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Histone cell cycle regulator
Protein HIRA PDB 2i32.png
PDB rendering based on 2i32.
Available structures
PDB Ortholog search: PDBe, RCSB
Symbols HIRA ; DGCR1; TUP1; TUPLE1
External IDs OMIM600237 MGI99430 HomoloGene48172 GeneCards: HIRA Gene
RNA expression pattern
PBB GE HIRA 217427 s at tn.png
More reference expression data
Species Human Mouse
Entrez 7290 15260
Ensembl ENSG00000100084 ENSMUSG00000022702
UniProt P54198 Q61666
RefSeq (mRNA) NM_003325 NM_001005228
RefSeq (protein) NP_003316 NP_034565
Location (UCSC) Chr 22:
19.32 – 19.44 Mb
Chr 16:
18.88 – 18.97 Mb
PubMed search [1] [2]

Protein HIRA is a protein that in humans is encoded by the HIRA gene.[1][2][3][4] This gene is mapped to 22q11.21, centromeric to COMT.[4]


The specific function of this protein has yet to be determined; however, it has been speculated to play a role in transcriptional regulation and/or chromatin and histone metabolism.[4]

Research done by Salomé Adam, Sophie E. Polo, and Geneviève Almouzni indicate that HIRA proteins are involved in restarting transcription after UVC damage[5]

Clinical significance[edit]

It is considered the primary candidate gene in some haploinsufficiency syndromes such as DiGeorge syndrome, and insufficient production of the gene may disrupt normal embryonic development.[4]

Model organisms[edit]

Model organisms have been used in the study of HIRA function. A conditional knockout mouse line, called Hiratm1a(EUCOMM)Wtsi[10][11] was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists.[12][13][14]

Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.[8][15] Twenty two tests were carried out on mutant mice and two significant abnormalities were observed.[8] No homozygous mutant mice survived until weaning. The remaining tests were carried out on heterozygous mutant adult mice and a decreased leukocyte cell number was recorded in male animals.[8]


HIRA has been shown to interact with HIST1H2BK.[16]


  1. ^ Halford S, Wadey R, Roberts C, Daw SC, Whiting JA, O'Donnell H, Dunham I, Bentley D, Lindsay E, Baldini A, et al. (Mar 1994). "Isolation of a putative transcriptional regulator from the region of 22q11 deleted in DiGeorge syndrome, Shprintzen syndrome and familial congenital heart disease". Hum Mol Genet 2 (12): 2099–107. doi:10.1093/hmg/2.12.2099. PMID 8111380. 
  2. ^ Lamour V, Lecluse Y, Desmaze C, Spector M, Bodescot M, Aurias A, Osley MA, Lipinski M (Sep 1995). "A human homolog of the S. cerevisiae HIR1 and HIR2 transcriptional repressors cloned from the DiGeorge syndrome critical region". Hum Mol Genet 4 (5): 791–9. doi:10.1093/hmg/4.5.791. PMID 7633437. 
  3. ^ Magnaghi P, Roberts C, Lorain S, Lipinski M, Scambler PJ (Oct 1998). "HIRA, a mammalian homologue of Saccharomyces cerevisiae transcriptional co-repressors, interacts with Pax3". Nat Genet 20 (1): 74–7. doi:10.1038/1739. PMID 9731536. 
  4. ^ a b c d "Entrez Gene: HIRA HIR histone cell cycle regulation defective homolog A (S. cerevisiae)". 
  5. ^ Adam, S., Polo, S. E., & Almouzni, G. (2013). Transcription Recovery after DNA Damage Requires Chromatin Priming by the H3.3 Histone Chaperone HIRA. Cell, 155(1), 94-106. Retrieved from http://www.cell.com/abstract/S0092-8674(13)01023-4
  6. ^ "Haematology data for Hira". Wellcome Trust Sanger Institute. 
  7. ^ "Salmonella infection data for Hira". Wellcome Trust Sanger Institute. 
  8. ^ a b c d Gerdin AK (2010). "The Sanger Mouse Genetics Programme: High throughput characterisation of knockout mice". Acta Ophthalmologica 88: 925–7. doi:10.1111/j.1755-3768.2010.4142.x. 
  9. ^ Mouse Resources Portal, Wellcome Trust Sanger Institute.
  10. ^ "International Knockout Mouse Consortium". 
  11. ^ "Mouse Genome Informatics". 
  12. ^ Skarnes, W. C.; Rosen, B.; West, A. P.; Koutsourakis, M.; Bushell, W.; Iyer, V.; Mujica, A. O.; Thomas, M.; Harrow, J.; Cox, T.; Jackson, D.; Severin, J.; Biggs, P.; Fu, J.; Nefedov, M.; De Jong, P. J.; Stewart, A. F.; Bradley, A. (2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature 474 (7351): 337–342. doi:10.1038/nature10163. PMC 3572410. PMID 21677750.  edit
  13. ^ Dolgin E (2011). "Mouse library set to be knockout". Nature 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718. 
  14. ^ Collins FS, Rossant J, Wurst W (2007). "A Mouse for All Reasons". Cell 128 (1): 9–13. doi:10.1016/j.cell.2006.12.018. PMID 17218247. 
  15. ^ van der Weyden L, White JK, Adams DJ, Logan DW (2011). "The mouse genetics toolkit: revealing function and mechanism.". Genome Biol 12 (6): 224. doi:10.1186/gb-2011-12-6-224. PMC 3218837. PMID 21722353. 
  16. ^ Lorain S, Quivy JP, Monier-Gavelle F, Scamps C, Lécluse Y, Almouzni G, Lipinski M (September 1998). "Core histones and HIRIP3, a novel histone-binding protein, directly interact with WD repeat protein HIRA". Mol. Cell. Biol. 18 (9): 5546–56. PMC 109139. PMID 9710638. 

Further reading[edit]