This gene encodes a member of the adaptor complexes large subunit protein family. These proteins are components of the heterotetrameric adaptor protein complexes, which play important roles in the secretory and endocytic pathways by mediating vesicle formation and sorting of integral membrane proteins. The encoded protein is a large subunit of adaptor protein complex-4, which i... See more...

Aliases for AP4E1 Gene

Aliases for AP4E1 Gene

  • Adaptor Related Protein Complex 4 Subunit Epsilon 1 2 3 5
  • Adaptor Related Protein Complex 4 Epsilon 1 Subunit 2 3
  • AP-4 Adaptor Complex Subunit Epsilon 3 4
  • AP-4 Complex Subunit Epsilon-1 3 4
  • Epsilon-Adaptin 3 4
  • SPG51 2 3
  • Adaptor-Related Protein Complex 4 Subunit Epsilon-1 4
  • Adaptor-Related Protein Complex AP-4 Epsilon 3
  • Epsilon Subunit Of AP-4 4
  • AP-4-EPSILON 2
  • CPSQ4 3
  • STUT1 3
  • AP4E1 5

External Ids for AP4E1 Gene

Previous GeneCards Identifiers for AP4E1 Gene

  • GC15P046758
  • GC15P044246
  • GC15P048780
  • GC15P048917
  • GC15P048988
  • GC15P051200
  • GC15P028030

Summaries for AP4E1 Gene

Entrez Gene Summary for AP4E1 Gene

  • This gene encodes a member of the adaptor complexes large subunit protein family. These proteins are components of the heterotetrameric adaptor protein complexes, which play important roles in the secretory and endocytic pathways by mediating vesicle formation and sorting of integral membrane proteins. The encoded protein is a large subunit of adaptor protein complex-4, which is associated with both clathrin- and nonclathrin-coated vesicles. Disruption of this gene may be associated with cerebral palsy. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Nov 2011]

GeneCards Summary for AP4E1 Gene

AP4E1 (Adaptor Related Protein Complex 4 Subunit Epsilon 1) is a Protein Coding gene. Diseases associated with AP4E1 include Spastic Paraplegia 51, Autosomal Recessive and Stuttering. Among its related pathways are Lysosome and Clathrin derived vesicle budding. Gene Ontology (GO) annotations related to this gene include binding and structural molecule activity. An important paralog of this gene is AP1G1.

UniProtKB/Swiss-Prot Summary for AP4E1 Gene

  • Component of the adaptor protein complex 4 (AP-4). Adaptor protein complexes are vesicle coat components involved both in vesicle formation and cargo selection. They control the vesicular transport of proteins in different trafficking pathways (PubMed:10066790, PubMed:10436028). AP-4 forms a non clathrin-associated coat on vesicles departing the trans-Golgi network (TGN) and may be involved in the targeting of proteins from the trans-Golgi network (TGN) to the endosomal-lysosomal system. It is also involved in protein sorting to the basolateral membrane in epithelial cells and the proper asymmetric localization of somatodendritic proteins in neurons. AP-4 is involved in the recognition and binding of tyrosine-based sorting signals found in the cytoplasmic part of cargos, but may also recognize other types of sorting signal (Probable).

Gene Wiki entry for AP4E1 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for AP4E1 Gene

Genomics for AP4E1 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for AP4E1 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 AP4E1 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for AP4E1

Top Transcription factor binding sites by QIAGEN in the AP4E1 gene promoter:
  • c-Ets-1
  • FOXJ2
  • FOXJ2 (long isoform)
  • FOXL1
  • Nkx3-1
  • Nkx3-1 v1
  • Nkx3-1 v2
  • Nkx3-1 v3
  • Nkx3-1 v4
  • TBP

Genomic Locations for AP4E1 Gene

Genomic Locations for AP4E1 Gene
chr15:50,908,569-51,005,900
(GRCh38/hg38)
Size:
97,332 bases
Orientation:
Plus strand
chr15:51,200,869-51,298,097
(GRCh37/hg19)
Size:
97,229 bases
Orientation:
Plus strand

Genomic View for AP4E1 Gene

Genes around AP4E1 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
AP4E1 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for AP4E1 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for AP4E1 Gene

Proteins for AP4E1 Gene

  • Protein details for AP4E1 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q9UPM8-AP4E1_HUMAN
    Recommended name:
    AP-4 complex subunit epsilon-1
    Protein Accession:
    Q9UPM8
    Secondary Accessions:
    • A0AVD6
    • A1L4A9
    • A6NNX7
    • H0YKX4
    • Q68D31
    • Q9Y588

    Protein attributes for AP4E1 Gene

    Size:
    1137 amino acids
    Molecular mass:
    127287 Da
    Quaternary structure:
    • Adaptor protein complex 4 (AP-4) is a heterotetramer composed of two large adaptins (epsilon-type subunit AP4E1 and beta-type subunit AP4B1), a medium adaptin (mu-type subunit AP4M1) and a small adaptin (sigma-type AP4S1) (PubMed:10436028, PubMed:10066790). Interacts with TEPSIN (PubMed:26542808). Interacts with GRIA2; probably indirect it mediates the somatodendritic localization of GRIA2 in neurons (By similarity).

    Alternative splice isoforms for AP4E1 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for AP4E1 Gene

Post-translational modifications for AP4E1 Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

No data available for DME Specific Peptides for AP4E1 Gene

Domains & Families for AP4E1 Gene

Gene Families for AP4E1 Gene

Protein Domains for AP4E1 Gene

InterPro:
Blocks:
  • Protein of unknown function DUF1606
ProtoNet:

Suggested Antigen Peptide Sequences for AP4E1 Gene

GenScript: Design optimal peptide antigens:
  • Epsilon-adaptin (AP4E1_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q9UPM8

UniProtKB/Swiss-Prot:

AP4E1_HUMAN :
  • Belongs to the adaptor complexes large subunit family.
Family:
  • Belongs to the adaptor complexes large subunit family.
genes like me logo Genes that share domains with AP4E1: view

Function for AP4E1 Gene

Molecular function for AP4E1 Gene

UniProtKB/Swiss-Prot Function:
Component of the adaptor protein complex 4 (AP-4). Adaptor protein complexes are vesicle coat components involved both in vesicle formation and cargo selection. They control the vesicular transport of proteins in different trafficking pathways (PubMed:10066790, PubMed:10436028). AP-4 forms a non clathrin-associated coat on vesicles departing the trans-Golgi network (TGN) and may be involved in the targeting of proteins from the trans-Golgi network (TGN) to the endosomal-lysosomal system. It is also involved in protein sorting to the basolateral membrane in epithelial cells and the proper asymmetric localization of somatodendritic proteins in neurons. AP-4 is involved in the recognition and binding of tyrosine-based sorting signals found in the cytoplasmic part of cargos, but may also recognize other types of sorting signal (Probable).

Phenotypes From GWAS Catalog for AP4E1 Gene

Gene Ontology (GO) - Molecular Function for AP4E1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005515 protein binding IPI 26542808
genes like me logo Genes that share ontologies with AP4E1: view
genes like me logo Genes that share phenotypes with AP4E1: view

Human Phenotype Ontology for AP4E1 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for AP4E1 Gene

MGI Knock Outs for AP4E1:
  • Ap4e1 Ap4e1<tm1a(KOMP)Wtsi>
  • Ap4e1 Ap4e1<tm1b(KOMP)Wtsi>

Animal Model Products

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for AP4E1

No data available for Enzyme Numbers (IUBMB) , Transcription Factor Targets and HOMER Transcription for AP4E1 Gene

Localization for AP4E1 Gene

Subcellular locations from UniProtKB/Swiss-Prot for AP4E1 Gene

Golgi apparatus, trans-Golgi network membrane. Peripheral membrane protein.

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 AP4E1 gene
Compartment Confidence
endosome 4
golgi apparatus 4
cytosol 3
plasma membrane 2
nucleus 2
extracellular 1
cytoskeleton 1
mitochondrion 1
endoplasmic reticulum 1
lysosome 1
peroxisome 0

Gene Ontology (GO) - Cellular Components for AP4E1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005794 Golgi apparatus IEA --
GO:0016020 membrane IEA --
GO:0030117 membrane coat IEA --
GO:0030124 AP-4 adaptor complex IDA 10066790
GO:0031904 endosome lumen TAS --
genes like me logo Genes that share ontologies with AP4E1: view

No data available for Subcellular locations from the Human Protein Atlas (HPA) for AP4E1 Gene

Pathways & Interactions for AP4E1 Gene

genes like me logo Genes that share pathways with AP4E1: view

Pathways by source for AP4E1 Gene

Gene Ontology (GO) - Biological Process for AP4E1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006605 protein targeting IC 10066790
GO:0006886 intracellular protein transport IEA --
GO:0006898 receptor-mediated endocytosis IBA 21873635
GO:0008104 protein localization IC 10066790
GO:0015031 protein transport IEA --
genes like me logo Genes that share ontologies with AP4E1: view

No data available for SIGNOR curated interactions for AP4E1 Gene

Drugs & Compounds for AP4E1 Gene

No Compound Related Data Available

Transcripts for AP4E1 Gene

mRNA/cDNA for AP4E1 Gene

2 REFSEQ mRNAs :
15 NCBI additional mRNA sequence :
7 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 AP4E1

Alternative Splicing Database (ASD) splice patterns (SP) for AP4E1 Gene

ExUns: 1 ^ 2 ^ 3 ^ 4 ^ 5 ^ 6 ^ 7 ^ 8 ^ 9 ^ 10 ^ 11 ^ 12 ^ 13 ^ 14 ^ 15 ^ 16 ^ 17 ^ 18a · 18b ^ 19 ^ 20 ^ 21a · 21b
SP1:
SP2: -

Relevant External Links for AP4E1 Gene

GeneLoc Exon Structure for
AP4E1

Expression for AP4E1 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for AP4E1 Gene

Protein differential expression in normal tissues from HIPED for AP4E1 Gene

This gene is overexpressed in Kidney (43.6).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for AP4E1 Gene



Protein tissue co-expression partners for AP4E1 Gene

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for AP4E1

SOURCE GeneReport for Unigene cluster for AP4E1 Gene:

Hs.413366

mRNA Expression by UniProt/SwissProt for AP4E1 Gene:

Q9UPM8-AP4E1_HUMAN
Tissue specificity: Widely expressed.

Evidence on tissue expression from TISSUES for AP4E1 Gene

  • Heart(4.3)
  • Liver(4.1)
  • Nervous system(2)

Phenotype-based relationships between genes and organs from Gene ORGANizer for AP4E1 Gene

Germ Layers:
  • ectoderm
  • endoderm
  • mesoderm
Systems:
  • digestive
  • integumentary
  • nervous
  • skeletal muscle
  • skeleton
Regions:
Head and neck:
  • brain
  • cerebellum
  • cheek
  • chin
  • cranial nerve
  • ear
  • eye
  • eyelid
  • face
  • forehead
  • head
  • jaw
  • lip
  • mandible
  • maxilla
  • mouth
  • nose
  • outer ear
  • salivary gland
  • skull
  • tooth
Limb:
  • ankle
  • digit
  • elbow
  • finger
  • foot
  • hand
  • hip
  • knee
  • lower limb
  • shoulder
  • toe
  • upper limb
  • wrist
General:
  • peripheral nerve
  • peripheral nervous system
  • skin
  • spinal cord
genes like me logo Genes that share expression patterns with AP4E1: view

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery and mRNA differential expression in normal tissues for AP4E1 Gene

Orthologs for AP4E1 Gene

This gene was present in the common ancestor of eukaryotes.

Orthologs for AP4E1 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia AP4E1 30 31
  • 99.65 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia AP4E1 30 31
  • 91.64 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia AP4E1 30 31
  • 91.41 (n)
OneToOne
Mouse
(Mus musculus)
Mammalia Ap4e1 30 17 31
  • 83.82 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Ap4e1 30
  • 83.38 (n)
Oppossum
(Monodelphis domestica)
Mammalia AP4E1 31
  • 79 (a)
OneToOne
Platypus
(Ornithorhynchus anatinus)
Mammalia AP4E1 31
  • 41 (a)
OneToOne
Chicken
(Gallus gallus)
Aves AP4E1 30 31
  • 72.2 (n)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia AP4E1 31
  • 85 (a)
OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia ap4e1 30
  • 64.88 (n)
African clawed frog
(Xenopus laevis)
Amphibia Xl.10831 30
Zebrafish
(Danio rerio)
Actinopterygii ap4e1 30 31
  • 56.99 (n)
OneToOne
Fruit Fly
(Drosophila melanogaster)
Insecta AP-1gamma 31
  • 19 (a)
OneToMany
Worm
(Caenorhabditis elegans)
Secernentea apg-1 31
  • 19 (a)
OneToMany
Baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes APL4 31
  • 17 (a)
OneToMany
Thale Cress
(Arabidopsis thaliana)
eudicotyledons AT1G31730 30
  • 48.92 (n)
Rice
(Oryza sativa)
Liliopsida Os01g0916200 30
  • 49.62 (n)
Sea Squirt
(Ciona savignyi)
Ascidiacea -- 31
  • 20 (a)
OneToMany
Species where no ortholog for AP4E1 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • 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 Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • 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 AP4E1 Gene

ENSEMBL:
Gene Tree for AP4E1 (if available)
TreeFam:
Gene Tree for AP4E1 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for AP4E1: view image

Paralogs for AP4E1 Gene

Paralogs for AP4E1 Gene

(2) SIMAP similar genes for AP4E1 Gene using alignment to 5 proteins:

  • AP4E1_HUMAN
  • H0YK94_HUMAN
  • H0YK95_HUMAN
  • H0YL95_HUMAN
  • L8ECD9_HUMAN
genes like me logo Genes that share paralogs with AP4E1: view

Variants for AP4E1 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for AP4E1 Gene

SNP ID Clinical significance and condition Chr 15 pos Variation AA Info Type
638418 Uncertain Significance: not specified 50,912,133(+) C/T MISSENSE_VARIANT,FIVE_PRIME_UTR_VARIANT
639770 Uncertain Significance: Spastic paraplegia 50,958,529(+) C/T MISSENSE_VARIANT
641707 Uncertain Significance: Spastic paraplegia 50,997,395(+) G/A MISSENSE_VARIANT
642679 Uncertain Significance: Spastic paraplegia 50,941,540(+) C/T MISSENSE_VARIANT
643004 Uncertain Significance: Spastic paraplegia 50,915,509(+) C/T MISSENSE_VARIANT

Additional dbSNP identifiers (rs#s) for AP4E1 Gene

Structural Variations from Database of Genomic Variants (DGV) for AP4E1 Gene

Variant ID Type Subtype PubMed ID
dgv4526n54 CNV gain 21841781
esv2452631 CNV insertion 19546169
esv2760031 CNV gain 17122850
esv3307487 CNV mobile element insertion 20981092
esv3361389 CNV insertion 20981092
esv3375902 CNV insertion 20981092
esv34532 CNV gain 17911159
nsv1038778 CNV loss 25217958
nsv1047443 CNV gain 25217958
nsv516168 CNV gain 19592680
nsv569398 CNV loss 21841781
nsv569403 CNV loss 21841781
nsv569404 CNV loss 21841781
nsv9264 CNV loss 18304495

Variation tolerance for AP4E1 Gene

Residual Variation Intolerance Score: 61% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 11.74; 93.31% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for AP4E1 Gene

Human Gene Mutation Database (HGMD)
AP4E1
SNPedia medical, phenotypic, and genealogical associations of SNPs for
AP4E1

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for AP4E1 Gene

Disorders for AP4E1 Gene

MalaCards: The human disease database

(24) MalaCards diseases for AP4E1 Gene - From: OMIM, ClinVar, GTR, Orphanet, DISEASES, and GeneCards

Disorder Aliases PubMed IDs
spastic paraplegia 51, autosomal recessive
  • spg51
stuttering
  • familial persistent stuttering
cerebral palsy
  • mixed cerebral palsy
hereditary spastic paraplegia 51
  • spastic paraplegia 51, autosomal recessive
paraplegia
  • paraplegia, lower
- elite association - COSMIC cancer census association via MalaCards
Search AP4E1 in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

AP4E1_HUMAN
  • Spastic paraplegia 51, autosomal recessive (SPG51) [MIM:613744]: A form of spastic paraplegia, a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. SPG51 is a non-progressive disorder of movement and/or posture resulting from defects in the developing central nervous system. Affected individuals manifest motor and posture impairments often associated with epilepsy and disturbances of cognition, behavior, sensation, and communication. {ECO:0000269 PubMed:20972249}. Note=The disease is caused by mutations affecting the gene represented in this entry.
  • Stuttering, familial persistent 1 (STUT1) [MIM:184450]: A familial form of stuttering, a disturbance in the normal fluency and time patterning of speech, characterized by frequent repetitions or prolongations of sounds or syllables, and by interruptions of speech known as blocks. STUT1 inheritance is autosomal dominant. {ECO:0000269 PubMed:26544806}. Note=The disease is caused by mutations affecting the gene represented in this entry.
genes like me logo Genes that share disorders with AP4E1: view

No data available for Genatlas for AP4E1 Gene

Publications for AP4E1 Gene

  1. Characterization of a fourth adaptor-related protein complex. (PMID: 10436028) Hirst J … Robinson MS (Molecular biology of the cell 1999) 2 3 4
  2. Bivalent Motif-Ear Interactions Mediate the Association of the Accessory Protein Tepsin with the AP-4 Adaptor Complex. (PMID: 26542808) Mattera R … Bonifacino JS (The Journal of biological chemistry 2015) 3 4
  3. Association between Rare Variants in AP4E1, a Component of Intracellular Trafficking, and Persistent Stuttering. (PMID: 26544806) Raza MH … Drayna D (American journal of human genetics 2015) 3 4
  4. Adaptor protein complex 4 deficiency causes severe autosomal-recessive intellectual disability, progressive spastic paraplegia, shy character, and short stature. (PMID: 21620353) Abou Jamra R … Colleaux L (American journal of human genetics 2011) 2 3
  5. Adaptor protein complex-4 (AP-4) deficiency causes a novel autosomal recessive cerebral palsy syndrome with microcephaly and intellectual disability. (PMID: 20972249) Moreno-De-Luca A … Martin CL (Journal of medical genetics 2011) 3 4

Products for AP4E1 Gene

Sources for AP4E1 Gene