VWA5A

Summary

VWA5A (von Willebrand factor A domain containing 5A, HGNC:6658) is a protein-coding gene on chromosome 11q24.2, encoding von Willebrand factor A domain-containing protein 5A (O00534). May play a role in tumorigenesis as a tumor suppressor.

Located in nucleoplasm.

Source: NCBI Gene 4013 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 151 total
• MANE Select transcript: NM_001130142

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6658
Approved symbol	VWA5A
Name	von Willebrand factor A domain containing 5A
Location	11q24.2
Locus type	gene with protein product
Status	Approved
Aliases	BCSC-1
Ensembl gene	ENSG00000110002
Ensembl biotype	protein_coding
OMIM	602929
Entrez	4013

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 15 protein_coding, 1 retained_intron

ENST00000361352, ENST00000392744, ENST00000392748, ENST00000449321, ENST00000456829, ENST00000533623, ENST00000869346, ENST00000869347, ENST00000869348, ENST00000869349, ENST00000869350, ENST00000869351, ENST00000869352, ENST00000924261, ENST00000924262, ENST00000924263

RefSeq mRNA: 3 — MANE Select: NM_001130142 NM_001130142, NM_014622, NM_198315

CCDS: CCDS8444, CCDS8445

Canonical transcript exons

ENST00000456829 — 19 exons

Exon	Start	End
ENSE00000749259	124134920	124135034
ENSE00000749260	124136129	124136293
ENSE00000749261	124136574	124136674
ENSE00000749262	124137015	124137268
ENSE00000815424	124118189	124118411
ENSE00000815427	124122960	124123129
ENSE00000815428	124123366	124123454
ENSE00000991301	124123660	124123804
ENSE00000991302	124124237	124124316
ENSE00001162070	124117497	124117554
ENSE00001288991	124118975	124119089
ENSE00001289000	124118533	124118708
ENSE00001289009	124117673	124117875
ENSE00001608212	124116566	124116680
ENSE00002166166	124145866	124147721
ENSE00002173542	124115450	124115482
ENSE00003535482	124141598	124141741
ENSE00003561935	124142442	124142572
ENSE00003583107	124145237	124145363

Expression profiles

Bgee: expression breadth ubiquitous, 271 present calls, max score 95.81.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 16.9683 / max 1879.6349, expressed in 1504 samples.

FANTOM5 promoters (14 alternative TSS)

Promoter ID	TPM avg	Samples expressed
117337	16.4482	1503
117346	0.2310	20
117354	0.0487	14
117340	0.0483	12
117348	0.0299	11
117336	0.0272	10
117343	0.0251	10
117338	0.0241	12
117344	0.0229	9
117341	0.0204	9

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
islet of Langerhans	UBERON:0000006	95.81	gold quality
amniotic fluid	UBERON:0000173	94.85	gold quality
rectum	UBERON:0001052	94.29	gold quality
gall bladder	UBERON:0002110	93.18	gold quality
adenohypophysis	UBERON:0002196	93.03	gold quality
pancreatic ductal cell	CL:0002079	92.74	gold quality
palpebral conjunctiva	UBERON:0001812	92.66	gold quality
ileal mucosa	UBERON:0000331	92.61	gold quality
pituitary gland	UBERON:0000007	92.39	gold quality
mucosa of transverse colon	UBERON:0004991	91.94	gold quality
calcaneal tendon	UBERON:0003701	91.20	gold quality
epithelium of bronchus	UBERON:0002031	91.15	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	91.14	gold quality
nasal cavity epithelium	UBERON:0005384	90.99	gold quality
right adrenal gland	UBERON:0001233	90.86	gold quality
bronchus	UBERON:0002185	90.78	gold quality
transverse colon	UBERON:0001157	90.71	gold quality
minor salivary gland	UBERON:0001830	90.58	gold quality
bronchial epithelial cell	CL:0002328	90.56	gold quality
skin of hip	UBERON:0001554	90.42	gold quality
pancreas	UBERON:0001264	90.33	gold quality
left adrenal gland	UBERON:0001234	90.28	gold quality
descending thoracic aorta	UBERON:0002345	90.20	gold quality
right adrenal gland cortex	UBERON:0035827	90.02	gold quality
epithelial cell of pancreas	CL:0000083	89.98	gold quality
upper leg skin	UBERON:0004262	89.95	gold quality
small intestine Peyer’s patch	UBERON:0003454	89.84	gold quality
tendon of biceps brachii	UBERON:0008188	89.79	gold quality
hypothalamus	UBERON:0001898	89.77	gold quality
tendon	UBERON:0000043	89.75	gold quality

Single-cell (SCXA)

Detected in 18 experiment(s), a significant marker in 17.

Experiment	Marker?	Max mean expression
E-MTAB-9801	yes	3319.65
E-MTAB-9067	yes	1748.85
E-GEOD-93593	yes	694.07
E-GEOD-70580	yes	654.43
E-HCAD-1	yes	46.93
E-CURD-88	yes	41.23
E-MTAB-8410	yes	19.32
E-CURD-122	yes	15.40
E-MTAB-8142	yes	14.75
E-GEOD-130148	yes	13.65
E-CURD-112	yes	10.71
E-CURD-46	yes	9.17
E-MTAB-10042	yes	8.55
E-HCAD-10	yes	7.69
E-GEOD-135922	yes	7.20

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): GATA2

miRNA regulators (miRDB)

55 targeting VWA5A, 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-4425	100.00	67.59	1049
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-520G-5P	99.99	66.76	658
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-433-3P	99.98	69.37	1203
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-6755-5P	99.95	65.59	464
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-302A-3P	99.89	71.23	1777
HSA-MIR-302B-3P	99.89	71.23	1777
HSA-MIR-302C-3P	99.89	71.20	1778
HSA-MIR-302D-3P	99.89	71.25	1777
HSA-MIR-369-3P	99.85	70.52	2264
HSA-MIR-6875-3P	99.82	70.26	2983
HSA-MIR-4668-5P	99.79	70.58	3782
HSA-MIR-1197	99.70	67.75	1027
HSA-MIR-7106-5P	99.53	67.47	3574
HSA-MIR-3609	99.52	69.89	2587
HSA-MIR-548AH-5P	99.52	69.73	2626
HSA-MIR-3147	99.52	66.34	388
HSA-MIR-6081	99.48	66.07	1446
HSA-MIR-6505-3P	99.34	67.39	1071
HSA-MIR-20B-3P	99.29	67.05	784
HSA-MIR-410-3P	99.27	69.98	2457
HSA-MIR-3125	99.14	68.49	2269
HSA-MIR-4650-3P	99.01	68.39	1062
HSA-MIR-3916	98.99	68.04	2155

Literature-anchored findings (GeneRIF, showing 3)

• BCSC-1 suppression might play roles in tumorigenesis of some nasopharyngeal carcinomas (PMID:19656157)
• BCSC-1 binds to Sox10, which down regulates MITF, and results in a switch of melanoma cells from a proliferative to a migratory phenotype. (PMID:22594792)
• Identification of VWA5A as a novel biomarker for inhibiting metastasis in breast cancer by machine-learning based protein prioritization. (PMID:38291227)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
mus_musculus	Vwa5a	ENSMUSG00000023186
mus_musculus	AW551984	ENSMUSG00000038112
rattus_norvegicus	Vwa5a	ENSRNOG00000000195
rattus_norvegicus	Vwa5al1	ENSRNOG00000005960

Paralogs (11): ITIH4 (ENSG00000055955), ITIH1 (ENSG00000055957), ITIH6 (ENSG00000102313), PARP4 (ENSG00000102699), ITIH5 (ENSG00000123243), VWA5B2 (ENSG00000145198), ITIH2 (ENSG00000151655), VWA5B1 (ENSG00000158816), ITIH3 (ENSG00000162267), VWA3B (ENSG00000168658), VWA3A (ENSG00000175267)

Protein

Protein identifiers

von Willebrand factor A domain-containing protein 5A — O00534 (reviewed: O00534)

Alternative names: Breast cancer suppressor candidate 1, Loss of heterozygosity 11 chromosomal region 2 gene A protein

All UniProt accessions (2): O00534, B4DHS6

UniProt curated annotations — full annotation on UniProt →

Function. May play a role in tumorigenesis as a tumor suppressor. Altered expression of this protein and disruption of the molecular pathway it is involved in, may contribute directly to or modify tumorigenesis.

Tissue specificity. Expressed at low level in many tissues. Not expressed in 80% of tumor cell lines tested.

Isoforms (4)

UniProt ID	Names	Canonical?
O00534-1	1, c/f	yes
O00534-2	2, g
O00534-3	3, a/d
O00534-4	4, b/e

RefSeq proteins (3): NP_001123614, NP_055437, NP_938057 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002035	VWF_A	Domain
IPR013694	VIT	Domain
IPR036465	vWFA_dom_sf	Homologous_superfamily

Pfam: PF08487, PF13768

UniProt features (14 total): sequence variant 6, splice variant 5, domain 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O00534-F1	84.61	0.65

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 217 (showing top): BROWNE_HCMV_INFECTION_30MIN_DN, GCANCTGNY_MYOD_Q6, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, LINDGREN_BLADDER_CANCER_CLUSTER_3_DN, AAAYRNCTG_UNKNOWN, CAGCTG_AP4_Q5, DAVICIONI_RHABDOMYOSARCOMA_PAX_FOXO1_FUSION_UP, GARGALOVIC_RESPONSE_TO_OXIDIZED_PHOSPHOLIPIDS_BLUE_DN, SENGUPTA_NASOPHARYNGEAL_CARCINOMA_DN, SCHAEFFER_PROSTATE_DEVELOPMENT_6HR_UP, BROWNE_HCMV_INFECTION_24HR_DN, RYTTCCTG_ETS2_B, HOOI_ST7_TARGETS_DN, RODRIGUES_DCC_TARGETS_DN, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_DN

GO Biological Process (0):

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (1): nucleoplasm (GO:0005654)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	1
nuclear lumen	1
cellular anatomical structure	1

Protein interactions and networks

STRING

703 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
VWA5A	SOX10	P56693	654
VWA5A	SPDYE6	P0CI01	507
VWA5A	TUT4	Q5TAX3	480
VWA5A	TMEM63C	Q9P1W3	459
VWA5A	SNX15	Q9NRS6	458
VWA5A	RNF150	Q9ULK6	451
VWA5A	PXMP2	Q9NR77	436
VWA5A	CILP2	Q8IUL8	414
VWA5A	MTBP	Q96DY7	412
VWA5A	ERLIN2	O94905	400
VWA5A	COX15	Q7KZN9	398
VWA5A	AOC1	P19801	388
VWA5A	HSD17B1	P14061	380
VWA5A	A0A2R8Y6X2	A0A2R8Y6X2	372
VWA5A	FITM1	A5D6W6	371

IntAct

17 interactions, top by confidence:

A	B	Type	Score
VWA5A	MEOX2	psi-mi:“MI:0915”(physical association)	0.560
	VWA5A	psi-mi:“MI:0915”(physical association)	0.560
VWA5A	SPSB1	psi-mi:“MI:0915”(physical association)	0.560
VWA5A	PRTFDC1	psi-mi:“MI:0915”(physical association)	0.560
STX17	A2ML1	psi-mi:“MI:0914”(association)	0.350
VWA5A	GTPBP6	psi-mi:“MI:0914”(association)	0.350
PRPS2	ARHGEF37	psi-mi:“MI:0914”(association)	0.350
TXNL4B	VWA5A	psi-mi:“MI:0914”(association)	0.350
VWA5A	PRTFDC1	psi-mi:“MI:0915”(physical association)	0.000
VWA5A	MEOX2	psi-mi:“MI:0915”(physical association)	0.000
VWA5A		psi-mi:“MI:0915”(physical association)	0.000
VWA5A	SPSB1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (73): VWA5A (Reconstituted Complex), MCM9 (Affinity Capture-MS), CREBZF (Affinity Capture-MS), MAN2C1 (Affinity Capture-MS), PKNOX2 (Affinity Capture-MS), PBX3 (Affinity Capture-MS), ARMCX3 (Affinity Capture-MS), HIC2 (Affinity Capture-MS), PTPN23 (Affinity Capture-MS), PBX1 (Affinity Capture-MS), ADD3 (Affinity Capture-MS), MCM8 (Affinity Capture-MS), UBB (Affinity Capture-MS), PEAK1 (Affinity Capture-MS), SETX (Affinity Capture-MS)

ESM2 similar proteins: A0A0R4IMY7, A0A0R4IY06, A0JPF9, A2AP18, A5PJN5, C0IN03, D2KX21, E1BVR9, E9PYK3, F1ND48, O00534, O75038, O94952, O95237, P0C1Q3, P53817, Q1LWG4, Q1LZ50, Q32PY6, Q4R3W5, Q4R6L3, Q5M7X9, Q5R5S1, Q5RJG7, Q5S6T3, Q5T8I9, Q6DC39, Q75WE7, Q7Z5M8, Q7ZU92, Q8BYI6, Q8C0L6, Q8CAE2, Q8CAS9, Q8K3R3, Q8NHH9, Q8SPR7, Q8VDH1, Q90678, Q93V51

Diamond homologs: A9Z1V5, C7G046, O00534, Q3UR50, Q54CQ8, Q54DU5, Q54DV3, Q54MG1, Q54MG4, Q55G98, Q5TIE3, Q75WE7, Q8N398, Q99KC8

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	109
Likely benign	10
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2602 predictions. Top by Δscore:

Variant	Effect	Δscore
11:124117667:CTCCA:C	acceptor_loss	1.0000
11:124117670:CA:C	acceptor_loss	1.0000
11:124117671:A:AG	acceptor_gain	1.0000
11:124117671:A:C	acceptor_loss	1.0000
11:124117671:AGT:A	acceptor_gain	1.0000
11:124117672:G:GA	acceptor_gain	1.0000
11:124117672:GT:G	acceptor_gain	1.0000
11:124117672:GTG:G	acceptor_gain	1.0000
11:124117672:GTGCC:G	acceptor_gain	1.0000
11:124117875:GG:G	donor_loss	1.0000
11:124118284:G:A	acceptor_gain	1.0000
11:124118970:CTCA:C	acceptor_loss	1.0000
11:124118972:CA:C	acceptor_loss	1.0000
11:124118973:A:AC	acceptor_loss	1.0000
11:124120738:T:TA	acceptor_gain	1.0000
11:124123125:CCAAG:C	donor_loss	1.0000
11:124123126:CAAG:C	donor_loss	1.0000
11:124123127:AAGG:A	donor_loss	1.0000
11:124123130:G:GA	donor_loss	1.0000
11:124123131:T:G	donor_loss	1.0000
11:124123455:G:GG	donor_gain	1.0000
11:124123655:CTCAG:C	acceptor_loss	1.0000
11:124123656:TCAGG:T	acceptor_loss	1.0000
11:124123657:CAG:C	acceptor_loss	1.0000
11:124123658:A:AG	acceptor_gain	1.0000
11:124123658:AG:A	acceptor_gain	1.0000
11:124123659:G:GG	acceptor_gain	1.0000
11:124123659:GG:G	acceptor_gain	1.0000
11:124123659:GGGA:G	acceptor_gain	1.0000
11:124123800:TACAG:T	donor_loss	1.0000

AlphaMissense

5192 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:124142498:T:A	W694R	0.994
11:124142498:T:C	W694R	0.994
11:124123426:T:C	F331L	0.993
11:124123428:T:A	F331L	0.993
11:124123428:T:G	F331L	0.993
11:124137115:A:C	S576R	0.990
11:124137117:C:A	S576R	0.990
11:124137117:C:G	S576R	0.990
11:124137136:A:C	S583R	0.989
11:124137138:C:A	S583R	0.989
11:124137138:C:G	S583R	0.989
11:124137148:G:C	A587P	0.988
11:124136186:T:A	W473R	0.987
11:124136186:T:C	W473R	0.987
11:124142500:G:C	W694C	0.985
11:124142500:G:T	W694C	0.985
11:124145315:T:A	W745R	0.985
11:124145315:T:C	W745R	0.985
11:124142482:A:C	Q688H	0.984
11:124142482:A:T	Q688H	0.984
11:124119018:T:C	L230P	0.982
11:124123373:T:C	L313P	0.981
11:124123062:G:C	R288P	0.980
11:124134921:T:C	C416R	0.980
11:124142499:G:C	W694S	0.980
11:124145336:G:C	A752P	0.980
11:124123050:T:C	F284S	0.978
11:124123053:T:C	L285P	0.978
11:124123411:T:C	F326L	0.978
11:124123413:C:A	F326L	0.978

dbSNP variants (sampled 300 via entrez): RS1000027527 (11:124119780 A>T), RS1000036042 (11:124128368 C>A), RS1000095752 (11:124127930 A>G), RS1000155719 (11:124137610 G>A), RS1000176817 (11:124145861 C>T), RS1000207640 (11:124129095 C>T), RS1000428307 (11:124128080 A>C), RS1000456257 (11:124136504 T>C), RS1000489035 (11:124136150 T>C), RS1000667591 (11:124129948 T>C), RS1000729274 (11:124138690 C>T), RS1000785396 (11:124145190 T>C), RS1000851274 (11:124122261 C>G), RS1000923278 (11:124121903 G>A,T), RS1001099612 (11:124138362 G>A)

Disease associations

OMIM: gene MIM:602929 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST001167_2	Aging (time to death)	2.000000e-06
GCST001762_56	Obesity-related traits	4.000000e-06
GCST001762_915	Obesity-related traits	9.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0022597	aging

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases expression	2
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression, increases expression	2
Benzo(a)pyrene	affects methylation, decreases expression	2
Rotenone	decreases expression	2
TAK-243	increases sumoylation	1
Esketamine	increases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	affects cotreatment, decreases methylation	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, decreases expression	1
beta-lapachone	increases expression	1
arsenite	increases methylation	1
sulforaphane	decreases expression	1
boron nitride	decreases expression	1
tobacco tar	decreases expression, decreases reaction	1
diallyl disulfide	decreases reaction, decreases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
CGP 52608	increases reaction, affects binding	1
abrine	decreases expression	1
Grape Seed Proanthocyanidins	affects cotreatment, increases expression	1
Sunitinib	decreases expression	1
Arsenic Trioxide	increases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Acetaminophen	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Calcitriol	increases expression, affects cotreatment	1
Catechin	affects cotreatment, increases expression	1
Cisplatin	affects response to substance	1
Folic Acid	decreases expression	1
Formaldehyde	increases expression	1

Clinical trials (associated diseases)

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