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10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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ACTR8
actin related protein 8
Chromosome 3 · 3p21.1
NCBI Gene: 93973Ensembl: ENSG00000113812.15HGNC: HGNC:14672UniProt: Q9H981
54PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
DNA RepairTranscription Factor
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
positive regulation of DNA-templated transcriptionregulation of DNA strand elongationregulation of cell cycleregulation of DNA replicationneurodegenerative diseasetympanic membrane diseasehypertensionbone remodeling disease
✦AI Summary

ACTR8 (actin-related protein 8) is a core component of the INO80 chr3 remodeling complex that plays essential roles in DNA repair, replication, and transcriptional regulation 12. The protein functions as a nucleosome recognition module, strongly preferring nucleosomes and H3-H4 tetramers over H2A-H2B dimers, which enables the INO80 complex to interact with chr3 substrates 3. Structurally, ACTR8 contains an ATP-bound actin fold with unique insertions that prevent polymerization and rigidify its domain architecture 3. The protein exhibits preferential binding to single-stranded DNA, with its ATP-binding pocket playing a regulatory role in DNA interactions 4. In DNA repair mechanisms, ACTR8 is required for efficient replication restart after replication stress and protection of stalled replication forks from collapse 1. The protein undergoes ATM- and ATR-regulated phosphorylation following DNA damage, which attenuates its interaction with INO80 and prevents excessive loading of repair factors, thereby maintaining DNA repair fidelity and preventing chromosome 3 5. Additionally, ACTR8 knockout has been associated with enhanced sensitivity to immune cell cytotoxicity in cancer contexts 6.

Sources cited
1
ACTR8 is required for efficient replication restart and protection of stalled forks
PMID: 25016522
2
ACTR8 is a core component of the INO80 chromatin remodeling complex
PMID: 29643506
3
ACTR8 functions as nucleosome recognition module and has unique structural insertions
PMID: 22977180
4
ACTR8 binds preferentially to single-stranded DNA and is involved in DNA repair
PMID: 25299602
5
ACTR8 undergoes ATM/ATR-regulated phosphorylation to prevent chromosome translocations
PMID: 29759113
6
ACTR8 knockout sensitizes ovarian cancer cells to immune cytotoxicity
PMID: 39179931
Disease Associationsⓘ20
neurodegenerative diseaseOpen Targets
0.38Weak
tympanic membrane diseaseOpen Targets
0.27Weak
hypertensionOpen Targets
0.09Suggestive
bone remodeling diseaseOpen Targets
0.08Suggestive
response to xenobiotic stimulusOpen Targets
0.07Suggestive
Hemoglobin E - beta-thalassemiaOpen Targets
0.05Suggestive
hemoglobin E-beta-thalassemia syndromeOpen Targets
0.05Suggestive
hemoglobin D diseaseOpen Targets
0.05Suggestive
primary familial polycythemia due to EPO receptor mutationOpen Targets
0.05Suggestive
hereditary persistence of fetal hemoglobin-sickle cell disease syndromeOpen Targets
0.05Suggestive
Hereditary persistence of fetal hemoglobin - beta-thalassemiaOpen Targets
0.05Suggestive
Blackfan-Diamond anemiaOpen Targets
0.05Suggestive
Adult-onset autosomal recessive sideroblastic anemiaOpen Targets
0.05Suggestive
familial pseudohyperkalemiaOpen Targets
0.05Suggestive
lysosomal storage diseaseOpen Targets
0.05Suggestive
microcytic anemia with liver iron overloadOpen Targets
0.05Suggestive
tuberculosisOpen Targets
0.04Suggestive
essential hypertensionOpen Targets
0.04Suggestive
alpha thalassemia-intellectual disability syndrome type 1Open Targets
0.04Suggestive
Alpha-thalassemia - intellectual disability syndrome linked to chromosome 16Open Targets
0.04Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
ACTL6AProtein interaction99%BRD8Protein interaction99%NFRKBProtein interaction96%DMAP1Protein interaction96%ACTBProtein interaction95%TRRAPProtein interaction94%
Tissue Expression6 tissues
Heart
100%
Brain
64%
Bone Marrow
47%
Ovary
36%
Lung
35%
Liver
33%
Gene Interaction Network
Click a node to explore
ACTR8ACTL6ABRD8NFRKBDMAP1ACTBTRRAP
PROTEIN STRUCTURE
Preparing viewer…
PDB4FO0 · 2.60 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
1.03LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.83 [0.67–1.03]
RankingsWhere ACTR8 stands among ~20K protein-coding genes
  • #8,274of 20,598
    Most Researched54
  • #10,241of 17,882
    Most Constrained (LOEUF)1.03
Genes detectedACTR8
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Mapping spatial organization and genetic cell-state regulators to target immune evasion in ovarian cancer.
PMID: 39179931
Nat Immunol · 2024
1.00
2
A single mutation in the ACTR8 gene associated with lineage-specific expression in primates.
PMID: 32503430
BMC Evol Biol · 2020
0.90
3
The identification of novel gene mutations for degenerative lumbar spinal stenosis using whole-exome sequencing in a Chinese cohort.
PMID: 34020649
BMC Med Genomics · 2021
0.80
4
Structure and regulation of the human INO80-nucleosome complex.
PMID: 29643506
Nature · 2018
0.70
5
The mammalian INO80 chromatin remodeling complex is required for replication stress recovery.
PMID: 25016522
Nucleic Acids Res · 2014
0.60