H2AZ1
protein-codingH2A.Z variant histone 1, 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. Nucleosomes consist of approximately 146 bp of DNA wrapped around a histone octamer composed of pairs of each of the four core histones (H2A, H2B, H3, and H4). The chromatin fiber is further compacted through the interaction of a linker histone, H1, with the DNA between the nucleosomes to form higher order chromatin structures. This gene encodes a replication-independent member of the histone H2A family that is distinct from other members of the family. Studies in mice have shown that this particular histone is required for embryonic development and indicate that lack of functional histone H2A leads to embryonic lethality. [provided by RefSeq, Jul 2008]
- H2AZ
- H2AFZ
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~2.3 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to H2AZ1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_002106.4. 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 | 0 | |||||
| missense | 5 | 5 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 5 | 0 | 0 | 5 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_002097.1 | 5 | MANE Select | |
| Ensembl | ENSP00000296417.5 | 5 | MANE Select | |
| Ensembl | ENSP00000498935.1 | 5 | Standard | |
| Ensembl | ENSP00000498935.1 | 5 | 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)
- Proteasome Degradation
- Retinoblastoma (RB) in Cancer
Biological Process
- chromatin organization
- positive regulation of transcription by RNA polymerase II
- cellular response to estradiol stimulus
Molecular Function
- RNA polymerase II proximal promoter sequence-specific DNA binding
- RNA polymerase II core promoter sequence-specific DNA binding
- RNA polymerase II distal enhancer sequence-specific DNA binding
- DNA binding
- protein binding
Cellular Component
- nucleosome
- nuclear chromatin
- Barr body
- nucleus
- nuclear euchromatin
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000296417
- Coding exons
- 5
- Length
- 2303
- Individuals with no LoFs
- 121936
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 1
- Defined
- 121937
- p
- 0.00000410
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.92 | 4 | 75.5 | 0.0530 | 0.00000359 | 806 |
| Missense (PolyPhen) | 0 | 15.078 | 0 | 197 | ||
| Synonymous | -1.47 | 38 | 28.1 | 1.35 | 0.00000123 | 275 |
| Loss of Function | 2.43 | 0 | 6.87 | 0.00 | 2.92e-7 | 86 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0 | 0.0 | absent |
| South Asian | 0.000034 | 0.000034 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Variant histone H2A which replaces conventional H2A in a subset of nucleosomes. 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. May be involved in the formation of constitutive heterochromatin. May be required for chromosome segregation during cell division. {ECO:0000269|PubMed:15878876}.;
Recessive Scores
- pRec
- 0.270
Intolerance Scores
- RVIS EVS
- 0.06
- RVIS percentile EVS
- 58
Essentials
- Essential (CRISPR)
- N
- Essential (gene trap)
- H
- Indispensability pred.
- E
- Indispensability score
- 0.925