NUPR1

Summary

NUPR1 (nuclear protein 1, transcriptional regulator, HGNC:29990) is a protein-coding gene on chromosome 16p11.2, encoding Nuclear protein 1 (O60356). Transcription regulator 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.

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.

Source: NCBI Gene 26471 — RefSeq curated summary.

At a glance

• GWAS associations: 24
• Clinical variants (ClinVar): 2 total
• MANE Select transcript: NM_012385

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29990
Approved symbol	NUPR1
Name	nuclear protein 1, transcriptional regulator
Location	16p11.2
Locus type	gene with protein product
Status	Approved
Aliases	COM1, p8
Ensembl gene	ENSG00000176046
Ensembl biotype	protein_coding
OMIM	614812
Entrez	26471

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 5 protein_coding, 1 nonsense_mediated_decay

ENST00000324873, ENST00000395641, ENST00000567646, ENST00000876798, ENST00000876799, ENST00000962926

RefSeq mRNA: 2 — MANE Select: NM_012385 NM_001042483, NM_012385

CCDS: CCDS10634, CCDS42137

Canonical transcript exons

ENST00000324873 — 3 exons

Exon	Start	End
ENSE00001247072	28538796	28538974
ENSE00001873907	28532708	28537669
ENSE00003530966	28538006	28538155

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 99.41.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 105.1013 / max 1239.4760, expressed in 1417 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
156891	83.5298	1353
156892	11.9161	1188
156890	5.1161	920
156893	4.5393	1077

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left lobe of thyroid gland	UBERON:0001120	99.41	gold quality
thyroid gland	UBERON:0002046	99.35	gold quality
right lobe of thyroid gland	UBERON:0001119	99.30	gold quality
body of pancreas	UBERON:0001150	99.25	gold quality
right adrenal gland cortex	UBERON:0035827	99.21	gold quality
right adrenal gland	UBERON:0001233	99.14	gold quality
mucosa of stomach	UBERON:0001199	99.01	gold quality
left adrenal gland	UBERON:0001234	98.97	gold quality
left adrenal gland cortex	UBERON:0035825	98.97	gold quality
muscle layer of sigmoid colon	UBERON:0035805	98.85	gold quality
skin of abdomen	UBERON:0001416	98.83	gold quality
skin of leg	UBERON:0001511	98.81	gold quality
zone of skin	UBERON:0000014	98.80	gold quality
right lung	UBERON:0002167	98.75	gold quality
prostate gland	UBERON:0002367	98.74	gold quality
right lobe of liver	UBERON:0001114	98.70	gold quality
left coronary artery	UBERON:0001626	98.69	gold quality
lower esophagus muscularis layer	UBERON:0035833	98.69	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	98.69	gold quality
lower esophagus	UBERON:0013473	98.68	gold quality
subcutaneous adipose tissue	UBERON:0002190	98.64	gold quality
right ovary	UBERON:0002118	98.63	gold quality
thoracic mammary gland	UBERON:0005200	98.60	gold quality
left ovary	UBERON:0002119	98.56	gold quality
right coronary artery	UBERON:0001625	98.55	gold quality
popliteal artery	UBERON:0002250	98.53	gold quality
tibial artery	UBERON:0007610	98.53	gold quality
endocervix	UBERON:0000458	98.50	gold quality
adipose tissue	UBERON:0001013	98.48	gold quality
body of uterus	UBERON:0009853	98.48	gold quality

Single-cell (SCXA)

Detected in 26 experiment(s), a significant marker in 22.

Experiment	Marker?	Max mean expression
E-MTAB-8142	yes	8163.22
E-MTAB-10855	yes	4637.19
E-MTAB-6701	yes	3011.04
E-MTAB-10885	yes	1840.65
E-GEOD-124263	yes	1011.57
E-CURD-98	yes	755.93
E-MTAB-10283	yes	517.77
E-HCAD-32	yes	433.62
E-HCAD-1	yes	98.60
E-MTAB-8410	yes	61.30
E-CURD-114	yes	53.92
E-MTAB-10287	yes	51.33
E-GEOD-125970	yes	48.80
E-HCAD-10	yes	43.85
E-HCAD-31	yes	30.63

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

6 targets.

Target	Regulation
ATF4	Activation
BCL2L1	Activation
CDKN1A	Activation
EP300	Unknown
MSL1	Repression
TP53	Unknown

Upstream regulators (CollecTRI, top): ATF4, NR1D1, NR2E3, ONECUT1, PAX8

miRNA regulators (miRDB)

10 targeting NUPR1, 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-4325	99.49	72.20	1342
HSA-MIR-3922-3P	99.25	64.96	1136
HSA-MIR-3176	99.25	64.35	954
HSA-MIR-5589-5P	98.34	64.82	1148
HSA-MIR-637	97.91	64.05	1517
HSA-MIR-3137	97.26	66.78	761
HSA-MIR-6748-3P	97.20	65.66	836
HSA-MIR-4749-3P	96.40	66.24	798
HSA-MIR-4264	96.35	64.76	1480
HSA-MIR-187-3P	81.56	59.38	111

Literature-anchored findings (GeneRIF, showing 40)

• The HMG-I/Y-related protein p8 binds to p300 and Pax2 trans-activation domain-interacting protein to regulate the trans-activation activity of the Pax2A and Pax2B transcription factors on the glucagon gene promoter. (PMID:11940591)
• clinical and cell line specific expression identified in experimental central nervous system metastases (PMID:12174869)
• The fate of Com-1 can be dually regulated by oestrogen and ubiquitin pathway (PMID:15781258)
• CCM1 gene mutation of 1292delAT may contribute to cerebral cavernous malformations. (PMID:15854263)
• p8 expression plays an important role in the progression of medullary thyroid carcinoma, but does not have an anti-apoptotic function. (PMID:16101158)
• The results suggest that p8 growth stage-dependent localization is regulated by acetylation, that p8 is not free within the cell but forming part of a complex and that it may exert a role in both subcellular localizations. (PMID:16294328)
• The knock-down of p8 expression results in a strong inhibition of Jab1 activity. (PMID:16300740)
• Antiapoptotic response of cells requires expression of both p8 and ProTalpha. (PMID:16478804)
• the anti-apoptotic effect previously attributed separately to p8 and prothymosin alpha is in fact borne by the p8/ProTalpha complex, the two proteins being individually inactive (PMID:16628001)
• Com-1/p8 is a potential tumour suppressor in human prostate cancer. (PMID:17016631)
• SYT-SSX1 fusion protein directly down-regulated the expression of COM1, a regulator of cell proliferation. (PMID:17101797)
• These results identify an unexpectedly broad involvement for p8 in key cellular events linked to cardiomyocyte hypertrophy and cardiac fibroblast matrix metalloproteases production, both of which occur in heart failure. (PMID:17116693)
• Upregulation of NUPR1 is associated with aggressive breast cancer. (PMID:18690848)
• nuclear protein 1 (NUPR1) has a role in cancer progression [review] (PMID:19153668)
• MSL1 plays an important role in mediating irradiation-induced DNA repair through formation of HAT complexes and interaction with 53BP1. P8 acts as a negative regulator of this process by interacting with MSL1 and preventing its role on HAT activity. (PMID:19650074)
• Role played by a pivotal actor of the cell stress response, the p8 protein, during carcinogenesis. (PMID:19942374)
• Nuclear protein 1 induced by ATF4 in response to various stressors acts as a positive regulator on the transcriptional activation of ATF4 (PMID:19946894)
• A role for the transcriptional regulator p8 in autophagy, is demonstrated. (PMID:20181828)
• COM-1, although overexpressed at the messenger level, appears to be distributed in a cytoplasmic fashion at the protein level in tumours. (PMID:20335521)
• Studies indicate that in pancreatic cancer, high levels of p8 protein expression correlate with low apoptosis. (PMID:20890585)
• p8 expression controls pancreatic cancer cell migration, invasion and adhesion, three processes required for metastasis, at least in part, through CDC42, a major regulator of cytoskeleton organization. (PMID:21344397)
• COM-1 is an anti-apoptotic gene and a cell growth promoter. Furthermore, the PPARgamma agonist could increase the inhibitory effect seen in COM-1 knock-down cell growth and to promote apoptosis (PMID:22493353)
• a NUPR1/RELB/IER3 stress-related pathway that is required for oncogenic Kras(G12D)-dependent transformation of the pancreas. (PMID:22565310)
• These data indicate a protective role for homotypic cell cannibalism in pancreatic adenocarcinoma and identifies Nupr1 as a molecular regulator of this process. (PMID:22821859)
• findings elucidate a NUPR1-PI-3-K/Akt-phospho-p21 axis that functions in p53-negative, inflammatory breast cancer cells to enhance chemoresistance (PMID:22858377)
• Our data reveal that Nupr1 is involved in a defense mechanism that promotes pancreatic cancer cell survival when exposed to metabolic stress (PMID:22899799)
• The simultaneous gain of NUPR1 and ERBB2 can be a significant predictor of poor prognosis in early-stage breast cancers. (PMID:22938721)
• NUPR1 gene represents a promising target for gene silencing therapy in nonsmall cell lung cancer. (PMID:22961798)
• NUPR1 negatively regulates autophagy-mediated cell death via AURKA, in line with the idea of a tumor suppressor role of autophagy in cancer. (PMID:23047430)
• COM1 is a potential tumour suppressor in human bladder cancer. (PMID:23443904)
• The Nupr1 protein bound to chemically-damaged-DNA with a slightly larger affinity (0.4 microM), but in an enthalpically-driven process. Nupr1 showed different interacting regions in the formed complexes with Nupr1 or DNA (PMID:24205110)
• Stress-inducible nuclear protein 1 regulates matrix metalloproteinase 13 expression in human articular chondrocytes. (PMID:24497499)
• NUPR1 has been conserved throughout evolution, and over time it has undergone duplications and transpositions to form other transcriptional regulators. (PMID:25056123)
• P8 and MEG3 mRNA levels were significantly lower in nonfunctioning and corticotroph adenomas compared with normal pituitary. (PMID:25126861)
• Functional characterization of NUPR1L as a new p53-induced gene, which negatively regulates the protumoral factor NUPR1. (PMID:25899918)
• Increase of NUPR1 protein expression is associated with endometrial cancer invasion. (PMID:25924802)
• Knockdown of Nupr1 inhibited the proliferation and migration of HepG2 hepatocellular carcinoma cells (PMID:26062422)
• Mitochondrial respiratory defects and subsequent retrograde signaling, particularly the NUPR1-granulin pathway, play pivotal roles in liver cancer progression (PMID:26173068)
• Hepatitis B virus X (HBx) protein can modulate NUPR1 expression through the Smad4 pathway and NUPR1 has a role in hepatocellular carcinoma progression. (PMID:26392315)
• Nupr1 acts as a gene modifier of the effect of Kras(G12D)-induced senescence by regulating Dnmt1 expression and consequently genome-wide levels of DNA methylation. (PMID:26617245)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	nupr1b	ENSDARG00000094557
mus_musculus	Nupr1	ENSMUSG00000030717
rattus_norvegicus	Nupr1	ENSRNOG00000019206
drosophila_melanogaster	CG6770	FBGN0032400

Paralogs (1): NUPR2 (ENSG00000185290)

Protein

Protein identifiers

Nuclear protein 1 — O60356 (reviewed: O60356)

Alternative names: Candidate of metastasis 1, Protein p8

All UniProt accessions (2): O60356, H3BS92

UniProt curated annotations — full annotation on UniProt →

Function. Transcription regulator 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. Thereby participates in the regulation of many processes namely cell-cycle, apoptosis, autophagy and DNA repair responses. Controls cell cycle progression and protects cells from genotoxic stress induced by doxorubicin through the complex formation with TP53 and EP300 that binds CDKN1A promoter leading to transcriptional induction of CDKN1A. Protects pancreatic cancer cells from stress-induced cell death by binding the RELB promoter and activating its transcription, leading to IER3 transactivation. Negatively regulates apoptosis through interaction with PTMA. Inhibits autophagy-induced apoptosis in cardiac cells through FOXO3 interaction, inducing cytoplasmic translocation of FOXO3 thereby preventing the FOXO3 association with the pro-autophagic BNIP3 promoter. Inhibits cell growth and facilitates programmed cell death by apoptosis after adriamycin-induced DNA damage through transactivation of TP53. Regulates methamphetamine-induced apoptosis and autophagy through DDIT3-mediated endoplasmic reticulum stress pathway. Participates in DNA repair following gamma-irradiation by facilitating DNA access of the transcription machinery through interaction with MSL1 leading to inhibition of histone H4’ Lys-16’ acetylation (H4K16ac). Coactivator of PAX2 transcription factor activity, both by recruiting EP300 to increase PAX2 transcription factor activity and by binding PAXIP1 to suppress PAXIP1-induced inhibition on PAX2. Positively regulates cell cycle progression through interaction with COPS5 inducing cytoplasmic translocation of CDKN1B leading to the CDKN1B degradation. Coordinates, through its interaction with EP300, the association of MYOD1, EP300 and DDX5 to the MYOG promoter, leading to inhibition of cell-cycle progression and myogenic differentiation promotion. Negatively regulates beta cell proliferation via inhibition of cell-cycle regulatory genes expression through the suppression of their promoter activities. Also required for LHB expression and ovarian maturation. Exacerbates CNS inflammation and demyelination upon cuprizone treatment.

Subunit / interactions. Monomer. Directly interacts with MSL1 and binds MORF4L1, two components of histone acetyltransferase complex; the interaction with MORF4L1 may be mediated by MSL1. Interacts with EP300; this interaction enhances the effect of EP300 on PAX2 transcription factor activity. Interacts with PAXIP1; this interaction prevents PAXIP1 inhibition of PAX2 transcription factor activity. Interacts with COPS5; this interaction allows COPS5-dependent CDKN1B nuclear to cytoplasm translocation. Interacts with RNF2. Interacts with FOXO3; this interaction represses FOXO3 transactivation. Interacts with PTMA; negatively regulates apoptotic process. Interacts with MYOD1, EP300 and DDX5; this interaction coordinates the association of anti-proliferative and pro-myogenic proteins at the myogenin promoter. Interacts with TP53; interaction is stress-dependent. Forms a complex with EP300 and TP53; this complex binds CDKN1A promoter leading to transcriptional induction of CDKN1A.

Subcellular location. Nucleus. Cytoplasm. Perinuclear region.

Tissue specificity. Widely expressed, with high levels in liver, pancreas, prostate, ovary, colon, thyroid, spinal cord, trachea and adrenal gland, moderate levels in heart, placenta, lung, skeletal muscle, kidney, testis, small intestine, stomach and lymph node, and low levels in brain, spleen, thymus and bone marrow. Not detected in peripheral blood leukocytes.

Post-translational modifications. Phosphorylated in vitro by PKA and CK. Phosphorylation promotes DNA-binding activity. Acetylated by EP300 in vitro.

Induction. Up-regulated by stress agents, such as nutrient deprivation (at protein level). Up-regulation by gamma-irradiation is eventually followed by down-regulation. Expression increases with the tumor aggressiveness. up-regulated by DNA-damaging agent such as doxorubicin.

Miscellaneous. Mediates resistance to anticancer drugs, namely taxol, doxorubicin, gemcitabine.

Similarity. Belongs to the NUPR family.

Isoforms (2)

UniProt ID	Names	Canonical?
O60356-1	1	yes
O60356-2	2

RefSeq proteins (2): NP_001035948, NP_036517* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR018792	NUPR1-like	Family

Pfam: PF10195

UniProt features (8 total): mutagenesis site 2, chain 1, region of interest 1, short sequence motif 1, compositionally biased region 1, splice variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O60356-F1	71.86	0.12

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Mutagenesis-validated functional residues (2):

Position	Phenotype
33	impairs interaction with rnf2.
68	impairs interaction with rnf2.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 434 (showing top): GOBP_NEGATIVE_REGULATION_OF_EPITHELIAL_CELL_PROLIFERATION, GOBP_INTRINSIC_APOPTOTIC_SIGNALING_PATHWAY_IN_RESPONSE_TO_DNA_DAMAGE_BY_P53_CLASS_MEDIATOR, GOBP_REGULATION_OF_AUTOPHAGY, KOBAYASHI_EGFR_SIGNALING_24HR_UP, GOBP_NUCLEOSIDE_DIPHOSPHATE_METABOLIC_PROCESS, GOBP_REGULATION_OF_EPITHELIAL_CELL_APOPTOTIC_PROCESS, GOBP_MUSCLE_TISSUE_DEVELOPMENT, CHIARADONNA_NEOPLASTIC_TRANSFORMATION_KRAS_DN, TSENG_IRS1_TARGETS_UP, GOBP_VACUOLE_ORGANIZATION, GOBP_INFLAMMATORY_RESPONSE, BHATI_G2M_ARREST_BY_2METHOXYESTRADIOL_DN, GOBP_RESPONSE_TO_ENDOPLASMIC_RETICULUM_STRESS, KAAB_HEART_ATRIUM_VS_VENTRICLE_UP, GOBP_POSITIVE_REGULATION_OF_PROTEIN_CATABOLIC_PROCESS

GO Biological Process (32): acute inflammatory response (GO:0002526), negative regulation of cell population proliferation (GO:0008285), male gonad development (GO:0008584), response to toxic substance (GO:0009636), regulation of autophagy (GO:0010506), negative regulation of autophagy (GO:0010507), negative regulation of cardiac muscle cell apoptotic process (GO:0010667), skeletal muscle cell differentiation (GO:0035914), intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator (GO:0042771), negative regulation of apoptotic process (GO:0043066), obsolete negative regulation of DNA-binding transcription factor activity (GO:0043433), positive regulation of neuron apoptotic process (GO:0043525), fibroblast apoptotic process (GO:0044346), negative regulation of cell cycle (GO:0045786), positive regulation of cell cycle (GO:0045787), negative regulation of glycolytic process (GO:0045820), fibroblast proliferation (GO:0048144), negative regulation of fibroblast proliferation (GO:0048147), negative regulation of epithelial cell proliferation (GO:0050680), negative regulation of programmed necrotic cell death (GO:0062099), protein-containing complex assembly (GO:0065003), positive regulation of neuroinflammatory response (GO:0150078), positive regulation of proteasomal protein catabolic process (GO:1901800), negative regulation of autophagosome assembly (GO:1902902), positive regulation of oxidative phosphorylation (GO:1903862), negative regulation of epithelial cell apoptotic process (GO:1904036), negative regulation of type B pancreatic cell proliferation (GO:1904691), regulation of response to endoplasmic reticulum stress (GO:1905897), regulation of female gonad development (GO:2000194), positive regulation of fibroblast apoptotic process (GO:2000271), positive regulation of intrinsic apoptotic signaling pathway (GO:2001244), positive regulation of DNA-templated transcription (GO:0045893)

GO Molecular Function (5): DNA binding (GO:0003677), chromatin binding (GO:0003682), transcription coactivator activity (GO:0003713), acetyltransferase activator activity (GO:0010698), protein binding (GO:0005515)

GO Cellular Component (6): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), protein-DNA complex (GO:0032993), intercellular bridge (GO:0045171), perinuclear region of cytoplasm (GO:0048471)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
cell population proliferation	2
negative regulation of cellular process	2
autophagy	2
apoptotic process	2
negative regulation of programmed cell death	2
cell cycle	2
regulation of cell cycle	2
negative regulation of cell population proliferation	2
binding	2
inflammatory response	1
regulation of cell population proliferation	1
gonad development	1
development of primary male sexual characteristics	1
response to chemical	1
regulation of catabolic process	1
negative regulation of catabolic process	1
regulation of autophagy	1
cardiac muscle cell apoptotic process	1
negative regulation of striated muscle cell apoptotic process	1
regulation of cardiac muscle cell apoptotic process	1
skeletal muscle tissue development	1
cell differentiation	1
intrinsic apoptotic signaling pathway in response to DNA damage	1
intrinsic apoptotic signaling pathway by p53 class mediator	1
regulation of apoptotic process	1
positive regulation of apoptotic process	1
regulation of neuron apoptotic process	1
neuron apoptotic process	1
positive regulation of cellular process	1
glycolytic process	1
regulation of glycolytic process	1
negative regulation of purine nucleotide catabolic process	1
negative regulation of carbohydrate metabolic process	1
negative regulation of ATP metabolic process	1
fibroblast proliferation	1
regulation of fibroblast proliferation	1
epithelial cell proliferation	1
regulation of epithelial cell proliferation	1
regulation of programmed necrotic cell death	1

Protein interactions and networks

STRING

2176 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NUPR1	PRM1	P04553	869
NUPR1	TNP1	P09430	838
NUPR1	NSA2	O95478	828
NUPR1	KDM3A	Q9Y4C1	809
NUPR1	TP53INP1	Q96A56	766
NUPR1	PTMA	P06454	713
NUPR1	EP300	Q09472	700
NUPR1	TP53	P04637	697
NUPR1	KPNA4	O00629	642
NUPR1	IL1B	P01584	548
NUPR1	RABEP2	Q9H5N1	526
NUPR1	PPARA	Q07869	514
NUPR1	RNF2	Q99496	513
NUPR1	TRIB3	Q96RU7	502
NUPR1	DDX5	P17844	472

IntAct

37 interactions, top by confidence:

A	B	Type	Score
PTMA	NUPR1	psi-mi:“MI:0915”(physical association)	0.670
PTMA	NUPR1	psi-mi:“MI:0407”(direct interaction)	0.670
NUPR1	CAPN2	psi-mi:“MI:0915”(physical association)	0.560
PER1	NUPR1	psi-mi:“MI:0915”(physical association)	0.560
NUPR1	CFAP100	psi-mi:“MI:0915”(physical association)	0.560
NUPR1	SEMG1	psi-mi:“MI:0914”(association)	0.530
NUPR1	PSMD4	psi-mi:“MI:0915”(physical association)	0.370
NUPR1	FUS	psi-mi:“MI:0915”(physical association)	0.370
NUPR1	MSL1	psi-mi:“MI:0915”(physical association)	0.370
NUPR1	NONO	psi-mi:“MI:0915”(physical association)	0.370
NUPR1	SEC11A	psi-mi:“MI:0915”(physical association)	0.370
NUPR1	RAN	psi-mi:“MI:0915”(physical association)	0.370
NUPR1	MAPRE1	psi-mi:“MI:0915”(physical association)	0.370
NUPR1	STX18	psi-mi:“MI:0915”(physical association)	0.370
NUPR1	KNSTRN	psi-mi:“MI:0915”(physical association)	0.370
NUPR1	RANBP1	psi-mi:“MI:0915”(physical association)	0.370
NUPR1	SYNCRIP	psi-mi:“MI:0915”(physical association)	0.370
NUPR1	MPHOSPH6	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (697): MSL1 (Co-localization), MSL1 (Reconstituted Complex), MSL1 (Two-hybrid), MSL1 (Affinity Capture-Western), NUPR1 (Affinity Capture-Western), MSL1 (Reconstituted Complex), MORF4L1 (Affinity Capture-Western), RAN (Two-hybrid), PTMA (Two-hybrid), MAPRE1 (Two-hybrid), MPHOSPH6 (Two-hybrid), NACA (Two-hybrid), PSMD4 (Two-hybrid), SEC11A (Two-hybrid), RANBP1 (Two-hybrid)

ESM2 similar proteins: A0A0U1RQF7, A6YQT5, O54842, O60356, O82286, P03131, P03238, P04602, P04605, P05909, P06937, P09267, P0C765, P17759, P18098, P19847, P23057, P24103, P24820, P27224, P27261, P27445, P35959, P50445, P54092, P54093, P69484, P69485, Q00039, Q06658, Q0VCV7, Q1X709, Q1X711, Q32LJ5, Q4JQX3, Q5R5R7, Q67684, Q8B912, Q8BG31, Q8C3M9

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

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
ATF4	“up-regulates quantity by expression”	NUPR1	“transcriptional regulation”
NUPR1	“up-regulates quantity by expression”	ATF4	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

487 predictions. Top by Δscore:

Variant	Effect	Δscore
16:28538002:TTA:T	donor_loss	1.0000
16:28538004:A:AC	donor_gain	1.0000
16:28538004:A:C	donor_loss	1.0000
16:28538004:ACCT:A	donor_gain	1.0000
16:28538005:C:CC	donor_gain	1.0000
16:28538005:C:CG	donor_loss	1.0000
16:28538005:CCT:C	donor_gain	1.0000
16:28538005:CCTC:C	donor_gain	1.0000
16:28538042:T:TA	donor_gain	1.0000
16:28537523:T:A	donor_gain	0.9900
16:28538007:T:TA	donor_gain	0.9900
16:28538152:CCTC:C	acceptor_gain	0.9900
16:28538153:CTC:C	acceptor_gain	0.9900
16:28538153:CTCC:C	acceptor_gain	0.9900
16:28538154:TCCT:T	acceptor_gain	0.9900
16:28538154:TCCTG:T	acceptor_loss	0.9900
16:28538156:C:CC	acceptor_gain	0.9900
16:28538156:CT:C	acceptor_loss	0.9900
16:28538163:C:CT	acceptor_gain	0.9900
16:28538163:C:T	acceptor_gain	0.9900
16:28538164:A:T	acceptor_gain	0.9900
16:28538154:TC:T	acceptor_gain	0.9600
16:28538155:CC:C	acceptor_gain	0.9600
16:28538789:GCCTT:G	donor_loss	0.9600
16:28538790:CCTTA:C	donor_loss	0.9600
16:28538791:CTTA:C	donor_loss	0.9600
16:28538792:TTA:T	donor_loss	0.9600
16:28538793:TACCG:T	donor_loss	0.9600
16:28538794:ACCG:A	donor_loss	0.9600
16:28538795:C:CG	donor_loss	0.9600

AlphaMissense

519 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:28538076:C:A	R64S	0.953
16:28538076:C:G	R64S	0.953
16:28538127:C:A	K47N	0.950
16:28538127:C:G	K47N	0.950
16:28538131:G:A	T46I	0.935
16:28538075:T:C	K65E	0.924
16:28538073:T:A	K65N	0.921
16:28538073:T:G	K65N	0.921
16:28538094:G:C	S58R	0.915
16:28538094:G:T	S58R	0.915
16:28538096:T:G	S58R	0.915
16:28538139:T:A	K43N	0.913
16:28538139:T:G	K43N	0.913
16:28538135:G:T	R45S	0.897
16:28538120:C:G	A50P	0.896
16:28538140:T:A	K43I	0.892
16:28538077:C:G	R64T	0.886
16:28538107:G:A	T54I	0.882
16:28538084:G:C	H62D	0.879
16:28538082:G:C	H62Q	0.877
16:28538082:G:T	H62Q	0.877
16:28538074:T:A	K65I	0.871
16:28538061:C:A	K69N	0.866
16:28538061:C:G	K69N	0.866
16:28538103:G:C	N55K	0.865
16:28538103:G:T	N55K	0.865
16:28538077:C:A	R64M	0.853
16:28538063:T:C	K69E	0.841
16:28538128:T:A	K47M	0.839
16:28538129:T:C	K47E	0.838

dbSNP variants (sampled 300 via entrez): RS1000079723 (16:28536522 CA>C,CAA), RS1000305246 (16:28536296 T>C), RS1000675632 (16:28534903 C>T), RS1001306893 (16:28535727 C>G), RS1002003813 (16:28540933 G>A,T), RS1002069950 (16:28537027 C>A), RS1002178380 (16:28534522 C>T), RS1002314057 (16:28534262 T>G), RS1003196334 (16:28533002 T>C), RS1003340043 (16:28538544 C>A,T), RS1003881896 (16:28538279 C>G,T), RS1004253813 (16:28538978 G>A,T), RS1004530976 (16:28535307 CTCTT>C), RS1004788327 (16:28539238 A>G,T), RS1004965827 (16:28535690 T>C)

Disease associations

OMIM: gene MIM:614812 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

24 associations (top):

Study	Trait	p-value
GCST000531_2	Inflammatory bowel disease (early onset)	2.000000e-09
GCST001725_52	Inflammatory bowel disease	1.000000e-21
GCST002598_62	Educational attainment	1.000000e-06
GCST004131_83	Inflammatory bowel disease	2.000000e-12
GCST004132_69	Crohn’s disease	3.000000e-10
GCST004904_98	Body mass index	4.000000e-10
GCST005316_518	Intelligence (MTAG)	2.000000e-19
GCST007044_23	Extremely high intelligence	2.000000e-08
GCST007293_116	Body fat distribution (arm fat ratio)	2.000000e-08
GCST007293_16	Body fat distribution (arm fat ratio)	4.000000e-09
GCST007293_43	Body fat distribution (arm fat ratio)	2.000000e-12
GCST007294_71	Body fat distribution (trunk fat ratio)	2.000000e-12
GCST007294_97	Body fat distribution (trunk fat ratio)	1.000000e-11
GCST007295_20	Body fat distribution (leg fat ratio)	3.000000e-06
GCST007295_44	Body fat distribution (leg fat ratio)	1.000000e-21
GCST007295_79	Body fat distribution (leg fat ratio)	2.000000e-24
GCST008363_125	Offspring birth weight	5.000000e-08
GCST008811_32	Alcohol consumption (drinks per week)	2.000000e-08
GCST009524_185	Household income (MTAG)	1.000000e-08
GCST009733_147	Urinary metabolite levels in chronic kidney disease	2.000000e-19
GCST009733_228	Urinary metabolite levels in chronic kidney disease	1.000000e-12
GCST010002_111	Refractive error	3.000000e-09
GCST010133_15	Lamb consumption	3.000000e-08
GCST010703_152	Brain morphology (MOSTest)	3.000000e-09

EFO canonical traits (10, from GWAS)

EFO ID	Trait name
EFO:0004784	self reported educational attainment
EFO:0004340	body mass index
EFO:0004337	intelligence
EFO:0004341	body fat distribution
EFO:0004344	birth weight
EFO:0005939	parental genotype effect measurement
EFO:0009695	household income
EFO:0005116	urinary metabolite measurement
EFO:0008111	diet measurement
EFO:0004346	neuroimaging measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

138 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression, increases expression	5
Dronabinol	affects reaction, decreases phosphorylation, increases reaction, increases expression, decreases expression (+1 more)	5
Cyclosporine	increases expression	5
Cadmium Chloride	decreases reaction, increases abundance, increases expression, decreases expression, affects reaction (+1 more)	5
bisphenol A	increases expression, affects expression, decreases methylation	4
sodium arsenite	decreases expression, increases abundance, increases expression	4
Cadmium	increases expression, decreases expression, affects reaction, increases metabolic processing, decreases reaction (+1 more)	4
Valproic Acid	affects cotreatment, increases expression, decreases expression, decreases methylation	4
Amiodarone	increases expression	3
Amitriptyline	increases expression	3
Cannabidiol	decreases expression, increases expression, affects reaction	3
Estradiol	affects expression, affects cotreatment, decreases expression	3
Fluoxetine	increases expression	3
Ketoconazole	increases expression	3
Tetrachlorodibenzodioxin	affects cotreatment, increases expression	3
methylmercuric chloride	decreases expression, increases expression	2
arsenite	increases abundance, increases expression, affects binding, increases reaction	2
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment, decreases expression	2
Arsenic	decreases expression, increases abundance, increases expression	2
Chlorpromazine	increases expression	2
Clomipramine	increases expression	2
Clozapine	increases expression	2
Diethylhexyl Phthalate	increases expression	2
Flecainide	increases expression	2
Imipramine	increases expression	2
Phenobarbital	affects expression, increases expression	2
Tamoxifen	increases expression	2
Thioridazine	increases expression	2
Tobacco Smoke Pollution	decreases expression, increases expression	2
Zimeldine	increases expression	2

Cellosaurus cell lines

5 cell lines: 3 embryonic stem cell, 2 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_A4Y7	SEES3-1V human NUPR1, clone1	Embryonic stem cell	Male
CVCL_A4Y8	SEES3-1V human NUPR1, clone2	Embryonic stem cell	Male
CVCL_A4Y9	SEES3-1V human NUPR1, clone3	Embryonic stem cell	Male
CVCL_B1ZE	Abcam HeLa NUPR1 KO	Cancer cell line	Female
CVCL_D6CW	HyCyte U-87MG KO-hNUPR1	Cancer cell line	Male

Clinical trials (associated diseases)

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