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

Summary

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

Location:: 19q13.2

Exon count:: 15

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	19	NC_000019.10 (40348695..40378485)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	19	NC_060943.1 (43169216..43199111)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	19	NC_000019.9 (40854602..40884392)

Chromosome 19 - NC_000019.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

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Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

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.
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.
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.
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.
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.
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.
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.
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.
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.
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)

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

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

D19S687E (e-PCR)
- UniSTS:150586

MARC_24344-24345:1030116039:1 (e-PCR)
- UniSTS:268892

D22S1129 (e-PCR)
- UniSTS:90614

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 more info	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

EC 3.1.16.1

NP_001278240.1

EC 3.1.16.1

NP_036400.2

EC 3.1.16.1

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

NG_034098.1 RefSeqGene

Range

5271..35061

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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
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
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