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25 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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NAP1L4
nucleosome assembly protein 1 like 4
Chromosome 11 · 11p15.4
NCBI Gene: 4676Ensembl: ENSG00000205531.15HGNC: HGNC:7640UniProt: Q99733
160PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein bindingnucleusnucleoplasmnucleosome bindingneurodegenerative diseasegoutpneumothoraxpleural empyema
✦AI Summary

NAP1L4 (nucleosome assembly protein 1 like 4) is a histone chaperone protein that mediates nucleosome assembly and chr11 remodeling 1. The protein contains N- and C-terminal domains required for histone binding and transfer onto DNA, and shuttles between the cytoplasm and nucleus to facilitate its chaperone functions 1. Beyond chr11 assembly, NAP1L4 plays regulatory roles in cellular stress responses by modulating p53 acetylation at specific lysine residues (Lys320 and Lys382), thereby controlling the expression of p53-responsive genes involved in cell cycle arrest and apoptosis 2. During viral infection, NAP1L4 interacts with Chikungunya virus nonstructural protein 3 (nsP3) in a phosphorylation-dependent manner to promote viral replication complex assembly 3. In disease contexts, NAP1L4 dysregulation is implicated in pulmonary hypertension, where a circular RNA derived from NAP1L4 regulates glycolysis-associated gene expression through super-enhancer mechanisms in pulmonary artery smooth muscle cells 4. Genomically, NAP1L4 resides within the KCNQ1 imprinted domain on chromosome 11, though its imprinting status differs between species: humans and cattle show biallelic expression 56, while pigs show tissue-specific imprinting patterns 7. These multifaceted functions position NAP1L4 as an important regulator of chr11 dynamics, cellular stress responses, and disease pathology.

Sources cited
1
NAP1L4 functions as a histone chaperone that interacts with histones, transfers them onto DNA, and shuttles between cytoplasm and nucleus
PMID: 9325046
2
NAP1L4 modulates p53 acetylation at Lys320 and Lys382 to regulate cell cycle arrest and apoptotic gene expression
PMID: 31634504
3
NAP1L4 interacts with phosphorylated Chikungunya virus nsP3 to promote viral replication complex assembly
PMID: 34076483
4
Circular NAP1L4 regulates glycolysis and smooth muscle cell proliferation in pulmonary hypertension via super-enhancer mechanisms
PMID: 39102213
5
NAP1L4 shows biallelic expression in human trophoblast stem cells and placenta
PMID: 20644730
6
NAP1L4 exhibits biallelic expression across multiple adult cattle tissues
PMID: 26440077
7
NAP1L4 shows biallelic expression in porcine neonatal tissues but may have tissue-specific imprinting patterns in pigs
PMID: 22500112
Disease Associationsⓘ20
neurodegenerative diseaseOpen Targets
0.50Moderate
goutOpen Targets
0.38Weak
pneumothoraxOpen Targets
0.26Weak
pleural empyemaOpen Targets
0.24Weak
hepatocellular carcinomaOpen Targets
0.09Suggestive
metabolic syndromeOpen Targets
0.08Suggestive
atrial fibrillationOpen Targets
0.08Suggestive
infectionOpen Targets
0.05Suggestive
neoplasmOpen Targets
0.05Suggestive
peripheral arterial diseaseOpen Targets
0.04Suggestive
melanomaOpen Targets
0.03Suggestive
microphthalmia with limb anomaliesOpen Targets
0.03Suggestive
lung cancerOpen Targets
0.03Suggestive
hepatitis B virus infectionOpen Targets
0.03Suggestive
human african trypanosomiasisOpen Targets
0.02Suggestive
hypospadiasOpen Targets
0.02Suggestive
systemic lupus erythematosusOpen Targets
0.02Suggestive
congestive heart failureOpen Targets
0.02Suggestive
pernicious anemiaOpen Targets
0.02Suggestive
sensory perception of smellOpen Targets
0.02Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
TSPY10Shared pathway100%TSPY8Shared pathway100%TSPY4Shared pathway100%TSPY3Shared pathway100%TSPY9Shared pathway100%TSPYL6Shared pathway100%
Tissue Expression6 tissues
Heart
100%
Bone Marrow
79%
Brain
60%
Liver
48%
Ovary
46%
Lung
44%
Gene Interaction Network
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NAP1L4TSPY10TSPY8TSPY4TSPY3TSPY9TSPYL6
PROTEIN STRUCTURE
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AlphaFoldAI-predicted · UniProt Q99733
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
0.39Moderately Constrained
pLIⓘ
1.00Intolerant
Observed/Expected LoF0.24 [0.16–0.39]
RankingsWhere NAP1L4 stands among ~20K protein-coding genes
  • #2,810of 20,598
    Most Researched160 · top quartile
  • #1,868of 17,882
    Most Constrained (LOEUF)0.39 · top quartile
Genes detectedNAP1L4
Sources retrieved25 papers
Response time—
📄 Sources
25▼
1
Telomeric NAP1L4 and OSBPL5 of the KCNQ1 cluster, and the DECORIN gene are not imprinted in human trophoblast stem cells.
PMID: 20644730
PLoS One · 2010
1.00
2
CircNAP1L4 regulates pulmonary artery smooth muscle cell proliferation via the NAP1L4-mediated super-enhancer-driven glycolysis gene hexokinase II (HK II) in pulmonary hypertension.
PMID: 39102213
FASEB J · 2024
0.90
3
Characterization, tissue expression, and imprinting analysis of the porcine CDKN1C and NAP1L4 genes.
PMID: 22500112
J Biomed Biotechnol · 2012
0.80
4
NAP1L1 and NAP1L4 Binding to Hypervariable Domain of Chikungunya Virus nsP3 Protein Is Bivalent and Requires Phosphorylation.
PMID: 34076483
J Virol · 2021
0.70
5
Nucleosome assembly protein 1-like 4, a new therapeutic target for proliferation and invasion of melanoma cells.
PMID: 33583643
J Dermatol Sci · 2021
0.68