NUPR1

Chr 16

nuclear protein 1, transcriptional regulator

Also known as: COM1, P8

NCBI Gene: 26471ENSG00000176046UniProt: O60356

Enables DNA binding activity and transcription coactivator activity. Involved in several processes, including negative regulation of programmed cell death; positive regulation of oxidative phosphorylation; and regulation of catabolic process. Acts upstream of or within negative regulation of cell cycle. Located in intercellular bridge; nucleoplasm; and perinuclear region of cytoplasm. Part of protein-DNA complex. [provided by Alliance of Genome Resources, Apr 2025]

118
ClinVar variants
71
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— NUPR1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
71 Pathogenic / Likely Pathogenic· 46 VUS of 118 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.91LOEUF
pLI 0.004
Z-score -0.41
OE 1.29 (0.52–1.91)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
-0.12Z-score
OE missense 1.04 (0.86–1.27)
68 obs / 65.3 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.1.29 (0.52–1.91)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.04 (0.86–1.27)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.99
0≤1.21.6
LoF obs/exp: 3 / 2.3Missense obs/exp: 68 / 65.3Syn Z: 0.02

ClinVar Variant Classifications

118 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic66
Likely Pathogenic5
VUS46
Likely Benign1
66
Pathogenic
5
Likely Pathogenic
46
VUS
1
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
66
0
66
Likely Pathogenic
0
0
5
0
5
VUS
0
25
21
0
46
Likely Benign
0
0
1
0
1
Benign
0
0
0
0
0
Total025930118

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

NUPR1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
NUPR1 contributes to radiation resistance by maintaining ROS homeostasis via AhR/CYP signal axis in hepatocellular carcinoma.
Zhan Y et al.·BMC Med
2022
Ageing limits stemness and tumorigenesis by reprogramming iron homeostasis.
Zhuang X et al.·Nature
2025
NUPR1 and its potential role in cancer and pathological conditions (Review).
Martin TA et al.·Int J Oncol
2021Review
Repurposing trifluoperazine for glioblastoma treatment.
De Silva MI et al.·Trends Pharmacol Sci
2025Review
NUPR1 Promotes Radioresistance in Colorectal Cancer Cells by Inhibiting Ferroptosis.
Fang Y et al.·J Cell Mol Med
2025
ScRNA-seq and bulk RNA-seq identified NUPR1 as novel biomarkers related to CD4 + T cells infiltration for abdominal aortic aneurysm.
Zhou Z et al.·Mol Biol Rep
2024
Development of an efficient NUPR1 inhibitor with anticancer activity.
Liu X et al.·Sci Rep
2024
NUPR1 participates in YAP-mediate gastric cancer malignancy and drug resistance via AKT and p21 activation.
Jiang L et al.·J Pharm Pharmacol
2021
Disruption of glutamine transport uncouples the NUPR1 stress-adaptation program and induces prostate cancer radiosensitivity.
Kahya U et al.·Cell Commun Signal
2025
Nupr1-mediated vascular smooth muscle cell phenotype transformation involved in methamphetamine induces pulmonary hypertension.
Zhou J et al.·Cell Biol Toxicol
2024
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Histone H4K8 lactylation promotes glioblastoma progression by inducing NUPR1-mediated autophagosome‒lysosome fusion.
Zhao J et al.·Theranostics
2026🔓 Open Access
Stress-Inducible Transcription Factor NUPR1 Is Involved in the Inhibitory Effects Exerted by Statins on Insulin Action in ER-Positive Breast Cancer Cells.
Scordamaglia D et al.·Cells
2026🔓 Open Access
MGMT, NUPR1, NDRG2, and GLI1 Gene Promoter Methylation in Glioblastoma Tissues and Association with Clinical Characteristics and Therapeutic Outcomes.
Gabr MM et al.·Int J Mol Sci
2026🔓 Open Access
Targeting intrinsically disordered nuclear protein 1 (NUPR1) with single-domain antibodies alleviates triple-negative breast cancer (TNBC) progression in vivo.
Wang T et al.·Cell Death Dis
2025🔓 Open Access
Evaluating the therapeutic role of salvianolic acid A on pancreatic cancer cells through interaction with the intrinsically disordered protein NUPR1.
Álvarez-Rodríguez MG et al.·Int J Biol Macromol
2026
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools