Free for academic non-profit institutions. Other users need a Commercial license

Aliases for APPL2 Gene

Aliases for APPL2 Gene

  • Adaptor Protein, Phosphotyrosine Interacting With PH Domain And Leucine Zipper 2 2 3 5
  • Adaptor Protein, Phosphotyrosine Interaction, PH Domain And Leucine Zipper Containing 2 2 3
  • Adapter Protein Containing PH Domain, PTB Domain And Leucine Zipper Motif 2 3 4
  • DCC-Interacting Protein 13-Beta 2 3
  • DIP13B 3 4
  • DIP13 Beta 3
  • Dip13-Beta 4

External Ids for APPL2 Gene

Previous GeneCards Identifiers for APPL2 Gene

  • GC12M104091
  • GC12M105568
  • GC12M102626

Summaries for APPL2 Gene

Entrez Gene Summary for APPL2 Gene

  • The protein encoded by this gene is one of two effectors of the small GTPase RAB5A/Rab5, which are involved in a signal transduction pathway. Both effectors contain an N-terminal Bin/Amphiphysin/Rvs (BAR) domain, a central pleckstrin homology (PH) domain, and a C-terminal phosphotyrosine binding (PTB) domain, and they bind the Rab5 through the BAR domain. They are associated with endosomal membranes and can be translocated to the nucleus in response to the EGF stimulus. They interact with the NuRD/MeCP1 complex (nucleosome remodeling and deacetylase /methyl-CpG-binding protein 1 complex) and are required for efficient cell proliferation. A chromosomal aberration t(12;22)(q24.1;q13.3) involving this gene and the PSAP2 gene results in 22q13.3 deletion syndrome, also known as Phelan-McDermid syndrome. [provided by RefSeq, Oct 2011]

GeneCards Summary for APPL2 Gene

APPL2 (Adaptor Protein, Phosphotyrosine Interacting With PH Domain And Leucine Zipper 2) is a Protein Coding gene. Diseases associated with APPL2 include Phelan-Mcdermid Syndrome. An important paralog of this gene is APPL1.

UniProtKB/Swiss-Prot for APPL2 Gene

  • Required for the regulation of cell proliferation in response to extracellular signals mediated by an early endosomal compartment. Links Rab5 to nuclear signal transduction.

Gene Wiki entry for APPL2 Gene

Additional gene information for APPL2 Gene

No data available for CIViC summary , Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for APPL2 Gene

Genomics for APPL2 Gene

GeneHancer (GH) Regulatory Elements for APPL2 Gene

Promoters and enhancers for APPL2 Gene
GeneHancer (GH) Identifier GH Type GH
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH12I105225 Promoter/Enhancer 2.7 EPDnew FANTOM5 Ensembl ENCODE dbSUPER 571.3 +4.9 4911 11.5 PKNOX1 ARID4B SIN3A DMAP1 YY1 POLR2B ZNF766 ZNF213 E2F8 ZNF143 APPL2 WASHC4 C12orf75 PIR46520 GC12P105208
GH12I105326 Promoter/Enhancer 2.1 EPDnew Ensembl ENCODE 16.3 -95.8 -95786 11.8 HDGF PKNOX1 SIN3A FEZF1 GLIS2 ZNF143 ATF7 KLF7 FOS RUNX3 C12orf75 APPL2 WASHC4 KCCAT198 LOC105369957
GH12I105106 Promoter/Enhancer 2.1 EPDnew Ensembl ENCODE 15.3 +127.1 127131 5.2 HDGF PKNOX1 CLOCK MLX ARNT ARID4B SIN3A FEZF1 DMAP1 ZNF2 WASHC4 LOC414300 APPL2 KCCAT198 GC12P105154
GH12I105210 Enhancer 1.2 Ensembl ENCODE dbSUPER 25.6 +22.1 22099 6.9 SOX13 FOXA2 BMI1 RAD21 YY1 GATA3 POLR2A RCOR1 FOS TCF7L2 PIR46520 WASHC4 APPL2 C12orf75 GC12P105208 LOC105369953
GH12I105091 Enhancer 1 FANTOM5 Ensembl ENCODE 24.1 +143.9 143941 1.8 PKNOX1 CBFA2T3 SP1 GATA3 POLR2A CREB1 ZBTB17 EZH2 WASHC4 APPL2 C12orf75 ALDH1L2
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data dump

GeneHancers around APPL2 on UCSC Golden Path with GeneCards custom track

Top Transcription factor binding sites by QIAGEN in the APPL2 gene promoter:

Genomic Locations for APPL2 Gene

Genomic Locations for APPL2 Gene
62,943 bases
Minus strand

Genomic View for APPL2 Gene

Genes around APPL2 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
APPL2 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for APPL2 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for APPL2 Gene

Proteins for APPL2 Gene

  • Protein details for APPL2 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Recommended name:
    DCC-interacting protein 13-beta
    Protein Accession:
    Secondary Accessions:
    • B7Z411
    • B7Z4B0
    • F5GZG0
    • F8W1P5
    • Q8N4R7
    • Q9NVL2

    Protein attributes for APPL2 Gene

    664 amino acids
    Molecular mass:
    74493 Da
    Quaternary structure:
    • Binds RAB5A/Rab5 through an N-terminal domain. This interaction is essential for its recruitment to endosomal membranes as well as its role in cell proliferation. Binds subunits of the NuRD/MeCP1 complex.

    Three dimensional structures from OCA and Proteopedia for APPL2 Gene

    Alternative splice isoforms for APPL2 Gene


neXtProt entry for APPL2 Gene

Post-translational modifications for APPL2 Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

No data available for DME Specific Peptides for APPL2 Gene

Domains & Families for APPL2 Gene

Gene Families for APPL2 Gene

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

Suggested Antigen Peptide Sequences for APPL2 Gene

Graphical View of Domain Structure for InterPro Entry

genes like me logo Genes that share domains with APPL2: view

No data available for UniProtKB/Swiss-Prot for APPL2 Gene

Function for APPL2 Gene

Molecular function for APPL2 Gene

UniProtKB/Swiss-Prot Function:
Required for the regulation of cell proliferation in response to extracellular signals mediated by an early endosomal compartment. Links Rab5 to nuclear signal transduction.

Phenotypes From GWAS Catalog for APPL2 Gene

Gene Ontology (GO) - Molecular Function for APPL2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005515 protein binding IPI 15016378
genes like me logo Genes that share ontologies with APPL2: view
genes like me logo Genes that share phenotypes with APPL2: view

Animal Models for APPL2 Gene

MGI Knock Outs for APPL2:

Animal Model Products

CRISPR Products

miRNA for APPL2 Gene

miRTarBase miRNAs that target APPL2

Inhibitory RNA Products

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for APPL2 Gene

Localization for APPL2 Gene

Subcellular locations from UniProtKB/Swiss-Prot for APPL2 Gene

Early endosome membrane; Peripheral membrane protein. Nucleus. Note=Early endosomal membrane-bound and nuclear. Translocated into the nucleus upon release from endosomal membranes following internalization of EGF.

Subcellular locations from

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 APPL2 gene
Compartment Confidence
extracellular 5
nucleus 5
endosome 5
cytosol 2

Gene Ontology (GO) - Cellular Components for APPL2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus IEA,IDA 15016378
GO:0005737 cytoplasm IC --
GO:0005768 endosome IEA --
GO:0010008 endosome membrane IDA 15016378
GO:0016020 membrane IEA --
genes like me logo Genes that share ontologies with APPL2: view

No data available for Subcellular locations from the Human Protein Atlas (HPA) for APPL2 Gene

Pathways & Interactions for APPL2 Gene

SuperPathways for APPL2 Gene

No Data Available

Gene Ontology (GO) - Biological Process for APPL2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0007049 cell cycle IEA --
GO:0007165 signal transduction TAS 15016378
GO:0008283 cell proliferation IDA 15016378
genes like me logo Genes that share ontologies with APPL2: view

No data available for Pathways by source and SIGNOR curated interactions for APPL2 Gene

Drugs & Compounds for APPL2 Gene

No Compound Related Data Available

Transcripts for APPL2 Gene

Unigene Clusters for APPL2 Gene

Adaptor protein, phosphotyrosine interaction, PH domain and leucine zipper containing 2:
Representative Sequences:

CRISPR Products

Inhibitory RNA Products

Alternative Splicing Database (ASD) splice patterns (SP) for APPL2 Gene

No ASD Table

Relevant External Links for APPL2 Gene

GeneLoc Exon Structure for
ECgene alternative splicing isoforms for

Expression for APPL2 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for APPL2 Gene

Protein differential expression in normal tissues from HIPED for APPL2 Gene

This gene is overexpressed in Peripheral blood mononuclear cells (22.0), Heart (12.0), and Platelet (9.7).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, MaxQB, and MOPED for APPL2 Gene

Protein tissue co-expression partners for APPL2 Gene

NURSA nuclear receptor signaling pathways regulating expression of APPL2 Gene:


SOURCE GeneReport for Unigene cluster for APPL2 Gene:


mRNA Expression by UniProt/SwissProt for APPL2 Gene:

Tissue specificity: High levels in brain, heart, kidney and skeletal muscle.

Evidence on tissue expression from TISSUES for APPL2 Gene

  • Intestine(4.3)
  • Nervous system(2.3)
genes like me logo Genes that share expression patterns with APPL2: view

Primer Products

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 APPL2 Gene

Orthologs for APPL2 Gene

This gene was present in the common ancestor of chordates.

Orthologs for APPL2 Gene

Organism Taxonomy Gene Similarity Type Details
(Pan troglodytes)
Mammalia APPL2 33 34
  • 99.6 (n)
(Bos Taurus)
Mammalia APPL2 33 34
  • 91.34 (n)
(Canis familiaris)
Mammalia APPL2 33 34
  • 89.68 (n)
(Monodelphis domestica)
Mammalia APPL2 34
  • 89 (a)
(Ornithorhynchus anatinus)
Mammalia APPL2 34
  • 89 (a)
(Mus musculus)
Mammalia Appl2 33 16 34
  • 87.92 (n)
(Rattus norvegicus)
Mammalia Appl2 33
  • 87.31 (n)
(Gallus gallus)
Aves -- 34
  • 86 (a)
-- 34
  • 79 (a)
LOC100857286 33
  • 77.25 (n)
(Anolis carolinensis)
Reptilia APPL2 34
  • 82 (a)
tropical clawed frog
(Silurana tropicalis)
Amphibia appl2 33
  • 72.21 (n)
(Danio rerio)
Actinopterygii appl2 33 34
  • 66.72 (n)
sea squirt
(Ciona savignyi)
Ascidiacea -- 34
  • 39 (a)
Species where no ortholog for APPL2 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)
  • baker's yeast (Saccharomyces cerevisiae)
  • 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)
  • fruit fly (Drosophila melanogaster)
  • 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)
  • worm (Caenorhabditis elegans)

Evolution for APPL2 Gene

Gene Tree for APPL2 (if available)
Gene Tree for APPL2 (if available)

Paralogs for APPL2 Gene

Paralogs for APPL2 Gene

(1) SIMAP similar genes for APPL2 Gene using alignment to 7 proteins:

genes like me logo Genes that share paralogs with APPL2: view

Variants for APPL2 Gene

Sequence variations from dbSNP and Humsavar for APPL2 Gene

SNP ID Clin Chr 12 pos Variation AA Info Type
rs1000063575 -- 105,232,252(-) C/G 5_prime_UTR_variant, genic_upstream_transcript_variant, intron_variant, upstream_transcript_variant
rs1000247758 -- 105,213,610(-) T/C intron_variant
rs1000327100 -- 105,203,337(-) T/C intron_variant
rs1000370326 -- 105,201,930(-) /T intron_variant
rs1000405220 -- 105,174,628(-) G/T intron_variant

Structural Variations from Database of Genomic Variants (DGV) for APPL2 Gene

Variant ID Type Subtype PubMed ID
nsv560053 CNV loss 21841781
nsv832506 CNV gain 17160897
nsv952469 CNV duplication 24416366

Variation tolerance for APPL2 Gene

Residual Variation Intolerance Score: 84.1% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 6.51; 77.64% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for APPL2 Gene

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

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for APPL2 Gene

Disorders for APPL2 Gene

MalaCards: The human disease database

(1) MalaCards diseases for APPL2 Gene - From: HGMD and GeneCards

Disorder Aliases PubMed IDs
phelan-mcdermid syndrome
  • phmds
- elite association - COSMIC cancer census association via MalaCards
Search APPL2 in MalaCards View complete list of genes associated with diseases


  • Note=A chromosomal aberration involving APPL2/DIP13B is found in patients with chromosome 22q13.3 deletion syndrome. Translocation t(12;22)(q24.1;q13.3) with SHANK3/PSAP2 (PubMed:11431708). {ECO:0000269 PubMed:11431708}.

Additional Disease Information for APPL2

genes like me logo Genes that share disorders with APPL2: view

No data available for Genatlas for APPL2 Gene

Publications for APPL2 Gene

  1. Disruption of the ProSAP2 gene in a t(12;22)(q24.1;q13.3) is associated with the 22q13.3 deletion syndrome. (PMID: 11431708) Bonaglia MC … Zuffardi O (American journal of human genetics 2001) 2 3 4 22 58
  2. APPL1, APPL2, Akt2 and FOXO1a interact with FSHR in a potential signaling complex. (PMID: 17030088) Nechamen CA … Dias JA (Molecular and cellular endocrinology 2007) 2 3 22 58
  3. Endosomal adaptor proteins APPL1 and APPL2 are novel activators of beta-catenin/TCF-mediated transcription. (PMID: 19433865) Rashid S … Miaczynska M (The Journal of biological chemistry 2009) 3 22 58
  4. Complete sequencing and characterization of 21,243 full-length human cDNAs. (PMID: 14702039) Ota T … Sugano S (Nature genetics 2004) 3 4 58
  5. The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). (PMID: 15489334) Gerhard DS … MGC Project Team (Genome research 2004) 3 4 58

Products for APPL2 Gene

Sources for APPL2 Gene

Loading form....