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    PLD3 phospholipase D family member 3 [ Homo sapiens (human) ]

    Gene ID: 23646, updated on 7-Apr-2024

    Summary

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    Official Symbol
    PLD3provided by HGNC
    Official Full Name
    phospholipase D family member 3provided by HGNC
    Primary source
    HGNC:HGNC:17158
    See related
    Ensembl:ENSG00000105223 MIM:615698; AllianceGenome:HGNC:17158
    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
    AD19; HUK4; HU-K4; SCA46
    Summary
    This gene encodes a member of the phospholipase D (PLD) family of enzymes that catalyze the hydrolysis of membrane phospholipids. The encoded protein is a single-pass type II membrane protein and contains two PLD phosphodiesterase domains. This protein influences processing of amyloid-beta precursor protein. Mutations in this gene are associated with Alzheimer disease risk. Alternatively spliced transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Apr 2014]
    Expression
    Ubiquitous expression in brain (RPKM 96.3), spleen (RPKM 74.5) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See PLD3 in Genome Data Viewer
    Location:
    19q13.2
    Exon count:
    15
    Annotation release Status Assembly Chr Location
    RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 19 NC_000019.10 (40348695..40378485)
    RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 19 NC_060943.1 (43169216..43199111)
    105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 19 NC_000019.9 (40854602..40884392)

    Chromosome 19 - NC_000019.10Genomic Context describing neighboring genes Neighboring gene AKT serine/threonine kinase 2 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14647 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10619 Neighboring gene NANOG-H3K27ac hESC enhancer GRCh37_chr19:40791573-40792404 Neighboring gene microRNA 641 Neighboring gene chromosome 19 open reading frame 47 Neighboring gene RNA, U6 small nuclear 945, pseudogene Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:40829016-40829516 Neighboring gene MPRA-validated peak3483 silencer Neighboring gene Sharpr-MPRA regulatory region 7250 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10620 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14648 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14649 Neighboring gene ReSE screen-validated silencer GRCh37_chr19:40873853-40874018 Neighboring gene Sharpr-MPRA regulatory region 12346 Neighboring gene microRNA 6796 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:40895441-40895990 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:40895991-40896540 Neighboring gene homeodomain interacting protein kinase 4 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10621 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14650 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10622 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14651 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:40915393-40915986 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:40915987-40916578 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:40920095-40920743 Neighboring gene periaxin

    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. PLD3 epigenetic changes in the hippocampus of Alzheimer's disease. Blanco-Luquin I, et al. Clin Epigenetics, 2018 Sep 12. PMID 30208929, Free PMC Article
    2. Common Variant in PLD3 Influencing Cerebrospinal Fluid Total Tau Levels and Hippocampal Volumes in Mild Cognitive Impairment Patients from the ADNI Cohort. Tan MS, et al. J Alzheimers Dis, 2018. PMID 30103332
    3. Rare Variants in PLD3 Increase Risk for Alzheimer's Disease in Han Chinese. Tan MS, et al. J Alzheimers Dis, 2018. PMID 29865074
    4. Rare Variants in PLD3 Do Not Affect Risk for Early-Onset Alzheimer Disease in a European Consortium Cohort. Cacace R, et al. Hum Mutat, 2015 Dec. PMID 26411346, Free PMC Article
    5. Common Variants in PLD3 and Correlation to Amyloid-Related Phenotypes in Alzheimer's Disease. Wang C, et al. J Alzheimers Dis, 2015. PMID 26402410, Free PMC Article

    See all (91) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Structural analysis of PLD3 reveals insights into the mechanism of lysosomal 5' exonuclease-mediated nucleic acid degradation.
      Title: Structural analysis of PLD3 reveals insights into the mechanism of lysosomal 5' exonuclease-mediated nucleic acid degradation.
    2. PLD3 is a neuronal lysosomal phospholipase D associated with beta-amyloid plaques and cognitive function in Alzheimer's disease.
      Title: PLD3 is a neuronal lysosomal phospholipase D associated with β-amyloid plaques and cognitive function in Alzheimer's disease.
    3. the V232M mutation of PLD3 may affect Alzheimer's disease pathogenesis
      Title: V232M substitution restricts a distinct O-glycosylation of PLD3 and its neuroprotective function.
    4. rs11667768 was significantly associated with CSF total-tau levels and hippocampal volumes at baseline and six-year follow-up in the total non-demented elderly group and the mild cognitive impairment subgroup, indicating a potential role of PLD3 common variants in influencing cognitive function through changing CSF total-tau levels and hippocampal volumes.
      Title: Common Variant in PLD3 Influencing Cerebrospinal Fluid Total Tau Levels and Hippocampal Volumes in Mild Cognitive Impairment Patients from the ADNI Cohort.
    5. PLD3 gene is downregulated in the hippocampus of Alzheimer's disease (AD) cases. Altered epigenetic mechanisms, such as differential DNA methylation within an alternative promoter of the gene, may be involved in the pathology of AD. PLD3 mRNA expression inversely correlates with hippocampal beta-amyloid burden, adding evidence that PLD3 protein may contribute to AD development by modifying APP processing.
      Title: PLD3 epigenetic changes in the hippocampus of Alzheimer's disease.
    6. The results of this study indicated that rare variants of PLD3 may play an important role in late-onset Alzheimer's Disease in northern Han Chinese.
      Title: Rare Variants in PLD3 Increase Risk for Alzheimer's Disease in Han Chinese.
    7. Data show that phospholipase D3 (PLD3) functions in endosomal protein sorting and plays an important role in regulating amyloid precursor protein (APP) processing.
      Title: Analysis of novel endosome-to-Golgi retrieval genes reveals a role for PLD3 in regulating endosomal protein sorting and amyloid precursor protein processing.
    8. PLD3 variant V232M was associated with Alzheimer's disease risk in overall sample sets.
      Title: PLD3 in Alzheimer's Disease: a Modest Effect as Revealed by Updated Association and Expression Analyses.
    9. main findings of our this provide evidence that support the possible role of PLD3 common variants in influencing AD-related neuroimaging phenotypes.
      Title: Impact of Common Variations in PLD3 on Neuroimaging Phenotypes in Non-demented Elders.
    10. Rare Variants in PLD3 Do Not Affect Risk for Early-Onset Alzheimer Disease in a European Consortium Cohort
      Title: Rare Variants in PLD3 Do Not Affect Risk for Early-Onset Alzheimer Disease in a European Consortium Cohort.
    Submit: New GeneRIF Correction See all GeneRIFs (18)

    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
    Spinocerebellar ataxia 46
    MedGen: C4540404 OMIM: 617770 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

    HIV-1 interactions

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    Protein interactions

    Protein Gene Interaction Pubs
    Envelope surface glycoprotein gp160, precursor env HIV-1 gp160 interacts with PLD3; predicted interaction to occur in the endoplasmic reticulum 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

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables phospholipase D activity TAS
    Traceable Author Statement
    more info
    		 PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables single-stranded DNA 5'-3' DNA exonuclease activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in DNA metabolic process IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in immune system process IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in inflammatory response IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in myotube differentiation IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in regulation of cytokine production involved in inflammatory response ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    Component Evidence Code Pubs
    located_in Golgi membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in early endosome membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in endoplasmic reticulum membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in extracellular exosome HDA PubMed 
    located_in late endosome membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in lysosomal lumen IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in lysosomal membrane IEA
    Inferred from Electronic Annotation
    more info
    		  

    General protein information

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    Preferred Names
    5'-3' exonuclease PLD3
    Names
    choline phosphatase 3
    hindIII K4L homolog
    phosphatidylcholine-hydrolyzing phospholipase D3
    NP_001026866.1
    NP_001278240.1
    NP_036400.2

    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_034098.1 RefSeqGene

      Range
      5271..35061
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001031696.4 → NP_001026866.1  5'-3' exonuclease PLD3

      See identical proteins and their annotated locations for NP_001026866.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) differs in the 5' UTR compared to variant 2. Variants 1, 2 and 3 encode the same protein.
      Source sequence(s)
      BC000553, BC096820, BQ640152, DB057420
      Consensus CDS
      CCDS33027.1
      UniProtKB/Swiss-Prot
      Q8IV08, Q92853, Q9BW87
      UniProtKB/TrEMBL
      A0A8V8TPY8
      Related
      ENSP00000348901.5, ENST00000356508.9
      Conserved Domains (1) summary
      cl28150
      Location:77 → 490
      PLDc; Phospholipase D Active site motif

    2. NM_001291311.2 → NP_001278240.1  5'-3' exonuclease PLD3

      See identical proteins and their annotated locations for NP_001278240.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) has an alternate 5' UTR exon, compared to variant 2. Variants 1, 2 and 3 encode the same protein.
      Source sequence(s)
      BC000553, BC096820, BP304863, BQ640152, U60644
      Consensus CDS
      CCDS33027.1
      UniProtKB/Swiss-Prot
      Q8IV08, Q92853, Q9BW87
      UniProtKB/TrEMBL
      A0A8V8TPY8
      Related
      ENSP00000387022.1, ENST00000409281.5
      Conserved Domains (1) summary
      cl28150
      Location:77 → 490
      PLDc; Phospholipase D Active site motif

    3. NM_012268.4 → NP_036400.2  5'-3' exonuclease PLD3

      See identical proteins and their annotated locations for NP_036400.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) represents the longer transcript. Variants 1, 2 and 3 encode the same protein.
      Source sequence(s)
      BC000553, BP304863, BQ640152, CX785201
      Consensus CDS
      CCDS33027.1
      UniProtKB/Swiss-Prot
      Q8IV08, Q92853, Q9BW87
      UniProtKB/TrEMBL
      A0A8V8TPY8
      Related
      ENSP00000386938.3, ENST00000409735.9
      Conserved Domains (1) summary
      cl28150
      Location:77 → 490
      PLDc; Phospholipase D Active site motif

    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_000019.10 Reference GRCh38.p14 Primary Assembly

      Range
      40348695..40378485
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060943.1 Alternate T2T-CHM13v2.0

      Range
      43169216..43199111
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q8IV08.1 GenPept UniProtKB/Swiss-Prot:Q8IV08

    Gene LinkOut

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

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