Details for: VWA3B

Gene ID: 200403

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: VWA3B

Ensembl ID: ENSG00000168658

Description: von Willebrand factor A domain containing 3B

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • ependymal cell CL0000065
    CSI 14.56
    rCSI 29.55%
    PRS 95.18
  • ciliated cell CL0000064
    CSI 9.94
    rCSI 16.1%
    PRS 97.43
  • ciliated epithelial cell CL0000067
    CSI 8.65
    rCSI 7.6%
    PRS 97.49
  • squamous epithelial cell CL0000076
    CSI 6.91
    rCSI 16.4%
    PRS 97.41
  • retinal cone cell CL0000573
    CSI 6.4
    rCSI 10.29%
    PRS 97.35
  • lung ciliated cell CL1000271
    CSI 6.17
    rCSI 7.14%
    PRS 98.14
  • ciliated columnar cell of tracheobronchial tree CL0002145
    CSI 4.57
    rCSI 10.42%
    PRS 97.31
  • melanocyte of skin CL1000458
    CSI 3.63
    rCSI 4.94%
    PRS 89.76
  • multi-ciliated epithelial cell CL0005012
    CSI 3.48
    rCSI 3.47%
    PRS 98.1
  • choroid plexus epithelial cell CL0000706
    CSI 3.12
    rCSI 5.11%
    PRS 97.99
  • basal cell of epidermis CL0002187
    CSI 2.4
    rCSI 4.25%
    PRS 88.49
  • deuterosomal cell CL4033044
    CSI 1.48
    rCSI 5.01%
    PRS 97.03

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

Explore relationships of the current gene. Select an Interaction Source: 'ONTOLOGY' for shared pathways (GO/Reactome) or 'STRING' for protein-protein interactions. Further refine by selecting context genes and comparing Cell Significance Index (CSI) scores between baseline and target cell types and their specific contexts.

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  • Query Gene
  • Node Color (Target Cell CSI, relative to current network):
    • Very High
    • High
    • Medium
    • Low
    • Very Low
    • CSI N/A
  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary [VWA3B](/details-gene/200403) (von Willebrand factor A domain containing 3B) is a protein-coding gene located on chromosome 2q11.2. Its protein product contains a von Willebrand factor A (vWA) domain, a module often involved in protein-protein interactions and cellular adhesion. Expression data indicates that [VWA3B](/details-gene/200403) is a highly specific marker for various ciliated and epithelial cell populations, with its most significant expression observed in [ependymal cells](/details-cell/CL0000065). Research has linked homozygous mutations in [VWA3B](/details-gene/200403) to a rare form of autosomal recessive cerebellar ataxia with intellectual disability, highlighting its critical role in the central nervous system ([Link](https://doi.org/10.1136/jnnp-2014-309828)). ## Cellular Roles and Expression Landscape The **Overall** expression profile of [VWA3B](/details-gene/200403) reveals a highly specialized role in ciliated and epithelial tissues across different organ systems. The gene shows the highest significance in [ependymal cells](/details-cell/CL0000065) (CSI: 14.56), which line the ventricles of the brain and are crucial for cerebrospinal fluid homeostasis. This pattern is reinforced by its high significance in other ciliated cell types, including general [ciliated cells](/details-cell/CL0000064), [ciliated epithelial cells](/details-cell/CL0000067), [lung ciliated cells](/details-cell/CL1000271), and [ciliated columnar cells of the tracheobronchial tree](/details-cell/CL0002145). This strong association with ciliation is further supported by its expression in [deuterosomal cells](/details-cell/CL4033044), which are precursors to multi-ciliated epithelial cells. Beyond ciliated lineages, [VWA3B](/details-gene/200403) is also a significant marker for other specialized epithelial and ectoderm-derived cells, including [squamous epithelial cells](/details-cell/CL0000076), [retinal cone cells](/details-cell/CL0000573), [melanocytes of the skin](/details-cell/CL1000458), and [choroid plexus epithelial cells](/details-cell/CL0000706). This collective expression pattern suggests a fundamental role for [VWA3B](/details-gene/200403) in the function or structural integrity of these specialized barrier and sensory tissues. ## Pathways and Molecular Function The functional annotation for [VWA3B](/details-gene/200403) indicates that its protein product is localized to the cytosol ([GO:0005829](https://www.ebi.ac.uk/QuickGO/term/GO:0005829)) and nucleoplasm ([GO:0005654](https://www.ebi.ac.uk/QuickGO/term/GO:0005654)). While specific pathway involvement is not well-defined, the presence of a von Willebrand factor A domain suggests a function related to mediating protein-protein interactions. In the context of its expression in ciliated and epithelial cells, this molecular function may be relevant to processes such as ciliogenesis, the structural organization of the cytoskeleton, or cell-cell adhesion within epithelial layers. The precise molecular activities, however, remain to be fully elucidated. ## Research Directions The strong link between [VWA3B](/details-gene/200403) loss-of-function and cerebellar ataxia, combined with its highly specific expression in [ependymal cells](/details-cell/CL0000065), provides a clear direction for future investigation into neurodevelopmental and neurodegenerative processes. Based on the available data, several testable hypotheses can be proposed: 1. Loss-of-function mutations in [VWA3B](/details-gene/200403) impair the development or function of motile cilia in [ependymal cells](/details-cell/CL0000065), leading to abnormal cerebrospinal fluid flow dynamics that disrupt cerebellar development and maintenance. 2. [VWA3B](/details-gene/200403) functions as a key scaffolding protein that connects the cytoskeleton to cellular junctions in epithelial cells, and its absence compromises the integrity of ependymal and other epithelial barriers, contributing to pathology. 3. The expression of [VWA3B](/details-gene/200403) in [retinal cone cells](/details-cell/CL0000573) suggests a potential, yet uncharacterized, role in photoreceptor function or maintenance, and patients with [VWA3B](/details-gene/200403) mutations may exhibit subtle retinal deficits. To test the first hypothesis regarding ependymal cell function, a compelling experimental approach would be to utilize patient-derived induced pluripotent stem cells (iPSCs). Differentiating iPSCs from individuals with [VWA3B](/details-gene/200403)-associated ataxia and from isogenic, CRISPR-corrected controls into brain organoids would allow for direct assessment. Subsequent analysis using high-resolution microscopy could evaluate ciliary structure and beat frequency in the organoid's ependymal-like rosettes, while particle tracking velocimetry could be used to measure fluid flow, thereby linking the molecular defect to a specific cellular and physiological phenotype. As a therapeutic target, [VWA3B](/details-gene/200403) is relevant in the context of monogenic recessive diseases. Since the pathology arises from a loss of function, therapeutic strategies would focus on gene replacement or functional restoration rather than inhibition. The primary challenge for treating the associated neurological disorder would be the effective and safe delivery of a functional copy of [VWA3B](/details-gene/200403) across the blood-brain barrier to the relevant cell types, potentially via adeno-associated virus (AAV) vectors engineered for central nervous system tropism.

Genular Protein ID: 1709672835

Symbol: VWA3B_HUMAN

Name: von Willebrand factor A domain-containing protein 3B

UniProtKB Accession Codes:

Q502W6 B9EK71 Q86T73 Q8N2D0 Q8N770 Q8NA79 Q8ND63 Q8ND65 Q8WW02

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 1 CTD 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 13 Ensembl 2 ExpressionAtlas 1 GO 2 Gene3D 1 GeneCards 1 GeneTree 1 GenomeRNAi 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 3 KEGG 1 MANE-Select 1 MIM 3 MalaCards 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PRO 1 PROSITE 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 2 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 8 Pumba 1 RNAct 1 RefSeq 3 SMART 1 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 14702039

Title: Complete sequencing and characterization of 21,243 full-length human cDNAs.

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 17974005

Title: The full-ORF clone resource of the German cDNA consortium.

PubMed ID: 17974005

DOI: 10.1186/1471-2164-8-399

PubMed ID: 15815621

Title: Generation and annotation of the DNA sequences of human chromosomes 2 and 4.

PubMed ID: 15815621

DOI: 10.1038/nature03466

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 26157035

Title: A homozygous mutation of VWA3B causes cerebellar ataxia with intellectual disability.

PubMed ID: 26157035

DOI: 10.1136/jnnp-2014-309828

PubMed ID: 26566883

Title: Homozygous missense mutation in the LMAN2L gene segregates with intellectual disability in a large consanguineous Pakistani family.

PubMed ID: 26566883

DOI: 10.1136/jmedgenet-2015-103179

Sequence Information:

  • Length: 1294
  • Mass: 145748
  • Checksum: 97D11C329C31060D
  • Sequence:
    • MEKSGPSSTI SEQQLQRQEG WINTKTDLAE QSLISSEKWL QLHGLKSNKL TLKQILSQIG 
FPHCEDYVAS LGRPVASRYA DGLFPQLYRA EDGRVYNLTA KSELIYQFVE HLTQAVESYK 
QRMDWLTSKS RQIFGVILEQ CVTIVLDFGG ILEGELDLCR EALTMVLQEQ VAHITEFNII 
RVSQEPVKWQ ENATPVTEQS IATAISWVEK LTVELTVSEA GRLDALLEAG RDKTIESIYY 
FVVGDVPEES KELLLQRALE IPCPVYTVSF NARGEGTIAF LKDLSAKTHS RFHAFAERTE 
CVEFPAFSTK DGDNVMTWNS RKLKGKLPPG AGVREDVFLV WQEMEEACST LAQIQRLVAE 
PPKPDVATVD CESETTSVEI ASNPEDTWDS KTWLQKYGLK AQKLSLYDVL ADCSFRHADG 
VVDIKAKPEN ESVQTSAETN KKTVHAKYCS RFVHAPWKDG SLVHVNITKE KCKWYSERIH 
TALARIRRRI KWLQDGSQSL FGRLHNDCIY ILIDTSHSMK SKLDLVKDKI IQFIQEQLKY 
KSKFNFVKFD GQAVAWREQL AEVNEDNLEQ AQSWIRDIKI GSSTNTLSAL KTAFADKETQ 
AIYLLTDGRP DQPPETVIDQ VKRFQEIPIY TISFNYNDEI ANRFLKEVAA LTGGEFHFYN 
FGCKDPTPPE AVQNEDLTLL VKEMEQGHSD LEKMQDLYSE SLIMDWWYNA EKDGDSKHQK 
EICSMISTPE KCAKPQSDVD STQTSSLNML KGPWGLSDQK VQKKKVLHAE STKTSLLRSQ 
MSSLRSSACS ERKDGLSNAS SRRTALSDKE MSILLAEEWL DDKSSEKVTR EGSQVYDHDS 
SDVSSENWLK TYGLVAKKLT LMDALSVAAV PHSSTYVPVL DKHVVSKVFD EVFPLAHVCN 
DTNKMTLINP QGAKLNIYKR KVEQAIQSYE KRLNKIVWRA LSQEEKEKLD ANKPIQYLEN 
KTVLNQALER LNWPISLKEL SMLESEILAG KMYIQQAMEL QEAAKKNYAN KAPGEQQKLQ 
GNPTKKTKSK RPDPLKGQKV IARCDENGFY FPGVVKKCVS RTQALVGFSY GDTKVVSTSF 
ITPVGGAMPC PLLQVGDYVF AKIVIPKGFD FYVPAIVIAL PNKHVATEKF YTVLKCNNRR 
EFCPRSALIK ISQNKYALSC SHIKSPPIPE DPEVEDVEAR NSAFLFWPLK EADTQDSREP 
RREKPRRKKR PAKQPLQQAA PSDSDGSSHG ISSHGSCQGT HPEPRTAHLH FPAAGRLGLS 
SHAIIATPPP RAALPCTLQA THSSKGLRSV PETL

Genular Protein ID: 2089363378

Symbol: B7Z3D8_HUMAN

Name: N/A

UniProtKB Accession Codes:

B7Z3D8

Database IDs:

AlphaFoldDB 1 BioGRID-ORCS 1 CDD 1 CTD 1 DNASU 1 DisGeNET 1 EMBL 2 Gene3D 1 InterPro 3 NCBI Taxonomy 1 OrthoDB 1 PANTHER 2 PROSITE 2 PeptideAtlas 1 Pfam 2 RefSeq 1 SAM 1 SMART 1 SUPFAM 1

Sequence Information:

  • Length: 951
  • Mass: 107003
  • Checksum: 3AA3FF4C15F82D6E
  • Sequence:
    • MEEACSTLAQ IQRLVAEPPK PDVATVDCES ETTSVEIASN PEDTWDSKTW LQKYGLKAQK 
LSLYDVLADC SFRHADGVVD IKAKPENESV QTSAETNKKT VHAKYCSRFV HAPWKDGSLV 
HVNITKEKCK WYSERIHTAL ARIRRRIKWL QDGSQSLFGR LHNDCIYILI DTSHSMKSKL 
DLVKDKIIQF IQEQLKYKSK FNFVKFDGQA VAWREQLAEV NEDNLEQAQS WIRDIKIGSS 
TNTLSALKTA FADKETQAIY LLTDGRPDQP PETVIDQVKR FQEIPIYTIS FNYNDEIANR 
FLKEVAALTG GEFHFYNFGC KDPTPPEAVQ NEDVTLLVKE MEQGHSDLEK MQDLYSESLI 
MDWWYNAEKD GDSKHQKEIC SMISTPEKCA KPQSDVDSTQ TSSLNMLKGP WGLSDQKVQK 
KKVLHAESTK TSLLRSQMSS LRSSACSERK DGLSNASSRR TALSDKEMSI LLAEEWLDDK 
SSEKVTREGS QVYDHDSSDV SSENWLKTYG LVAKKLTLMD ALSVAAVPHS STYVPVLDKH 
VMSKVFDEVF PLAHVCNDTN KMTLINPQGA KLNIYKRKVE QAIQSYEKRL NKIVWRALSQ 
EEKEKLDANK PIQYLENKTV LNQALERLNW PISLKELSML ESEILAGKMY IQQAMELQEA 
AKKNYANKAP GEQQKLQGNP TKKTKSKRPD PLKGQKVIAR CDENGFYFPG VVKKCVSRTQ 
ALVGFSYGDT KVVSTSFITP VGGAMPCPLL QVGDYVFAKI VIPKGFDFYV PAIVIALPNK 
HVATEKFYTV LKCNNRREFC PRSALIKISQ NKYALSCSHI KSPPIPEDPE VEDVEARNSA 
FLFWPLKEAD TQDSREPRRE KPRRKKRPAK QPLQQAAPSD SDGSSHGISS HGSCQGTHPE 
PKTAHLHFPA AGRLGLSSHA IIATPPPRAA LPCTLQATHS SKGLRSVPET L