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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
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Genomic context

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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
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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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