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    PACS1 phosphofurin acidic cluster sorting protein 1 [ Homo sapiens (human) ]

    Gene ID: 55690, updated on 5-Mar-2024

    Summary

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    Official Symbol
    PACS1provided by HGNC
    Official Full Name
    phosphofurin acidic cluster sorting protein 1provided by HGNC
    Primary source
    HGNC:HGNC:30032
    See related
    Ensembl:ENSG00000175115 MIM:607492; AllianceGenome:HGNC:30032
    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
    SHMS; MRD17
    Summary
    This gene encodes a protein with a putative role in the localization of trans-Golgi network (TGN) membrane proteins. Mouse and rat homologs have been identified and studies of the homologous rat protein indicate a role in directing TGN localization of furin by binding to the protease's phosphorylated cytosolic domain. In addition, the human protein plays a role in HIV-1 Nef-mediated downregulation of cell surface MHC-I molecules to the TGN, thereby enabling HIV-1 to escape immune surveillance. [provided by RefSeq, Jul 2008]
    Expression
    Ubiquitous expression in testis (RPKM 20.8), lymph node (RPKM 16.2) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    Location:
    11q13.1-q13.2
    Exon count:
    26
    Annotation release Status Assembly Chr Location
    RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 11 NC_000011.10 (66070272..66244744)
    RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 11 NC_060935.1 (66064409..66238837)
    105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 11 NC_000011.9 (65837743..66012215)

    Chromosome 11 - NC_000011.10Genomic Context describing neighboring genes Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 3570 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 5026 Neighboring gene H3K27ac hESC enhancer GRCh37_chr11:65818833-65819384 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 3571 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 5028 Neighboring gene galactose-3-O-sulfotransferase 3 Neighboring gene small nucleolar RNA, C/D box 13F Neighboring gene ATAC-STARR-seq lymphoblastoid active region 5029 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 3572 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 3573 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 3576 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 3574 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 3575 Neighboring gene ReSE screen-validated silencer GRCh37_chr11:65838483-65838687 Neighboring gene splicing factor 3b subunit 2 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 5030 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 5031 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:65866985-65867894 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:65867895-65868802 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr11:65874431-65875274 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 5034 Neighboring gene Sharpr-MPRA regulatory region 6316 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr11:65894813-65895472 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 3579 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 3580 Neighboring gene small nucleolar RNA U13 Neighboring gene uncharacterized LOC105369354 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 5036 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:65990246-65990746 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:65990747-65991247 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:66006167-66006678 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:66006679-66007190 Neighboring gene uncharacterized LOC124902694 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:66021063-66021564 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 3581 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr11:66025772-66026740 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr11:66033680-66034562 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 3583 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 3584 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 5039 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 5040 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 5041 Neighboring gene kinesin light chain 2 Neighboring gene KLC2 antisense RNA 1 Neighboring gene KLC2 antisense RNA 2

    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. Expanding the clinical spectrum associated with the PACS1 p.Arg203Trp mutational hot-spot: Two additional Italian patients. Bruno LP, et al. Am J Med Genet A, 2023 Jan. PMID 36210549, Free PMC Article
    2. A Novel Multi-Exon Deletion of PACS1 in a Three-Generation Pedigree: Supplements to PACS1 Neurodevelopmental Disorder Spectrum. Liu Y, et al. Front Genet, 2021. PMID 34373684, Free PMC Article
    3. Schuurs-Hoeijmakers Syndrome (PACS1 Neurodevelopmental Disorder): Seven Novel Patients and a Review. Tenorio-Castaño J, et al. Genes (Basel), 2021 May 13. PMID 34068396, Free PMC Article
    4. Integration of whole genome sequencing into a healthcare setting: high diagnostic rates across multiple clinical entities in 3219 rare disease patients. Stranneheim H, et al. Genome Med, 2021 Mar 17. PMID 33726816, Free PMC Article
    5. Prenatal and postnatal diagnosis of Schuurs-Hoeijmakers syndrome: Case series and review of the literature. Seto MT, et al. Am J Med Genet A, 2021 Feb. PMID 33166031

    See all (73) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Do PACS1 variants impeding adaptor protein binding predispose to syndromic intellectual disability?
      Title: Do PACS1 variants impeding adaptor protein binding predispose to syndromic intellectual disability?
    2. Expanding the clinical spectrum associated with the PACS1 p.Arg203Trp mutational hot-spot: Two additional Italian patients.
      Title: Expanding the clinical spectrum associated with the PACS1 p.Arg203Trp mutational hot-spot: Two additional Italian patients.
    3. Schuurs-Hoeijmakers Syndrome (PACS1 Neurodevelopmental Disorder): Seven Novel Patients and a Review.
      Title: Schuurs-Hoeijmakers Syndrome (PACS1 Neurodevelopmental Disorder): Seven Novel Patients and a Review.
    4. Coloboma may be a shared feature in a spectrum of disorders caused by mutations in the WDR37-PACS1-PACS2 axis.
      Title: Coloboma may be a shared feature in a spectrum of disorders caused by mutations in the WDR37-PACS1-PACS2 axis.
    5. Prenatal and postnatal diagnosis of Schuurs-Hoeijmakers syndrome: Case series and review of the literature.
      Title: Prenatal and postnatal diagnosis of Schuurs-Hoeijmakers syndrome: Case series and review of the literature.
    6. Dysregulation of hsa-miR-34a and hsa-miR-449a leads to overexpression of PACS-1 and loss of DNA damage response (DDR) in cervical cancer.
      Title: Dysregulation of hsa-miR-34a and hsa-miR-449a leads to overexpression of PACS-1 and loss of DNA damage response (DDR) in cervical cancer.
    7. The multifunctional protein PACS-1 is required for HDAC2- and HDAC3-dependent chromatin maturation and genomic stability.
      Title: The multifunctional protein PACS-1 is required for HDAC2- and HDAC3-dependent chromatin maturation and genomic stability.
    8. Using whole exome sequencing (WES), we identified eight additional individuals with the same p.Arg203Trp missense variant in PACS1 that we demonstrated were de novo in seven individuals with available parental DNA.
      Title: Association of the missense variant p.Arg203Trp in PACS1 as a cause of intellectual disability and seizures.
    9. PCAF and ADA3 transcriptionally regulate PACS1 and PACS1 is a key regulator of BAX/BAK oligomerization and the intrinsic (mitochondrial) pathway to apoptosis.
      Title: Epigenetic control of mitochondrial cell death through PACS1-mediated regulation of BAX/BAK oligomerization.
    10. Protein adaptation and the expanding roles of the PACS1 and PACS2 proteins in tissue homeostasis and disease has been summarized. (Review)
      Title: Caught in the act - protein adaptation and the expanding roles of the PACS proteins in tissue homeostasis and disease.
    Submit: New GeneRIF Correction See all GeneRIFs (22)

    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
    Schuurs-Hoeijmakers syndrome
    MedGen: C3554343 OMIM: 615009 GeneReviews: PACS1 Neurodevelopmental Disorder
    		Compare labs

    Copy number response

    Description
    Copy number response
    Triplosensitivity

    No evidence available (Last evaluated 2021-12-14)

    ClinGen Genome Curation Page
    Haploinsufficency

    No evidence available (Last evaluated 2021-12-14)

    ClinGen Genome Curation PagePubMed

    EBI GWAS Catalog

    Description
    Genome-wide SNP and CNV analysis identifies common and low-frequency variants associated with severe early-onset obesity.
    EBI GWAS Catalog
    Large-scale genome-wide association analysis of bipolar disorder identifies a new susceptibility locus near ODZ4.
    EBI GWAS Catalog

    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

    HIV-1 interactions

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    Protein interactions

    Protein Gene Interaction Pubs
    Nef nef Interaction of HIV-1 Nef with PACS-1 occurs in cellular endosomes with markers RAB5 and LAMP-1 PubMed
    nef HIV-1 Nef-induced downregulation of MHC-I expression and MHC-I targeting to the trans-Golgi network (TGN) require the binding of Nef (amino acid residues 62-65) to PACS-1, a molecule that controls the TGN localization of the cellular protein furin PubMed
    nef Pro78 and helix alphaB (residues 104-119) in HIV-1 Nef are required for the binding between PACS-1 and Nef PubMed
    nef Amino-acid residues 181-195 in the FBR region of PACS-1 bind to HIV-1 Nef and alanine-scanning analysis reveals that amino acids N188, K189, and Q195 are required for the binding between PACS-1 and Nef PubMed
    nef PACS-1S278A mutant blocks the association of Nef with Hck on cell membrane, while wild-type PACS-1 has no effect PubMed
    Rev rev Depletion of PACS1 inhibits HIV-1 Rev activity, leading to reduced HIV-1 p24 expression from the Rev-mediated reporter plasmid PubMed
    capsid gag Depletion of PACS1 inhibits HIV-1 Rev activity, leading to reduced HIV-1 p24 expression from the Rev-mediated reporter plasmid PubMed

    Go to the HIV-1, Human Interaction Database

    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

    • FLJ10209, KIAA1175

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables transmembrane transporter binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables transmembrane transporter binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in lymphocyte homeostasis ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in protein localization to Golgi apparatus IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in protein localization to plasma membrane IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in protein localization to plasma membrane IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    Component Evidence Code Pubs
    located_in COPI-coated vesicle IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in Golgi apparatus IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in cytosol TAS
    Traceable Author Statement
    more info
    		  

    General protein information

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    Preferred Names
    phosphofurin acidic cluster sorting protein 1
    Names
    PACS-1
    cytosolic sorting protein PACS-1

    NCBI Reference Sequences (RefSeq)

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    NEW Try the new Transcript table

    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_033900.1 RefSeqGene

      Range
      4920..179392
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_018026.4 → NP_060496.2  phosphofurin acidic cluster sorting protein 1

      See identical proteins and their annotated locations for NP_060496.2

      Status: REVIEWED

      Source sequence(s)
      AK096644, AP006287, BC010096, BQ772654
      Consensus CDS
      CCDS8129.1
      UniProtKB/Swiss-Prot
      Q6PJY6, Q6PKB6, Q6VY07, Q7Z590, Q7Z5W4, Q8N8K6, Q96MW0, Q9NW92, Q9ULP5
      Related
      ENSP00000316454.4, ENST00000320580.9
      Conserved Domains (1) summary
      pfam10254
      Location:548 → 960
      Pacs-1; PACS-1 cytosolic sorting protein

    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_000011.10 Reference GRCh38.p14 Primary Assembly

      Range
      66070272..66244744
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_011545164.3 → XP_011543466.1  phosphofurin acidic cluster sorting protein 1 isoform X2

      Conserved Domains (1) summary
      pfam10254
      Location:435 → 847
      Pacs-1; PACS-1 cytosolic sorting protein

    2. XM_011545162.2 → XP_011543464.2  phosphofurin acidic cluster sorting protein 1 isoform X1

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060935.1 Alternate T2T-CHM13v2.0

      Range
      66064409..66238837
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054369345.1 → XP_054225320.1  phosphofurin acidic cluster sorting protein 1 isoform X2

    2. XM_054369344.1 → XP_054225319.1  phosphofurin acidic cluster sorting protein 1 isoform X1

    Suppressed Reference Sequence(s)

    The following Reference Sequences have been suppressed. Explain

    1. NM_178178.1: Suppressed sequence

      Description
      NM_178178.1: This RefSeq record was removed by NCBI staff. Contact info@ncbi.nlm.nih.gov for further information.
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q6VY07.2 GenPept UniProtKB/Swiss-Prot:Q6VY07

    Gene LinkOut

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

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