H1-8
protein-codingH1.8 linker histone, the group of H1 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. The protein encoded is a replication-independent histone that is a member of the histone H1 family. This gene contains introns, unlike most histone genes. The related mouse gene is expressed only in oocytes. [provided by RefSeq, Oct 2015]
- H1FOO
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~8.3 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 H1-8 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_153833.3. 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 | 1 | 1 | ||||
| missense | 62 | 11 | 73 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 62 | 12 | 0 | 74 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_722575.1 | 5 | MANE Select | |
| Ensembl | ENSP00000319799.2 | 5 | MANE Select | |
| RefSeq | NP_001295191.1 | 3 | Standard | |
| Ensembl | ENSP00000422964.1 | 3 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- apoptotic dna-fragmentation and tissue homeostasis
Biological Process
- nucleosome assembly
- regulation of transcription, DNA-templated
- nucleosome positioning
- chromosome condensation
- negative regulation of chromatin silencing
Molecular Function
- double-stranded DNA binding
- protein binding
- nucleosomal DNA binding
Cellular Component
- nucleosome
- female germ cell nucleus
- nucleus
- nucleolus
- cytoplasm
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000324382
- Coding exons
- 5
- Length
- 8254
- Individuals with no LoFs
- 125555
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 3
- Defined
- 125558
- p
- 0.0000119
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.367 | 191 | 206 | 0.928 | 0.0000123 | 2188 |
| Missense (PolyPhen) | 36 | 40.493 | 0.88905 | 488 | ||
| Synonymous | -0.591 | 92 | 85.1 | 1.08 | 0.00000548 | 736 |
| Loss of Function | 1.64 | 3 | 8.00 | 0.375 | 3.35e-7 | 120 |
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) | 0.000028 | 0.000026 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: May play a key role in the control of gene expression during oogenesis and early embryogenesis, presumably through the perturbation of chromatin structure. Essential for meiotic maturation of germinal vesicle-stage oocytes. The somatic type linker histone H1c is rapidly replaced by H1oo in a donor nucleus transplanted into an oocyte. The greater mobility of H1oo as compared to H1c may contribute to this rapid replacement and increased instability of the embryonic chromatin structure. The rapid replacement of H1c with H1oo may play an important role in nuclear remodeling (By similarity). {ECO:0000250}.;
Recessive Scores
- pRec
- 0.105
Intolerance Scores
- LoFtool
- 0.604
- RVIS EVS
- 0.66
- RVIS percentile EVS
- 84.44
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.798
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |