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    AP4E1 adaptor related protein complex 4 subunit epsilon 1 [ Homo sapiens (human) ]

    Gene ID: 23431, updated on 28-Oct-2024

    Summary

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    Official Symbol
    AP4E1provided by HGNC
    Official Full Name
    adaptor related protein complex 4 subunit epsilon 1provided by HGNC
    Primary source
    HGNC:HGNC:573
    See related
    Ensembl:ENSG00000081014 MIM:607244; AllianceGenome:HGNC:573
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    CPSQ4; SPG51; STUT1
    Summary
    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]
    Expression
    Ubiquitous expression in lymph node (RPKM 2.9), testis (RPKM 2.9) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See AP4E1 in Genome Data Viewer
    Location:
    15q21.2
    Exon count:
    24
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 15 NC_000015.10 (50907492..51005895)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 15 NC_060939.1 (48714133..48813558)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 15 NC_000015.9 (51200880..51298092)

    Chromosome 15 - NC_000015.10Genomic Context describing neighboring genes Neighboring gene Sharpr-MPRA regulatory region 3374 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr15:51104171-51104690 Neighboring gene ribosomal protein L32 pseudogene 30 Neighboring gene uncharacterized LOC124903490 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 9398 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 9399 Neighboring gene ReSE screen-validated silencer GRCh37_chr15:51174366-51174535 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 9400 Neighboring gene NANOG-H3K27ac hESC enhancer GRCh37_chr15:51200473-51201214 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr15:51201215-51201956 Neighboring gene ReSE screen-validated silencer GRCh37_chr15:51258822-51259047 Neighboring gene DDB1 and CUL4 associated factor 13 pseudogene 3 Neighboring gene ReSE screen-validated silencer GRCh37_chr15:51296421-51296666 Neighboring gene MPRA-validated peak2335 silencer Neighboring gene NANOG hESC enhancer GRCh37_chr15:51336200-51336731 Neighboring gene MIR4713 host gene Neighboring gene TNF alpha induced protein 8 like 3 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr15:51368968-51369524 Neighboring gene Sharpr-MPRA regulatory region 8572 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 9403 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr15:51386125-51386855 Neighboring gene uncharacterized LOC124903491 Neighboring gene uncharacterized LOC124903492

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

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    Related articles in PubMed

    1. Comprehensive genotype-phenotype correlation in AP-4 deficiency syndrome; Adding data from a large cohort of Iranian patients. Beheshtian M, et al. Clin Genet, 2021 Jan. PMID 32895917
    2. Defining the clinical, molecular and imaging spectrum of adaptor protein complex 4-associated hereditary spastic paraplegia. Ebrahimi-Fakhari D, et al. Brain, 2020 Oct 1. PMID 32979048, Free PMC Article
    3. A new family with spastic paraplegia type 51 and novel mutations in AP4E1. Winkler I, et al. BMC Med Genomics, 2021 May 18. PMID 34006278, Free PMC Article
    4. Adaptor protein complex-4 (AP-4) deficiency causes a novel autosomal recessive cerebral palsy syndrome with microcephaly and intellectual disability. Moreno-De-Luca A, et al. J Med Genet, 2011 Feb. PMID 20972249, Free PMC Article
    5. Genetic factors and therapy outcomes in persistent developmental stuttering. Frigerio-Domingues CE, et al. J Commun Disord, 2019 Jul-Aug. PMID 31003007

    See all (43) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. A new family with spastic paraplegia type 51 and novel mutations in AP4E1.
      Title: A new family with spastic paraplegia type 51 and novel mutations in AP4E1.
    2. The Reelin receptor ApoER2 is a cargo for the adaptor protein complex AP-4: Implications for Hereditary Spastic Paraplegia.
      Title: The Reelin receptor ApoER2 is a cargo for the adaptor protein complex AP-4: Implications for Hereditary Spastic Paraplegia.
    3. Comprehensive genotype-phenotype correlation in AP-4 deficiency syndrome; Adding data from a large cohort of Iranian patients.
      Title: Comprehensive genotype-phenotype correlation in AP-4 deficiency syndrome; Adding data from a large cohort of Iranian patients.
    4. Defining the clinical, molecular and imaging spectrum of adaptor protein complex 4-associated hereditary spastic paraplegia.
      Title: Defining the clinical, molecular and imaging spectrum of adaptor protein complex 4-associated hereditary spastic paraplegia.
    5. We evaluated 51 stuttering individuals with a mutation in either the GNPTAB, GNPTG, NAGPA, or AP4E1 gene. Mutation carriers achieved significantly less resolution in PSI following therapy, with PSI scores showing significantly less improvement in individuals who carry a mutation (p = 0.0157, RR = 1.75, OR = 2.92) while the group difference in DWS between carriers and non-carriers was statistically not significant.
      Title: Genetic factors and therapy outcomes in persistent developmental stuttering.
    6. The bivalency of the interactions contributes to a higher avidity of tepsin for AP-4.
      Title: Bivalent Motif-Ear Interactions Mediate the Association of the Accessory Protein Tepsin with the AP-4 Adaptor Complex.
    7. Rare Variants in AP4E1 is associated with deficits in intracellular trafficking, and Persistent Stuttering.
      Title: Association between Rare Variants in AP4E1, a Component of Intracellular Trafficking, and Persistent Stuttering.
    8. An autosomal recessive form of spastic tetraplegic cerebral palsy with profound intellectual disability, microcephaly, epilepsy and white matter loss in a consanguineous family resulting from a homozygous deletion involving AP4E1.
      Title: Adaptor protein complex-4 (AP-4) deficiency causes a novel autosomal recessive cerebral palsy syndrome with microcephaly and intellectual disability.
    Submit: New GeneRIF Correction

    Phenotypes

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    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    Associated conditions

    Description Tests
    Hereditary spastic paraplegia 51
    MedGen: C3151056 OMIM: 613744 GeneReviews: AP-4-Associated Hereditary Spastic Paraplegia
    		Compare labs
    Stuttering, familial persistent, 1
    MedGen: C3489627 OMIM: 184450 GeneReviews: Not available
    		Compare labs

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Genotypes

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Clone Names

    • DKFZp686L12167

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables cargo adaptor activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in intracellular protein transport IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in protein localization IC
    Inferred by Curator
    more info
    		 PubMed 
    involved_in protein targeting IC
    Inferred by Curator
    more info
    		 PubMed 
    involved_in vesicle-mediated transport NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    Component Evidence Code Pubs
    part_of AP-4 adaptor complex IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    part_of AP-4 adaptor complex IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    part_of AP-4 adaptor complex NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    located_in endosome lumen TAS
    Traceable Author Statement
    more info
    		  
    located_in trans-Golgi network NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    located_in trans-Golgi network membrane TAS
    Traceable Author Statement
    more info
    		  

    General protein information

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    Preferred Names
    AP-4 complex subunit epsilon-1
    Names
    AP-4 adaptor complex subunit epsilon
    adaptor related protein complex 4 epsilon 1 subunit
    adaptor-related protein complex AP-4 epsilon
    epsilon-adaptin

    NCBI Reference Sequences (RefSeq)

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    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    Genomic

    1. NG_031875.2 RefSeqGene

      Range
      5012..102224
      Download
      GenBank, FASTA, Sequence Viewer (Graphics), LRG_732

    mRNA and Protein(s)

    1. NM_001252127.2 → NP_001239056.1  AP-4 complex subunit epsilon-1 isoform 2

      See identical proteins and their annotated locations for NP_001239056.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) uses an alternate splice site and a downstream, in-frame start codon, compared to variant 1. The encoded isoform (2) has a shorter N-terminus, compared to isoform 1.
      Source sequence(s)
      AI143020, AK297290, AK308644, BC130466, CR627314, CR749604
      Consensus CDS
      CCDS58362.1
      UniProtKB/Swiss-Prot
      Q9UPM8
      UniProtKB/TrEMBL
      B4DM48
      Related
      ENSP00000452976.1, ENST00000560508.1
      Conserved Domains (2) summary
      pfam01602
      Location:3 → 521
      Adaptin_N; Adaptin N terminal region
      pfam14807
      Location:958 → 1057
      AP4E_app_platf; Adaptin AP4 complex epsilon appendage platform

    2. NM_007347.5 → NP_031373.2  AP-4 complex subunit epsilon-1 isoform 1

      See identical proteins and their annotated locations for NP_031373.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the shorter transcript and encodes the longer isoform (1).
      Source sequence(s)
      AI143020, AK308644, BC130466, CR627314, CR749604
      Consensus CDS
      CCDS32240.1
      UniProtKB/Swiss-Prot
      A0AVD6, A1L4A9, A6NNX7, H0YKX4, Q68D31, Q9UPM8, Q9Y588
      Related
      ENSP00000261842.5, ENST00000261842.10
      Conserved Domains (2) summary
      pfam14807
      Location:1033 → 1132
      AP4E_app_platf; Adaptin AP4 complex epsilon appendage platform
      cl26317
      Location:52 → 596
      Adaptin_N; Adaptin N terminal region

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000015.10 Reference GRCh38.p14 Primary Assembly

      Range
      50907492..51005895
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_005254264.5 → XP_005254321.1  AP-4 complex subunit epsilon-1 isoform X1

      See identical proteins and their annotated locations for XP_005254321.1

      UniProtKB/Swiss-Prot
      Q9UPM8
      Conserved Domains (2) summary
      pfam01602
      Location:3 → 521
      Adaptin_N; Adaptin N terminal region
      pfam14807
      Location:958 → 1057
      AP4E_app_platf; Adaptin AP4 complex epsilon appendage platform

    2. XM_047432325.1 → XP_047288281.1  AP-4 complex subunit epsilon-1 isoform X1

    3. XM_006720447.5 → XP_006720510.1  AP-4 complex subunit epsilon-1 isoform X1

      See identical proteins and their annotated locations for XP_006720510.1

      UniProtKB/Swiss-Prot
      Q9UPM8
      Conserved Domains (2) summary
      pfam01602
      Location:3 → 521
      Adaptin_N; Adaptin N terminal region
      pfam14807
      Location:958 → 1057
      AP4E_app_platf; Adaptin AP4 complex epsilon appendage platform

    4. XM_047432324.1 → XP_047288280.1  AP-4 complex subunit epsilon-1 isoform X1

    5. XM_047432326.1 → XP_047288282.1  AP-4 complex subunit epsilon-1 isoform X2

    6. XM_047432327.1 → XP_047288283.1  AP-4 complex subunit epsilon-1 isoform X3

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060939.1 Alternate T2T-CHM13v2.0

      Range
      48714133..48813558
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054377642.1 → XP_054233617.1  AP-4 complex subunit epsilon-1 isoform X1

    2. XM_054377643.1 → XP_054233618.1  AP-4 complex subunit epsilon-1 isoform X1

    3. XM_054377641.1 → XP_054233616.1  AP-4 complex subunit epsilon-1 isoform X1

    4. XM_054377640.1 → XP_054233615.1  AP-4 complex subunit epsilon-1 isoform X1

    5. XM_054377644.1 → XP_054233619.1  AP-4 complex subunit epsilon-1 isoform X2

    6. XM_054377645.1 → XP_054233620.1  AP-4 complex subunit epsilon-1 isoform X3

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q9UPM8.2 GenPept UniProtKB/Swiss-Prot:Q9UPM8

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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