This gene encodes a scaffold protein that is a component of the PIKfyve protein kinase complex. This complex is responsible for the synthesis of phosphatidylinositol 3,5-bisphosphate, an important component of cellular membranes, from phosphatidylinositol 3-phosphate. Mice lacking a functional copy of this gene exhibit severe neurodegeneration. Mutations in the human gene have ... See more...

Aliases for VAC14 Gene

Aliases for VAC14 Gene

  • VAC14 Component Of PIKFYVE Complex 2 3 5
  • Vac14, PIKFYVE Complex Component 2 3
  • Protein VAC14 Homolog 3 4
  • TAX1BP2 3 4
  • TRX 3 4
  • Tax1 (Human T-Cell Leukemia Virus Type I) Binding Protein 2 2
  • Tax1 (Human T-Cell Leukemia Virus Type I) Binding Protein 3
  • Vac14 Homolog (S. Cerevisiae) 2
  • Tax1-Binding Protein 2 4
  • ArPIKfyve 3

External Ids for VAC14 Gene

Previous HGNC Symbols for VAC14 Gene

  • TAX1BP2

Previous GeneCards Identifiers for VAC14 Gene

  • GC16M069280
  • GC16M070721
  • GC16M056552

Summaries for VAC14 Gene

Entrez Gene Summary for VAC14 Gene

  • This gene encodes a scaffold protein that is a component of the PIKfyve protein kinase complex. This complex is responsible for the synthesis of phosphatidylinositol 3,5-bisphosphate, an important component of cellular membranes, from phosphatidylinositol 3-phosphate. Mice lacking a functional copy of this gene exhibit severe neurodegeneration. Mutations in the human gene have been identified in patients with a childhood onset progressive neurological disorder characterized by impaired movement, dystonia, and striatal abnormalities. [provided by RefSeq, May 2017]

GeneCards Summary for VAC14 Gene

VAC14 (VAC14 Component Of PIKFYVE Complex) is a Protein Coding gene. Diseases associated with VAC14 include Striatonigral Degeneration, Childhood-Onset and Yunis-Varon Syndrome. Among its related pathways are Metabolism and Human T-cell leukemia virus 1 infection. Gene Ontology (GO) annotations related to this gene include binding.

UniProtKB/Swiss-Prot Summary for VAC14 Gene

  • The PI(3,5)P2 regulatory complex regulates both the synthesis and turnover of phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2). Acts as a positive activator of PIKfyve kinase activity. Also required to maintain normal levels of phosphatidylinositol 3-phosphate (PtdIns(3)P) and phosphatidylinositol 5-phosphate (PtdIns(5)P). Plays a role in the biogenesis of endosome carrier vesicles (ECV) / multivesicular bodies (MVB) transport intermediates from early endosomes.

Gene Wiki entry for VAC14 Gene

Additional gene information for VAC14 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for VAC14 Gene

Genomics for VAC14 Gene

GeneHancer (GH) Regulatory Elements for VAC14 Gene

Promoters and enhancers for VAC14 Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around VAC14 on UCSC Golden Path with GeneCards custom track

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for VAC14

Top Transcription factor binding sites by QIAGEN in the VAC14 gene promoter:
  • ARP-1
  • CREB
  • deltaCREB
  • GCNF
  • GCNF-1
  • GCNF-2
  • Ik-1
  • NF-1
  • Nkx2-5
  • Pbx1a

Genomic Locations for VAC14 Gene

Genomic Locations for VAC14 Gene
chr16:70,687,439-70,801,166
(GRCh38/hg38)
Size:
113,728 bases
Orientation:
Minus strand
chr16:70,721,342-70,835,064
(GRCh37/hg19)
Size:
113,723 bases
Orientation:
Minus strand

Genomic View for VAC14 Gene

Genes around VAC14 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
VAC14 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for VAC14 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for VAC14 Gene

Proteins for VAC14 Gene

  • Protein details for VAC14 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q08AM6-VAC14_HUMAN
    Recommended name:
    Protein VAC14 homolog
    Protein Accession:
    Q08AM6
    Secondary Accessions:
    • B3KPJ5
    • B3KSM8
    • Q13174
    • Q6IA12
    • Q7L4Y1
    • Q9BW96
    • Q9H6V6

    Protein attributes for VAC14 Gene

    Size:
    782 amino acids
    Molecular mass:
    87973 Da
    Quaternary structure:
    • Forms homooligomers. Component of the PI(3,5)P2 regulatory complex/PAS complex, at least composed of PIKFYVE, FIG4 and VAC14. VAC14 nucleates the assembly of the complex and serves as a scaffold. Interacts with NOS1.
    • (Microbial infection) Interacts with HTLV-1 Tax.
    SequenceCaution:
    • Sequence=AAB03813.1; Type=Miscellaneous discrepancy; Note=Unknown C-terminal region.; Evidence={ECO:0000305}; Sequence=BAB15145.1; Type=Erroneous initiation; Evidence={ECO:0000305};

    Alternative splice isoforms for VAC14 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for VAC14 Gene

Post-translational modifications for VAC14 Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

No data available for DME Specific Peptides for VAC14 Gene

Domains & Families for VAC14 Gene

Gene Families for VAC14 Gene

HGNC:
Human Protein Atlas (HPA):
  • Disease related genes
  • Predicted intracellular proteins

Protein Domains for VAC14 Gene

Blocks:
  • HEAT repeat
InterPro:
ProtoNet:

Suggested Antigen Peptide Sequences for VAC14 Gene

GenScript: Design optimal peptide antigens:
  • cDNA FLJ36622 fis, clone TRACH2016690, highly similar to Homo sapiens Vac14 homolog (VAC14), mRNA (B3KSM8_HUMAN)
  • Tax1-binding protein 2 (VAC14_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q08AM6

UniProtKB/Swiss-Prot:

VAC14_HUMAN :
  • The C-terminal domain (residues 523-782) mediates homomeric interactions and is necessary for the formation and maintenance of the PI(3,5)P2 regulatory complex.
  • Belongs to the VAC14 family.
Domain:
  • The C-terminal domain (residues 523-782) mediates homomeric interactions and is necessary for the formation and maintenance of the PI(3,5)P2 regulatory complex.
Family:
  • Belongs to the VAC14 family.
genes like me logo Genes that share domains with VAC14: view

Function for VAC14 Gene

Molecular function for VAC14 Gene

UniProtKB/Swiss-Prot Function:
The PI(3,5)P2 regulatory complex regulates both the synthesis and turnover of phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2). Acts as a positive activator of PIKfyve kinase activity. Also required to maintain normal levels of phosphatidylinositol 3-phosphate (PtdIns(3)P) and phosphatidylinositol 5-phosphate (PtdIns(5)P). Plays a role in the biogenesis of endosome carrier vesicles (ECV) / multivesicular bodies (MVB) transport intermediates from early endosomes.

Phenotypes From GWAS Catalog for VAC14 Gene

Gene Ontology (GO) - Molecular Function for VAC14 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005515 protein binding IPI 17161399
GO:0038023 signaling receptor activity NAS 8611628
genes like me logo Genes that share ontologies with VAC14: view
genes like me logo Genes that share phenotypes with VAC14: view

Human Phenotype Ontology for VAC14 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Model Products

CRISPR Products

Clone Products

  • Addgene plasmids for VAC14

No data available for Enzyme Numbers (IUBMB) , Animal Models , Transcription Factor Targets and HOMER Transcription for VAC14 Gene

Localization for VAC14 Gene

Subcellular locations from UniProtKB/Swiss-Prot for VAC14 Gene

Endosome membrane. Microsome membrane. Note=Mainly associated with membranes of the late endocytic pathway.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for VAC14 gene
Compartment Confidence
endosome 5
cytosol 5
golgi apparatus 4
endoplasmic reticulum 3
lysosome 2
plasma membrane 1
extracellular 1
cytoskeleton 1
mitochondrion 1
peroxisome 1
nucleus 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Vesicles (4)
  • Cytosol (2)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for VAC14 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000139 Golgi membrane TAS --
GO:0000306 extrinsic component of vacuolar membrane IBA 21873635
GO:0005768 endosome IEA --
GO:0005783 endoplasmic reticulum IEA --
GO:0005829 cytosol IDA --
genes like me logo Genes that share ontologies with VAC14: view

Pathways & Interactions for VAC14 Gene

genes like me logo Genes that share pathways with VAC14: view

SIGNOR curated interactions for VAC14 Gene

Activates:

Gene Ontology (GO) - Biological Process for VAC14 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006661 phosphatidylinositol biosynthetic process IEA,TAS --
GO:0007165 signal transduction NAS 8611628
GO:0016032 viral process IEA --
genes like me logo Genes that share ontologies with VAC14: view

Drugs & Compounds for VAC14 Gene

(1) Drugs for VAC14 Gene - From: PharmGKB

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Docetaxel Approved, Investigational Pharma Microtubulin disassembly inhibitor, Tubulin and VEGF inhibitor, Taxanes 2273
genes like me logo Genes that share compounds with VAC14: view

Transcripts for VAC14 Gene

mRNA/cDNA for VAC14 Gene

2 REFSEQ mRNAs :
19 NCBI additional mRNA sequence :
12 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Clone Products

  • Addgene plasmids for VAC14

Alternative Splicing Database (ASD) splice patterns (SP) for VAC14 Gene

ExUns: 1a · 1b ^ 2 ^ 3 ^ 4 ^ 5 ^ 6a · 6b ^ 7a · 7b ^ 8 ^ 9a · 9b ^ 10a · 10b ^ 11a · 11b ^ 12a · 12b ^ 13 ^ 14a · 14b ^ 15 ^ 16 ^ 17a · 17b ^
SP1:
SP2:
SP3: - -
SP4: - - -
SP5:
SP6: -
SP7: -
SP8:

ExUns: 18 ^ 19 ^ 20a · 20b
SP1:
SP2:
SP3:
SP4:
SP5:
SP6:
SP7:
SP8:

Relevant External Links for VAC14 Gene

GeneLoc Exon Structure for
VAC14

Expression for VAC14 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for VAC14 Gene

Protein differential expression in normal tissues from HIPED for VAC14 Gene

This gene is overexpressed in Bone (32.6).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for VAC14 Gene



Protein tissue co-expression partners for VAC14 Gene

- Elite partner

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for VAC14

SOURCE GeneReport for Unigene cluster for VAC14 Gene:

Hs.445061

mRNA Expression by UniProt/SwissProt for VAC14 Gene:

Q08AM6-VAC14_HUMAN
Tissue specificity: Ubiquitously expressed.

Evidence on tissue expression from TISSUES for VAC14 Gene

  • Nervous system(4.7)
  • Lung(4.3)
  • Liver(4.2)
genes like me logo Genes that share expression patterns with VAC14: view

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery , mRNA differential expression in normal tissues and Phenotype-based relationships between genes and organs from Gene ORGANizer for VAC14 Gene

Orthologs for VAC14 Gene

This gene was present in the common ancestor of eukaryotes.

Orthologs for VAC14 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia VAC14 31 30
  • 99.49 (n)
OneToOne
dog
(Canis familiaris)
Mammalia VAC14 31 30
  • 91.6 (n)
OneToOne
cow
(Bos Taurus)
Mammalia VAC14 31 30
  • 89.86 (n)
OneToOne
mouse
(Mus musculus)
Mammalia Vac14 17 31 30
  • 89.5 (n)
rat
(Rattus norvegicus)
Mammalia Vac14 30
  • 89.09 (n)
platypus
(Ornithorhynchus anatinus)
Mammalia VAC14 31
  • 87 (a)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia VAC14 31
  • 86 (a)
OneToOne
chicken
(Gallus gallus)
Aves VAC14 31 30
  • 81.81 (n)
OneToOne
lizard
(Anolis carolinensis)
Reptilia VAC14 31
  • 85 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia vac14 30
  • 73.28 (n)
zebrafish
(Danio rerio)
Actinopterygii vac14 31 30
  • 72.9 (n)
OneToOne
wufb68e05 30
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP000770 30
  • 59.28 (n)
fruit fly
(Drosophila melanogaster)
Insecta CG5608 31 30
  • 55.84 (n)
OneToOne
worm
(Caenorhabditis elegans)
Secernentea K04G2.6 30
  • 47.71 (n)
vacl-14 31
  • 38 (a)
OneToOne
A. gosspyii yeast
(Ashbya gossypii)
Saccharomycetes AGOS_AER049W 30
  • 49.03 (n)
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes VAC14 33 31 30
  • 47.26 (n)
K. lactis yeast
(Kluyveromyces lactis)
Saccharomycetes KLLA0E05193g 30
  • 46.7 (n)
thale cress
(Arabidopsis thaliana)
eudicotyledons AT2G01690 30
  • 52.07 (n)
rice
(Oryza sativa)
Liliopsida Os03g0223700 30
  • 53.5 (n)
Os.11686 30
bread mold
(Neurospora crassa)
Ascomycetes NCU02409 30
  • 51.04 (n)
sea squirt
(Ciona savignyi)
Ascidiacea CSA.10719 31
  • 50 (a)
OneToOne
fission yeast
(Schizosaccharomyces pombe)
Schizosaccharomycetes SPBC25H2.03 30
  • 46.94 (n)
Species where no ortholog for VAC14 was found in the sources mined by GeneCards:
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for VAC14 Gene

ENSEMBL:
Gene Tree for VAC14 (if available)
TreeFam:
Gene Tree for VAC14 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for VAC14: view image

Paralogs for VAC14 Gene

(1) SIMAP similar genes for VAC14 Gene using alignment to 6 proteins:

  • VAC14_HUMAN
  • B3KSM8_HUMAN
  • H3BN23_HUMAN
  • H3BQD9_HUMAN
  • H3BUU8_HUMAN
  • J3QLC3_HUMAN

Pseudogenes.org Pseudogenes for VAC14 Gene

genes like me logo Genes that share paralogs with VAC14: view

No data available for Paralogs for VAC14 Gene

Variants for VAC14 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for VAC14 Gene

SNP ID Clinical significance and condition Chr 16 pos Variation AA Info Type
638191 Uncertain Significance: Striatonigral degeneration, childhood-onset 70,695,574(-) C/A MISSENSE_VARIANT
713668 Likely Benign: not provided 70,781,942(-) G/A SYNONYMOUS_VARIANT
717100 Benign: not provided 70,781,935(-) G/A SYNONYMOUS_VARIANT
725469 Likely Benign: not provided 70,688,033(-) G/A SYNONYMOUS_VARIANT
730063 Likely Benign: not provided 70,695,605(-) G/C SYNONYMOUS_VARIANT

Additional dbSNP identifiers (rs#s) for VAC14 Gene

Structural Variations from Database of Genomic Variants (DGV) for VAC14 Gene

Variant ID Type Subtype PubMed ID
esv2758653 CNV gain 17122850
esv3892881 CNV gain 25118596
nsv1059226 CNV gain 25217958
nsv471094 CNV loss 18288195
nsv475686 CNV novel sequence insertion 20440878
nsv517391 CNV loss 19592680
nsv572945 CNV gain 21841781
nsv572946 CNV loss 21841781
nsv572947 CNV loss 21841781
nsv572948 CNV loss 21841781
nsv7285 OTHER inversion 18451855

Variation tolerance for VAC14 Gene

Residual Variation Intolerance Score: 6.26% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 2.21; 39.93% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for VAC14 Gene

Human Gene Mutation Database (HGMD)
VAC14
SNPedia medical, phenotypic, and genealogical associations of SNPs for
VAC14

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for VAC14 Gene

Disorders for VAC14 Gene

MalaCards: The human disease database

(13) MalaCards diseases for VAC14 Gene - From: UniProtKB/Swiss-Prot, OMIM, ClinVar, GTR, Orphanet, DISEASES, and GeneCards

- elite association - COSMIC cancer census association via MalaCards
Search VAC14 in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

VAC14_HUMAN
  • Striatonigral degeneration, childhood-onset (SNDC) [MIM:617054]: An autosomal recessive neurological disorder characterized by sudden childhood onset of developmental regression. Affected children develop impaired movements with dystonia, progressively become non-ambulatory and non-verbal, and exhibit striatal abnormalities on MRI. {ECO:0000269 PubMed:27292112}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Additional Disease Information for VAC14

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
genes like me logo Genes that share disorders with VAC14: view

No data available for Genatlas for VAC14 Gene

Publications for VAC14 Gene

  1. A mammalian ortholog of Saccharomyces cerevisiae Vac14 that associates with and up-regulates PIKfyve phosphoinositide 5-kinase activity. (PMID: 15542851) Sbrissa D … Shisheva A (Molecular and cellular biology 2004) 2 3 4 23 54
  2. Core protein machinery for mammalian phosphatidylinositol 3,5-bisphosphate synthesis and turnover that regulates the progression of endosomal transport. Novel Sac phosphatase joins the ArPIKfyve-PIKfyve complex. (PMID: 17556371) Sbrissa D … Shisheva A (The Journal of biological chemistry 2007) 3 4 23 54
  3. Binding of Vac14 to neuronal nitric oxide synthase: Characterisation of a new internal PDZ-recognition motif. (PMID: 17161399) Lemaire JF … McPherson PS (FEBS letters 2006) 3 4 23 54
  4. Isolation of a cDNA clone, TRX encoding a human T-cell lymphotrophic virus type-I Tax1 binding protein. (PMID: 8611628) Mireskandari A … Brady JN (Biochimica et biophysica acta 1996) 3 4 23 54
  5. Biallelic Mutations of VAC14 in Pediatric-Onset Neurological Disease. (PMID: 27292112) Lenk GM … Ploski R (American journal of human genetics 2016) 3 4 54

Products for VAC14 Gene

Sources for VAC14 Gene