VWDE

Summary

VWDE (von Willebrand factor D and EGF domains, HGNC:21897) is a protein-coding gene on chromosome 7p21.3, encoding von Willebrand factor D and EGF domain-containing protein (Q8N2E2).

Predicted to enable signaling receptor binding activity. Predicted to be active in cell surface and extracellular region.

Source: NCBI Gene 221806 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 312 total — 1 likely-pathogenic
• MANE Select transcript: NM_001135924

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21897
Approved symbol	VWDE
Name	von Willebrand factor D and EGF domains
Location	7p21.3
Locus type	gene with protein product
Status	Approved
Aliases	FLJ14712
Ensembl gene	ENSG00000146530
Ensembl biotype	protein_coding
Entrez	221806

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 5 protein_coding, 3 nonsense_mediated_decay, 1 retained_intron

ENST00000275358, ENST00000326715, ENST00000452576, ENST00000485526, ENST00000521169, ENST00000644150, ENST00000649524, ENST00000930527, ENST00000941987

RefSeq mRNA: 3 — MANE Select: NM_001135924 NM_001135924, NM_001346972, NM_001346973

CCDS: CCDS47544

Canonical transcript exons

ENST00000275358 — 29 exons

Exon	Start	End
ENSE00001085089	12330885	12331197
ENSE00001230336	12389127	12389358
ENSE00001230347	12393594	12393778
ENSE00001421307	12403659	12403865
ENSE00001727793	12374689	12374762
ENSE00001741348	12372977	12373247
ENSE00001758250	12375010	12375227
ENSE00001766980	12377776	12377920
ENSE00003476930	12380486	12380733
ENSE00003478767	12344195	12344290
ENSE00003486595	12379477	12379566
ENSE00003487723	12370656	12370864
ENSE00003494254	12344374	12344469
ENSE00003502459	12343083	12343178
ENSE00003528352	12357265	12357515
ENSE00003532180	12383536	12383601
ENSE00003534441	12359578	12359692
ENSE00003549564	12356111	12356330
ENSE00003552404	12367357	12367493
ENSE00003556180	12333465	12333568
ENSE00003558497	12361147	12361251
ENSE00003568345	12336988	12337083
ENSE00003614835	12340322	12340417
ENSE00003620084	12369545	12370509
ENSE00003624344	12336141	12336236
ENSE00003641197	12337177	12337272
ENSE00003655765	12351573	12351713
ENSE00003662381	12361366	12361521
ENSE00003679821	12342059	12342154

Expression profiles

Bgee: expression breadth ubiquitous, 159 present calls, max score 81.59.

FANTOM5 (CAGE): breadth broad, TPM avg 5.5196 / max 227.0157, expressed in 540 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
82779	2.8005	468
82778	2.1561	264
82777	0.5630	61

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
pituitary gland	UBERON:0000007	81.59	gold quality
right uterine tube	UBERON:0001302	79.79	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	79.15	gold quality
right atrium auricular region	UBERON:0006631	78.23	gold quality
islet of Langerhans	UBERON:0000006	77.97	gold quality
adenohypophysis	UBERON:0002196	77.61	gold quality
cardiac atrium	UBERON:0002081	76.89	gold quality
left lobe of thyroid gland	UBERON:0001120	73.42	gold quality
corpus epididymis	UBERON:0004359	73.22	gold quality
right lobe of thyroid gland	UBERON:0001119	72.82	gold quality
thyroid gland	UBERON:0002046	72.78	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	72.39	gold quality
oviduct epithelium	UBERON:0004804	71.04	gold quality
parotid gland	UBERON:0001831	69.55	silver quality
fallopian tube	UBERON:0003889	67.07	gold quality
pancreas	UBERON:0001264	65.87	gold quality
saliva-secreting gland	UBERON:0001044	65.36	gold quality
nasal cavity mucosa	UBERON:0001826	64.18	gold quality
minor salivary gland	UBERON:0001830	63.96	gold quality
prostate gland	UBERON:0002367	62.95	gold quality
tibial nerve	UBERON:0001323	62.77	gold quality
caput epididymis	UBERON:0004358	62.04	gold quality
left uterine tube	UBERON:0001303	61.82	gold quality
pancreatic ductal cell	CL:0002079	61.57	silver quality
body of pancreas	UBERON:0001150	60.93	gold quality
mouth mucosa	UBERON:0003729	60.90	gold quality
ectocervix	UBERON:0012249	60.64	gold quality
metanephros cortex	UBERON:0010533	60.48	gold quality
lower esophagus mucosa	UBERON:0035834	60.21	gold quality
bone marrow cell	CL:0002092	59.94	silver quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-83139	yes	7.92
E-ANND-3	yes	7.34

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

25 targeting VWDE, 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-3924	100.00	72.09	2394
HSA-MIR-4760-3P	99.93	70.50	2385
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-4760-5P	99.80	69.88	1619
HSA-MIR-6745	99.74	65.33	1321
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-4756-3P	99.62	66.30	1319
HSA-MIR-363-5P	99.46	64.51	1015
HSA-MIR-4762-3P	99.43	69.72	2363
HSA-MIR-5695	99.41	67.48	1047
HSA-MIR-4251	99.40	69.19	3363
HSA-MIR-622	98.99	66.48	1050
HSA-MIR-361-5P	98.95	70.16	1340
HSA-MIR-3145-3P	98.85	69.07	2031
HSA-MIR-4656	98.79	66.22	1306
HSA-MIR-619-3P	98.38	65.58	693
HSA-MIR-4483	98.09	64.12	1642
HSA-MIR-876-5P	97.99	68.49	1345
HSA-MIR-4438	97.96	63.70	947
HSA-MIR-4446-3P	97.91	64.29	991
HSA-MIR-3074-3P	97.83	67.26	922
HSA-MIR-1293	96.16	64.69	916

Cross-species orthologs

1 orthologs

Organism	Symbol	Gene ID
danio_rerio	si:ch211-246m6.5	ENSDARG00000011673

Paralogs (6): FBLN1 (ENSG00000077942), EFEMP1 (ENSG00000115380), FBLN5 (ENSG00000140092), FBLN2 (ENSG00000163520), EFEMP2 (ENSG00000172638), EYS (ENSG00000188107)

Protein

Protein identifiers

von Willebrand factor D and EGF domain-containing protein — Q8N2E2 (reviewed: Q8N2E2)

All UniProt accessions (6): Q8N2E2, A0A0C4DH13, A0A2R8YEP3, A0A3B3IT21, E5RG96, J3KQJ9

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Secreted.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8N2E2-1	1	yes
Q8N2E2-3	2

RefSeq proteins (3): NP_001129396, NP_001333901, NP_001333902 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000742	EGF	Domain
IPR001846	VWF_type-D	Domain
IPR050969	Dev_Signal_Modulators	Family
IPR057774	D8C_UMOD/GP2/OIT3-like	Domain
IPR057885	Ig_VWDE	Domain
IPR058727	Helical_Vwde	Domain

Pfam: PF00094, PF23283, PF25776, PF26129

UniProt features (52 total): disulfide bond 27, domain 9, sequence variant 5, glycosylation site 3, sequence conflict 3, signal peptide 1, chain 1, region of interest 1, compositionally biased region 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8N2E2-F1	71.33	0.11

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 (27): 23–138, 55–152, 79–126, 85–156, 113–127, 425–565, 468–477, 1181–1189, 1183–1204, 1206–1215, 1298–1308, 1302–1314, 1316–1325, 1362–1372, 1366–1378, 1380–1389, 1426–1436, 1430–1442, 1444–1453, 1458–1468 …

Glycosylation sites (3): 367, 703, 968

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 32 (showing top): GOCC_CELL_SURFACE, ACEVEDO_LIVER_CANCER_WITH_H3K27ME3_UP, GOZGIT_ESR1_TARGETS_UP, JAATINEN_HEMATOPOIETIC_STEM_CELL_UP, GOMF_SIGNALING_RECEPTOR_BINDING, SENGUPTA_NASOPHARYNGEAL_CARCINOMA_WITH_LMP1_UP, ZWANG_DOWN_BY_2ND_EGF_PULSE, HOXC6_TARGET_GENES, NABA_ECM_GLYCOPROTEINS, MIR4760_3P, MIR6745, MIR363_5P, MIR4446_3P, MANNO_MIDBRAIN_NEUROTYPES_HNBM, MANNO_MIDBRAIN_NEUROTYPES_HNBML1

GO Biological Process (0):

GO Molecular Function (2): signaling receptor binding (GO:0005102), calcium ion binding (GO:0005509)

GO Cellular Component (2): extracellular region (GO:0005576), cell surface (GO:0009986)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
protein binding	1
metal ion binding	1

Protein interactions and networks

STRING

979 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
VWDE	TTC9C	Q8N5M4	561
VWDE	SMPDL3A	Q92484	493
VWDE	CDC40	O60508	425
VWDE	ARL4A	P40617	413
VWDE	GAS2L2	Q8NHY3	412
VWDE	TMEM106B	Q9NUM4	383
VWDE	THSD7A	Q9UPZ6	379
VWDE	CDC27	P30260	360
VWDE	MUC21	Q5SSG8	350
VWDE	OR13C2	Q8NGS9	348
VWDE	PNMA8A	Q86V59	342
VWDE	LAMB4	A4D0S4	341
VWDE	CEMIP	Q8WUJ3	336
VWDE	EGFLAM	Q63HQ2	331
VWDE	KLHDC1	Q8N7A1	328

IntAct

78 interactions, top by confidence:

A	B	Type	Score
SCGB1D1	FAM234B	psi-mi:“MI:0914”(association)	0.530
PSG8	PEX7	psi-mi:“MI:0914”(association)	0.530
DEFB121	COL6A2	psi-mi:“MI:0914”(association)	0.530
CTSG	MANBA	psi-mi:“MI:0914”(association)	0.530
CMA1	MANBA	psi-mi:“MI:0914”(association)	0.530
GREM2	ZZEF1	psi-mi:“MI:0914”(association)	0.530
IGFBP4	MYCBP2	psi-mi:“MI:0914”(association)	0.530
PRG2	ZSWIM8	psi-mi:“MI:0914”(association)	0.350
TAZ	MANBA	psi-mi:“MI:0914”(association)	0.350
LYZL2	MANBA	psi-mi:“MI:0914”(association)	0.350
LYPD1	HSPA5	psi-mi:“MI:0914”(association)	0.350
LLCFC1	POTEF	psi-mi:“MI:0914”(association)	0.350
RLN1	RTL8C	psi-mi:“MI:0914”(association)	0.350
CEACAM8	PRRT4	psi-mi:“MI:0914”(association)	0.350
GPIHBP1	SAC3D1	psi-mi:“MI:0914”(association)	0.350
IGFL3	CBX4	psi-mi:“MI:0914”(association)	0.350
CCL19	DCTN6	psi-mi:“MI:0914”(association)	0.350
NOG	TCAF2	psi-mi:“MI:0914”(association)	0.350
TAFAZZIN	MANBA	psi-mi:“MI:0914”(association)	0.350
MFAP5	MANBA	psi-mi:“MI:0914”(association)	0.350
DEFB135	MANBA	psi-mi:“MI:0914”(association)	0.350
LYZL2	ZZEF1	psi-mi:“MI:0914”(association)	0.350
PMCH	B4GALT5	psi-mi:“MI:0914”(association)	0.350
HYOU1	SNX2	psi-mi:“MI:0914”(association)	0.350
IL17F	TBL1X	psi-mi:“MI:0914”(association)	0.350
CCL26	TBL1X	psi-mi:“MI:0914”(association)	0.350

BioGRID (76): VWDE (Affinity Capture-MS), VWDE (Affinity Capture-MS), VWDE (Affinity Capture-MS), VWDE (Affinity Capture-MS), VWDE (Affinity Capture-MS), VWDE (Affinity Capture-MS), VWDE (Affinity Capture-MS), VWDE (Affinity Capture-MS), VWDE (Affinity Capture-MS), VWDE (Affinity Capture-MS), VWDE (Affinity Capture-RNA), VWDE (Affinity Capture-MS), VWDE (Affinity Capture-MS), VWDE (Affinity Capture-MS), VWDE (Affinity Capture-MS)

ESM2 similar proteins: A0A0B5GR44, A0A0D3QS97, A1L314, A4IH88, A7MCS3, B9DFR3, E7F0Z8, F4I107, F4I839, O35298, O54728, O80731, P38566, P38567, P38568, P70683, Q03311, Q0P6H9, Q3TTY0, Q3UUQ7, Q3V5L5, Q4V398, Q5GF25, Q5RBP9, Q60963, Q66GM8, Q6DBP4, Q6E279, Q6NQ51, Q75T13, Q765A7, Q765H6, Q812F3, Q84JS1, Q84WF0, Q8BG22, Q8BXJ9, Q8N2E2, Q93ZR8, Q940J8

Diamond homologs: O08523, O75443, P07911, P19218, P25291, P27590, P48733, P55259, Q5R5C1, Q66IR0, Q6DFV8, Q862Z3, Q8N2E2, Q91X17, Q9D733, Q9YH85, O08524, Q8R4V5, Q96PL2, Q5DID0, Q29RU2, Q6V0K7, Q8WWZ8, D3ZHH1, Q8K1E3

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	266
Likely benign	22
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
3779244	NM_001135924.3(VWDE):c.4759-36_4759-35del	Likely pathogenic

SpliceAI

4555 predictions. Top by Δscore:

Variant	Effect	Δscore
7:12336127:T:TA	donor_gain	1.0000
7:12336139:A:AC	donor_gain	1.0000
7:12336140:C:CC	donor_gain	1.0000
7:12337175:A:AC	donor_gain	1.0000
7:12337176:C:CC	donor_gain	1.0000
7:12340413:CAAAG:C	acceptor_gain	1.0000
7:12342150:AACCA:A	acceptor_gain	1.0000
7:12342152:CCA:C	acceptor_gain	1.0000
7:12342153:CAC:C	acceptor_gain	1.0000
7:12342162:CA:C	acceptor_gain	1.0000
7:12342163:A:AC	acceptor_gain	1.0000
7:12342163:A:C	acceptor_gain	1.0000
7:12343081:A:AC	donor_gain	1.0000
7:12343082:C:CC	donor_gain	1.0000
7:12344291:C:CC	acceptor_gain	1.0000
7:12344372:A:AC	donor_gain	1.0000
7:12344373:C:CC	donor_gain	1.0000
7:12344467:TGG:T	acceptor_gain	1.0000
7:12344470:C:CC	acceptor_gain	1.0000
7:12351564:ATTAC:A	donor_loss	1.0000
7:12351565:TTACT:T	donor_loss	1.0000
7:12351566:TACTT:T	donor_loss	1.0000
7:12351567:A:AC	donor_gain	1.0000
7:12351567:ACT:A	donor_loss	1.0000
7:12351568:C:CC	donor_gain	1.0000
7:12351568:CTTA:C	donor_gain	1.0000
7:12351568:CTTAC:C	donor_loss	1.0000
7:12351569:TTA:T	donor_loss	1.0000
7:12351570:TACT:T	donor_loss	1.0000
7:12351571:A:AC	donor_gain	1.0000

AlphaMissense

10576 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:12342066:A:C	C1421W	0.995
7:12342067:C:G	C1421S	0.994
7:12342068:A:G	C1421R	0.994
7:12342068:A:T	C1421S	0.994
7:12342118:C:G	C1404S	0.994
7:12342119:A:T	C1404S	0.994
7:12342136:C:G	C1398S	0.994
7:12342137:A:T	C1398S	0.994
7:12342067:C:T	C1421Y	0.993
7:12342100:C:G	C1410S	0.993
7:12342101:A:T	C1410S	0.993
7:12342119:A:G	C1404R	0.992
7:12343091:C:G	C1389S	0.992
7:12343092:A:T	C1389S	0.992
7:12342081:C:A	W1416C	0.991
7:12342081:C:G	W1416C	0.991
7:12342094:C:G	C1412S	0.991
7:12342095:A:T	C1412S	0.991
7:12342101:A:G	C1410R	0.991
7:12342136:C:T	C1398Y	0.990
7:12342067:C:A	C1421F	0.989
7:12342135:A:C	C1398W	0.989
7:12342137:A:G	C1398R	0.989
7:12342148:C:G	C1394S	0.989
7:12342149:A:T	C1394S	0.989
7:12342099:G:C	C1410W	0.988
7:12342149:A:G	C1394R	0.988
7:12343092:A:G	C1389R	0.988
7:12342095:A:G	C1412R	0.987
7:12342100:C:T	C1410Y	0.986

dbSNP variants (sampled 300 via entrez): RS1000032445 (7:12382844 T>G), RS1000061523 (7:12351902 T>A,C), RS1000107725 (7:12392876 C>A,G), RS1000126592 (7:12388762 G>T), RS1000152630 (7:12368628 A>G,T), RS1000178027 (7:12352102 C>A), RS1000234594 (7:12357572 C>A,T), RS1000245918 (7:12357347 C>T), RS1000279197 (7:12394049 C>A,T), RS1000370333 (7:12368789 G>C), RS1000383288 (7:12333811 A>C), RS1000387054 (7:12403668 A>C,T), RS1000427174 (7:12362757 T>C), RS1000440032 (7:12398870 C>A), RS1000444128 (7:12363087 A>G)

Disease associations

OMIM: gene `` | disease phenotypes: MIM:189800, MIM:618977

GenCC curated gene-disease

Mondo (2): preeclampsia (MONDO:0005081), optic atrophy 12 (MONDO:0033549)

Orphanet (1): Preeclampsia (Orphanet:275555)

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST005194_222	Coronary artery disease	2.000000e-06
GCST005839_11	Depression	3.000000e-08
GCST006952_28	Feeling tense	1.000000e-09
GCST010652_3	Early-onset ischemic stroke	9.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0009596	feeling tense measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D011225	Pre-Eclampsia	C12.050.703.395.249

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
Valproic Acid	affects cotreatment, decreases expression	5
trichostatin A	increases expression, decreases expression	2
sodium arsenite	affects cotreatment, decreases expression, increases abundance, increases expression	2
Benzo(a)pyrene	affects methylation, decreases methylation, increases expression	2
Phenylmercuric Acetate	decreases expression, affects cotreatment	2
aristolochic acid I	decreases expression	1
bisphenol F	affects cotreatment, decreases methylation	1
methylmercuric chloride	decreases expression	1
bisphenol A	affects cotreatment, decreases methylation	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
potassium chromate(VI)	increases expression	1
hydroquinone	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
dorsomorphin	affects cotreatment, decreases expression	1
Temozolomide	increases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Aldehydes	decreases expression	1
Arsenic	affects cotreatment, decreases expression, increases abundance	1
Carbamazepine	affects expression	1
Manganese	increases abundance, affects cotreatment, decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Triclosan	decreases expression	1
Cyclosporine	decreases expression	1
Aflatoxin B1	decreases methylation	1
Okadaic Acid	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00117546	PHASE4	UNKNOWN	Cardiovascular and Autonomic Reactivity in Women With a History of Pre-eclampsia
NCT00567957	PHASE4	UNKNOWN	Remifentanil for General Anesthesia in Preeclamptics
NCT01030627	PHASE4	COMPLETED	Treatment Approaches to Preeclampsia
NCT01352234	PHASE4	COMPLETED	Comparison of Doses of Acetylsalicylic Acid in Women With Previous History of Preeclampsia
NCT01361425	PHASE4	UNKNOWN	Anti-Hypertensive Treatment In Stable Pregnant Women With Severe Pre-Eclampsia (Metildopape)
NCT01729468	PHASE4	COMPLETED	Prevention of Pre-eclampsia and SGA by Low-Dose Aspirin in Nulliparous Women With Abnormal First-trimester Uterine Artery Dopplers
NCT01761916	PHASE4	COMPLETED	Clonidine Versus Captopril for Treatment of Postpartum Very High Blood Pressure
NCT01912677	PHASE4	COMPLETED	Oral Antihypertensive Regimens for Management of Hypertension in Pregnancy
NCT02025426	PHASE4	TERMINATED	Phenylephrine Versus Ephedrine in Pre-eclampsia
NCT02091401	PHASE4	COMPLETED	A Trial Comparing Treatment With the Springfusor Infusion Pump to the IV Magnesium Sulfate Regimen
NCT02163655	PHASE4	COMPLETED	Diuretics for Postpartum High Blood Pressure in Preeclampsia
NCT02338687	PHASE4	COMPLETED	Low Dose Calcium to Prevent Preeclampsia
NCT02396030	PHASE4	TERMINATED	Different Schemes of Magnesium Sulfate for Preeclampsia
NCT02531490	PHASE4	UNKNOWN	Early Vascular Adjustments During Hypertensive Pregnancy
NCT02699827	PHASE4	COMPLETED	Adding MgSO4 to Epidural Levobupivacaine in CS for Patients With Preeclampsia
NCT02835339	PHASE4	COMPLETED	Magnesium Sulfate in Obese Preeclamptics
NCT02891174	PHASE4	COMPLETED	The Effect of Ibuprofen on Post-partum Blood Pressure in Women With Hypertensive Disorders of Pregnancy
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