VOPP1

Summary

VOPP1 (VOPP1 WW domain binding protein, HGNC:34518) is a protein-coding gene on chromosome 7p11.2, encoding WW domain binding protein VOPP1 (Q96AW1). Increases the transcriptional activity of NFKB1 by facilitating its nuclear translocation, DNA-binding and associated apoptotic response, when overexpressed. It is a selective cancer dependency (DepMap: 12.5% of cell lines).

Enables enzyme binding activity. Located in cytoplasmic vesicle membrane; late endosome; and lysosome.

Source: NCBI Gene 81552 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 32 total
• Cancer dependency (DepMap): dependent in 12.5% of screened cell lines
• MANE Select transcript: NM_030796

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:34518
Approved symbol	VOPP1
Name	VOPP1 WW domain binding protein
Location	7p11.2
Locus type	gene with protein product
Status	Approved
Aliases	ECop, GASP, FLJ20532, DKFZp564K0822, WBP1L2
Ensembl gene	ENSG00000154978
Ensembl biotype	protein_coding
OMIM	611915
Entrez	81552

Gene structure

Transcript identifiers

Ensembl transcripts: 18 — 14 protein_coding, 3 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000285279, ENST00000414113, ENST00000417399, ENST00000418904, ENST00000427700, ENST00000428097, ENST00000428648, ENST00000433959, ENST00000452832, ENST00000453112, ENST00000453256, ENST00000454227, ENST00000455023, ENST00000462326, ENST00000471168, ENST00000481197, ENST00000625836, ENST00000922470

RefSeq mRNA: 13 — MANE Select: NM_030796 NM_001284282, NM_001284283, NM_001284284, NM_001321242, NM_001321243, NM_001321244, NM_001321246, NM_001321247, NM_001321248, NM_001321249, NM_001321250, NM_001321251, NM_030796

CCDS: CCDS47588, CCDS64654, CCDS64655, CCDS64656, CCDS83186, CCDS83187

Canonical transcript exons

ENST00000285279 — 5 exons

Exon	Start	End
ENSE00001122599	55572271	55572502
ENSE00001922832	55470613	55473045
ENSE00003555011	55492282	55492418
ENSE00003558107	55497613	55497690
ENSE00003649017	55521072	55521130

Expression profiles

Bgee: expression breadth ubiquitous, 300 present calls, max score 98.21.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 13.0944 / max 148.7481, expressed in 1781 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
84164	8.4056	1764
84163	3.4201	1525
84160	0.6987	189
84162	0.4170	102
84154	0.1103	43
84153	0.0427	17

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
thymus	UBERON:0002370	98.21	gold quality
type B pancreatic cell	CL:0000169	98.09	silver quality
ventricular zone	UBERON:0003053	97.48	gold quality
lymph node	UBERON:0000029	97.45	gold quality
stromal cell of endometrium	CL:0002255	97.02	gold quality
pylorus	UBERON:0001166	96.83	gold quality
cortical plate	UBERON:0005343	96.82	gold quality
epithelium of nasopharynx	UBERON:0001951	96.80	gold quality
nasopharynx	UBERON:0001728	96.78	gold quality
parotid gland	UBERON:0001831	96.65	gold quality
lateral nuclear group of thalamus	UBERON:0002736	96.65	gold quality
caecum	UBERON:0001153	96.46	gold quality
islet of Langerhans	UBERON:0000006	96.44	gold quality
vermiform appendix	UBERON:0001154	96.43	gold quality
tendon of biceps brachii	UBERON:0008188	96.42	gold quality
decidua	UBERON:0002450	96.34	gold quality
ganglionic eminence	UBERON:0004023	96.07	gold quality
periodontal ligament	UBERON:0008266	96.07	gold quality
cardia of stomach	UBERON:0001162	95.79	gold quality
spleen	UBERON:0002106	95.73	gold quality
ventral tegmental area	UBERON:0002691	95.52	gold quality
dorsal plus ventral thalamus	UBERON:0001897	95.47	gold quality
renal medulla	UBERON:0000362	95.30	gold quality
middle temporal gyrus	UBERON:0002771	95.28	gold quality
trigeminal ganglion	UBERON:0001675	95.16	gold quality
superior vestibular nucleus	UBERON:0007227	95.16	gold quality
blood	UBERON:0000178	95.03	gold quality
medulla oblongata	UBERON:0001896	94.89	gold quality
substantia nigra pars reticulata	UBERON:0001966	94.83	gold quality
embryo	UBERON:0000922	94.78	gold quality

Single-cell (SCXA)

Detected in 9 experiment(s), a significant marker in 8.

Experiment	Marker?	Max mean expression
E-MTAB-9467	yes	49.29
E-HCAD-1	yes	44.10
E-MTAB-8142	yes	26.55
E-CURD-122	yes	21.96
E-ANND-3	yes	21.56
E-HCAD-9	yes	14.66
E-CURD-46	yes	10.89
E-CURD-88	yes	4.60
E-HCAD-5	no	2.36

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

67 targeting VOPP1, 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-3613-3P	100.00	76.36	7965
HSA-MIR-7110-3P	100.00	73.18	2486
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-6077	99.99	68.04	2299
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-557	99.96	70.01	1640
HSA-MIR-6845-3P	99.94	66.88	1439
HSA-MIR-218-5P	99.93	72.22	2103
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-329-3P	99.91	66.56	1234
HSA-MIR-362-3P	99.91	66.38	1267
HSA-MIR-4496	99.88	68.89	2236
HSA-MIR-636	99.80	69.58	1500
HSA-MIR-6764-5P	99.75	67.89	2304
HSA-MIR-3617-5P	99.75	69.41	1968
HSA-MIR-641	99.75	69.35	1975
HSA-MIR-4524A-3P	99.72	66.85	2406
HSA-MIR-12124	99.68	69.17	2700
HSA-MIR-651-5P	99.64	68.49	1104
HSA-MIR-4261	99.59	70.30	3415
HSA-MIR-1915-3P	99.58	66.79	1988
HSA-MIR-486-3P	99.51	66.82	1901
HSA-MIR-766-5P	99.47	67.91	2225
HSA-MIR-147B-5P	99.45	70.62	2432

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 12.5% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 10)

• ECOP was used as a molecular marker in patients with chronic wounds to guide surgical debridement. (PMID:17515955)
• Results identify ECOP as a protein relevant to the biology of SCC. (PMID:19525979)
• overexpression in cancer participates in the control of the intracellular redox state; its loss leads to oxidative cellular injury leading to cell death by the intrinsic apoptotic pathway (PMID:21519330)
• Upregulation of ECOP is associated with glioma. (PMID:23243056)
• VOPP1 is overexpressed in gastric adenocarcinoma, which is involved in promoting cell proliferation and migration and thus might serve as a putative oncogene. (PMID:25398664)
• Candidate gene eQTL showed a trans-acting association between variants of G protein-coupled receptor kinase 5 gene, previously linked to altered BB response, and high expression of VOPP1. (PMID:26860460)
• miR-218 inhibits human lung adenocarcinoma cell migration and invasion via the suppression of Ecop and Robo1 expression (PMID:28936884)
• VOPP1 expression was negatively regulated by microRNA-218. (PMID:30229837)
• The findings emphasize the importance of the sequestration of WWOX by VOPP1 in addition to WWOX loss in breast tumors and define VOPP1 as a novel oncogene promoting breast carcinogenesis by inhibiting the anti-tumoral effect of WWOX. (PMID:30285739)
• The role of vesicular overexpressed in cancer pro-survival protein 1 in hepatocellular carcinoma proliferation. (PMID:32083568)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	vopp1a	ENSDARG00000038979
danio_rerio	vopp1b	ENSDARG00000076373
mus_musculus	Vopp1	ENSMUSG00000037788
rattus_norvegicus	Vopp1	ENSRNOG00000006646

Protein

Protein identifiers

WW domain binding protein VOPP1 — Q96AW1 (reviewed: Q96AW1)

Alternative names: EGFR-coamplified and overexpressed protein, Glioblastoma-amplified secreted protein, Putative NF-kappa-B-activating protein 055N, Vesicular, overexpressed in cancer, prosurvival protein 1

All UniProt accessions (8): Q96AW1, C9J548, C9J827, C9JF99, C9JIM1, C9JQ18, C9JTY8, C9JVH1

UniProt curated annotations — full annotation on UniProt →

Function. Increases the transcriptional activity of NFKB1 by facilitating its nuclear translocation, DNA-binding and associated apoptotic response, when overexpressed. May sequester WWOX in lysosomal vesicles and thereby regulate WWOX role as tumor suppressor.

Subunit / interactions. Interacts with WWOX (via WW domain).

Subcellular location. Cytoplasmic vesicle membrane. Late endosome membrane. Lysosome membrane.

Tissue specificity. Widely expressed with highest levels in thymus and ovary.

Similarity. Belongs to the VOPP1/ECOP family.

Isoforms (4)

UniProt ID	Names	Canonical?
Q96AW1-1	1	yes
Q96AW1-2	2
Q96AW1-3	3
Q96AW1-4	4

RefSeq proteins (13): NP_001271211, NP_001271212, NP_001271213, NP_001308171, NP_001308172, NP_001308173, NP_001308175, NP_001308176, NP_001308177, NP_001308178, NP_001308179, NP_001308180, NP_110423* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR026229	VOPP1	Family

UniProt features (16 total): mutagenesis site 3, sequence conflict 3, splice variant 3, topological domain 2, signal peptide 1, chain 1, transmembrane region 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96AW1-F1	66.58	0.03

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 (3):

Position	Phenotype
119	does not affect binding to wwox.
157	does not affect binding to wwox.
165	reduces binding to wwox.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 226 (showing top): MULLIGHAN_NPM1_SIGNATURE_3_UP, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, GOCC_VACUOLAR_MEMBRANE, GOZGIT_ESR1_TARGETS_DN, ONKEN_UVEAL_MELANOMA_UP, ACEVEDO_LIVER_CANCER_UP, GOCC_LATE_ENDOSOME_MEMBRANE, ZHENG_BOUND_BY_FOXP3, ZHENG_FOXP3_TARGETS_IN_THYMUS_UP, BOYLAN_MULTIPLE_MYELOMA_PCA3_UP, CASORELLI_ACUTE_PROMYELOCYTIC_LEUKEMIA_DN, MULLIGHAN_NPM1_MUTATED_SIGNATURE_1_UP, CHEN_METABOLIC_SYNDROM_NETWORK, YAGI_AML_WITH_T_8_21_TRANSLOCATION, REN_ALVEOLAR_RHABDOMYOSARCOMA_DN

GO Biological Process (0):

GO Molecular Function (2): enzyme binding (GO:0019899), protein binding (GO:0005515)

GO Cellular Component (9): lysosome (GO:0005764), lysosomal membrane (GO:0005765), endosome (GO:0005768), late endosome (GO:0005770), cytoplasmic vesicle membrane (GO:0030659), organelle membrane (GO:0031090), late endosome membrane (GO:0031902), membrane (GO:0016020), cytoplasmic vesicle (GO:0031410)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cytoplasmic vesicle	2
protein binding	1
binding	1
lytic vacuole	1
lysosome	1
lytic vacuole membrane	1
endomembrane system	1
endosome	1
vesicle membrane	1
membrane	1
membrane-bounded organelle	1
late endosome	1
endosome membrane	1
cellular anatomical structure	1
cytoplasm	1
intracellular vesicle	1

Protein interactions and networks

STRING

410 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
VOPP1	LANCL2	Q9NS86	653
VOPP1	TMEM207	Q6UWW9	617
VOPP1	VWA7	Q9Y334	613
VOPP1	SEC61G	P38384	590
VOPP1	EGFR	P00533	567
VOPP1	WBP1	Q96G27	564
VOPP1	VSTM2A	Q8TAG5	522
VOPP1	SEPTIN14	Q6ZU15	496
VOPP1	C7orf25	Q9BPX7	496
VOPP1	PARP1	P09874	491
VOPP1	C5orf63	A6NC05	478
VOPP1	GLYAT	Q6IB77	476
VOPP1	ARMCX5	Q6P1M9	464
VOPP1	DENND5B	Q6ZUT9	464
VOPP1	CYYR1	Q96J86	445

IntAct

26 interactions, top by confidence:

A	B	Type	Score
WWOX	VOPP1	psi-mi:“MI:0915”(physical association)	0.690
WWOX	VOPP1	psi-mi:“MI:0403”(colocalization)	0.690
WWOX	TP73	psi-mi:“MI:0914”(association)	0.640
WWOX	VOPP1	psi-mi:“MI:0915”(physical association)	0.370
VOPP1	EPHA2	psi-mi:“MI:0914”(association)	0.350
CRIP1	VOPP1	psi-mi:“MI:0915”(physical association)	0.000
MAP7D1	VOPP1	psi-mi:“MI:0915”(physical association)	0.000
C8orf33	VOPP1	psi-mi:“MI:0915”(physical association)	0.000
GLYAT	VOPP1	psi-mi:“MI:0915”(physical association)	0.000
LAMTOR5	VOPP1	psi-mi:“MI:0915”(physical association)	0.000
HMOX2	VOPP1	psi-mi:“MI:0915”(physical association)	0.000
C8orf30A	VOPP1	psi-mi:“MI:0915”(physical association)	0.000
OFD1	VOPP1	psi-mi:“MI:0915”(physical association)	0.000
PFDN1	VOPP1	psi-mi:“MI:0915”(physical association)	0.000
SNAPIN	VOPP1	psi-mi:“MI:0915”(physical association)	0.000
STMN2	VOPP1	psi-mi:“MI:0915”(physical association)	0.000
VOPP1	TAC3	psi-mi:“MI:0915”(physical association)	0.000
TFG	VOPP1	psi-mi:“MI:0915”(physical association)	0.000
SMPD3	VOPP1	psi-mi:“MI:0915”(physical association)	0.000
PBK	VOPP1	psi-mi:“MI:0915”(physical association)	0.000
MTF2	VOPP1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (16): VOPP1 (Affinity Capture-MS), WWOX (Affinity Capture-Western), VOPP1 (Affinity Capture-Western), EPHA2 (Affinity Capture-MS), NEDD4 (Affinity Capture-MS), WWOX (Affinity Capture-MS), MLST8 (Affinity Capture-MS), LRRC15 (Affinity Capture-MS), ZER1 (Affinity Capture-MS), TMEM259 (Affinity Capture-MS), GBF1 (Affinity Capture-MS), VOPP1 (Negative Genetic), VOPP1 (Positive Genetic), VOPP1 (Affinity Capture-RNA), VOPP1 (Affinity Capture-MS)

ESM2 similar proteins: A0PJX4, A6QNZ8, B5DEK8, O60320, O73612, P01134, P01344, P01346, P07456, P10764, P48030, P51459, P52796, P52799, P52800, P98172, Q0V9A8, Q0VBP7, Q3SXP7, Q3SZ48, Q3UPR0, Q5E943, Q5HZN7, Q5JRV8, Q5PQS5, Q5R8M2, Q5RDG5, Q5RDV6, Q5VX71, Q5XGS4, Q5ZIS9, Q68FW3, Q6A044, Q7TMP6, Q8BGZ2, Q8BH32, Q8BHW5, Q8CA71, Q8N114, Q8R092

Diamond homologs: A6QNZ8, B5DEK8, Q0V9A8, Q5RDG5, Q5XGS4, Q8R1C3, Q96AW1

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	27
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1838 predictions. Top by Δscore:

Variant	Effect	Δscore
7:55521070:A:AC	donor_gain	1.0000
7:55521071:C:CC	donor_gain	1.0000
7:55521071:CA:C	donor_gain	1.0000
7:55521071:CAT:C	donor_gain	1.0000
7:55521128:GCAC:G	acceptor_loss	1.0000
7:55521129:CA:C	acceptor_gain	1.0000
7:55521131:C:CA	acceptor_loss	1.0000
7:55521131:C:CC	acceptor_gain	1.0000
7:55472934:C:A	donor_gain	0.9900
7:55473043:CTC:C	acceptor_gain	0.9900
7:55473045:CCTG:C	acceptor_loss	0.9900
7:55473046:C:G	acceptor_loss	0.9900
7:55473047:T:C	acceptor_loss	0.9900
7:55492729:T:TA	donor_gain	0.9900
7:55497606:GACCT:G	donor_loss	0.9900
7:55497607:ACCT:A	donor_loss	0.9900
7:55497608:CCTAC:C	donor_loss	0.9900
7:55497609:CTACC:C	donor_loss	0.9900
7:55497610:TA:T	donor_loss	0.9900
7:55497611:ACC:A	donor_loss	0.9900
7:55497612:C:A	donor_loss	0.9900
7:55497687:GCATC:G	acceptor_loss	0.9900
7:55497689:ATC:A	acceptor_loss	0.9900
7:55497690:TCTG:T	acceptor_loss	0.9900
7:55497691:CTGT:C	acceptor_loss	0.9900
7:55497692:T:A	acceptor_loss	0.9900
7:55521064:ATACT:A	donor_loss	0.9900
7:55521065:TACTT:T	donor_loss	0.9900
7:55521066:ACT:A	donor_loss	0.9900
7:55521067:CTTAC:C	donor_loss	0.9900

AlphaMissense

1108 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:55492383:C:T	G76E	0.999
7:55492390:A:G	C74R	0.999
7:55492402:C:G	G70R	0.999
7:55492407:A:C	M68R	0.999
7:55497623:A:G	W61R	0.999
7:55497623:A:T	W61R	0.999
7:55497667:C:T	C46Y	0.999
7:55497688:C:T	C39Y	0.999
7:55492377:C:T	G78D	0.998
7:55492387:A:G	C75R	0.998
7:55492389:C:T	C74Y	0.998
7:55492401:C:T	G70D	0.998
7:55492407:A:T	M68K	0.998
7:55497651:A:C	C51W	0.998
7:55497652:C:T	C51Y	0.998
7:55497654:G:C	C50W	0.998
7:55497655:C:G	C50S	0.998
7:55497656:A:G	C50R	0.998
7:55497656:A:T	C50S	0.998
7:55497666:A:C	C46W	0.998
7:55497668:A:G	C46R	0.998
7:55497669:G:C	C45W	0.998
7:55497670:C:T	C45Y	0.998
7:55497671:A:G	C45R	0.998
7:55497687:G:C	C39W	0.998
7:55497688:C:G	C39S	0.998
7:55497689:A:G	C39R	0.998
7:55497689:A:T	C39S	0.998
7:55521107:G:C	C26W	0.998
7:55521108:C:T	C26Y	0.998

dbSNP variants (sampled 300 via entrez): RS1000023890 (7:55548636 G>A), RS1000035364 (7:55548976 T>G), RS1000042283 (7:55469601 A>C,G), RS1000047186 (7:55453747 A>T), RS1000109684 (7:55472799 C>T), RS1000138728 (7:55441961 C>T), RS1000156435 (7:55463236 A>G), RS1000158717 (7:55568932 G>A), RS1000159346 (7:55461097 G>C), RS1000164979 (7:55489871 G>C,T), RS1000193319 (7:55536338 G>T), RS1000196601 (7:55505125 G>C), RS1000243186 (7:55497561 G>A,C,T), RS1000256575 (7:55462944 C>A,T), RS1000280979 (7:55478313 A>G)

Disease associations

OMIM: gene MIM:611915 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST002938_33	Copper levels	7.000000e-06

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
trichostatin A	decreases expression, affects cotreatment	2
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	2
Acrolein	affects cotreatment, increases oxidation, increases abundance	2
Air Pollutants	affects cotreatment, increases abundance, increases oxidation, decreases expression	2
Benzo(a)pyrene	decreases methylation, increases expression	2
Doxorubicin	affects expression, decreases expression	2
Ozone	affects cotreatment, increases oxidation, increases abundance	2
Valproic Acid	increases expression, decreases methylation	2
bisphenol F	affects cotreatment, decreases expression	1
alpha-pinene	increases oxidation, increases abundance, affects cotreatment	1
bisphenol A	affects cotreatment, decreases methylation	1
salinomycin	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	increases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
K 7174	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
eprenetapopt	affects expression, affects reaction	1
bisphenol S	affects cotreatment, decreases expression	1
Fulvestrant	affects cotreatment, decreases methylation, increases methylation	1
Benzene	increases expression	1
Dexamethasone	affects cotreatment, decreases expression	1
Indomethacin	affects cotreatment, decreases expression	1
Lead	affects expression	1
Tetrachlorodibenzodioxin	affects expression	1
Tobacco Smoke Pollution	increases expression	1
Tretinoin	increases expression	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B2L4	Abcam HeLa VOPP1 KO	Cancer cell line	Female

Clinical trials (associated diseases)

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