This gene encodes a WD40 repeat protein. Members of the WD40 repeat family are key components of many essential biologic functions. They regulate the assembly of multiprotein complexes by presenting a beta-propeller platform for simultaneous and reversible protein-protein interactions. Members of the WIPI subfamily of WD40 repeat proteins have a 7-bladed propeller structure and... See more...

Aliases for WIPI1 Gene

Aliases for WIPI1 Gene

  • WD Repeat Domain, Phosphoinositide Interacting 1 2 3 5
  • WD Repeat Domain Phosphoinositide-Interacting Protein 1 3 4
  • Atg18 Protein Homolog 3 4
  • WIPI49 3 4
  • WD40 Repeat Protein Interacting With Phosphoinositides Of 49 KDa 4
  • WIPI-1 Alpha 3
  • WIPI 49 KDa 4
  • ATG18A 3
  • WIPI-1 4
  • ATG18 3

External Ids for WIPI1 Gene

Previous GeneCards Identifiers for WIPI1 Gene

  • GC17M063930
  • GC17M066417
  • GC17M061803

Summaries for WIPI1 Gene

Entrez Gene Summary for WIPI1 Gene

  • This gene encodes a WD40 repeat protein. Members of the WD40 repeat family are key components of many essential biologic functions. They regulate the assembly of multiprotein complexes by presenting a beta-propeller platform for simultaneous and reversible protein-protein interactions. Members of the WIPI subfamily of WD40 repeat proteins have a 7-bladed propeller structure and contain a conserved motif for interaction with phospholipids. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2016]

GeneCards Summary for WIPI1 Gene

WIPI1 (WD Repeat Domain, Phosphoinositide Interacting 1) is a Protein Coding gene. Diseases associated with WIPI1 include Neurodegeneration With Brain Iron Accumulation 5 and Neurodegeneration With Brain Iron Accumulation. Among its related pathways are Autophagy - animal and Autophagy Pathway. Gene Ontology (GO) annotations related to this gene include signaling receptor binding and estrogen receptor binding. An important paralog of this gene is WIPI2.

UniProtKB/Swiss-Prot Summary for WIPI1 Gene

  • Component of the autophagy machinery that controls the major intracellular degradation process by which cytoplasmic materials are packaged into autophagosomes and delivered to lysosomes for degradation (PubMed:28561066). Plays an important role in starvation- and calcium-mediated autophagy, as well as in mitophagy (PubMed:28561066). Functions downstream of the ULK1 and PI3-kinases that produce phosphatidylinositol 3-phosphate (PtdIns3P) on membranes of the endoplasmic reticulum once activated (PubMed:28561066). Binds phosphatidylinositol 3-phosphate (PtdIns3P), and maybe other phosphoinositides including PtdIns3,5P2 and PtdIns5P, and is recruited to phagophore assembly sites at the endoplasmic reticulum membranes (PubMed:28561066). There, it assists WIPI2 in the recruitment of ATG12-ATG5-ATG16L1, a complex that directly controls the elongation of the nascent autophagosomal membrane (PubMed:28561066). Involved in xenophagy of Staphylococcus aureus. Invading S.aureus cells become entrapped in autophagosome-like WIPI1 positive vesicles targeted for lysosomal degradation. Plays also a distinct role in controlling the transcription of melanogenic enzymes and melanosome maturation, a process that is distinct from starvation-induced autophagy. May also regulate the trafficking of proteins involved in the mannose-6-phosphate receptor (MPR) recycling pathway.

Gene Wiki entry for WIPI1 Gene

Additional gene information for WIPI1 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for WIPI1 Gene

Genomics for WIPI1 Gene

GeneHancer (GH) Regulatory Elements for WIPI1 Gene

Promoters and enhancers for WIPI1 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 WIPI1 on UCSC Golden Path with GeneCards custom track

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for WIPI1

Top Transcription factor binding sites by QIAGEN in the WIPI1 gene promoter:
  • aMEF-2
  • FOXD1
  • FOXO3b
  • FOXO4
  • MEF-2A
  • NCX
  • Pbx1a
  • POU3F2
  • POU3F2 (N-Oct-5a)
  • POU3F2 (N-Oct-5b)

Genomic Locations for WIPI1 Gene

Genomic Locations for WIPI1 Gene
chr17:68,420,948-68,457,513
(GRCh38/hg38)
Size:
36,566 bases
Orientation:
Minus strand
chr17:66,417,089-66,453,654
(GRCh37/hg19)
Size:
36,566 bases
Orientation:
Minus strand

Genomic View for WIPI1 Gene

Genes around WIPI1 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
WIPI1 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for WIPI1 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for WIPI1 Gene

Proteins for WIPI1 Gene

  • Protein details for WIPI1 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q5MNZ9-WIPI1_HUMAN
    Recommended name:
    WD repeat domain phosphoinositide-interacting protein 1
    Protein Accession:
    Q5MNZ9
    Secondary Accessions:
    • Q8IXM5
    • Q9NWF8

    Protein attributes for WIPI1 Gene

    Size:
    446 amino acids
    Molecular mass:
    48673 Da
    Quaternary structure:
    • Interacts with androgen receptor (AR) and the estrogen receptors ESR1 and ESR2 (PubMed:15602573). Interacts with WIPI2 (PubMed:28561066). Interacts with WDR45 (PubMed:28561066). Interacts with ATG16L1 (PubMed:28561066). May interact with NUDC (PubMed:28561066).

    Alternative splice isoforms for WIPI1 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for WIPI1 Gene

Post-translational modifications for WIPI1 Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

No data available for DME Specific Peptides for WIPI1 Gene

Domains & Families for WIPI1 Gene

Gene Families for WIPI1 Gene

Protein Domains for WIPI1 Gene

Suggested Antigen Peptide Sequences for WIPI1 Gene

GenScript: Design optimal peptide antigens:
  • WD40 repeat protein interacting with phosphoinositides of 49 kDa (WIPI1_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q5MNZ9

UniProtKB/Swiss-Prot:

WIPI1_HUMAN :
  • The N-terminus might form a beta-propeller domain involved in specific binding to phosphatidylinositol 3,5-bisphosphate (PIP2), leading to the association of the protein to the membrane. Association to the membrane can also occur through binding to phosphatidylinositol 3-monophosphate (PI3P).
  • Belongs to the WD repeat SVP1 family.
Domain:
  • The N-terminus might form a beta-propeller domain involved in specific binding to phosphatidylinositol 3,5-bisphosphate (PIP2), leading to the association of the protein to the membrane. Association to the membrane can also occur through binding to phosphatidylinositol 3-monophosphate (PI3P).
Family:
  • Belongs to the WD repeat SVP1 family.
genes like me logo Genes that share domains with WIPI1: view

Function for WIPI1 Gene

Molecular function for WIPI1 Gene

UniProtKB/Swiss-Prot Function:
Component of the autophagy machinery that controls the major intracellular degradation process by which cytoplasmic materials are packaged into autophagosomes and delivered to lysosomes for degradation (PubMed:28561066). Plays an important role in starvation- and calcium-mediated autophagy, as well as in mitophagy (PubMed:28561066). Functions downstream of the ULK1 and PI3-kinases that produce phosphatidylinositol 3-phosphate (PtdIns3P) on membranes of the endoplasmic reticulum once activated (PubMed:28561066). Binds phosphatidylinositol 3-phosphate (PtdIns3P), and maybe other phosphoinositides including PtdIns3,5P2 and PtdIns5P, and is recruited to phagophore assembly sites at the endoplasmic reticulum membranes (PubMed:28561066). There, it assists WIPI2 in the recruitment of ATG12-ATG5-ATG16L1, a complex that directly controls the elongation of the nascent autophagosomal membrane (PubMed:28561066). Involved in xenophagy of Staphylococcus aureus. Invading S.aureus cells become entrapped in autophagosome-like WIPI1 positive vesicles targeted for lysosomal degradation. Plays also a distinct role in controlling the transcription of melanogenic enzymes and melanosome maturation, a process that is distinct from starvation-induced autophagy. May also regulate the trafficking of proteins involved in the mannose-6-phosphate receptor (MPR) recycling pathway.

Phenotypes From GWAS Catalog for WIPI1 Gene

Gene Ontology (GO) - Molecular Function for WIPI1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005102 signaling receptor binding IDA 15602573
GO:0005515 protein binding IEA,IPI 28561066
GO:0008289 lipid binding IEA --
GO:0030331 estrogen receptor binding IDA 15602573
GO:0032266 phosphatidylinositol-3-phosphate binding IEA,IDA 15020712
genes like me logo Genes that share ontologies with WIPI1: view
genes like me logo Genes that share phenotypes with WIPI1: view

Animal Model Products

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for WIPI1

Clone Products

  • Addgene plasmids for WIPI1

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Animal Models , miRNA , Transcription Factor Targets and HOMER Transcription for WIPI1 Gene

Localization for WIPI1 Gene

Subcellular locations from UniProtKB/Swiss-Prot for WIPI1 Gene

Golgi apparatus, trans-Golgi network. Endosome. Cytoplasmic vesicle, clathrin-coated vesicle. Preautophagosomal structure membrane; Peripheral membrane protein. Cytoplasm, cytoskeleton. Note=Trans elements of the Golgi and peripheral endosomes. Dynamically cycles through these compartments and is susceptible to conditions that modulate membrane flux. Enriched in clathrin-coated vesicles. Upon starvation-induced autophagy, accumulates at subcellular structures in the cytoplasm: enlarged vesicular and lasso-like structures, and large cup-shaped structures predominantly around the nucleus. Recruitment to autophagic membranes is controlled by MTMR14. Labile microtubules specifically recruit markers of autophagosome formation like WIPI1, whereas mature autophagosomes may bind to stable microtubules.

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 WIPI1 gene
Compartment Confidence
cytoskeleton 5
endosome 5
golgi apparatus 5
cytosol 4
mitochondrion 3
lysosome 3
plasma membrane 2
peroxisome 2
nucleus 2
endoplasmic reticulum 2
extracellular 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Golgi apparatus (3)
  • Cytosol (2)
  • Nucleoplasm (2)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for WIPI1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000139 Golgi membrane TAS --
GO:0000407 phagophore assembly site IDA,IEA 15602573
GO:0000421 autophagosome membrane IDA 17618624
GO:0005737 cytoplasm IEA,IDA 17618624
GO:0005768 endosome IEA --
genes like me logo Genes that share ontologies with WIPI1: view

Pathways & Interactions for WIPI1 Gene

genes like me logo Genes that share pathways with WIPI1: view

Pathways by source for WIPI1 Gene

Gene Ontology (GO) - Biological Process for WIPI1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000045 autophagosome assembly IMP 28561066
GO:0000422 autophagy of mitochondrion IBA 21873635
GO:0006497 protein lipidation IBA 21873635
GO:0006914 autophagy IEA,IEP 15602573
GO:0009267 cellular response to starvation IDA 28561066
genes like me logo Genes that share ontologies with WIPI1: view

No data available for SIGNOR curated interactions for WIPI1 Gene

Drugs & Compounds for WIPI1 Gene

(1) Drugs for WIPI1 Gene - From: HMDB

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Mannose 6-phosphate Investigational Pharma 0
genes like me logo Genes that share compounds with WIPI1: view

Transcripts for WIPI1 Gene

mRNA/cDNA for WIPI1 Gene

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

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for WIPI1

Clone Products

  • Addgene plasmids for WIPI1

Alternative Splicing Database (ASD) splice patterns (SP) for WIPI1 Gene

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

Relevant External Links for WIPI1 Gene

GeneLoc Exon Structure for
WIPI1

Expression for WIPI1 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for WIPI1 Gene

mRNA differential expression in normal tissues according to GTEx for WIPI1 Gene

This gene is overexpressed in Muscle - Skeletal (x4.3).

Protein differential expression in normal tissues from HIPED for WIPI1 Gene

This gene is overexpressed in Placenta (15.0), Skin (9.8), Salivary gland (9.0), and Heart (7.6).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for WIPI1 Gene



Transcriptomic regulation report from SPP (The Signaling Pathways Project) for WIPI1

SOURCE GeneReport for Unigene cluster for WIPI1 Gene:

Hs.463964

mRNA Expression by UniProt/SwissProt for WIPI1 Gene:

Q5MNZ9-WIPI1_HUMAN
Tissue specificity: Ubiquitously expressed. Highly expressed in skeletal muscle, heart, testis, pancreas and placenta. Highly expressed in G361, Sk-mel-28, Sk-mel-13, WM852 and WM451 cells. Up-regulated in a variety of tumor tissues.

Evidence on tissue expression from TISSUES for WIPI1 Gene

  • Skin(4.2)
  • Muscle(2)
genes like me logo Genes that share expression patterns with WIPI1: view

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery , Protein tissue co-expression partners and Phenotype-based relationships between genes and organs from Gene ORGANizer for WIPI1 Gene

Orthologs for WIPI1 Gene

This gene was present in the common ancestor of animals and fungi.

Orthologs for WIPI1 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia WIPI1 31 30
  • 99.4 (n)
OneToOne
cow
(Bos Taurus)
Mammalia MGC159964 31
  • 90 (a)
OneToOne
WIPI1 30
  • 83.71 (n)
dog
(Canis familiaris)
Mammalia WIPI1 31 30
  • 89.61 (n)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia WIPI1 31
  • 88 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Wipi1 17 31 30
  • 87.44 (n)
rat
(Rattus norvegicus)
Mammalia Wipi1 30
  • 87.22 (n)
platypus
(Ornithorhynchus anatinus)
Mammalia -- 31
  • 80 (a)
OneToMany
-- 31
  • 77 (a)
OneToMany
chicken
(Gallus gallus)
Aves WIPI1 31 30
  • 80.05 (n)
OneToOne
lizard
(Anolis carolinensis)
Reptilia WIPI1 31
  • 81 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia wipi1 30
  • 71.65 (n)
zebrafish
(Danio rerio)
Actinopterygii wipi1 31 30
  • 68.4 (n)
OneToMany
WIPI1 (1 of 2) 31
  • 60 (a)
OneToMany
zgc64205 30
fruit fly
(Drosophila melanogaster)
Insecta Atg18 31
  • 41 (a)
OneToMany
worm
(Caenorhabditis elegans)
Secernentea atg-18 31
  • 38 (a)
OneToMany
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes ATG18 31
  • 23 (a)
OneToMany
sea squirt
(Ciona savignyi)
Ascidiacea -- 31
  • 58 (a)
ManyToMany
-- 31
  • 48 (a)
ManyToMany
Species where no ortholog for WIPI1 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • 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 (Oryza sativa)
  • 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)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for WIPI1 Gene

ENSEMBL:
Gene Tree for WIPI1 (if available)
TreeFam:
Gene Tree for WIPI1 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for WIPI1: view image

Paralogs for WIPI1 Gene

Paralogs for WIPI1 Gene

(3) SIMAP similar genes for WIPI1 Gene using alignment to 6 proteins:

  • WIPI1_HUMAN
  • G5EA37_HUMAN
  • K7EK57_HUMAN
  • K7EKC5_HUMAN
  • K7EKN0_HUMAN
  • K7ELY0_HUMAN
genes like me logo Genes that share paralogs with WIPI1: view

Variants for WIPI1 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for WIPI1 Gene

SNP ID Clinical significance and condition Chr 17 pos Variation AA Info Type
626260 Affects: Neural tube defect 68,428,919(-) C/T MISSENSE_VARIANT,NON_CODING_TRANSCRIPT_VARIANT,THREE_PRIME_UTR_VARIANT,INTRON_VARIANT
rs36084378 - p.Arg308His
rs883541 - p.Thr31Ile

Additional dbSNP identifiers (rs#s) for WIPI1 Gene

Structural Variations from Database of Genomic Variants (DGV) for WIPI1 Gene

Variant ID Type Subtype PubMed ID
esv1105165 CNV insertion 17803354
esv2557973 CNV insertion 19546169
esv3310445 CNV novel sequence insertion 20981092
esv3446295 CNV insertion 20981092
esv3447514 CNV insertion 20981092
esv993931 CNV insertion 20482838
nsv1111149 CNV tandem duplication 24896259
nsv833523 CNV gain 17160897

Variation tolerance for WIPI1 Gene

Residual Variation Intolerance Score: 39% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 2.30; 41.15% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for WIPI1 Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
WIPI1

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for WIPI1 Gene

Disorders for WIPI1 Gene

MalaCards: The human disease database

(3) MalaCards diseases for WIPI1 Gene - From: DISEASES

- elite association - COSMIC cancer census association via MalaCards
Search WIPI1 in MalaCards View complete list of genes associated with diseases

Additional Disease Information for WIPI1

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 WIPI1: view

No data available for UniProtKB/Swiss-Prot and Genatlas for WIPI1 Gene

Publications for WIPI1 Gene

  1. PtdIns-specific MPR pathway association of a novel WD40 repeat protein, WIPI49. (PMID: 15020712) Jeffries TR … Parker PJ (Molecular biology of the cell 2004) 2 3 4 23 54
  2. WIPI-1alpha (WIPI49), a member of the novel 7-bladed WIPI protein family, is aberrantly expressed in human cancer and is linked to starvation-induced autophagy. (PMID: 15602573) Proikas-Cezanne T … Nordheim A (Oncogene 2004) 2 3 4 54
  3. WIPI3 and WIPI4 β-propellers are scaffolds for LKB1-AMPK-TSC signalling circuits in the control of autophagy. (PMID: 28561066) Bakula D … Proikas-Cezanne T (Nature communications 2017) 3 4 54
  4. WIPI1 coordinates melanogenic gene transcription and melanosome formation via TORC1 inhibition. (PMID: 21317285) Ho H … Ganesan AK (The Journal of biological chemistry 2011) 3 4 54
  5. Freeze-fracture replica immunolabelling reveals human WIPI-1 and WIPI-2 as membrane proteins of autophagosomes. (PMID: 21564513) Proikas-Cezanne T … Robenek H (Journal of cellular and molecular medicine 2011) 3 4 54

Products for WIPI1 Gene

Sources for WIPI1 Gene