NUPR1
protein-codingnuclear protein 1, transcriptional regulator
Gene summary
Enables DNA binding activity and transcription coactivator activity. Involved in several processes, including negative regulation of autophagosome assembly; negative regulation of programmed cell death; and regulation of generation of precursor metabolites and energy. Acts upstream of or within negative regulation of cell cycle. Located in nucleoplasm and perinuclear region of cytoplasm. Part of protein-DNA complex. [provided by Alliance of Genome Resources, Jun 2026]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~6.3 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to NUPR1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_012385.3. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 0 | |||||
| missense | 25 | 25 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 2 | 2 | ||||
| Total | 0 | 0 | 27 | 0 | 0 | 27 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_036517.1 | 2 | MANE Select | |
| Ensembl | ENSP00000315559.7 | 2 | MANE Select | |
| RefSeq | NP_001035948.1 | 2 | Standard | |
| Ensembl | ENSP00000379003.2 | 2 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Transcriptional misregulation in cancer - Homo sapiens (human)
- TNFalpha
Biological Process
- acute inflammatory response
- protein acetylation
- cell population proliferation
- negative regulation of cell population proliferation
- male gonad development
Molecular Function
- DNA binding
- chromatin binding
- protein binding
Cellular Component
- nucleus
- cytosol
- protein-DNA complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000395641
- Coding exons
- 2
- Length
- 1890
- Individuals with no LoFs
- 125732
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 10
- Defined
- 125742
- p
- 0.0000398
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.120 | 68 | 65.3 | 1.04 | 0.00000400 | 628 |
| Missense (PolyPhen) | 13 | 6.6371 | 1.9587 | 55 | ||
| Synonymous | 0.0222 | 25 | 25.1 | 0.994 | 0.00000143 | 225 |
| Loss of Function | -0.414 | 3 | 2.32 | 1.29 | 9.67e-8 | 32 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.00012 | 0.00012 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00027 | 0.00027 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0 | 0.0 | absent |
| South Asian | 0.000033 | 0.000033 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Chromatin-binding protein that converts stress signals into a program of gene expression that empowers cells with resistance to the stress induced by a change in their microenvironment. Interacts with MSL1 and inhibits its activity on histone H4 'Lys-16' acetylation (H4K16ac). Binds the RELB promoter and activates its transcription, leading to the transactivation of IER3. The NUPR1/RELB/IER3 survival pathway may provide pancreatic ductal adenocarcinoma with remarkable resistance to cell stress, such as starvation or gemcitabine treatment. In breast cancer cells, NUPR1 overexpression leads to the activation of PI3K/AKT signaling pathway, CDKN1A/p21 phosphorylation and relocalization from the nucleus to the cytoplasm, leading to resistance to chemotherapeutic agents, such as doxorubicin. {ECO:0000269|PubMed:19650074, ECO:0000269|PubMed:22565310, ECO:0000269|PubMed:22858377}.;
Intolerance Scores
- LoFtool
- 0.433
- RVIS EVS
- 0.13
- RVIS percentile EVS
- 62.74
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.749
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |