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GeneE
6 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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NUPR2
nuclear protein 2, transcriptional regulator
Chromosome 7 · 7p11.2
NCBI Gene: 389493Ensembl: ENSG00000185290.4HGNC: HGNC:44164UniProt: A6NF83
3PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Transcription Factor
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
negative regulation of transcription by RNA polymerase IIcellular response to starvationregulation of cell cyclenucleusesophageal ulcerAbnormal nasolacrimal system morphologyosteomyelitisedema
✦AI Summary

NUPR2 is a nuclear transcriptional regulator that functions as a negative regulator of the protumoral protein NUPR1. As a p53-dependent transcriptional repressor, NUPR2 inhibits gene expression at the NUPR1 promoter in cancer cells, thereby suppressing cell proliferation and promoting G1 cell cycle arrest 1. NUPR2 belongs to a conserved family of small chr7-binding proteins structurally related to helix-loop-helix HMG proteins, yet distinct in their posttranslational modification sites and DNA-binding properties 2. Mechanistically, NUPR2 operates as an intrinsically disordered protein capable of binding nuclear import machinery and interacting with other chr7 regulators 3. Beyond cancer biology, NUPR2 appears relevant to neurodegenerative disease; it was the only gene in the DNA damage response pathway differentially expressed between sporadic and C9orf72-repeat-expansion frontotemporal dementia patient-derived neurons, suggesting a potential role in neurodegeneration-associated DNA repair mechanisms 4. Through its dual capacity to suppress NUPR1 expression and regulate cell cycle progression, NUPR2 may function as a stress-response tumor suppressor, though its clinical significance and therapeutic potential remain incompletely characterized compared to its well-studied paralogue NUPR1.

Sources cited
1
NUPR2 (NUPR1L) acts as a p53-regulated transcriptional repressor that inhibits NUPR1 promoter activity, promotes G1 cell cycle arrest, and decreases cell viability
PMID: 25899918
2
NUPR2 is a member of a conserved family of small chromatin-binding proteins structurally distinct from AT-hook HMG proteins
PMID: 25056123
3
NUPR2 (NUPR1L) is an intrinsically disordered protein that interacts with other chromatin regulators and NUPR1 partners
PMID: 29925531
4
NUPR2 is the only gene involved in DNA damage response differentially expressed between sporadic and C9orf72-repeat-expansion frontotemporal dementia neurons
PMID: 41006764
⚠Limited data available — This gene has 4 indexed publications. Summary and analysis may be incomplete.
Disease Associationsⓘ20
esophageal ulcerOpen Targets
0.23Weak
Abnormal nasolacrimal system morphologyOpen Targets
0.22Weak
osteomyelitisOpen Targets
0.19Weak
brain compressionOpen Targets
0.16Weak
edemaOpen Targets
0.16Weak
chronic ulcer of skinOpen Targets
0.13Weak
neuropathyOpen Targets
0.12Weak
diabetes mellitusOpen Targets
0.09Suggestive
frozen shoulderOpen Targets
0.09Suggestive
colorectal carcinomaOpen Targets
0.06Suggestive
cancerOpen Targets
0.05Suggestive
neoplasmOpen Targets
0.05Suggestive
gastric carcinomaOpen Targets
0.03Suggestive
breast carcinomaOpen Targets
0.02Suggestive
oral squamous cell carcinomaOpen Targets
0.02Suggestive
infectionOpen Targets
0.02Suggestive
adolescent idiopathic scoliosisOpen Targets
0.02Suggestive
Insulin resistanceOpen Targets
0.02Suggestive
chronic pancreatitisOpen Targets
0.02Suggestive
myocardial infarctionOpen Targets
0.02Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
TPP1Protein interaction99%TERF1Protein interaction99%POT1Protein interaction99%ACDProtein interaction99%NUDT6Shared pathway40%BTG4Shared pathway33%
Tissue Expression6 tissues
Brain
100%
Bone Marrow
46%
Lung
38%
Liver
8%
Heart
8%
Ovary
8%
Gene Interaction Network
Click a node to explore
NUPR2TPP1TERF1POT1ACDNUDT6BTG4
PROTEIN STRUCTURE
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AlphaFoldAI-predicted · UniProt A6NF83
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
1.97LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF1.98 [1.17–1.97]
RankingsWhere NUPR2 stands among ~20K protein-coding genes
  • #18,919of 20,598
    Most Researched3
  • #17,791of 17,882
    Most Constrained (LOEUF)1.97
Genes detectedNUPR2
Sources retrieved6 papers
Response time—
📄 Sources
6▼
1
Frontotemporal dementia patient-derived iPSC neurons show cell pathological hallmarks and evidence for synaptic dysfunction and DNA damage.
PMID: 41006764
Mol Psychiatry · 2026
1.00
2
Evidence supporting the existence of a NUPR1-like family of helix-loop-helix chromatin proteins related to, yet distinct from, AT hook-containing HMG proteins.
PMID: 25056123
J Mol Model · 2014
0.83
3
NUPR1 and its potential role in cancer and pathological conditions (Review).
PMID: 33760183
Int J Oncol · 2021
0.67
4
The chromatin nuclear protein NUPR1L is intrinsically disordered and binds to the same proteins as its paralogue.
PMID: 29925531
Biochem J · 2018
0.50
5
Functional Characterization of Nupr1L, A Novel p53-Regulated Isoform of the High-Mobility Group (HMG)-Related Protumoral Protein Nupr1.
PMID: 25899918
J Cell Physiol · 2015
0.33