VWA3A

Summary

VWA3A (von Willebrand factor A domain containing 3A, HGNC:27088) is a protein-coding gene on chromosome 16p12.2, encoding von Willebrand factor A domain-containing protein 3A (A6NCI4).

Predicted to be located in extracellular region.

Source: NCBI Gene 146177 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 211 total
• MANE Select transcript: NM_173615

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:27088
Approved symbol	VWA3A
Name	von Willebrand factor A domain containing 3A
Location	16p12.2
Locus type	gene with protein product
Status	Approved
Aliases	FLJ46765, FLJ40941
Ensembl gene	ENSG00000175267
Ensembl biotype	protein_coding
OMIM	621113
Entrez	146177

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 6 protein_coding, 2 retained_intron, 1 nonsense_mediated_decay

ENST00000299840, ENST00000389398, ENST00000562340, ENST00000563389, ENST00000563755, ENST00000566668, ENST00000567131, ENST00000568328, ENST00000877573

RefSeq mRNA: 1 — MANE Select: NM_173615 NM_173615

CCDS: CCDS45441

Canonical transcript exons

ENST00000389398 — 34 exons

Exon	Start	End
ENSE00002614196	22156032	22156964
ENSE00003461351	22134368	22134438
ENSE00003466134	22126178	22126297
ENSE00003473632	22118902	22119027
ENSE00003481590	22123613	22123707
ENSE00003485826	22155851	22155916
ENSE00003491465	22131205	22131279
ENSE00003498551	22132900	22133095
ENSE00003512140	22152511	22152634
ENSE00003514883	22150695	22150846
ENSE00003517326	22131585	22131729
ENSE00003518523	22100416	22100493
ENSE00003525427	22120968	22121103
ENSE00003534289	22142668	22142765
ENSE00003543867	22140154	22140244
ENSE00003550495	22116759	22116867
ENSE00003562194	22110888	22110994
ENSE00003568785	22144247	22144384
ENSE00003589907	22121514	22121617
ENSE00003592457	22117111	22117176
ENSE00003594019	22123085	22123165
ENSE00003619792	22100194	22100318
ENSE00003635292	22115347	22115472
ENSE00003643328	22103475	22103529
ENSE00003648433	22146236	22146344
ENSE00003660180	22149787	22149931
ENSE00003665280	22097572	22097695
ENSE00003669973	22109482	22109580
ENSE00003673607	22138360	22138512
ENSE00003677604	22141582	22141692
ENSE00003681268	22148162	22148306
ENSE00003687843	22155567	22155664
ENSE00003690195	22096859	22096945
ENSE00003850023	22092541	22092651

Expression profiles

Bgee: expression breadth ubiquitous, 171 present calls, max score 99.51.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.8719 / max 100.4753, expressed in 140 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
153123	0.8719	140

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	99.51	gold quality
superficial temporal artery	UBERON:0001614	97.06	silver quality
mucosa of paranasal sinus	UBERON:0005030	96.15	gold quality
bronchial epithelial cell	CL:0002328	94.97	gold quality
bronchus	UBERON:0002185	94.73	gold quality
gingival epithelium	UBERON:0001949	92.80	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	91.49	gold quality
epithelium of nasopharynx	UBERON:0001951	90.51	silver quality
nasopharynx	UBERON:0001728	90.49	silver quality
vena cava	UBERON:0004087	90.42	silver quality
superior vestibular nucleus	UBERON:0007227	89.57	silver quality
superior surface of tongue	UBERON:0007371	89.19	silver quality
oviduct epithelium	UBERON:0004804	89.13	gold quality
body of tongue	UBERON:0011876	89.03	gold quality
tongue	UBERON:0001723	88.78	gold quality
medulla oblongata	UBERON:0001896	88.54	silver quality
fallopian tube	UBERON:0003889	88.53	gold quality
trachea	UBERON:0003126	88.48	gold quality
pericardium	UBERON:0002407	88.42	gold quality
lower lobe of lung	UBERON:0008949	88.36	silver quality
pons	UBERON:0000988	87.92	gold quality
nipple	UBERON:0002030	87.15	gold quality
pituitary gland	UBERON:0000007	87.13	gold quality
germinal epithelium of ovary	UBERON:0001304	86.89	silver quality
lateral nuclear group of thalamus	UBERON:0002736	86.72	gold quality
nasal cavity epithelium	UBERON:0005384	86.63	gold quality
adenohypophysis	UBERON:0002196	86.36	gold quality
mammary duct	UBERON:0001765	86.29	gold quality
cardiac muscle of right atrium	UBERON:0003379	86.24	gold quality
epithelium of mammary gland	UBERON:0003244	86.21	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	11.19

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

47 targeting VWA3A, 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-6798-5P	100.00	65.77	699
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-6744-5P	99.93	66.82	748
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-6764-5P	99.75	67.89	2304
HSA-MIR-1255A	99.74	68.09	744
HSA-MIR-1255B-5P	99.74	68.16	741
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-561-3P	99.64	70.90	3647
HSA-MIR-4516	99.61	67.78	3390
HSA-MIR-1915-3P	99.58	66.79	1988
HSA-MIR-762	99.58	66.61	1994
HSA-MIR-1207-5P	99.49	69.11	2983
HSA-MIR-4498	99.47	67.42	2360
HSA-MIR-6722-3P	99.45	67.62	1919
HSA-MIR-520A-5P	99.35	66.72	1632
HSA-MIR-525-5P	99.35	66.85	1615
HSA-MIR-4434	99.10	67.01	1984
HSA-MIR-5703	99.10	67.09	2053
HSA-MIR-4763-3P	99.10	67.83	2649
HSA-MIR-5001-5P	99.05	66.76	1972
HSA-MIR-1909-3P	99.03	66.56	1662
HSA-MIR-6877-3P	98.98	65.83	560
HSA-MIR-6819-3P	98.95	65.57	572
HSA-MIR-6889-3P	98.84	67.35	1198
HSA-MIR-5197-3P	98.71	67.05	1905

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	vwa3a	ENSDARG00000087210
mus_musculus	Vwa3a	ENSMUSG00000030889
rattus_norvegicus	Vwa3a	ENSRNOG00000025110

Paralogs (11): ITIH4 (ENSG00000055955), ITIH1 (ENSG00000055957), ITIH6 (ENSG00000102313), PARP4 (ENSG00000102699), VWA5A (ENSG00000110002), ITIH5 (ENSG00000123243), VWA5B2 (ENSG00000145198), ITIH2 (ENSG00000151655), VWA5B1 (ENSG00000158816), ITIH3 (ENSG00000162267), VWA3B (ENSG00000168658)

Protein

Protein identifiers

von Willebrand factor A domain-containing protein 3A — A6NCI4 (reviewed: A6NCI4)

All UniProt accessions (5): A6NCI4, H3BTG8, H3BTX3, H3BUS3, H7BXL8

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Secreted.

Isoforms (4)

UniProt ID	Names	Canonical?
A6NCI4-1	1	yes
A6NCI4-2	2
A6NCI4-3	3
A6NCI4-4	4

RefSeq proteins (1): NP_775886* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002035	VWF_A	Domain
IPR036465	vWFA_dom_sf	Homologous_superfamily

Pfam: PF13768

UniProt features (19 total): splice variant 4, sequence variant 3, sequence conflict 2, domain 2, region of interest 2, compositionally biased region 2, signal peptide 1, chain 1, coiled-coil region 1, glycosylation site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A6NCI4-F1	74.14	0.31

Functional residue map

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

Glycosylation sites (1): 709

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 53 (showing top): GSE45365_NK_CELL_VS_CD11B_DC_UP, chr16p12, LEIN_CHOROID_PLEXUS_MARKERS, DODD_NASOPHARYNGEAL_CARCINOMA_DN, MIKKELSEN_IPS_LCP_WITH_H3K4ME3, MIKKELSEN_ES_LCP_WITH_H3K4ME3, NABA_ECM_GLYCOPROTEINS, MIR4492, MIR6764_5P, MIR924, MIR5192, GSE13485_CTRL_VS_DAY1_YF17D_VACCINE_PBMC_DN, GSE13485_DAY1_VS_DAY3_YF17D_VACCINE_PBMC_UP, GSE13485_DAY1_VS_DAY7_YF17D_VACCINE_PBMC_UP, MANNO_MIDBRAIN_NEUROTYPES_HRGL2C

GO Biological Process (0):

GO Molecular Function (0):

GO Cellular Component (1): extracellular region (GO:0005576)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	1

Protein interactions and networks

STRING

512 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
VWA3A	PDZD9	Q8IXQ8	753
VWA3A	POLR3E	Q9NVU0	620
VWA3A	MOSMO	Q8NHV5	584
VWA3A	CFAP144	A6NL82	540
VWA3A	DRC10	Q96DY2	539
VWA3A	MYCBPAP	Q8TBZ2	514
VWA3A	OR5T1	Q8NG75	479
VWA3A	SNRPF	P62306	478
VWA3A	ARMC3	Q5W041	476
VWA3A	DRC5	Q5JU00	457
VWA3A	WDR19	Q8NEZ3	448
VWA3A	ZC2HC1C	Q53FD0	446
VWA3A	ZBBX	A8MT70	435
VWA3A	EEF2K	O00418	430
VWA3A	EFCAB6	Q5THR3	420
VWA3A	OR1Q1	Q15612	420

IntAct

2 interactions, top by confidence:

A	B	Type	Score
VWA3A	H1-4	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (5): VWA3A (Synthetic Lethality), HIST1H1E (Proximity Label-MS), VWA3A (Affinity Capture-MS), PNO1 (Cross-Linking-MS (XL-MS)), VWA3A (Cross-Linking-MS (XL-MS))

ESM2 similar proteins: A0JPF9, A1A5Q7, A2RT67, A2RUS2, A4D126, A5PKL6, A6NCI4, A6QPR9, D4ACE5, E9PYK3, F1ND48, Q05AA6, Q09M05, Q13474, Q15061, Q32PJ3, Q3TTL0, Q3UMR0, Q3UVV9, Q3UY96, Q498D5, Q49MI3, Q4R6Y8, Q4U2V3, Q502W6, Q5F204, Q5JPI3, Q5M8J0, Q5REW9, Q5RL51, Q5XIJ6, Q6DJG6, Q6RI63, Q7TNH6, Q7TPQ3, Q80V94, Q8BSE0, Q8CEL2, Q8IZC4, Q8N392

Diamond homologs: A1A5Q7, A6NCI4, Q14624, Q29052, Q3T052, Q3UVV9, A2VE29, A6X935, O02668, P19823, P19827, P56652, P79263, P97278, P97279, P97280, Q06033, Q0VCM5, Q5RB37, Q5RER0, Q61702, Q61703, Q61704, Q63416, Q6UXX5, Q86UX2, Q8BJD1, Q8CFG5, Q8IZS8, Q9GLY5, Q9Z1L5, A8XP97, P34374, Q9ZQ46

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	176
Likely benign	14
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

5242 predictions. Top by Δscore:

Variant	Effect	Δscore
16:22100314:GTGCT:G	donor_gain	1.0000
16:22100316:GCT:G	donor_gain	1.0000
16:22100319:G:GG	donor_gain	1.0000
16:22109578:ATGG:A	donor_loss	1.0000
16:22109581:G:GA	donor_loss	1.0000
16:22109582:T:G	donor_loss	1.0000
16:22110978:G:GT	donor_gain	1.0000
16:22110994:CGT:C	donor_loss	1.0000
16:22110995:G:GG	donor_gain	1.0000
16:22110995:G:T	donor_loss	1.0000
16:22110996:T:A	donor_loss	1.0000
16:22110997:G:GT	donor_loss	1.0000
16:22115345:A:AG	acceptor_gain	1.0000
16:22115346:G:GT	acceptor_gain	1.0000
16:22115346:GC:G	acceptor_gain	1.0000
16:22115346:GCC:G	acceptor_gain	1.0000
16:22115468:AGCTG:A	donor_gain	1.0000
16:22115469:GCTG:G	donor_gain	1.0000
16:22115469:GCTGG:G	donor_gain	1.0000
16:22115471:TGG:T	donor_loss	1.0000
16:22115472:GGTAG:G	donor_loss	1.0000
16:22115473:G:GG	donor_gain	1.0000
16:22115473:GTA:G	donor_loss	1.0000
16:22116745:T:A	acceptor_gain	1.0000
16:22116755:A:AG	acceptor_gain	1.0000
16:22116756:C:G	acceptor_gain	1.0000
16:22116757:A:AG	acceptor_gain	1.0000
16:22116757:A:T	acceptor_loss	1.0000
16:22116758:G:GT	acceptor_gain	1.0000
16:22116758:GC:G	acceptor_gain	1.0000

AlphaMissense

7847 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:22123106:T:A	W460R	0.992
16:22123106:T:C	W460R	0.992
16:22123685:T:A	W504R	0.988
16:22123685:T:C	W504R	0.988
16:22134379:A:C	S694R	0.988
16:22134381:C:A	S694R	0.988
16:22134381:C:G	S694R	0.988
16:22121079:T:A	W410R	0.987
16:22121079:T:C	W410R	0.987
16:22142757:A:C	S862R	0.985
16:22142759:C:A	S862R	0.985
16:22142759:C:G	S862R	0.985
16:22123673:A:C	S500R	0.982
16:22123675:C:A	S500R	0.982
16:22123675:C:G	S500R	0.982
16:22144247:T:A	W865R	0.981
16:22144247:T:C	W865R	0.981
16:22123108:G:C	W460C	0.980
16:22123108:G:T	W460C	0.980
16:22121555:T:C	F432L	0.979
16:22121557:C:A	F432L	0.979
16:22121557:C:G	F432L	0.979
16:22148207:T:A	I962K	0.978
16:22121573:T:C	F438L	0.977
16:22121575:T:A	F438L	0.977
16:22121575:T:G	F438L	0.977
16:22149803:T:C	F1001L	0.977
16:22149805:T:A	F1001L	0.977
16:22149805:T:G	F1001L	0.977
16:22123620:T:C	L482P	0.975

dbSNP variants (sampled 300 via entrez): RS1000032270 (16:22127795 T>C), RS1000058282 (16:22124503 A>C,T), RS1000100238 (16:22120676 C>A), RS1000189972 (16:22092497 T>A,C,G), RS1000210271 (16:22138680 C>T), RS1000259470 (16:22116366 GGAA>G), RS1000289228 (16:22130550 A>G), RS1000332688 (16:22144819 C>T), RS1000485218 (16:22151610 G>A,T), RS1000533708 (16:22096396 G>A), RS1000597121 (16:22103818 C>A,T), RS1000599380 (16:22148013 C>T), RS1000603574 (16:22138468 A>C), RS1000636590 (16:22126263 C>A,G,T), RS1000642082 (16:22131983 C>T)

Disease associations

OMIM: gene MIM:621113 | 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

15 total (human), top 15 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
aristolochic acid I	increases expression	1
pirinixic acid	increases activity, affects binding, decreases expression	1
sodium arsenite	affects expression	1
aflatoxin B2	increases methylation	1
ciguatoxin 1B (CTX 1B)	decreases expression	1
Grape Seed Proanthocyanidins	affects cotreatment, decreases expression	1
licochalcone B	increases expression	1
theaflavin-3,3’-digallate	affects expression	1
Arbutin	decreases expression	1
Arsenicals	increases methylation	1
Benzo(a)pyrene	decreases methylation	1
Caffeine	decreases phosphorylation	1
Catechin	affects cotreatment, decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Copper Sulfate	decreases expression	1

Clinical trials (associated diseases)

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