H1-4
H1.4 Linker Histone, Cluster Member
Gene Information Card
| Symbol | H1-4 |
|---|---|
| Full Name | H1.4 linker histone, cluster member |
| Gene Type | protein-coding |
| Chromosomal Location | 6p22.2 |
| NCBI Gene ID | 3008 ncbi.nlm.nih.gov/gene/3008 |
| Ensembl ID | ENSG00000124529 |
| UniProt ID | P10412 |
| OMIM ID | 142710 |
| HGNC ID | 4717 |
| Aliases | HIST1H1E, H1F4, H1.4 |
Description
H1-4 (H1.4 linker histone, cluster member) encodes a member of the histone H1 family, which binds to linker DNA between nucleosomes and facilitates higher-order chromatin compaction. H1.4 is involved in transcriptional regulation, DNA repair, and cell cycle control. Mutations in H1-4 are associated with Rahman syndrome and certain cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Rahman syndrome | Heterozygous loss-of-function mutations in H1-4 lead to reduced chromatin compaction and altered gene expression, causing intellectual disability and overgrowth. | ClinVar, OMIM #617537 |
| Huntington disease | Altered H1.4 post-translational modifications (e.g., phosphorylation) are observed in Huntington disease models, contributing to chromatin dysregulation. | NCBI Gene, PubMed |
| Breast cancer | H1.4 downregulation is associated with poor prognosis and increased metastasis in breast cancer. | COSMIC, PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 42.1 | High |
| Lymph node | 31.5 | High |
| Spleen | 28.9 | High |
| Bone marrow | 25.3 | High |
| Brain | 12.4 | Medium |
| Liver | 8.7 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| K562 (leukemia) | 35.2 | High expression |
| HeLa (cervical) | 28.6 | High expression |
| HepG2 (liver) | 15.1 | Medium expression |
| A549 (lung) | 12.8 | Medium expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.435_438del (p.Lys146Asnfs*5) | Frameshift deletion | Rare | Loss of function; associated with Rahman syndrome |
| c.374G>A (p.Arg125Gln) | Missense | <0.01% | Reduced DNA binding affinity; potential gain-of-function in cancer |
| c.1A>G (p.Met1Val) | Start loss | Very rare | Loss of function; likely pathogenic |
Mutation functional classification
Loss of Function (LOF)
Frameshift and start-loss mutations (e.g., p.Lys146Asnfs*5, p.Met1Val) lead to truncated or absent H1.4 protein, reducing chromatin compaction and causing Rahman syndrome.
Gain of Function (GOF)
Missense mutations (e.g., p.Arg125Gln) may alter H1.4 binding to DNA, potentially enhancing oncogenic transcription in cancer.
Dominant Negative (DN)
No dominant-negative mutations have been reported for H1-4.
View complete mutation data：
Gene Ontology (GO)
| • nucleosome (GO:0000786) | • nucleus (GO:0005634) |
| • nucleosome assembly (GO:0006334) | • DNA binding (GO:0003677) |
| • protein heterodimerization activity (GO:0046982) |
Pathways
• Chromatin organization (Reactome R-HSA-4839726)
• Packaging of telomere ends (Reactome R-HSA-171306)
• Formation of senescence-associated heterochromatin foci (Reactome R-HSA-2559580)
Protein Summary
Histone H1.4 is a 219-amino-acid linker histone protein with a central globular domain flanked by N- and C-terminal tails. It binds to the linker DNA between nucleosomes, promoting chromatin compaction and regulating transcription. Post-translational modifications (e.g., phosphorylation, acetylation) modulate its chromatin-binding affinity and function. H1.4 is ubiquitously expressed, with highest levels in testis and lymphoid tissues.
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