H2AC6
protein-codingH2A clustered histone 6, the group of H2A histones
Gene summary
Histones are basic nuclear proteins that are responsible for the nucleosome structure of the chromosomal fiber in eukaryotes. Two molecules of each of the four core histones (H2A, H2B, H3, and H4) form an octamer, around which approximately 146 bp of DNA is wrapped in repeating units, called nucleosomes. The linker histone, H1, interacts with linker DNA between nucleosomes and functions in the compaction of chromatin into higher order structures. This gene is intronless and encodes a replication-dependent histone that is a member of the histone H2A family. Transcripts from this gene lack polyA tails but instead contain a palindromic termination element. This gene is found in the large histone gene cluster on chromosome 6. [provided by RefSeq, Aug 2015]
- H2AFL
- HIST1H2AC
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~15.0 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AD
Disease ID:MONDO:0700092
Submitter: G2P
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to H2AC6 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_003512.4. 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.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 2 | 2 | ||||
| missense | 14 | 14 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 14 | 2 | 0 | 16 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_003503.1 | 1 | MANE Select | |
| Ensembl | ENSP00000367022.2 | 1 | MANE Select | |
| Ensembl | ENSP00000321389.5 | 1 | Standard | |
| Ensembl | ENSP00000473534.1 | 1 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Systemic lupus erythematosus - Homo sapiens (human)
- Necroptosis - Homo sapiens (human)
- Alcoholism - Homo sapiens (human)
- B-WICH complex positively regulates rRNA expression
- ERCC6 (CSB) and EHMT2 (G9a) positively regulate rRNA expression
Biological Process
- chromatin organization
- negative regulation of cell population proliferation
Molecular Function
- molecular_function
- DNA binding
- protein heterodimerization activity
Cellular Component
- nucleosome
- nuclear chromatin
- nucleus
- nucleoplasm
- extracellular exosome
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000602637
- Coding exons
- 1
- Length
- 14972
- Individuals with no LoFs
- 125730
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 6
- Defined
- 125736
- p
- 0.0000239
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.533 | 66 | 79.4 | 0.832 | 0.00000364 | 812 |
| Missense (PolyPhen) | 20 | 30.678 | 0.65193 | 312 | ||
| Synonymous | -7.32 | 91 | 35.5 | 2.56 | 0.00000165 | 299 |
| Loss of Function | 1.56 | 0 | 2.84 | 0.00 | 1.24e-7 | 36 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000062 | 0.000062 | rare |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0.000092 | 0.000092 | rare |
| European (Non-Finnish) | 0 | 0.0 | absent |
| South Asian | 0.000098 | 0.000098 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Core component of nucleosome. 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.;
Recessive Scores
- pRec
- 0.113
Intolerance Scores
- LoFtool
- 0.264
- RVIS EVS
- -0.16
- RVIS percentile EVS
- 41.25
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.998
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Low | Medium |
| Primary Immunodeficiency | Medium | Low | Medium |
| Cancer | Medium | Medium | Medium |