NUPR2

Summary

NUPR2 (nuclear protein 2, transcriptional regulator, HGNC:44164) is a protein-coding gene on chromosome 7p11.2, encoding Nuclear protein 2 (A6NF83). Acts as a transcriptional repressor by inhibiting gene expression at the NUPR1 promoter in a p53/TP53-dependent manner in cancer cells.

Involved in several processes, including cellular response to starvation; negative regulation of cell population proliferation; and negative regulation of transcription by RNA polymerase II. Located in nucleus.

Source: NCBI Gene 389493 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 6 total
• MANE Select transcript: NM_001145712

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:44164
Approved symbol	NUPR2
Name	nuclear protein 2, transcriptional regulator
Location	7p11.2
Locus type	gene with protein product
Status	Approved
Aliases	P8
Ensembl gene	ENSG00000185290
Ensembl biotype	protein_coding
Entrez	389493

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000329309

RefSeq mRNA: 1 — MANE Select: NM_001145712 NM_001145712

CCDS: CCDS59058

Canonical transcript exons

ENST00000329309 — 2 exons

Exon	Start	End
ENSE00001323943	56116015	56116417
ENSE00001486712	56114681	56114897

Expression profiles

Bgee: expression breadth ubiquitous, 118 present calls, max score 98.48.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.6841 / max 349.5909, expressed in 139 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
84183	0.3766	100
84184	0.3075	85

Top tissues by expression

130 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
left testis	UBERON:0004533	98.48	gold quality
right testis	UBERON:0004534	98.41	gold quality
testis	UBERON:0000473	97.77	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	90.11	gold quality
adult mammalian kidney	UBERON:0000082	81.51	gold quality
left lobe of thyroid gland	UBERON:0001120	80.16	gold quality
thyroid gland	UBERON:0002046	79.40	gold quality
adenohypophysis	UBERON:0002196	79.33	gold quality
pituitary gland	UBERON:0000007	79.18	gold quality
right lobe of thyroid gland	UBERON:0001119	78.66	gold quality
metanephros cortex	UBERON:0010533	74.41	gold quality
descending thoracic aorta	UBERON:0002345	74.24	gold quality
kidney	UBERON:0002113	73.94	gold quality
thoracic aorta	UBERON:0001515	72.53	gold quality
ascending aorta	UBERON:0001496	72.50	gold quality
nucleus accumbens	UBERON:0001882	71.81	gold quality
islet of Langerhans	UBERON:0000006	71.53	gold quality
right hemisphere of cerebellum	UBERON:0014890	71.36	gold quality
temporal lobe	UBERON:0001871	71.35	gold quality
amygdala	UBERON:0001876	71.29	gold quality
cerebellum	UBERON:0002037	71.02	gold quality
cerebellar cortex	UBERON:0002129	70.98	gold quality
cerebellar hemisphere	UBERON:0002245	70.82	gold quality
prostate gland	UBERON:0002367	69.06	gold quality
prefrontal cortex	UBERON:0000451	68.61	gold quality
hypothalamus	UBERON:0001898	68.45	gold quality
superior frontal gyrus	UBERON:0002661	68.23	gold quality
brain	UBERON:0000955	68.13	gold quality
fundus of stomach	UBERON:0001160	68.06	gold quality
body of stomach	UBERON:0001161	68.04	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-GEOD-134144	yes	7867.95
E-HCAD-38	yes	5506.76
E-ANND-3	yes	13.38

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

20 targeting NUPR2, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-4802-3P	99.72	70.13	1273
HSA-MIR-545-5P	99.66	70.18	2308
HSA-MIR-582-5P	99.47	70.79	2635
HSA-MIR-520F-5P	99.34	70.40	1632
HSA-MIR-130A-5P	99.33	70.26	2623
HSA-MIR-12120	98.05	68.44	1768
HSA-MIR-3198	97.84	65.64	579
HSA-MIR-4309	97.84	65.45	588
HSA-MIR-618	97.62	67.46	861
HSA-MIR-148B-5P	97.29	66.30	992
HSA-MIR-6874-3P	97.29	66.34	975
HSA-MIR-490-5P	96.75	65.81	661
HSA-MIR-4653-3P	96.26	67.03	725
HSA-MIR-9900	96.06	65.48	557
HSA-MIR-635	96.00	65.54	687
HSA-MIR-6774-5P	95.94	65.18	722
HSA-MIR-2277-3P	91.94	62.27	299

Literature-anchored findings (GeneRIF, showing 2)

• Functional characterization of NUPR1L as a new p53-induced gene, which negatively regulates the protumoral factor NUPR1. (PMID:25899918)
• NUPR1L hetero-associated with NUPR1 with an affinity of 0.4 microM and interacted with the ‘hot-spot’ region of NUPR1. (PMID:29925531)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	nupr1b	ENSDARG00000094557
mus_musculus	Nupr2	ENSMUSG00000095789
rattus_norvegicus	Nupr2	ENSRNOG00000074054
drosophila_melanogaster	CG6770	FBGN0032400

Paralogs (1): NUPR1 (ENSG00000176046)

Protein

Protein identifiers

Nuclear protein 2 — A6NF83 (reviewed: A6NF83)

Alternative names: Nuclear transcriptional regulator 1-like protein, Nuclear transcriptional regulator protein 2

All UniProt accessions (1): A6NF83

UniProt curated annotations — full annotation on UniProt →

Function. Acts as a transcriptional repressor by inhibiting gene expression at the NUPR1 promoter in a p53/TP53-dependent manner in cancer cells. Involved in the G1 cell cycle arrest, and in a decrease in cell viability and cell proliferation. Plays a role as a negative regulator of the protumoral factor NUPR1.

Subcellular location. Nucleus.

Induction. Up-regulated by p53/TP53 in cancer cells. Up-regulated by DNA damage stimulus or starvation.

Similarity. Belongs to the NUPR family.

RefSeq proteins (1): NP_001139184* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR018792	NUPR1-like	Family

Pfam: PF10195

UniProt features (3 total): chain 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A6NF83-F1	73.07	0.00

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 28 (showing top): HOFFMANN_SMALL_PRE_BII_TO_IMMATURE_B_LYMPHOCYTE_DN, GOBP_NEGATIVE_REGULATION_OF_CELL_CYCLE, GOBP_REGULATION_OF_CELL_CYCLE, GOBP_DNA_DAMAGE_RESPONSE, GOBP_CELLULAR_RESPONSE_TO_STARVATION, GOBP_RESPONSE_TO_STARVATION, GOBP_NEGATIVE_REGULATION_OF_TRANSCRIPTION_BY_RNA_POLYMERASE_II, GOBP_NEGATIVE_REGULATION_OF_NUCLEOBASE_CONTAINING_COMPOUND_METABOLIC_PROCESS, MIR651_3P, MIR130A_5P, MIR2277_3P, FAN_EMBRYONIC_CTX_BIG_GROUPS_CAJAL_RETZIUS, DESCARTES_MAIN_FETAL_PARIETAL_AND_CHIEF_CELLS, GOBP_CELLULAR_RESPONSE_TO_STRESS, GSE20366_CD103_KLRG1_DP_VS_DN_TREG_DN

GO Biological Process (7): negative regulation of transcription by RNA polymerase II (GO:0000122), regulation of transcription by RNA polymerase II (GO:0006357), DNA damage response (GO:0006974), negative regulation of cell population proliferation (GO:0008285), cellular response to starvation (GO:0009267), negative regulation of cell cycle (GO:0045786), regulation of cell cycle (GO:0051726)

GO Molecular Function (0):

GO Cellular Component (1): nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transcription by RNA polymerase II	2
cellular response to stress	2
negative regulation of cellular process	2
cell cycle	2
regulation of transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription	1
regulation of DNA-templated transcription	1
cell population proliferation	1
regulation of cell population proliferation	1
cellular response to nutrient levels	1
response to starvation	1
regulation of cell cycle	1
regulation of cellular process	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

304 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NUPR2	TERF1	P54274	991
NUPR2	POT1	Q9NUX5	868
NUPR2	TPP1	O14773	820
NUPR2	SMARCB1	Q12824	763
NUPR2	ACD	Q96AP0	759
NUPR2	TNP2	Q05952	633
NUPR2	TP53INP2	Q8IXH6	628
NUPR2	TINF2	Q9BSI4	621
NUPR2	TERF2	Q15554	535
NUPR2	VMP1	Q96GC9	498
NUPR2	TSACC	Q96A04	457
NUPR2	SUMF2	Q8NBJ7	442
NUPR2	RPA1	P27694	437
NUPR2	GTF2B	Q00403	421
NUPR2	GABARAP	O95166	420

IntAct

0 interactions, top by confidence:

ESM2 similar proteins: A0A0U1RRK4, A0A1W2PPE3, A0A1W2PR82, A0A2R8Y2Y2, A0A494C0N9, A0A494C0Y3, A0JNN8, A6NF83, A6NHQ4, A6QPM6, A8E4L3, A8MTW9, B2KGE5, C9JVW0, I3L1E1, O43541, O75474, O75638, P0C7X2, P70339, P89439, Q02080, Q05215, Q12950, Q3SYB3, Q5T230, Q5VV16, Q6NZ36, Q6NZY7, Q6P1X6, Q6VB84, Q6VUC0, Q6VUP9, Q6ZSJ8, Q7RTU5, Q7TNS8, Q80WY3, Q86SI9, Q86UU5, Q8K025

Diamond homologs: A6NF83, O54842, O60356, Q32PB4, Q497P3, Q9WTK0

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

6 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	3
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

67 predictions. Top by Δscore:

Variant	Effect	Δscore
7:56116011:GTAC:G	donor_loss	1.0000
7:56116012:TAC:T	donor_loss	1.0000
7:56116013:A:AC	donor_gain	1.0000
7:56116013:AC:A	donor_gain	1.0000
7:56116013:ACCC:A	donor_loss	1.0000
7:56116014:C:CC	donor_gain	1.0000
7:56116014:C:G	donor_loss	1.0000
7:56116014:CC:C	donor_gain	1.0000
7:56114895:ATCC:A	acceptor_loss	0.9900
7:56114896:TC:T	acceptor_gain	0.9900
7:56114896:TCC:T	acceptor_loss	0.9900
7:56114897:CC:C	acceptor_gain	0.9900
7:56114897:CCTG:C	acceptor_loss	0.9900
7:56116013:ACC:A	donor_gain	0.9900
7:56116014:CCC:C	donor_gain	0.9900
7:56116014:CCCA:C	donor_gain	0.9900
7:56116014:CCCAG:C	donor_gain	0.9900
7:56116041:T:C	donor_gain	0.9900
7:56114898:C:CC	acceptor_gain	0.9800
7:56116009:ACGT:A	donor_loss	0.9800
7:56114894:TATC:T	acceptor_gain	0.9700
7:56114893:GTATC:G	acceptor_gain	0.9600
7:56114895:ATC:A	acceptor_gain	0.9600
7:56114907:A:AC	acceptor_gain	0.9500
7:56114907:A:C	acceptor_gain	0.9400
7:56114910:C:CT	acceptor_gain	0.9400
7:56114900:G:GC	acceptor_gain	0.9200
7:56114900:G:C	acceptor_gain	0.8900
7:56116010:CGTA:C	donor_gain	0.8500
7:56114911:A:T	acceptor_gain	0.8200

AlphaMissense

611 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:56116168:C:A	K49N	0.964
7:56116168:C:G	K49N	0.964
7:56116195:G:C	F40L	0.953
7:56116195:G:T	F40L	0.953
7:56116197:A:G	F40L	0.953
7:56116160:G:A	T52I	0.950
7:56116169:T:A	K49M	0.915
7:56116170:T:C	K49E	0.911
7:56116167:C:G	G50R	0.910
7:56116150:C:A	E55D	0.909
7:56116150:C:G	E55D	0.909
7:56116171:G:C	S48R	0.905
7:56116171:G:T	S48R	0.905
7:56116173:T:G	S48R	0.905
7:56116107:G:T	R70S	0.904
7:56116102:C:A	K71N	0.900
7:56116102:C:G	K71N	0.900
7:56116166:C:T	G50D	0.898
7:56116169:T:G	K49T	0.883
7:56116196:A:G	F40S	0.883
7:56116111:G:C	H68Q	0.876
7:56116111:G:T	H68Q	0.876
7:56116155:G:T	R54S	0.873
7:56116170:T:G	K49Q	0.871
7:56116196:A:C	F40C	0.871
7:56116217:T:A	D33V	0.871
7:56116151:T:A	E55V	0.869
7:56116136:G:A	T60I	0.862
7:56116113:G:C	H68D	0.855
7:56116167:C:A	G50C	0.848

dbSNP variants (sampled 300 via entrez): RS1000213717 (7:56115324 A>G), RS1001225071 (7:56114932 A>G), RS1002913605 (7:56116535 C>T), RS1003514720 (7:56118403 T>G), RS1003565940 (7:56118105 C>A,T), RS1003808604 (7:56114572 T>A,C), RS1004395886 (7:56115934 A>C), RS1004448245 (7:56115521 T>C), RS1005768062 (7:56115000 A>G,T), RS1006938748 (7:56115578 C>T), RS1007397445 (7:56115939 G>A,C), RS1008131858 (7:56116879 C>T), RS1008660724 (7:56117065 T>G), RS1009947063 (7:56114333 A>C,G), RS1009953744 (7:56114555 C>G)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST009144_12	Disease progression in age-related macular degeneration (adjusted for baseline)	2.000000e-06
GCST010219_11	Attention deficit hyperactivity disorder (inattention symptoms)	2.000000e-07
GCST012251_16	Macular telangiectasia type 2	3.000000e-07
GCST012252_7	Macular telangiectasia type 2	6.000000e-09

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0008336	disease progression measurement
EFO:1002009	macular telangiectasia type 2

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

8 total (human), top 8 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression	1
jinfukang	affects cotreatment, increases expression	1
Benzo(a)pyrene	decreases methylation, increases methylation	1
Cisplatin	affects cotreatment, increases expression	1
Niclosamide	increases expression	1
Rotenone	increases expression	1
Valproic Acid	increases methylation	1
Aflatoxin B1	increases methylation	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.