VWA3B

Summary

VWA3B (von Willebrand factor A domain containing 3B, HGNC:28385) is a protein-coding gene on chromosome 2q11.2, encoding von Willebrand factor A domain-containing protein 3B (Q502W6).

This gene encodes an intracellular protein that contains a von Willebrand factor type A domain. Intracellular proteins with VWA domains are thought to function in transcription, DNA repair, ribosomal and membrane transport and the proteasome. Mutations in this gene are associated with Spinocerebellar ataxia, autosomal recessive 22. Alternatively spliced transcript variants have been found for this gene.

Source: NCBI Gene 200403 — RefSeq curated summary.

At a glance

• Gene–disease (curated): spinocerebellar ataxia, autosomal recessive 22 (Limited, GenCC)
• GWAS associations: 5
• Clinical variants (ClinVar): 285 total — 1 pathogenic, 6 likely-pathogenic
• Phenotypes (HPO): 15
• MANE Select transcript: NM_144992

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28385
Approved symbol	VWA3B
Name	von Willebrand factor A domain containing 3B
Location	2q11.2
Locus type	gene with protein product
Status	Approved
Aliases	DKFZp686F2227, MGC26733
Ensembl gene	ENSG00000168658
Ensembl biotype	protein_coding
OMIM	614884
Entrez	200403

Gene structure

Transcript identifiers

Ensembl transcripts: 20 — 7 nonsense_mediated_decay, 7 protein_coding_CDS_not_defined, 3 retained_intron, 3 protein_coding

ENST00000409460, ENST00000416277, ENST00000422503, ENST00000432242, ENST00000433678, ENST00000448079, ENST00000448638, ENST00000463635, ENST00000465555, ENST00000465930, ENST00000466852, ENST00000473149, ENST00000477737, ENST00000483669, ENST00000484571, ENST00000485216, ENST00000489630, ENST00000489968, ENST00000490947, ENST00000495571

RefSeq mRNA: 2 — MANE Select: NM_144992 NM_001345864, NM_144992

CCDS: CCDS42718

Canonical transcript exons

ENST00000477737 — 28 exons

Exon	Start	End
ENSE00001914142	98312200	98313299
ENSE00001918645	98087167	98087363
ENSE00003486778	98236574	98236730
ENSE00003487666	98300079	98300216
ENSE00003492265	98303702	98303802
ENSE00003497929	98217846	98218028
ENSE00003501878	98187975	98188129
ENSE00003525712	98256124	98256174
ENSE00003533387	98121299	98121458
ENSE00003534360	98290511	98290622
ENSE00003545264	98194361	98194492
ENSE00003547175	98133824	98133939
ENSE00003550476	98162851	98162976
ENSE00003563123	98181016	98181212
ENSE00003566110	98128239	98128408
ENSE00003581839	98115652	98115746
ENSE00003590430	98211930	98212028
ENSE00003592695	98234648	98234767
ENSE00003594002	98311819	98312032
ENSE00003618566	98119513	98119763
ENSE00003644583	98250318	98250436
ENSE00003654569	98230050	98230207
ENSE00003658811	98270682	98270883
ENSE00003664426	98297907	98298031
ENSE00003668834	98236390	98236477
ENSE00003670635	98093061	98093288
ENSE00003676527	98192898	98193036
ENSE00003680604	98228202	98228332

Expression profiles

Bgee: expression breadth ubiquitous, 165 present calls, max score 98.96.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.3667 / max 113.2223, expressed in 107 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
21537	0.1529	53
21536	0.1195	52
21541	0.0395	17
21544	0.0222	3
21539	0.0161	5
21538	0.0095	4
21543	0.0036	3
21542	0.0033	2

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
bronchial epithelial cell	CL:0002328	98.96	gold quality
sperm	CL:0000019	98.91	gold quality
bronchus	UBERON:0002185	97.51	gold quality
right uterine tube	UBERON:0001302	96.36	gold quality
buccal mucosa cell	CL:0002336	95.22	gold quality
left testis	UBERON:0004533	94.64	gold quality
right testis	UBERON:0004534	94.61	gold quality
mucosa of paranasal sinus	UBERON:0005030	92.39	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	91.72	gold quality
testis	UBERON:0000473	91.16	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.38	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	82.86	gold quality
oviduct epithelium	UBERON:0004804	81.06	gold quality
fallopian tube	UBERON:0003889	79.93	gold quality
epithelium of nasopharynx	UBERON:0001951	76.57	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	73.54	gold quality
caput epididymis	UBERON:0004358	72.86	gold quality
ventricular zone	UBERON:0003053	71.74	gold quality
endothelial cell	CL:0000115	70.87	gold quality
nasal cavity mucosa	UBERON:0001826	70.17	gold quality
mucosa of transverse colon	UBERON:0004991	69.92	gold quality
right lung	UBERON:0002167	69.32	gold quality
adult organism	UBERON:0007023	67.38	gold quality
trachea	UBERON:0003126	65.31	gold quality
corpus callosum	UBERON:0002336	63.68	gold quality
amygdala	UBERON:0001876	63.03	gold quality
endometrium	UBERON:0001295	62.92	gold quality
hypothalamus	UBERON:0001898	62.57	gold quality
rectum	UBERON:0001052	62.50	gold quality
nasal cavity epithelium	UBERON:0005384	62.26	silver quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	9.74

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

24 targeting VWA3B, 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-3646	100.00	73.56	5283
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-6798-5P	100.00	65.77	699
HSA-MIR-3529-3P	99.90	73.55	3045
HSA-MIR-3133	99.81	70.92	3506
HSA-MIR-132-3P	99.73	70.56	1424
HSA-MIR-212-3P	99.73	70.65	1424
HSA-MIR-33A-3P	99.70	70.27	3362
HSA-MIR-6733-3P	99.54	67.80	1281
HSA-MIR-4437	99.52	65.29	1266
HSA-MIR-4735-5P	99.43	68.49	1780
HSA-MIR-302A-5P	99.39	68.21	1913
HSA-MIR-32-3P	99.36	68.20	2517
HSA-MIR-548V	99.29	69.47	1157
HSA-MIR-7160-5P	99.11	67.17	2207
HSA-MIR-625-5P	99.02	68.64	2031
HSA-MIR-4680-3P	98.64	68.60	2093
HSA-MIR-4773	98.35	67.30	1710
HSA-MIR-1262	98.17	66.52	757
HSA-MIR-4701-3P	98.17	66.25	788
HSA-MIR-6736-5P	98.17	66.43	760
HSA-MIR-1910-5P	97.42	66.36	844
HSA-MIR-576-3P	96.14	65.63	773
HSA-MIR-3944-3P	91.01	62.27	44

Literature-anchored findings (GeneRIF, showing 1)

• Mutated VWA3B was found to be likely associated with cerebellar degeneration with intellectual disability. Although a rare cause of cerebellar degeneration, these findings indicate a critical role for VWA3B in the apoptosis pathway in neuronal tissues. (PMID:26157035)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Vwa3b	ENSMUSG00000050122
rattus_norvegicus	Vwa3b	ENSRNOG00000023566

Paralogs (11): ITIH4 (ENSG00000055955), ITIH1 (ENSG00000055957), ITIH6 (ENSG00000102313), PARP4 (ENSG00000102699), VWA5A (ENSG00000110002), ITIH5 (ENSG00000123243), VWA5B2 (ENSG00000145198), ITIH2 (ENSG00000151655), VWA5B1 (ENSG00000158816), ITIH3 (ENSG00000162267), VWA3A (ENSG00000175267)

Protein

Protein identifiers

von Willebrand factor A domain-containing protein 3B — Q502W6 (reviewed: Q502W6)

All UniProt accessions (9): Q502W6, F8W737, F8WBX4, F8WD48, F8WD56, H0YCW7, H0YDS6, H0YEM4, H0YF54

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Cytoplasm.

Disease relevance. Spinocerebellar ataxia, autosomal recessive, 22 (SCAR22) [MIM:616948] A form of spinocerebellar ataxia, a clinically and genetically heterogeneous group of cerebellar disorders due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCAR22 patients manifest variable severity of intellectual disability associated with adult-onset cerebellar ataxia. The disease may be caused by variants affecting the gene represented in this entry.

Isoforms (8)

UniProt ID	Names	Canonical?
Q502W6-1	1	yes
Q502W6-2	2
Q502W6-3	3
Q502W6-4	4
Q502W6-5	5
Q502W6-6	6
Q502W6-7	7
Q502W6-8	8

RefSeq proteins (2): NP_001332793, NP_659429* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002035	VWF_A	Domain
IPR032770	DUF4537	Domain
IPR036465	vWFA_dom_sf	Homologous_superfamily

Pfam: PF13768, PF15057

UniProt features (37 total): splice variant 11, sequence variant 9, sequence conflict 6, compositionally biased region 5, region of interest 4, chain 1, domain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q502W6-F1	69.26	0.16

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 79 (showing top): SENGUPTA_NASOPHARYNGEAL_CARCINOMA_DN, chr2q11, DODD_NASOPHARYNGEAL_CARCINOMA_DN, TGATTTRY_GFI1_01, EGR_Q6, MYC_UP.V1_UP, SRC_UP.V1_UP, GREB1_TARGET_GENES, NABA_ECM_GLYCOPROTEINS, ZBTB12_TARGET_GENES, ZBTB18_TARGET_GENES, MIR3646, MIR3133, MIR32_3P, MIR4735_5P

GO Biological Process (0):

GO Molecular Function (0):

GO Cellular Component (3): nucleoplasm (GO:0005654), cytosol (GO:0005829), cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
nuclear lumen	1
cytoplasm	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

676 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
VWA3B	TOM1L1	O75674	478
VWA3B	OR2L2	Q8NH16	447
VWA3B	FAHD2B	Q6P2I3	419
VWA3B	FAM178B	Q8IXR5	399
VWA3B	ZNF514	Q96K75	397
VWA3B	ANKRD39	Q53RE8	397
VWA3B	FAHD2A	Q96GK7	370
VWA3B	CFAP47	Q6ZTR5	370
VWA3B	ANKRD36B	Q8N2N9	351
VWA3B	TMEM248	Q9NWD8	348
VWA3B	BTBD9	Q96Q07	323
VWA3B	ITPRIPL1	Q6GPH6	321
VWA3B	SH3TC2	Q8TF17	318
VWA3B	FER1L5	A0AVI2	310
VWA3B	TTC1	Q99614	308

IntAct

3 interactions, top by confidence:

A	B	Type	Score
VWA3B	SIRT1	psi-mi:“MI:0915”(physical association)	0.400
VWA3B	SERPINB7	psi-mi:“MI:0914”(association)	0.350

BioGRID (14): SIRT1 (Affinity Capture-MS), INA (Affinity Capture-MS), SIRT1 (Affinity Capture-MS), SERPINB7 (Affinity Capture-MS), ARG1 (Affinity Capture-MS), TGM3 (Affinity Capture-MS), GSDMA (Affinity Capture-MS), CTSH (Affinity Capture-MS), SERPINA12 (Affinity Capture-MS), KPRP (Affinity Capture-MS), AZGP1 (Affinity Capture-MS), HAL (Affinity Capture-MS), VWA3B (Cross-Linking-MS (XL-MS)), VWA3B (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

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	6
Uncertain significance	192
Likely benign	41
Benign	20

Top pathogenic / likely-pathogenic (7)

Variant ID	HGVS	Classification
226428	NM_144992.5(VWA3B):c.1865A>C (p.Lys622Thr)	Pathogenic
1808615	GRCh37/hg19 2q11.1-11.2(chr2:95341388-100340514)x3	Likely pathogenic
4845934	NM_144992.5(VWA3B):c.402del (p.Phe134fs)	Likely pathogenic
4849280	NM_144992.5(VWA3B):c.2072del (p.Leu691fs)	Likely pathogenic
4849329	NM_144992.5(VWA3B):c.3688_3713delinsTGCC (p.Gly1230fs)	Likely pathogenic
4849369	NM_144992.5(VWA3B):c.3014del (p.Lys1005fs)	Likely pathogenic
4849393	NM_144992.5(VWA3B):c.592dup (p.Glu198fs)	Likely pathogenic

SpliceAI

5279 predictions. Top by Δscore:

Variant	Effect	Δscore
2:98119501:A:AG	acceptor_gain	1.0000
2:98119502:T:G	acceptor_gain	1.0000
2:98119507:A:AG	acceptor_gain	1.0000
2:98119508:T:G	acceptor_gain	1.0000
2:98119510:A:AG	acceptor_gain	1.0000
2:98119510:AAGCT:A	acceptor_gain	1.0000
2:98119511:A:AG	acceptor_gain	1.0000
2:98119512:G:GG	acceptor_gain	1.0000
2:98119760:TACG:T	donor_gain	1.0000
2:98119762:CGG:C	donor_loss	1.0000
2:98119763:GGT:G	donor_loss	1.0000
2:98119764:G:GG	donor_gain	1.0000
2:98119764:GTG:G	donor_loss	1.0000
2:98119765:T:A	donor_loss	1.0000
2:98119766:GAGT:G	donor_loss	1.0000
2:98120577:G:GT	donor_gain	1.0000
2:98120597:GT:G	donor_gain	1.0000
2:98121454:AGACT:A	donor_gain	1.0000
2:98121455:GACT:G	donor_gain	1.0000
2:98121455:GACTG:G	donor_gain	1.0000
2:98121459:G:GG	donor_gain	1.0000
2:98181208:GTGCG:G	donor_gain	1.0000
2:98181213:G:GG	donor_gain	1.0000
2:98188127:G:GT	donor_gain	1.0000
2:98188147:G:GT	donor_gain	1.0000
2:98192892:GCCTA:G	acceptor_loss	1.0000
2:98192894:CTAG:C	acceptor_loss	1.0000
2:98192896:A:AG	acceptor_gain	1.0000
2:98192896:A:AT	acceptor_loss	1.0000
2:98192897:G:GG	acceptor_gain	1.0000

AlphaMissense

8530 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:98300139:G:C	A1115P	0.999
2:98300146:T:A	V1117D	0.999
2:98300194:T:A	V1133D	0.999
2:98290590:C:A	A1042E	0.998
2:98290622:G:T	G1053W	0.998
2:98300137:C:A	P1114H	0.998
2:98303724:T:C	L1148P	0.998
2:98270827:G:C	A997P	0.997
2:98290589:G:C	A1042P	0.997
2:98290613:T:G	Y1050D	0.997
2:98297907:G:A	G1053E	0.997
2:98300092:T:A	V1099E	0.997
2:98303724:T:A	L1148H	0.997
2:98188017:T:C	F452L	0.996
2:98188019:T:A	F452L	0.996
2:98188019:T:G	F452L	0.996
2:98194400:T:C	F549L	0.996
2:98194402:T:A	F549L	0.996
2:98194402:T:G	F549L	0.996
2:98290584:T:A	V1040D	0.996
2:98290587:T:A	I1041N	0.996
2:98300086:A:T	D1097V	0.996
2:98300095:T:C	F1100S	0.996
2:98300130:T:G	Y1112D	0.996
2:98300140:C:A	A1115D	0.996
2:98181144:T:C	F415L	0.995
2:98181146:C:A	F415L	0.995
2:98181146:C:G	F415L	0.995
2:98290622:G:A	G1053R	0.995
2:98290622:G:C	G1053R	0.995

dbSNP variants (sampled 300 via entrez): RS1000012104 (2:98271586 G>A), RS1000026034 (2:98188231 G>A,T), RS1000065826 (2:98180464 T>G), RS1000068827 (2:98310815 G>A,C), RS1000085721 (2:98183978 A>G), RS1000103480 (2:98094660 T>G), RS1000116171 (2:98296920 AAT>A), RS1000117908 (2:98171620 A>G), RS1000140442 (2:98264446 C>G), RS1000148211 (2:98228251 A>G), RS1000156797 (2:98212217 G>T), RS1000190685 (2:98132473 T>A,C), RS1000191395 (2:98305293 G>A), RS1000208331 (2:98247133 G>T), RS1000215065 (2:98132125 A>G)

Disease associations

OMIM: gene MIM:614884 | disease phenotypes: MIM:616948

GenCC curated gene-disease

Disease	Classification	Inheritance
spinocerebellar ataxia, autosomal recessive 22	Limited	Autosomal recessive

Mondo (1): spinocerebellar ataxia, autosomal recessive 22 (MONDO:0014845)

Orphanet (0):

HPO phenotypes

15 total (15 of 15 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000639	Nystagmus
HP:0001249	Intellectual disability
HP:0001251	Ataxia
HP:0001260	Dysarthria
HP:0001272	Cerebellar atrophy
HP:0001310	Dysmetria
HP:0001347	Hyperreflexia
HP:0002061	Lower limb spasticity
HP:0002078	Truncal ataxia
HP:0002079	Hypoplasia of the corpus callosum
HP:0002080	Intention tremor
HP:0002317	Unsteady gait
HP:0003677	Slowly progressive
HP:0007256	Abnormal pyramidal sign

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST008922_1	Triacylglyceride levels	2.000000e-08
GCST009028_48	Adverse response to drug	1.000000e-07
GCST012167_4	Adiponectin levels	5.000000e-06
GCST012490_347	Femur bone mineral density x serum urate levels interaction	2.000000e-13
GCST012490_8	Femur bone mineral density x serum urate levels interaction	3.000000e-14

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004530	triglyceride measurement
EFO:0009658	adverse effect
EFO:0004502	adiponectin measurement
EFO:0004531	urate measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

13 total (human), top 13 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Aflatoxin B1	decreases methylation, increases methylation	2
GSK-J4	increases expression	1
bisphenol A	affects cotreatment, increases methylation	1
Zoledronic Acid	increases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Air Pollutants	increases abundance, increases expression	1
Arsenic	affects methylation	1
Benzo(a)pyrene	increases methylation, affects methylation	1
Ivermectin	decreases expression	1
Phthalic Acids	decreases methylation	1
Smoke	increases abundance, increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Copper Sulfate	affects expression	1

Clinical trials (associated diseases)

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