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

Gene ID: 23431, updated on 31-Mar-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
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Genomic context

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Location:
15q21.2
Exon count:
24
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 15 NC_000015.10 (50907492..51005895)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 15 NC_060939.1 (48714133..48813558)
105.20220307 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
  • 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. 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
  2. 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
  3. 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
  4. Genetic factors and therapy outcomes in persistent developmental stuttering. Frigerio-Domingues CE, et al. J Commun Disord, 2019 Jul-Aug. PMID 31003007
  5. AP-4-Associated Hereditary Spastic Paraplegia. Adam MP, et al. , 1993. PMID 30543385

See all (41) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. 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.
  2. 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.
  3. 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.
  4. 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.
  5. 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.
  6. 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.
  7. 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_2023_10

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

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