H3-3A
H3.3 histone A, the group of H3 histones
Basic information
Region (hg38): 1:226061851-226072019
Previous symbols: [ "H3F3", "H3F3A" ]
Links
Phenotypes
GenCC
Source:
- Bryant-Li-Bhoj neurodevelopmental syndrome 1 (Definitive), mode of inheritance: AD
- Bryant-Li-Bhoj neurodevelopmental syndrome 1 (Definitive), mode of inheritance: AD
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Bryant-Li-Bhoj neurodevelopmental syndrome 1 | 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
- Bryant-Li-Bhoj neurodevelopmental syndrome 1 (2 variants)
- not provided (1 variants)
- Intellectual disability;Delayed speech and language development;Short stature;Brain imaging abnormality;Global developmental delay (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the H3-3A 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 | |||||
| missense | 19 | 27 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 1 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region | 1 | 1 | 2 | |||
| non coding | 0 | |||||
| Total | 2 | 6 | 20 | 1 | 0 |
Variants in H3-3A
This is a list of pathogenic ClinVar variants found in the H3-3A region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 1-226064371-C-G | Uncertain significance (Jun 20, 2019) | |||
| 1-226064376-C-G | not specified | Likely pathogenic (Aug 24, 2021) | ||
| 1-226064403-A-G | Bryant-Li-Bhoj neurodevelopmental syndrome 1 | Pathogenic (Jul 26, 2022) | ||
| 1-226064419-C-T | H3-3A-related disorder | Pathogenic (Feb 02, 2024) | ||
| 1-226064429-T-C | H3-3A-related disorder | Likely benign (Mar 19, 2019) | ||
| 1-226064434-A-T | Brainstem glioma • Astrocytoma | Likely pathogenic (May 31, 2016) | ||
| 1-226064438-T-G | Uncertain significance (May 15, 2023) | |||
| 1-226064439-G-A | Likely pathogenic (Jun 05, 2024) | |||
| 1-226064443-C-T | Likely pathogenic (Jan 17, 2024) | |||
| 1-226064451-G-C | Brainstem glioma • Adrenal cortex carcinoma • Glioblastoma • Neoplasm of brain | Likely pathogenic (May 31, 2016) | ||
| 1-226064454-G-A | Glioblastoma | other (May 01, 2016) | ||
| 1-226064458-T-C | Inborn genetic diseases | Uncertain significance (Oct 15, 2018) | ||
| 1-226064472-C-T | Intellectual disability;Brain imaging abnormality;Delayed speech and language development;Short stature;Global developmental delay • Bryant-Li-Bhoj neurodevelopmental syndrome 1 | Pathogenic/Likely pathogenic (Feb 01, 2022) | ||
| 1-226064485-A-T | not specified | Uncertain significance (Sep 01, 2023) | ||
| 1-226065658-C-T | Uncertain significance (Feb 01, 2020) | |||
| 1-226065661-G-A | Bryant-Li-Bhoj neurodevelopmental syndrome 1 | Uncertain significance (Feb 20, 2024) | ||
| 1-226065664-C-A | Bryant-Li-Bhoj neurodevelopmental syndrome 1 | Uncertain significance (Feb 23, 2023) | ||
| 1-226065664-C-T | Inborn genetic diseases • Bryant-Li-Bhoj neurodevelopmental syndrome 1 | Likely pathogenic (Dec 07, 2018) | ||
| 1-226065670-C-T | not specified | Uncertain significance (Nov 30, 2023) | ||
| 1-226065676-G-A | Uncertain significance (May 09, 2022) | |||
| 1-226065693-C-A | Intellectual disability;Brain imaging abnormality;Delayed speech and language development;Short stature;Global developmental delay | Likely pathogenic (Jul 15, 2021) | ||
| 1-226065712-T-G | Uncertain significance (Nov 11, 2019) | |||
| 1-226065760-A-G | Uncertain significance (Jun 10, 2019) | |||
| 1-226065766-A-C | Uncertain significance (Jul 26, 2017) | |||
| 1-226065771-G-C | Inborn genetic diseases • H3-3A-related disorder | Likely pathogenic (Mar 07, 2018) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| H3-3A | protein_coding | protein_coding | ENST00000366813 | 3 | 10151 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.123 | 0.788 | 125293 | 0 | 2 | 125295 | 0.00000798 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 3.16 | 5 | 88.6 | 0.0564 | 0.00000561 | 862 |
| Missense in Polyphen | 0 | 12.39 | 0 | 184 | ||
| Synonymous | -0.328 | 30 | 27.8 | 1.08 | 0.00000143 | 298 |
| Loss of Function | 1.36 | 2 | 5.40 | 0.370 | 3.10e-7 | 63 |
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) | 0.0000196 | 0.0000176 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.00 | 0.00 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- 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);Gastric Cancer Network 1;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)
Recessive Scores
- pRec
- 0.174
Intolerance Scores
- loftool
- 0.264
- rvis_EVS
- 0.15
- rvis_percentile_EVS
- 63.81
Haploinsufficiency Scores
- pHI
- 0.814
- hipred
- Y
- hipred_score
- 0.750
- ghis
- 0.554
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.924
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Low | Low | Low |
| Primary Immunodeficiency | Low | Low | Low |
| Cancer | Low | Low | Low |
Mouse Genome Informatics
- Gene name
- H3f3a
- Phenotype
- behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); normal 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); reproductive system phenotype; growth/size/body region phenotype;
Zebrafish Information Network
- Gene name
- h3f3a
- Affected structure
- melanocyte
- Phenotype tag
- abnormal
- Phenotype quality
- decreased amount
Gene ontology
- Biological process
- chromatin silencing at rDNA;osteoblast differentiation;nucleosome assembly;DNA replication-independent nucleosome assembly;nucleus organization;spermatid development;single fertilization;brain development;embryo implantation;blood coagulation;cell population proliferation;male gonad development;response to hormone;positive regulation of cell growth;pericentric heterochromatin assembly;telomeric heterochromatin assembly;telomere organization;multicellular organism growth;muscle cell differentiation;cellular protein metabolic process;regulation of megakaryocyte differentiation;negative regulation of gene expression, epigenetic;oogenesis;regulation of gene silencing by miRNA;regulation of centromere complex assembly;negative regulation of chromosome condensation
- Cellular component
- nuclear chromosome;nuclear chromosome, telomeric region;nucleosome;nuclear nucleosome;Barr body;extracellular region;nucleus;nucleoplasm;protein-containing complex;extracellular exosome
- Molecular function
- RNA polymerase II core promoter sequence-specific DNA binding;RNA polymerase II distal enhancer sequence-specific DNA binding;protein binding;nucleosomal DNA binding;protein heterodimerization activity