URGCP

Summary

URGCP (upregulator of cell proliferation, HGNC:30890) is a protein-coding gene on chromosome 7p13, encoding Up-regulator of cell proliferation (Q8TCY9). May be involved in cell cycle progression through the regulation of cyclin D1 expression.

URG4 is upregulated in the presence of hepatitis B virus (HBV)-encoded X antigen (HBxAg) and may contribute to the development of hepatocellular carcinoma by promoting hepatocellular growth and survival (Tufan et al., 2002 [PubMed 12082552]).

Source: NCBI Gene 55665 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 98 total
• MANE Select transcript: NM_001077663

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30890
Approved symbol	URGCP
Name	upregulator of cell proliferation
Location	7p13
Locus type	gene with protein product
Status	Approved
Aliases	URG4, KIAA1507, FLJ20654, DKFZp666G166, DKFZp686O0457
Ensembl gene	ENSG00000106608
Ensembl biotype	protein_coding
OMIM	610337
Entrez	55665

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 11 protein_coding, 3 retained_intron, 2 protein_coding_CDS_not_defined

ENST00000336086, ENST00000402306, ENST00000426198, ENST00000439702, ENST00000443736, ENST00000446958, ENST00000453200, ENST00000455877, ENST00000467410, ENST00000474376, ENST00000477768, ENST00000478747, ENST00000497914, ENST00000865240, ENST00000926966, ENST00000969119

RefSeq mRNA: 5 — MANE Select: NM_001077663 NM_001077663, NM_001077664, NM_001290075, NM_001290076, NM_017920

CCDS: CCDS43572, CCDS47577, CCDS47578

Canonical transcript exons

ENST00000453200 — 6 exons

Exon	Start	End
ENSE00001634422	43906562	43906596
ENSE00001785941	43875913	43879260
ENSE00003529148	43887415	43887485
ENSE00003588079	43881659	43881697
ENSE00003611429	43887790	43887816
ENSE00003664802	43881907	43881957

Expression profiles

Bgee: expression breadth ubiquitous, 274 present calls, max score 92.68.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 3.7388 / max 68.5220, expressed in 1461 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
83818	6.8861	1724
83820	1.5810	1000
83823	0.8590	518
83822	0.8320	458
83821	0.3155	151
83819	0.1512	57

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right adrenal gland cortex	UBERON:0035827	92.68	gold quality
right adrenal gland	UBERON:0001233	92.58	gold quality
left adrenal gland	UBERON:0001234	92.33	gold quality
left adrenal gland cortex	UBERON:0035825	92.03	gold quality
adrenal cortex	UBERON:0001235	91.98	gold quality
adrenal gland	UBERON:0002369	91.87	gold quality
apex of heart	UBERON:0002098	91.78	gold quality
cerebellar hemisphere	UBERON:0002245	91.70	gold quality
cerebellar cortex	UBERON:0002129	91.69	gold quality
right hemisphere of cerebellum	UBERON:0014890	91.63	gold quality
gluteal muscle	UBERON:0002000	91.32	gold quality
triceps brachii	UBERON:0001509	91.26	gold quality
cerebellum	UBERON:0002037	91.19	gold quality
gastrocnemius	UBERON:0001388	90.77	gold quality
muscle of leg	UBERON:0001383	90.60	gold quality
pituitary gland	UBERON:0000007	90.54	gold quality
hindlimb stylopod muscle	UBERON:0004252	90.52	gold quality
cerebellar vermis	UBERON:0004720	90.47	gold quality
mucosa of transverse colon	UBERON:0004991	90.40	gold quality
right frontal lobe	UBERON:0002810	90.27	gold quality
adenohypophysis	UBERON:0002196	90.16	gold quality
islet of Langerhans	UBERON:0000006	89.92	gold quality
muscle organ	UBERON:0001630	89.69	gold quality
colonic epithelium	UBERON:0000397	89.62	gold quality
metanephros cortex	UBERON:0010533	89.57	gold quality
transverse colon	UBERON:0001157	89.38	gold quality
prefrontal cortex	UBERON:0000451	89.31	gold quality
Brodmann (1909) area 9	UBERON:0013540	89.30	gold quality
lower esophagus muscularis layer	UBERON:0035833	89.29	gold quality
lower esophagus	UBERON:0013473	89.27	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.29

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

43 targeting URGCP, 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-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-4487	99.96	64.58	1252
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-6753-3P	99.93	66.57	637
HSA-MIR-7107-3P	99.93	66.73	627
HSA-MIR-6783-3P	99.89	67.92	2059
HSA-MIR-1343-3P	99.89	66.78	1815
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-3151-5P	99.86	63.83	1069
HSA-MIR-202-3P	99.84	71.41	1290
HSA-MIR-6758-3P	99.57	67.55	1078
HSA-MIR-4643	99.49	67.63	1791
HSA-MIR-516A-3P	99.46	67.96	1378
HSA-MIR-516B-3P	99.46	67.96	1378
HSA-MIR-7162-5P	99.46	68.08	1368
HSA-MIR-6852-5P	99.17	66.69	2073
HSA-MIR-4758-3P	99.12	63.96	869
HSA-MIR-939-3P	98.97	65.07	2347
HSA-MIR-10A-5P	98.89	69.85	712

Literature-anchored findings (GeneRIF, showing 23)

• URG4 may be a natural effector of HBxAg that contributes importantly to multistep hepatocarcinogenesis. (PMID:12082552)
• URG4 plays an important role in the development of human gastric cancer by regulating the expression of cyclin D1. (PMID:17217616)
• URG4 may play important roles in the development of osteosarcoma, and might be a useful molecular marker for predicting the prognosis of osteosarcoma. (PMID:18972316)
• Expression of URG4 in hepatocellular carcinoma is closely related with the expression of HBx. (PMID:20491173)
• The data suggest that URG4 may play an important role in the development of hepatocellular carcinoma by partially regulating the expression of cyclin D1. (PMID:20714998)
• higher expression of URG4 in our 2 patients suggests that URG4 might be involved in leukemogenesis (PMID:22677619)
• The effects of URGCP/URG4-overexpression or -knockdown on expression of cell cycle regulators and transcriptional activity of FOXO3a, were examined. (PMID:22815774)
• Rapamycin diminishes URGCP gene expression in DU145 and PC3 cells, but increases expression in LNCaP cells. (PMID:23007575)
• microRNA profiles were analyzedin HepG2 cells in presence or absence of URG4/URGCP gene using RNA interference. (PMID:23053999)
• Data suggest that neuroblastoma (NB) cell differentiation might associate with peroxisome proliferator-activated receptor alpha (PPARalpha) and URG4/URGCP gene expression profile after retinoic acid (RA) treatment. (PMID:23821302)
• URG4 overexpression is correlated with cervical cancer progression and poor prognosis in patients with early-stage cervical cancer. (PMID:25427922)
• We presented first mechanisms of TMZ and URG4/URGCP relationship in neuroblastoma cells in this study. As a result, TMZ may be a novel candidate agent for treatment of neuroblastoma as a single or agent or together with other therapeutic agents (PMID:25835972)
• This study suggests that URG4/URGCP plays an important pro-angiogenic role in HCC via a mechanism linked to activation of the NF-kappaB pathway (PMID:25947641)
• FA caused a decrease in the expression of novel gene URG4/URGCP. (PMID:26334619)
• URG4 overexpression increased the resistance to cisplatin-induced apoptosis in bladder cancer. (PMID:26429874)
• Findings indicate that URGCP plays an important role in promoting NSCLC cell invasion and metastasis by enhancing NF-kappaB-activated MMP-9 expression (PMID:26429875)
• site-directed mutagenesis of potential SP1 binding sites diminished both DNA-protein complexes and SP1-mediated upregulation of URG-4 promoter activity. These findings are valuable for understanding transcriptional regulation of URG4/URGCP that has a pivotal role in cancer progression. (PMID:27766531)
• miR-519 inhibited URG4 expression by directly binding to the 3’UTR of URG4. miR-519 inhibited Cyclin D1 expression and the phosphorylation level of Rb, and increased p21 and p27 expression, confirming miR-519 blocked G1/S transition. (PMID:28315691)
• All these results suggested that URGCP accelerates glioma growth through the NF-kappaB/c-myc/miR-16/Cyclin D1/E1 pathway, and both URGCP and miR-16 function as a novel cell cycle regulators in glioma and could be considered as potential targets for glioma therapy. (PMID:29044221)
• Relationship between URG4/URGCP expression and clinicopathologic characteristics were evaluated and significant results were in various cancer types (review). (PMID:29775749)
• URG4 overexpression in breast ductal carcinomas is significantly associated with good prognostic parameters. (PMID:30680688)
• TNF-alpha Induces URG-4/URGCP Gene Expression in Hepatoma Cells through Starvation Dependent Manner. (PMID:33034821)
• [Epidermal Growth Factor Mediates Up-regulation of URGCP Oncogene in Human Hepatoma Cancer Cells]. (PMID:34432785)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	urgcp	ENSDARG00000036767
danio_rerio	si:dkey-204a24.11	ENSDARG00000058685
danio_rerio	si:dkey-85k7.12	ENSDARG00000078731
danio_rerio	gvin1l2	ENSDARG00000102364
mus_musculus	Urgcp	ENSMUSG00000049680
rattus_norvegicus	Urgcp	ENSRNOG00000012184

Protein

Protein identifiers

Up-regulator of cell proliferation — Q8TCY9 (reviewed: Q8TCY9)

Alternative names: HBV X protein up-regulated gene 4 protein, HBxAg up-regulated gene 4 protein

All UniProt accessions (5): Q8TCY9, C9J0W2, C9JKA8, F8WCC3, F8WDN0

UniProt curated annotations — full annotation on UniProt →

Function. May be involved in cell cycle progression through the regulation of cyclin D1 expression. May participate in the development of hepatocellular carcinoma (HCC) by promoting hepatocellular growth and survival. May play an important role in development of gastric cancer.

Subcellular location. Cytoplasm. Nucleus.

Tissue specificity. Strongly expressed in hepatitis B virus-infected liver and in HCC cells. Also highly expressed in well-differentiated gastric cancer tissues and various gastric cancer cell lines.

Induction. By HBxAg. Up-regulated in gastric cancer tissues and also in gastric cancer cell lines (at protein level).

Similarity. Belongs to the TRAFAC class dynamin-like GTPase superfamily. Very large inducible GTPase (VLIG) family.

Isoforms (4)

UniProt ID	Names	Canonical?
Q8TCY9-1	1	yes
Q8TCY9-2	2
Q8TCY9-3	3
Q8TCY9-4	4

RefSeq proteins (5): NP_001071131, NP_001071132, NP_001277004, NP_001277005, NP_060390 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006073	GTP-bd	Domain
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR030383	G_VLIG_dom	Domain
IPR057365	URGCP	Domain

Pfam: PF25496, PF25683

UniProt features (19 total): sequence conflict 10, splice variant 3, sequence variant 3, chain 1, domain 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8TCY9-F1	76.78	0.39

Functional residue map

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

Post-translational modifications (1): 3

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 82 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_COLON_TUMORAL_MACROPHAGE_DN, RORA1_01, GCM_DDX11, chr7p13, GCM_NF2, DOUGLAS_BMI1_TARGETS_UP, GCM_USP6, CHENG_RESPONSE_TO_NICKEL_ACETATE, FEVR_CTNNB1_TARGETS_UP, KRIEG_KDM3A_TARGETS_NOT_HYPOXIA, ERR1_Q2, ZWANG_CLASS_1_TRANSIENTLY_INDUCED_BY_EGF, CBX7_TARGET_GENES, CSHL1_TARGET_GENES, LHX9_TARGET_GENES

GO Biological Process (0):

GO Molecular Function (2): GTP binding (GO:0005525), nucleotide binding (GO:0000166)

GO Cellular Component (3): nucleus (GO:0005634), cytosol (GO:0005829), cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
guanyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
intracellular membrane-bounded organelle	1
cytoplasm	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

396 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
URGCP	MINDY3	Q9H8M7	637
URGCP	VWCE	Q96DN2	401
URGCP	CARD8	Q9Y2G2	386
URGCP	RIPK1	Q13546	385
URGCP	INTS15	Q96N11	356
URGCP	CCDC117	Q8IWD4	348
URGCP	RIPK2	O43353	341
URGCP	NOD1	Q9Y239	339
URGCP	NLRP1	Q9C000	336
URGCP	CARD6	Q9BX69	334
URGCP	SMIM12	Q96EX1	324
URGCP	RTRAF	Q9Y224	311
URGCP	AP4E1	Q9UPM8	301
URGCP	GGPS1	O95749	300
URGCP	ARID4B	Q4LE39	296

IntAct

18 interactions, top by confidence:

A	B	Type	Score
URGCP	CHMP5	psi-mi:“MI:0915”(physical association)	0.370
Prdm16	ESYT2	psi-mi:“MI:0914”(association)	0.350
P		psi-mi:“MI:0914”(association)	0.350
	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
	HLA-C	psi-mi:“MI:0914”(association)	0.350
PTGES3	SBNO1	psi-mi:“MI:0914”(association)	0.350
URGCP	DNAJA2	psi-mi:“MI:0914”(association)	0.350
UBE2D4	UBB	psi-mi:“MI:0914”(association)	0.350
UBE2D1	UBE2D3	psi-mi:“MI:0914”(association)	0.350
URGCP	BAG2	psi-mi:“MI:0914”(association)	0.350
URGCP	TOM1	psi-mi:“MI:0914”(association)	0.350
URGCP	PPIP5K2	psi-mi:“MI:0915”(physical association)	0.000
SEC24B	URGCP	psi-mi:“MI:0915”(physical association)	0.000
EYA4	URGCP	psi-mi:“MI:0915”(physical association)	0.000
PLEC	URGCP	psi-mi:“MI:0915”(physical association)	0.000
AAK1	URGCP	psi-mi:“MI:0915”(physical association)	0.000
CCDC88A	URGCP	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (37): URGCP (Affinity Capture-MS), URGCP (Affinity Capture-MS), URGCP (Affinity Capture-MS), URGCP (Affinity Capture-MS), PPIP5K2 (Affinity Capture-MS), URGCP (Affinity Capture-MS), URGCP (Affinity Capture-MS), URGCP (Affinity Capture-MS), URGCP (Affinity Capture-RNA), URGCP (Affinity Capture-MS), URGCP (Affinity Capture-MS), URGCP (Affinity Capture-RNA), STUB1 (Affinity Capture-MS), HECTD1 (Affinity Capture-MS), URGCP (Affinity Capture-MS)

ESM2 similar proteins: A0A140LIF8, A0A2P1BRP3, A0A386CAB9, A0JN92, A1A4Y4, O14791, P27473, P59045, P86448, P86449, Q0GUM3, Q13075, Q3B7D9, Q3T9E4, Q3TL54, Q53G44, Q5NCI0, Q5RFJ8, Q60766, Q62293, Q66X01, Q66X03, Q66X05, Q66X22, Q6AYC2, Q6ZSC3, Q7Z745, Q84WJ0, Q86W28, Q8BV66, Q8BVM9, Q8C6J9, Q8CBA2, Q8CCN1, Q8TCB0, Q8TCY9, Q8TD90, Q90597, Q99388, Q99J64

Diamond homologs: A0JN92, Q5NCI0, Q5RFJ8, Q8TCY9, Q9BX69, O60936, Q62881, Q9D1X0

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	80
Likely benign	8
Benign	8

Top pathogenic / likely-pathogenic (0)

SpliceAI

1159 predictions. Top by Δscore:

Variant	Effect	Δscore
7:43879256:CTCCA:C	acceptor_gain	1.0000
7:43879258:CCA:C	acceptor_gain	1.0000
7:43879259:CAC:C	acceptor_gain	1.0000
7:43879261:C:CC	acceptor_gain	1.0000
7:43881657:A:AC	donor_gain	1.0000
7:43881657:A:C	donor_loss	1.0000
7:43881658:C:CC	donor_gain	1.0000
7:43881694:CCAT:C	acceptor_gain	1.0000
7:43881695:CATC:C	acceptor_gain	1.0000
7:43881698:C:CC	acceptor_gain	1.0000
7:43881908:T:TA	donor_gain	1.0000
7:43887409:CTTTA:C	donor_loss	1.0000
7:43887411:TTA:T	donor_loss	1.0000
7:43887412:TAC:T	donor_loss	1.0000
7:43887413:A:AG	donor_loss	1.0000
7:43887414:CCT:C	donor_loss	1.0000
7:43887483:TGC:T	acceptor_gain	1.0000
7:43887483:TGCC:T	acceptor_loss	1.0000
7:43887486:C:CA	acceptor_loss	1.0000
7:43879257:TCCA:T	acceptor_gain	0.9900
7:43879257:TCCAC:T	acceptor_loss	0.9900
7:43879258:CCAC:C	acceptor_gain	0.9900
7:43879259:CA:C	acceptor_gain	0.9900
7:43879260:ACT:A	acceptor_loss	0.9900
7:43879262:T:G	acceptor_loss	0.9900
7:43879263:G:C	acceptor_gain	0.9900
7:43881653:GCTTA:G	acceptor_loss	0.9900
7:43881654:CTTA:C	acceptor_loss	0.9900
7:43881654:CTTAC:C	acceptor_loss	0.9900
7:43881655:TTAC:T	acceptor_loss	0.9900

AlphaMissense

6113 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:43878384:A:T	I360K	0.998
7:43878638:C:A	K275N	0.998
7:43878638:C:G	K275N	0.998
7:43878309:A:G	F385S	0.997
7:43878455:G:C	N336K	0.997
7:43878455:G:T	N336K	0.997
7:43878639:T:A	K275M	0.997
7:43878219:A:T	V415D	0.996
7:43878252:A:G	L404S	0.995
7:43878375:T:A	D363V	0.995
7:43878384:A:C	I360R	0.995
7:43878447:C:A	G339V	0.995
7:43878299:A:C	S388R	0.994
7:43878299:A:T	S388R	0.994
7:43878301:T:G	S388R	0.994
7:43878376:C:G	D363H	0.994
7:43878450:C:A	R338I	0.994
7:43878453:A:G	L337P	0.994
7:43878640:T:G	K275Q	0.994
7:43876754:C:A	K903N	0.993
7:43876754:C:G	K903N	0.993
7:43878261:A:G	L401P	0.993
7:43878387:A:G	F359S	0.993
7:43878584:G:C	F293L	0.993
7:43878584:G:T	F293L	0.993
7:43878586:A:G	F293L	0.993
7:43878640:T:C	K275E	0.993
7:43878376:C:A	D363Y	0.992
7:43878450:C:G	R338T	0.992
7:43878650:A:C	S271R	0.992

dbSNP variants (sampled 300 via entrez): RS1000024429 (7:43921396 T>C), RS1000100883 (7:43909428 T>C), RS1000269745 (7:43895872 G>A), RS1000284610 (7:43915922 T>C), RS1000405676 (7:43877124 C>T), RS1000427084 (7:43911804 T>C,G), RS1000475857 (7:43928492 T>C), RS1000528694 (7:43884343 C>T), RS1000700634 (7:43890801 A>C,G), RS1000760060 (7:43913419 C>T), RS1000821556 (7:43921606 C>A), RS1000878304 (7:43906523 G>A), RS1000892465 (7:43903914 A>T), RS1000892789 (7:43897111 G>A), RS1000949515 (7:43903686 C>G)

Disease associations

OMIM: gene MIM:610337 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST004487_8	Peak insulin response	4.000000e-08
GCST012381_5	Eosinophilic esophagitis	9.000000e-09

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0008000	peak insulin response measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

25 total (human), top 25 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Vorinostat	affects cotreatment, decreases expression	2
Acetaminophen	decreases expression, increases expression	2
Valproic Acid	affects expression, decreases expression	2
aristolochic acid I	increases expression	1
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
FR900359	decreases phosphorylation	1
triphenyl phosphate	affects expression	1
bisphenol A	increases expression	1
beta-lapachone	decreases expression, increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
ferrous chloride	decreases expression	1
beta-methylcholine	affects expression	1
di-n-butylphosphoric acid	affects expression	1
nickel acetate	affects expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
ICG 001	increases expression	1
abrine	increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
Benzo(a)pyrene	affects methylation	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Doxorubicin	decreases expression	1
Lead	affects expression	1
Smoke	decreases expression	1
Aflatoxin B1	increases methylation	1
Cadmium Chloride	decreases expression	1

Clinical trials (associated diseases)

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