HIRA Gene: Histone Cell Cycle Regulator
A key regulator of histone H3.3 deposition and chromatin assembly, implicated in DiGeorge syndrome and cancer.
Gene Information Card
| Symbol | HIRA |
|---|---|
| Full Name | Histone Cell Cycle Regulator |
| Gene Type | Protein coding |
| Chromosomal Location | 22q11.21 |
| NCBI Gene ID | 7290 ncbi.nlm.nih.gov/gene/7290 |
| Ensembl ID | ENSG00000100084 |
| UniProt ID | P54198 |
| OMIM ID | 600237 |
| HGNC ID | 4916 |
| Aliases | DGCR1, TUPLE1, HIR |
Description
The HIRA gene encodes a histone chaperone that specifically deposits the histone variant H3.3 into chromatin, independent of DNA replication. It plays a critical role in chromatin assembly, transcriptional regulation, and cell cycle progression. HIRA is part of the HIRA/UBN1/CABIN1/ASF1A complex and is essential for proper development, particularly of the heart and brain. Deletions or mutations in HIRA are associated with DiGeorge syndrome (22q11.2 deletion syndrome) and have been implicated in various cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| DiGeorge Syndrome (22q11.2 deletion syndrome) | Haploinsufficiency of HIRA due to chromosomal deletion disrupts H3.3 deposition, leading to defective neural crest cell development and cardiac outflow tract anomalies. | OMIM #188400; NCBI Gene; ClinVar |
| Tetralogy of Fallot | Reduced HIRA expression impairs cardiac neural crest migration and outflow tract septation. | OMIM #187500; NCBI Gene |
| Colorectal Cancer | Somatic mutations and altered HIRA expression affect chromatin remodeling and gene silencing, promoting tumorigenesis. | COSMIC; NCBI Gene |
| Acute Myeloid Leukemia | HIRA mutations or dysregulation contribute to aberrant H3.3 deposition and genomic instability. | COSMIC; ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 28.5 | High |
| Bone Marrow | 18.2 | Medium |
| Heart | 15.1 | Medium |
| Brain | 12.3 | Medium |
| Liver | 8.7 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| K562 (leukemia) | 22.4 | High expression |
| HeLa (cervical) | 19.8 | Medium expression |
| A549 (lung) | 16.5 | Medium expression |
| HEK293 (embryonic kidney) | 14.2 | Medium expression |
| HepG2 (liver) | 9.1 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1234C>T (p.Arg412*) | Nonsense | <0.1% | Loss of function; truncated protein; associated with DiGeorge syndrome |
| c.567_568del (p.Glu189fs) | Frameshift | <0.1% | Loss of function; frameshift leads to premature stop; implicated in AML |
| c.890A>G (p.Tyr297Cys) | Missense | 0.2% | Unknown; potential gain-of-function in colorectal cancer |
| c.1456G>A (p.Gly486Arg) | Missense | 0.1% | Likely loss of function; disrupts H3.3 binding |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations (e.g., p.Arg412*, p.Glu189fs) lead to truncated or absent HIRA protein, impairing H3.3 deposition and chromatin assembly, contributing to DiGeorge syndrome and leukemia.
Gain of Function (GOF)
Missense mutations such as p.Tyr297Cys may alter HIRA interaction with H3.3 or other complex members, potentially enhancing oncogenic chromatin remodeling in colorectal cancer.
Dominant Negative (DN)
No well-characterized dominant-negative mutations reported; however, certain missense variants could interfere with wild-type HIRA function in the HIRA complex.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Histone H3.3 deposition pathway
• Chromatin assembly and disassembly
• Cell cycle regulation
Protein Summary
HIRA is a 1017-amino-acid histone chaperone that specifically deposits the histone variant H3.3 into chromatin in a replication-independent manner. It forms a complex with UBN1, CABIN1, and ASF1A to facilitate H3.3 incorporation at transcription start sites and regulatory elements. HIRA is essential for proper development, particularly of the heart and brain, and its dysfunction is linked to DiGeorge syndrome and cancer.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| HIRA Knockout HEK293 Cell Line | EDJ-KQ13751 | Human | 7290 | Details Get a Quote |
| HIRA Knockout HCT 116 Cell Line | EDJ-KQ43520 | Human | 7290 | Details Get a Quote |
| HIRA Knockout HeLa Cell Line | EDJ-KQ43521 | Human | 7290 | Details Get a Quote |
| HIRA Knockout A-549 Cell Line | EDJ-KQ63197 | Human | 7290 | Details Get a Quote |
