This gene encodes a member of the adaptor complexes small 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 the small subunit of adaptor protein complex-4, which... See more...

Aliases for AP4S1 Gene

Aliases for AP4S1 Gene

  • Adaptor Related Protein Complex 4 Subunit Sigma 1 2 3 5
  • Adaptor Related Protein Complex 4 Sigma 1 Subunit 2 3
  • AP-4 Adaptor Complex Subunit Sigma-1 3 4
  • AP-4 Complex Subunit Sigma-1 3 4
  • Sigma-4-Adaptin 3 4
  • Clathrin-Associated/Assembly/Adaptor Protein, Sigma 4 3
  • Adaptor-Related Protein Complex 4 Subunit Sigma-1 4
  • AP-4 Adapter Complex Subunit Sigma-1 3
  • Sigma-1 Subunit Of AP-4 4
  • Sigma4-Adaptin 4
  • CLAPS4 3
  • AP47B 3
  • CLA20 3
  • CPSQ6 3
  • SPG52 3

External Ids for AP4S1 Gene

Previous GeneCards Identifiers for AP4S1 Gene

  • GC14P028870
  • GC14P025282
  • GC14P029484
  • GC14P030564
  • GC14P031494
  • GC14P011612

Summaries for AP4S1 Gene

Entrez Gene Summary for AP4S1 Gene

  • This gene encodes a member of the adaptor complexes small 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 the small subunit of adaptor protein complex-4, which is associated with both clathrin- and nonclathrin-coated vesicles. Mutations in this gene are associated with spastic quadriplegic cerebral palsy-6. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene, and a pseudogene of this gene is located on the long arm of chromosome 6. [provided by RefSeq, Dec 2011]

GeneCards Summary for AP4S1 Gene

AP4S1 (Adaptor Related Protein Complex 4 Subunit Sigma 1) is a Protein Coding gene. Diseases associated with AP4S1 include Spastic Paraplegia 52, Autosomal Recessive and Ap-4-Associated Hereditary Spastic Paraplegia. Among its related pathways are Vesicle-mediated transport and Clathrin derived vesicle budding. Gene Ontology (GO) annotations related to this gene include transporter activity and protein transporter activity. An important paralog of this gene is AP3S1.

UniProtKB/Swiss-Prot Summary for AP4S1 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 AP4S1 Gene

Additional gene information for AP4S1 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for AP4S1 Gene

Genomics for AP4S1 Gene

GeneHancer (GH) Regulatory Elements for AP4S1 Gene

Promoters and enhancers for AP4S1 Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH14J031023 Promoter/Enhancer 2.1 EPDnew Ensembl ENCODE CraniofacialAtlas 756 +0.6 595 5 ZBTB6 LCORL MLX RBPJ SMARCE1 POLR2A NR2F6 MIXL1 ZNF362 CC2D1A STRN3 AP4S1 G2E3 DTD2
GH14J031036 Promoter 0.4 EPDnew 750.4 +11.4 11428 0.1 ZNF18 AP4S1 piR-50437-165 STRN3
GH14J031204 Promoter/Enhancer 2.1 Ensembl ENCODE CraniofacialAtlas dbSUPER 15.7 +182.0 182017 5.4 GTF3C2 ZNF785 SIN3A ZNF24 ZBTB40 CTCF LCORL MLX RBPJ POLR2A HECTD1 lnc-HEATR5A-2 G2E3 ARHGAP5 AP4S1 RPL21P5 RNU6-8 ARHGAP5-AS1 SCFD1 HEATR5A
GH14J030980 Enhancer 1 Ensembl ENCODE 18.1 -43.1 -43106 4 CTCF LCORL ATF1 MIXL1 ZNF362 CC2D1A RAD21 ZNF121 DACH1 ZNF148 AP4S1 MIR624 RNU6-541P STRN3 piR-38852-003 lnc-AP4S1-3
GH14J030988 Enhancer 1 Ensembl ENCODE 18.7 -30.7 -30705 13.2 ZBTB6 CTBP1 HLF ZNF121 SP1 ZNF384 ZNF644 FOSL2 PKNOX1 POLR2A STRN3 AP4S1 MIR624 RNU6-541P HECTD1 DTD2 lnc-AP4S1-3 piR-38852-003
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around AP4S1 on UCSC Golden Path with GeneCards custom track

Top Transcription factor binding sites by QIAGEN in the AP4S1 gene promoter:
  • Cdc5
  • Chx10
  • CREB
  • deltaCREB
  • E47
  • FOXL1
  • Lmo2
  • Meis-1
  • Meis-1a
  • Meis-1b

Genomic Locations for AP4S1 Gene

Genomic Locations for AP4S1 Gene
chr14:31,025,106-31,096,450
(GRCh38/hg38)
Size:
71,345 bases
Orientation:
Plus strand
chr14:31,494,312-31,562,818
(GRCh37/hg19)
Size:
68,507 bases
Orientation:
Plus strand

Genomic View for AP4S1 Gene

Genes around AP4S1 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
AP4S1 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for AP4S1 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for AP4S1 Gene

Proteins for AP4S1 Gene

  • Protein details for AP4S1 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q9Y587-AP4S1_HUMAN
    Recommended name:
    AP-4 complex subunit sigma-1
    Protein Accession:
    Q9Y587
    Secondary Accessions:
    • G3V2N8
    • Q6IAQ4
    • Q86U36
    • Q9BVE7

    Protein attributes for AP4S1 Gene

    Size:
    144 amino acids
    Molecular mass:
    17005 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).

    Alternative splice isoforms for AP4S1 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for AP4S1 Gene

Post-translational modifications for AP4S1 Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

No data available for DME Specific Peptides for AP4S1 Gene

Domains & Families for AP4S1 Gene

Gene Families for AP4S1 Gene

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

Protein Domains for AP4S1 Gene

Suggested Antigen Peptide Sequences for AP4S1 Gene

GenScript: Design optimal peptide antigens:
  • Sigma-4-adaptin (AP4S1_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q9Y587

UniProtKB/Swiss-Prot:

AP4S1_HUMAN :
  • Belongs to the adaptor complexes small subunit family.
Family:
  • Belongs to the adaptor complexes small subunit family.
genes like me logo Genes that share domains with AP4S1: view

Function for AP4S1 Gene

Molecular function for AP4S1 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 AP4S1 Gene

genes like me logo Genes that share phenotypes with AP4S1: view

Human Phenotype Ontology for AP4S1 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Model Products

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for AP4S1

Clone Products

No data available for Enzyme Numbers (IUBMB) , Gene Ontology (GO) - Molecular Function , Animal Models , Transcription Factor Targets and HOMER Transcription for AP4S1 Gene

Localization for AP4S1 Gene

Subcellular locations from UniProtKB/Swiss-Prot for AP4S1 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 AP4S1 gene
Compartment Confidence
endosome 4
golgi apparatus 4
cytosol 2
mitochondrion 1
peroxisome 1
nucleus 1
extracellular 0
endoplasmic reticulum 0

Subcellular locations from the

Human Protein Atlas (HPA)

Gene Ontology (GO) - Cellular Components for AP4S1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005794 Golgi apparatus IEA --
GO:0016020 membrane IEA --
GO:0030124 AP-4 adaptor complex IDA 10066790
GO:0031904 endosome lumen TAS --
GO:0032588 trans-Golgi network membrane TAS --
genes like me logo Genes that share ontologies with AP4S1: view

Pathways & Interactions for AP4S1 Gene

genes like me logo Genes that share pathways with AP4S1: view

Pathways by source for AP4S1 Gene

Gene Ontology (GO) - Biological Process for AP4S1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006605 protein targeting IC 10066790
GO:0006886 intracellular protein transport IEA --
GO:0008104 protein localization IC 10066790
GO:0015031 protein transport IEA --
GO:0016192 vesicle-mediated transport IBA 21873635
genes like me logo Genes that share ontologies with AP4S1: view

No data available for SIGNOR curated interactions for AP4S1 Gene

Drugs & Compounds for AP4S1 Gene

No Compound Related Data Available

Transcripts for AP4S1 Gene

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for AP4S1

Clone Products

Alternative Splicing Database (ASD) splice patterns (SP) for AP4S1 Gene

ExUns: 1a · 1b ^ 2 ^ 3 ^ 4 ^ 5 ^ 6 ^ 7a · 7b · 7c
SP1:
SP2: -
SP3: - -

Relevant External Links for AP4S1 Gene

GeneLoc Exon Structure for
AP4S1
ECgene alternative splicing isoforms for
AP4S1

Expression for AP4S1 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for AP4S1 Gene

Protein differential expression in normal tissues from HIPED for AP4S1 Gene

This gene is overexpressed in Pancreas (27.3), Esophagus (15.5), and Breast (13.8).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for AP4S1 Gene



Protein tissue co-expression partners for AP4S1 Gene

NURSA nuclear receptor signaling pathways regulating expression of AP4S1 Gene:

AP4S1

SOURCE GeneReport for Unigene cluster for AP4S1 Gene:

Hs.293411

mRNA Expression by UniProt/SwissProt for AP4S1 Gene:

Q9Y587-AP4S1_HUMAN
Tissue specificity: Widely expressed.

Evidence on tissue expression from TISSUES for AP4S1 Gene

  • Nervous system(4.6)

Phenotype-based relationships between genes and organs from Gene ORGANizer for AP4S1 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 AP4S1: view

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery and mRNA differential expression in normal tissues for AP4S1 Gene

Orthologs for AP4S1 Gene

This gene was present in the common ancestor of eukaryotes.

Orthologs for AP4S1 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia AP4S1 33 32
  • 100 (n)
OneToOne
cow
(Bos Taurus)
Mammalia AP4S1 33 32
  • 95.14 (n)
OneToOne
dog
(Canis familiaris)
Mammalia AP4S1 32
  • 93.29 (n)
mouse
(Mus musculus)
Mammalia Ap4s1 17 33 32
  • 88.89 (n)
rat
(Rattus norvegicus)
Mammalia Ap4s1 32
  • 88.19 (n)
oppossum
(Monodelphis domestica)
Mammalia AP4S1 33
  • 67 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia AP4S1 33
  • 66 (a)
OneToOne
chicken
(Gallus gallus)
Aves AP4S1 33 32
  • 78.94 (n)
OneToOne
lizard
(Anolis carolinensis)
Reptilia AP4S1 33
  • 65 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia ap4s1 32
  • 74.31 (n)
Str.17786 32
African clawed frog
(Xenopus laevis)
Amphibia Xl.20886 32
zebrafish
(Danio rerio)
Actinopterygii ap4s1 33 32
  • 71.9 (n)
OneToOne
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes APS1 33
  • 29 (a)
OneToMany
thale cress
(Arabidopsis thaliana)
eudicotyledons AT2G19790 32
  • 64.27 (n)
rice
(Oryza sativa)
Liliopsida Os10g0368400 32
  • 59.34 (n)
Species where no ortholog for AP4S1 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya 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)
  • 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 blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea squirt (Ciona intestinalis)
  • sea squirt (Ciona savignyi)
  • 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)
  • worm (Caenorhabditis elegans)

Evolution for AP4S1 Gene

ENSEMBL:
Gene Tree for AP4S1 (if available)
TreeFam:
Gene Tree for AP4S1 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for AP4S1: view image

Paralogs for AP4S1 Gene

Paralogs for AP4S1 Gene

(8) SIMAP similar genes for AP4S1 Gene using alignment to 6 proteins:

  • AP4S1_HUMAN
  • G3V3X7_HUMAN
  • G3V4P7_HUMAN
  • G3V5J6_HUMAN
  • H0YJI3_HUMAN
  • J3KNK4_HUMAN

Pseudogenes.org Pseudogenes for AP4S1 Gene

genes like me logo Genes that share paralogs with AP4S1: view

Variants for AP4S1 Gene

Sequence variations from dbSNP and Humsavar for AP4S1 Gene

SNP ID Clin Chr 14 pos Variation AA Info Type
rs1252944335 likely-benign, Spastic paraplegia 31,069,884(+) G/A coding_sequence_variant, synonymous_variant
rs1301666938 likely-benign, Spastic paraplegia 31,084,813(+) C/T 3_prime_UTR_variant, coding_sequence_variant, intron_variant, synonymous_variant
rs1335804396 likely-pathogenic, Inborn genetic diseases 31,066,213(+) T/C coding_sequence_variant, missense_variant
rs147135554 uncertain-significance, not specified, Spastic paraplegia, not provided 31,066,225(+) A/G coding_sequence_variant, missense_variant
rs200440467 likely-pathogenic, pathogenic, uncertain-significance, Spastic paraplegia 52, autosomal recessive, not provided, not specified, Spastic paraplegia 31,072,968(+) C/A/T coding_sequence_variant, stop_gained, synonymous_variant

Structural Variations from Database of Genomic Variants (DGV) for AP4S1 Gene

Variant ID Type Subtype PubMed ID
dgv124e215 CNV deletion 23714750
esv2664388 CNV deletion 23128226
esv33189 CNV loss 17666407
esv3584215 CNV gain 25503493
esv3892495 CNV gain 25118596
nsv1043033 CNV gain 25217958
nsv1049063 CNV gain 25217958
nsv1050054 CNV gain 25217958
nsv1127377 CNV deletion 24896259
nsv1233 CNV insertion 18451855
nsv564169 CNV gain 21841781
nsv832763 CNV loss 17160897

Variation tolerance for AP4S1 Gene

Residual Variation Intolerance Score: 69.4% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 0.72; 15.26% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for AP4S1 Gene

Human Gene Mutation Database (HGMD)
AP4S1
SNPedia medical, phenotypic, and genealogical associations of SNPs for
AP4S1

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for AP4S1 Gene

Disorders for AP4S1 Gene

MalaCards: The human disease database

(12) MalaCards diseases for AP4S1 Gene - From: HGMD, OMIM, ClinVar, GTR, Orphanet, DISEASES, and GeneCards

Disorder Aliases PubMed IDs
spastic paraplegia 52, autosomal recessive
  • spg52
ap-4-associated hereditary spastic paraplegia
  • adaptor protein complex 4 deficiency
hereditary spastic paraplegia 51
  • spastic paraplegia 51, autosomal recessive
cerebral palsy
  • mixed cerebral palsy
spastic paraplegia 50, autosomal recessive
  • spg50
- elite association - COSMIC cancer census association via MalaCards
Search AP4S1 in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

AP4S1_HUMAN
  • Spastic paraplegia 52, autosomal recessive (SPG52) [MIM:614067]: A form of spastic paraplegia, a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. SPG52 is characterized by neonatal hypotonia that progresses to hypertonia and spasticity, and severe mental retardation with poor or absent speech development. Some patients may have seizures. {ECO:0000269 PubMed:21620353}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Additional Disease Information for AP4S1

genes like me logo Genes that share disorders with AP4S1: view

No data available for Genatlas for AP4S1 Gene

Publications for AP4S1 Gene

  1. 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 4 56
  2. Characterization of a fourth adaptor-related protein complex. (PMID: 10436028) Hirst J … Robinson MS (Molecular biology of the cell 1999) 2 3 4 56
  3. Complete sequencing and characterization of 21,243 full-length human cDNAs. (PMID: 14702039) Ota T … Sugano S (Nature genetics 2004) 3 4 56
  4. AP-4, a novel protein complex related to clathrin adaptors. (PMID: 10066790) Dell'Angelica EC … Bonifacino JS (The Journal of biological chemistry 1999) 3 4 56
  5. An AP-MS- and BioID-compatible MAC-tag enables comprehensive mapping of protein interactions and subcellular localizations. (PMID: 29568061) Liu X … Varjosalo M (Nature communications 2018) 3 56

Products for AP4S1 Gene

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