VWCE

Summary

VWCE (von Willebrand factor C and EGF domains, HGNC:26487) is a protein-coding gene on chromosome 11q12.2, encoding von Willebrand factor C and EGF domain-containing protein (Q96DN2). May be a regulatory element in the beta-catenin signaling pathway and a target for chemoprevention of hapatocellular carcinoma.

Predicted to enable calcium ion binding activity. Predicted to be involved in cellular response to virus. Located in cytoplasm.

Source: NCBI Gene 220001 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 156 total — 1 pathogenic
• MANE Select transcript: NM_152718

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26487
Approved symbol	VWCE
Name	von Willebrand factor C and EGF domains
Location	11q12.2
Locus type	gene with protein product
Status	Approved
Aliases	URG11, FLJ32009, VWC1
Ensembl gene	ENSG00000167992
Ensembl biotype	protein_coding
OMIM	611115
Entrez	220001

Gene structure

Transcript identifiers

Ensembl transcripts: 28 — 23 protein_coding, 3 retained_intron, 2 nonsense_mediated_decay

ENST00000301770, ENST00000335613, ENST00000398808, ENST00000535599, ENST00000535710, ENST00000538438, ENST00000538579, ENST00000870658, ENST00000870659, ENST00000870660, ENST00000870661, ENST00000870662, ENST00000870663, ENST00000870664, ENST00000870665, ENST00000870666, ENST00000870667, ENST00000870668, ENST00000917388, ENST00000917389, ENST00000917390, ENST00000917391, ENST00000917392, ENST00000917393, ENST00000917394, ENST00000917395, ENST00000917396, ENST00000917397

RefSeq mRNA: 1 — MANE Select: NM_152718 NM_152718

CCDS: CCDS8002

Canonical transcript exons

ENST00000335613 — 20 exons

Exon	Start	End
ENSE00001119097	61268922	61269018
ENSE00002283863	61294928	61295316
ENSE00003458919	61273199	61273316
ENSE00003483968	61290799	61290927
ENSE00003508168	61265122	61265212
ENSE00003532043	61274499	61274584
ENSE00003539796	61280624	61280717
ENSE00003550245	61281786	61281914
ENSE00003586247	61271675	61271760
ENSE00003586390	61267462	61267544
ENSE00003593803	61258286	61259312
ENSE00003594335	61291482	61291576
ENSE00003596616	61291264	61291353
ENSE00003603775	61278394	61278476
ENSE00003613710	61286314	61286430
ENSE00003629155	61276593	61276680
ENSE00003635552	61280793	61281235
ENSE00003650704	61264956	61265038
ENSE00003660469	61282789	61282905
ENSE00003663169	61264487	61264577

Expression profiles

Bgee: expression breadth ubiquitous, 171 present calls, max score 88.39.

FANTOM5 (CAGE): breadth broad, TPM avg 1.3033 / max 55.5793, expressed in 477 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
119963	0.9760	417
119962	0.3273	182

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	88.39	gold quality
left ovary	UBERON:0002119	86.82	gold quality
right ovary	UBERON:0002118	86.72	gold quality
right lobe of liver	UBERON:0001114	86.22	gold quality
ovary	UBERON:0000992	81.85	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	81.55	silver quality
liver	UBERON:0002107	80.96	gold quality
blood	UBERON:0000178	78.41	gold quality
pancreatic ductal cell	CL:0002079	77.84	silver quality
left uterine tube	UBERON:0001303	77.75	gold quality
omental fat pad	UBERON:0010414	77.08	gold quality
peritoneum	UBERON:0002358	77.04	gold quality
stromal cell of endometrium	CL:0002255	76.95	gold quality
adipose tissue of abdominal region	UBERON:0007808	76.25	gold quality
right frontal lobe	UBERON:0002810	73.82	gold quality
epithelial cell of pancreas	CL:0000083	73.75	gold quality
endocervix	UBERON:0000458	73.72	gold quality
ectocervix	UBERON:0012249	73.47	gold quality
subcutaneous adipose tissue	UBERON:0002190	73.38	gold quality
right adrenal gland	UBERON:0001233	73.05	gold quality
fallopian tube	UBERON:0003889	73.02	gold quality
cortical plate	UBERON:0005343	72.88	gold quality
decidua	UBERON:0002450	72.84	gold quality
mucosa of stomach	UBERON:0001199	72.80	gold quality
right adrenal gland cortex	UBERON:0035827	72.72	gold quality
kidney epithelium	UBERON:0004819	72.48	gold quality
anterior cingulate cortex	UBERON:0009835	72.47	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	72.46	gold quality
hypothalamus	UBERON:0001898	72.13	gold quality
right hemisphere of cerebellum	UBERON:0014890	72.11	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-MTAB-9388	yes	86.54
E-ANND-3	no	4.39

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

9 targeting VWCE, 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-9718	99.94	68.91	918
HSA-MIR-6512-3P	99.65	66.07	1468
HSA-MIR-6720-5P	99.65	66.22	1459
HSA-MIR-4691-5P	98.41	66.77	1343
HSA-MIR-6792-3P	98.41	66.86	1359
HSA-MIR-628-5P	98.36	67.74	844
HSA-MIR-3183	97.40	65.68	978
HSA-MIR-6849-3P	97.25	64.57	1371
HSA-MIR-5588-3P	94.96	65.59	500

Literature-anchored findings (GeneRIF, showing 10)

• beta-catenin is activated by HBxAg, in part, through the upregulated expression of the HBxAg effector URG11; URG11 stimulates the beta-catenin promoter and hepatocellular growth and survival (PMID:16496348)
• Data suggest that URG11 contributes to gastric cancer growth and metastasis at least partially through activation of beta-catenin signalling pathway. (PMID:19413886)
• URG11 mediates hypoxia-induced epithelial-to-mesenchymal transition through the suppression of E-cadherin and the activation of the beta-catenin/T-cell factor pathway. (PMID:19900406)
• Increased expression of both URG11 was associated with decrease renal function in IgA nephropathy. (PMID:23828164)
• Up-regulation of URG11 in pancreatic cancer leads to enhancing epithelial-mesenchymal transition-driven invasion and thus lead to poor prognosis. (PMID:24930007)
• URG11 could promote hepatocellular carcinoma (HCC) cell growth and proliferation. It might play an important role in HCC development. (PMID:26522362)
• the study reported here provided evidence that URG11 downregulation suppresses proliferation, invasion, and beta-catenin expression in NSCLC cells. Our study uncovered a novel role for URG11 in NSCLC progression; thus, URG11 may be a novel potential therapeutic target for NSCLC. (PMID:27458101)
• silencing of URG11 altered the expression levels of cell cycleassociated genes, epithelialmesenchymal transitionassociated genes, and RhoA and ROCK1 protein levels. Thus, the results of the present study suggest that URG11 may be a potential therapeutic target, which may be important to inhibit the development and progression of prostatic hyperplasia. (PMID:29749520)
• URG11 is critical for the proliferation, migration, and invasion in prostate cancer cells (PMID:29955600)
• URG11 served an oncogenic role in the development of prostate cancer cells. (PMID:30864678)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Vwce	ENSMUSG00000043789
rattus_norvegicus	Vwce	ENSRNOG00000060269

Paralogs (19): CHRDL2 (ENSG00000054938), CHRD (ENSG00000090539), CHRDL1 (ENSG00000101938), TECTA (ENSG00000109927), VWF (ENSG00000110799), MUC5B (ENSG00000117983), KCP (ENSG00000135253), ZAN (ENSG00000146839), CRIM1 (ENSG00000150938), BMPER (ENSG00000164619), OTOGL (ENSG00000165899), VWC2L (ENSG00000174453), MUC6 (ENSG00000184956), OTOG (ENSG00000188162), VWC2 (ENSG00000188730), MUC2 (ENSG00000198788), MUC19 (ENSG00000205592), MUC5AC (ENSG00000215182), FCGBP (ENSG00000275395)

Protein

Protein identifiers

von Willebrand factor C and EGF domain-containing protein — Q96DN2 (reviewed: Q96DN2)

Alternative names: HBV X protein up-regulated gene 11 protein, HBxAg up-regulated gene 11 protein

All UniProt accessions (3): B4DS56, B4DY31, Q96DN2

UniProt curated annotations — full annotation on UniProt →

Function. May be a regulatory element in the beta-catenin signaling pathway and a target for chemoprevention of hapatocellular carcinoma.

Subcellular location. Secreted.

Tissue specificity. Expressed in liver.

Induction. By HBxAg.

Isoforms (2)

UniProt ID	Names	Canonical?
Q96DN2-1	1	yes
Q96DN2-2	2

RefSeq proteins (1): NP_689931* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000152	EGF-type_Asp/Asn_hydroxyl_site	PTM
IPR000742	EGF	Domain
IPR001007	VWF_dom	Domain
IPR001881	EGF-like_Ca-bd_dom	Domain
IPR009030	Growth_fac_rcpt_cys_sf	Homologous_superfamily
IPR018097	EGF_Ca-bd_CS	Conserved_site
IPR026823	cEGF	Domain
IPR052080	vWF_C/EGF_Fibrillin	Family

Pfam: PF00093, PF12662, PF23334

UniProt features (34 total): domain 10, disulfide bond 9, region of interest 4, compositionally biased region 3, glycosylation site 2, splice variant 2, signal peptide 1, chain 1, sequence variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96DN2-F1	63.23	0.09

Functional residue map

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

Disulfide bonds (9): 146–155, 151–164, 166–179, 185–194, 190–203, 205–218, 224–237, 233–246, 248–261

Glycosylation sites (2): 462, 472

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 56 (showing top): GSE45365_NK_CELL_VS_CD11B_DC_UP, RNGTGGGC_UNKNOWN, GOBP_CELLULAR_RESPONSE_TO_VIRUS, SP3_Q3, HNF4_DR1_Q3, HNF4_01, CHIANG_LIVER_CANCER_SUBCLASS_INTERFERON_DN, NIKOLSKY_BREAST_CANCER_11Q12_Q14_AMPLICON, DOUGLAS_BMI1_TARGETS_UP, AP2_Q6_01, GOBP_RESPONSE_TO_VIRUS, HATADA_METHYLATED_IN_LUNG_CANCER_UP, OHGUCHI_LIVER_HNF4A_TARGETS_DN, MTF1_Q4, GHANDHI_DIRECT_IRRADIATION_UP

GO Biological Process (1): cellular response to virus (GO:0098586)

GO Molecular Function (2): calcium ion binding (GO:0005509), protein binding (GO:0005515)

GO Cellular Component (2): extracellular region (GO:0005576), cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
response to virus	1
metal ion binding	1
binding	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1064 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
VWCE	TWSG1	Q9GZX9	723
VWCE	BMP2	P12643	669
VWCE	BMPR2	Q13873	669
VWCE	BMPR1A	P36894	663
VWCE	BMP7	P18075	657
VWCE	BMP6	P22004	609
VWCE	GDF5	P43026	604
VWCE	VWC2	Q2TAL6	601
VWCE	VWF	P04275	556
VWCE	ACVR2B	Q13705	506
VWCE	FDXR	P22570	484
VWCE	BMP5	P22003	475
VWCE	ZNF114	Q8NC26	474
VWCE	VMA12	Q8N511	467
VWCE	MAMDC4	Q6UXC1	460

IntAct

17 interactions, top by confidence:

A	B	Type	Score
VWCE	NUFIP2	psi-mi:“MI:0915”(physical association)	0.740
VWCE	HSPA5	psi-mi:“MI:0914”(association)	0.640
VWCE	ZNF20	psi-mi:“MI:0915”(physical association)	0.560
MEOX2	VWCE	psi-mi:“MI:0915”(physical association)	0.560
KRTAP15-1	VWCE	psi-mi:“MI:0915”(physical association)	0.560
ZNF20	VWCE	psi-mi:“MI:0915”(physical association)	0.560
VWCE	ZNF316	psi-mi:“MI:0914”(association)	0.530
SCRIB	VWCE	psi-mi:“MI:0915”(physical association)	0.400
VWCE	HOXA1	psi-mi:“MI:0915”(physical association)	0.370
VWCE	MEOX2	psi-mi:“MI:0915”(physical association)	0.000
VWCE	KRTAP15-1	psi-mi:“MI:0915”(physical association)	0.000
VWCE	nhaP	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (114): VWCE (Synthetic Growth Defect), HSPA1A (Affinity Capture-MS), ZNF444 (Affinity Capture-MS), ZNF747 (Affinity Capture-MS), ZNF669 (Affinity Capture-MS), ZNF764 (Affinity Capture-MS), KPTN (Affinity Capture-MS), ZNF664 (Affinity Capture-MS), ITFG2 (Affinity Capture-MS), ZNF627 (Affinity Capture-MS), ZNF620 (Affinity Capture-MS), FIZ1 (Affinity Capture-MS), ZNF77 (Affinity Capture-MS), TTLL5 (Affinity Capture-MS), ZSCAN21 (Affinity Capture-MS)

ESM2 similar proteins: A1L0T3, A1L4H1, A6QNY1, D3YZF7, O95428, P28698, P30203, P55068, P55106, P59222, P98162, Q04756, Q14767, Q28019, Q28062, Q28256, Q28343, Q28670, Q3U515, Q4G0T1, Q5F378, Q5HZW5, Q61003, Q61361, Q6H9L7, Q6KF10, Q6PGE4, Q6QNF4, Q7TQH7, Q7Z4F1, Q86T13, Q86VR7, Q86VZ4, Q8BV57, Q8BZE1, Q8CB67, Q8VCP9, Q8WTU2, Q91V98, Q96DN2

Diamond homologs: A1A5Y0, A2VCU8, A4IGL7, A5A8Y8, A6QR11, B5DFC9, O75095, O88322, P07996, P10493, P14585, P35441, P35448, P82279, P98118, Q14112, Q20911, Q24025, Q28178, Q2PC93, Q2VWQ2, Q3MHH9, Q5FW85, Q5R3Z7, Q61220, Q62918, Q62919, Q6AZ60, Q6GUQ1, Q6MG84, Q75N90, Q7T3Q2, Q7ZXL5, Q80T14, Q8AVH7, Q8AWW5, Q8VHS2, Q90827, Q90ZD5, Q91X17

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	128
Likely benign	11
Benign	3

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
599545	NM_152718.2(VWCE):c.1633C>T (p.Arg545Ter)	Pathogenic

SpliceAI

3480 predictions. Top by Δscore:

Variant	Effect	Δscore
11:61264951:CTCAC:C	donor_loss	1.0000
11:61264952:TCA:T	donor_loss	1.0000
11:61264953:CACCT:C	donor_loss	1.0000
11:61265034:GCAGT:G	acceptor_gain	1.0000
11:61265035:CAGT:C	acceptor_gain	1.0000
11:61265035:CAGTC:C	acceptor_gain	1.0000
11:61265036:AGT:A	acceptor_gain	1.0000
11:61265037:GT:G	acceptor_gain	1.0000
11:61265037:GTCTG:G	acceptor_loss	1.0000
11:61265038:TCTGT:T	acceptor_loss	1.0000
11:61265039:C:CC	acceptor_gain	1.0000
11:61265039:CT:C	acceptor_loss	1.0000
11:61265041:G:C	acceptor_gain	1.0000
11:61286427:ATGTC:A	acceptor_loss	1.0000
11:61286428:TGT:T	acceptor_gain	1.0000
11:61286428:TGTC:T	acceptor_loss	1.0000
11:61286430:TCTGG:T	acceptor_loss	1.0000
11:61286431:C:CC	acceptor_gain	1.0000
11:61286431:CTGG:C	acceptor_loss	1.0000
11:61286432:T:A	acceptor_loss	1.0000
11:61294922:GCTTA:G	donor_loss	1.0000
11:61294923:CTTAC:C	donor_loss	1.0000
11:61294924:TTAC:T	donor_loss	1.0000
11:61294925:TACCT:T	donor_loss	1.0000
11:61264482:CTTA:C	donor_loss	0.9900
11:61264483:TTAC:T	donor_loss	0.9900
11:61264484:TA:T	donor_loss	0.9900
11:61264486:C:CT	donor_loss	0.9900
11:61264572:TCCCA:T	acceptor_gain	0.9900
11:61264573:CCCAG:C	acceptor_gain	0.9900

AlphaMissense

6103 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:61291516:C:A	W57C	1.000
11:61291516:C:G	W57C	1.000
11:61267465:G:C	C654W	0.999
11:61267467:A:G	C654R	0.999
11:61271711:C:A	W583C	0.999
11:61271711:C:G	W583C	0.999
11:61290804:C:G	C140S	0.999
11:61290805:A:T	C140S	0.999
11:61290850:A:G	C125R	0.999
11:61265196:C:T	C661Y	0.998
11:61265197:A:G	C661R	0.998
11:61267466:C:T	C654Y	0.998
11:61267471:G:C	C652W	0.998
11:61267473:A:G	C652R	0.998
11:61267502:A:C	F642C	0.998
11:61267541:C:G	C629S	0.998
11:61267542:A:G	C629R	0.998
11:61267542:A:T	C629S	0.998
11:61271686:A:G	C592R	0.998
11:61282866:C:G	C194S	0.998
11:61282867:A:T	C194S	0.998
11:61290805:A:G	C140R	0.998
11:61290836:G:C	F129L	0.998
11:61290836:G:T	F129L	0.998
11:61290837:A:C	F129C	0.998
11:61290838:A:G	F129L	0.998
11:61290848:G:C	C125W	0.998
11:61290849:C:G	C125S	0.998
11:61290849:C:T	C125Y	0.998
11:61290850:A:T	C125S	0.998

dbSNP variants (sampled 300 via entrez): RS1000005426 (11:61294270 C>A), RS1000052842 (11:61287501 G>A), RS1000282236 (11:61261452 A>T), RS1000291661 (11:61269169 A>G,T), RS1000348749 (11:61261598 T>G), RS1000367617 (11:61267662 G>A), RS1000407490 (11:61268879 A>G), RS1000452817 (11:61280768 A>G), RS1000619306 (11:61267280 A>C), RS1000717615 (11:61261729 C>A), RS1000825612 (11:61286153 A>C), RS1000865539 (11:61267334 G>C), RS1000955056 (11:61292043 T>A,C), RS1001135449 (11:61291592 G>T), RS1001166188 (11:61293757 G>GCAC)

Disease associations

OMIM: gene MIM:611115 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	increases expression, increases methylation	5
Aflatoxin B1	affects expression, decreases methylation, increases expression, increases methylation	5
Tetrachlorodibenzodioxin	affects expression, increases expression	3
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Tobacco Smoke Pollution	decreases expression	2
Valproic Acid	affects expression, decreases expression	2
aristolochic acid I	increases expression	1
dicrotophos	increases expression	1
tungsten carbide	increases expression, affects cotreatment	1
propionaldehyde	increases expression	1
trichostatin A	increases expression	1
sodium arsenite	increases expression	1
2-palmitoylglycerol	increases 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, increases expression	1
abrine	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
jinfukang	affects cotreatment, increases expression	1
Rosiglitazone	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Air Pollutants	increases abundance, affects expression	1
Cisplatin	affects cotreatment, increases expression	1
Cobalt	affects cotreatment, increases expression	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Doxorubicin	increases expression	1
Formaldehyde	increases expression	1
Hydrogen Peroxide	affects expression	1
Ibuprofen	decreases expression	1
Methyl Methanesulfonate	increases expression	1
Methylcholanthrene	affects binding, increases reaction	1

Clinical trials (associated diseases)

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