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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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HIRIP3
HIRA interacting protein 3
Chromosome 16 · 16p11.2
NCBI Gene: 8479Ensembl: ENSG00000149929.17HGNC: HGNC:4917UniProt: Q9BW71
57PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
H2A-H2B histone complex chaperone activityprotein bindingchromatin organizationnucleusneurodegenerative diseasecervical carcinomasmoking behaviorschizophrenia
✦AI Summary

HIRIP3 (HIRA interacting protein 3) functions as a histone chaperone that specifically carries H2A-H2B histone dimers and facilitates their deposition onto chr16 1. The protein acts as an H2A histone chaperone, physically interacting with the H2A αC helix through an extended CHZ domain and playing a crucial role in depositing canonical core histones onto naked DNA 1. HIRIP3 is associated in vivo with H2A-H2B dimers and CK2 kinase, which shows preference for H2A phosphorylation at serine 1 1. Originally identified through its interaction with the HIRA histone chaperone, HIRIP3 directly interacts with core histones H2B and H3, suggesting it functions as part of a HIRA-HIRIP3-containing complex involved in chr16 and histone metabolism 2. The protein is nuclear throughout the cell cycle, excluded from condensed chr16 during mitosis, and is heavily phosphorylated by CK2 kinase 3. HIRIP3 expression is regulated through sense/antisense interactions with the overlapping INO80E gene, forming RNA:RNA duplexes that stabilize mRNAs 4. The gene is expressed in neural progenitors during human fetal cerebral cortex development and has been identified as a potential diagnostic biomarker in Alzheimer's disease 56.

Sources cited
1
HIRIP3 functions as histone chaperone carrying H2A-H2B dimers, interacts with CK2 kinase, and deposits histones onto DNA
PMID: 38334665
2
HIRIP3 was identified through interaction with HIRA histone chaperone and directly interacts with core histones H2B and H3
PMID: 9710638
3
HIRIP3 is nuclear throughout cell cycle, heavily phosphorylated, and phosphorylated by CK2 kinase
PMID: 17391060
4
HIRIP3 expression is regulated through sense/antisense interactions with overlapping INO80E gene via RNA:RNA duplex formation
PMID: 40057624
5
HIRIP3 is expressed in neural progenitors during human fetal cerebral cortex development
PMID: 33825894
6
HIRIP3 identified as potential diagnostic biomarker in Alzheimer's disease through machine learning analysis
PMID: 40547214
Disease Associationsⓘ20
neurodegenerative diseaseOpen Targets
0.48Moderate
cervical carcinomaOpen Targets
0.12Weak
smoking behaviorOpen Targets
0.06Suggestive
schizophreniaOpen Targets
0.04Suggestive
metabolic syndromeOpen Targets
0.03Suggestive
hypertensionOpen Targets
0.03Suggestive
obesityOpen Targets
0.03Suggestive
type 2 diabetes mellitusOpen Targets
0.02Suggestive
tympanic membrane perforationOpen Targets
0.02Suggestive
Alzheimer diseaseOpen Targets
0.02Suggestive
bipolar disorderOpen Targets
0.02Suggestive
diabetic neuropathyOpen Targets
0.02Suggestive
intelligenceOpen Targets
0.02Suggestive
morbid obesityOpen Targets
0.02Suggestive
essential hypertensionOpen Targets
0.02Suggestive
coronary artery diseaseOpen Targets
0.02Suggestive
Duane retraction syndromeOpen Targets
0.01Suggestive
psoriasisOpen Targets
0.00Suggestive
Invasive Breast CarcinomaOpen Targets
0.00Suggestive
diabetes mellitusOpen Targets
0.00Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
H2BK1Shared pathway100%H2BW2Shared pathway100%ZCWPW2Shared pathway100%MSL3BShared pathway100%CDYL2Shared pathway100%ZNF618Shared pathway100%
Tissue Expression6 tissues
Brain
100%
Heart
60%
Bone Marrow
54%
Ovary
44%
Liver
37%
Lung
31%
Gene Interaction Network
Click a node to explore
HIRIP3H2BK1H2BW2ZCWPW2MSL3BCDYL2ZNF618
PROTEIN STRUCTURE
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AlphaFoldAI-predicted · UniProt Q9BW71
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
1.01LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.79 [0.62–1.01]
RankingsWhere HIRIP3 stands among ~20K protein-coding genes
  • #7,972of 20,598
    Most Researched57
  • #9,901of 17,882
    Most Constrained (LOEUF)1.01
Genes detectedHIRIP3
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Integrative bioinformatics and machine learning identify iron metabolism genes MAP4, GPT, and HIRIP3 as diagnostic biomarkers and therapeutic targets in Alzheimer's disease.
PMID: 40547214
Front Cell Neurosci · 2025
1.00
2
Mechanism of expression regulation of head-to-head overlapping protein-coding genes INO80E and HIRIP3.
PMID: 40057624
Commun Biol · 2025
0.90
3
Identification and Characterization of HIRIP3 as a Histone H2A Chaperone.
PMID: 38334665
Cells · 2024
0.80
4
Core histones and HIRIP3, a novel histone-binding protein, directly interact with WD repeat protein HIRA.
PMID: 9710638
Mol Cell Biol · 1998
0.70
5
A rare triplication of 16p11.2: Unravelling the genomic complexity and review of the literature.
PMID: 40180152
Eur J Med Genet · 2025
0.60