May 01, 2023)
17-75779084-GAGCGCTTTTCCT-G			Uncertain significance (Sep 09, 2022)
17-75779087-C-G		Bryant-Li-Bhoj neurodevelopmental syndrome 2	Pathogenic (Feb 02, 2022)
17-75779107-G-C		Bryant-Li-Bhoj neurodevelopmental syndrome 2	Likely pathogenic (Jan 31, 2023)
17-75779107-G-T		Intellectual disability;Delayed speech and language development;Short stature;Brain imaging abnormality;Global developmental delay	Likely pathogenic (Jul 15, 2021)
17-75779123-G-A		Bryant-Li-Bhoj neurodevelopmental syndrome 2	Likely pathogenic (Nov 27, 2023)
17-75779138-C-T			Likely pathogenic (Jul 06, 2021)
17-75779140-G-A		Bryant-Li-Bhoj neurodevelopmental syndrome 2	Likely pathogenic (Sep 01, 2022)
17-75779144-A-G			Pathogenic (Jul 15, 2022)
17-75779147-T-C		Intellectual disability;Delayed speech and language development;Short stature;Brain imaging abnormality;Global developmental delay	Likely pathogenic (Jul 15, 2021)
17-75779150-G-A		Inborn genetic diseases • Short stature;Global developmental delay;Brain imaging abnormality;Intellectual disability;Delayed speech and language development • Bryant-Li-Bhoj neurodevelopmental syndrome 2	Uncertain significance (Feb 22, 2018)
17-75779152-G-A		Inborn genetic diseases • Brain imaging abnormality;Global developmental delay;Delayed speech and language development;Short stature;Intellectual disability • Bryant-Li-Bhoj neurodevelopmental syndrome 2	Conflicting classifications of pathogenicity (Jun 09, 2023)
17-75779174-T-C			Uncertain significance (Oct 11, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
H3-3B	protein_coding	protein_coding	ENST00000254810	3	9460

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.807	0.189	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.88	8	80.8	0.0990	0.00000363	862
Missense in Polyphen		1	14.871	0.067244		190
Synonymous	-7.71	89	32.8	2.71	0.00000150	295
Loss of Function	2.16	0	5.44	0.00	2.37e-7	62

LoF frequencies by population

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

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Variant histone H3 which replaces conventional H3 in a wide range of nucleosomes in active genes. Constitutes the predominant form of histone H3 in non-dividing cells and is incorporated into chromatin independently of DNA synthesis. Deposited at sites of nucleosomal displacement throughout transcribed genes, suggesting that it represents an epigenetic imprint of transcriptionally active chromatin. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling. {ECO:0000269|PubMed:14718166, ECO:0000269|PubMed:15776021, ECO:0000269|PubMed:16258499}.
• Disease: DISEASE: Glioma (GLM) [MIM:137800]: Gliomas are benign or malignant central nervous system neoplasms derived from glial cells. They comprise astrocytomas and glioblastoma multiforme that are derived from astrocytes, oligodendrogliomas derived from oligodendrocytes and ependymomas derived from ependymocytes. {ECO:0000269|PubMed:22286061, ECO:0000269|PubMed:22286216, ECO:0000269|PubMed:23539269}. Note=The gene represented in this entry is involved in disease pathogenesis. H3F3A mutations affecting residues involved in post-translational modifications of histone H3.3 are recurrent in malignant, aggressive gliomas including glioblastoma multiforme (GBM) and diffuse intrinsic pontine glioma (DIPG) (PubMed:22286061, PubMed:22286216). The mechanism through which mutations lead to tumorigenesis involves altered histones methylation, impaired regulation of Polycomb repressive complex 2 (PRC2) activity, and aberrant epigenetic regulation of gene expression (PubMed:23539269, PubMed:23539183, PubMed:23603901). {ECO:0000269|PubMed:22286061, ECO:0000269|PubMed:22286216, ECO:0000269|PubMed:23539183, ECO:0000269|PubMed:23539269, ECO:0000269|PubMed:23603901}.; DISEASE: Note=H3F3A and H3F3B mutations affecting residues involved in post-translational modifications of histone H3.3 are implicated in the pathogenesis of some bone and cartilage neoplasms. Mutations have been found with high prevalence in chondroblastoma and giant cell tumors of bone, and with low frequency in osteosarcoma, conventional chondrosarcoma and clear cell chondrosarcoma. Chondroblastoma samples frequently carry a H3F3B mutation affecting residue Lys-37 (H3K36), although H3F3A is mutated in some cases. Most giant cell tumors of bone harbor H3F3A mutations affecting residue Gly-35 (H3G34). {ECO:0000269|PubMed:24162739}.
• Pathway: Systemic lupus erythematosus - Homo sapiens (human);Transcriptional misregulation in cancer - Homo sapiens (human);Alcoholism - Homo sapiens (human);Histone Modifications;Tumor suppressor activity of SMARCB1;B-WICH complex positively regulates rRNA expression;ERCC6 (CSB) and EHMT2 (G9a) positively regulate rRNA expression;Positive epigenetic regulation of rRNA expression;SIRT1 negatively regulates rRNA expression;NoRC negatively regulates rRNA expression;Negative epigenetic regulation of rRNA expression;Signaling by WNT;Signal Transduction;DNA methylation;Epigenetic regulation of gene expression;Gene expression (Transcription);the prc2 complex sets long-term gene silencing through modification of histone tails;p38 mapk signaling pathway;Generic Transcription Pathway;Oxidative Stress Induced Senescence;Senescence-Associated Secretory Phenotype (SASP);Cellular Senescence;Factors involved in megakaryocyte development and platelet production;Cellular responses to stress;Metabolism of proteins;Reproduction;RNA Polymerase I Promoter Clearance;RNA Polymerase I Promoter Opening;RNA Polymerase II Transcription;RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function;RNA Polymerase I Transcription;Amyloid fiber formation;RNA Polymerase I Chain Elongation;akap95 role in mitosis and chromosome dynamics;Meiotic recombination;Meiosis;Activated PKN1 stimulates transcription of AR (androgen receptor) regulated genes KLK2 and KLK3;RHO GTPases activate PKNs;Cellular responses to external stimuli;RHO GTPase Effectors;Signaling by Rho GTPases;Hemostasis;Condensation of Prophase Chromosomes;Signaling by Nuclear Receptors;Mitotic Prophase;M Phase;Estrogen-dependent gene expression;Transcriptional regulation by small RNAs;RUNX1 regulates transcription of genes involved in differentiation of HSCs;Cell Cycle;Cell Cycle, Mitotic;ESR-mediated signaling;Aurora C signaling;Transcriptional regulation by RUNX1;Aurora B signaling;Formation of the beta-catenin:TCF transactivating complex;TCF dependent signaling in response to WNT;Gene Silencing by RNA;PRC2 methylates histones and DNA (Consensus)

Intolerance Scores

• rvis_EVS: -0.21
• rvis_percentile_EVS: 38.28

Haploinsufficiency Scores

• pHI: 0.298
• hipred: Y
• hipred_score: 0.752
• ghis: 0.501

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.997

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: H3f3b
• Phenotype: growth/size/body region phenotype; cellular phenotype; reproductive system 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); normal phenotype; embryo phenotype