NAPEPLD is a phospholipase D type enzyme that catalyzes the release of N-acylethanolamine (NAE) from N-acyl-phosphatidylethanolamine (NAPE) in the second step of the biosynthesis of N-acylethanolamine (Okamoto et al., 2004 [PubMed 14634025]).[supplied by OMIM, Oct 2008] See more...

Aliases for NAPEPLD Gene

Aliases for NAPEPLD Gene

  • N-Acyl Phosphatidylethanolamine Phospholipase D 2 3 4 5
  • NAPE-PLD 2 3 4
  • C7orf18 2 3 4
  • N-Acyl-Phosphatidylethanolamine-Hydrolyzing Phospholipase D 3 4
  • NAPE-Hydrolyzing Phospholipase D 3 4
  • FMP30 2 3
  • Chromosome 7 Open Reading Frame 18, N-Acyl-Phosphatidylethanolamine-Hydrolyzing Phospholipase D 2
  • EC 3.1.4.54 4
  • EC 3.1.4 51
  • NAPEPLD 5

External Ids for NAPEPLD Gene

Previous GeneCards Identifiers for NAPEPLD Gene

  • GC07M102528
  • GC07M102742
  • GC07M097103

Summaries for NAPEPLD Gene

Entrez Gene Summary for NAPEPLD Gene

  • NAPEPLD is a phospholipase D type enzyme that catalyzes the release of N-acylethanolamine (NAE) from N-acyl-phosphatidylethanolamine (NAPE) in the second step of the biosynthesis of N-acylethanolamine (Okamoto et al., 2004 [PubMed 14634025]).[supplied by OMIM, Oct 2008]

GeneCards Summary for NAPEPLD Gene

NAPEPLD (N-Acyl Phosphatidylethanolamine Phospholipase D) is a Protein Coding gene. Diseases associated with NAPEPLD include Cannabis Abuse and Hallucinogen Dependence. Among its related pathways are GABAergic synapse and Signaling by GPCR. Gene Ontology (GO) annotations related to this gene include phospholipase activity and N-acylphosphatidylethanolamine-specific phospholipase D activity.

UniProtKB/Swiss-Prot Summary for NAPEPLD Gene

  • Hydrolyzes N-acyl-phosphatidylethanolamines (NAPEs) to produce N-acylethanolamines (NAEs) and phosphatidic acid (PubMed:25684574, PubMed:14634025, PubMed:16527816). Responsible for the generation of these bioactive fatty acid ethanolamides (FAEs), including anandamide (N-arachidonoylethanolamine), the ligand of cannabinoid and vanilloid receptors (PubMed:14634025). As a regulator of lipid metabolism in the adipose tissue, mediates the crosstalk between adipocytes, gut microbiota and immune cells to control body temperature and weight. In particular, regulates energy homeostasis by promoting cold-induced brown or beige adipocyte differentiation program to generate heat from fatty acids and glucose (By similarity).

No data available for CIViC Summary , Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for NAPEPLD Gene

Genomics for NAPEPLD Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for NAPEPLD Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around NAPEPLD on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for NAPEPLD

Top Transcription factor binding sites by QIAGEN in the NAPEPLD gene promoter:
  • AP-4
  • COUP
  • COUP-TF
  • COUP-TF1
  • HNF-4alpha1
  • HNF-4alpha2
  • POU6F1 (c2)
  • SRF
  • SRF (504 AA)
  • TBP

Genomic Locations for NAPEPLD Gene

Genomic Locations for NAPEPLD Gene
chr7:103,099,576-103,149,560
(GRCh38/hg38)
Size:
49,985 bases
Orientation:
Minus strand
chr7:102,740,023-102,790,007
(GRCh37/hg19)
Size:
49,985 bases
Orientation:
Minus strand

Genomic View for NAPEPLD Gene

Genes around NAPEPLD on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
NAPEPLD Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for NAPEPLD Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for NAPEPLD Gene

Proteins for NAPEPLD Gene

  • Protein details for NAPEPLD Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q6IQ20-NAPEP_HUMAN
    Recommended name:
    N-acyl-phosphatidylethanolamine-hydrolyzing phospholipase D
    Protein Accession:
    Q6IQ20
    Secondary Accessions:
    • Q5CZ87
    • Q769K1

    Protein attributes for NAPEPLD Gene

    Size:
    393 amino acids
    Molecular mass:
    45596 Da
    Cofactor:
    Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
    Quaternary structure:
    • Homodimer. Bile acids promote the assembly of inactive monomers into an active dimer and enable catalysis.

    Three dimensional structures from OCA and Proteopedia for NAPEPLD Gene

neXtProt entry for NAPEPLD Gene

Selected DME Specific Peptides for NAPEPLD Gene

Q6IQ20:
  • SHNHYDHLD
  • DDNKVLWGSWSVLGPW
  • ALNERFG
  • MGPKRFRR
  • SRKSFKLDYRLEEDVTKSKKGKDGRFVNPWPTWKN
  • ELRWFVPLGLLDWMQKCGCENVIELDWWEENCVPGHDKVT
  • MVEMDELI

Post-translational modifications for NAPEPLD Gene

  • Ubiquitination at Lys73 and Lys296
  • Modification sites at PhosphoSitePlus

Domains & Families for NAPEPLD Gene

Gene Families for NAPEPLD Gene

IUPHAR :
Human Protein Atlas (HPA):
  • Enzymes
  • Predicted intracellular proteins

Protein Domains for NAPEPLD Gene

Suggested Antigen Peptide Sequences for NAPEPLD Gene

GenScript: Design optimal peptide antigens:
  • N-acyl-phosphatidylethanolamine-hydrolyzing phospholipase D (NAPEP_HUMAN)
  • NAPEPLD protein (Q4G0T7_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q6IQ20

UniProtKB/Swiss-Prot:

NAPEP_HUMAN :
  • Belongs to the NAPE-PLD family.
Family:
  • Belongs to the NAPE-PLD family.
genes like me logo Genes that share domains with NAPEPLD: view

Function for NAPEPLD Gene

Molecular function for NAPEPLD Gene

UniProtKB/Swiss-Prot Function:
Hydrolyzes N-acyl-phosphatidylethanolamines (NAPEs) to produce N-acylethanolamines (NAEs) and phosphatidic acid (PubMed:25684574, PubMed:14634025, PubMed:16527816). Responsible for the generation of these bioactive fatty acid ethanolamides (FAEs), including anandamide (N-arachidonoylethanolamine), the ligand of cannabinoid and vanilloid receptors (PubMed:14634025). As a regulator of lipid metabolism in the adipose tissue, mediates the crosstalk between adipocytes, gut microbiota and immune cells to control body temperature and weight. In particular, regulates energy homeostasis by promoting cold-induced brown or beige adipocyte differentiation program to generate heat from fatty acids and glucose (By similarity).
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=H2O + N-acyl-1,2-diacyl-sn-glycero-3-phosphoethanolamine = a 1,2-diacyl-sn-glycero-3-phosphate + an N-acylethanolamine + H(+); Xref=Rhea:RHEA:33159, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:52640, ChEBI:CHEBI:58608, ChEBI:CHEBI:62537; EC=3.1.4.54; Evidence={ECO:0000269|PubMed:14634025, ECO:0000269|PubMed:16527816, ECO:0000269|PubMed:25684574};.
UniProtKB/Swiss-Prot EnzymeRegulation:
Activated by divalent cations (PubMed:16527816). Activated by bile acids (PubMed:25684574). Inhibited by phosphatidylethanolamines (PubMed:25684574).

Enzyme Numbers (IUBMB) for NAPEPLD Gene

Phenotypes From GWAS Catalog for NAPEPLD Gene

Gene Ontology (GO) - Molecular Function for NAPEPLD Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004620 phospholipase activity IEA --
GO:0008270 zinc ion binding IDA 25684574
GO:0016787 hydrolase activity IEA --
GO:0042802 identical protein binding IPI 25684574
GO:0046872 metal ion binding IEA --
genes like me logo Genes that share ontologies with NAPEPLD: view
genes like me logo Genes that share phenotypes with NAPEPLD: view

Animal Models for NAPEPLD Gene

MGI Knock Outs for NAPEPLD:

Animal Model Products

  • Taconic Biosciences Mouse Models for NAPEPLD

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for NAPEPLD

No data available for Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for NAPEPLD Gene

Localization for NAPEPLD Gene

Subcellular locations from UniProtKB/Swiss-Prot for NAPEPLD Gene

Golgi apparatus membrane. Peripheral membrane protein. Early endosome membrane. Peripheral membrane protein. Nucleus envelope. Nucleus, nucleoplasm. Note=Localized in the proximity of the cellular membranes likely through interaction with membrane phospholipids. {ECO:0000269 PubMed:25684574}.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for NAPEPLD gene
Compartment Confidence
nucleus 5
cytosol 5
golgi apparatus 5
plasma membrane 4
extracellular 4
endosome 4
mitochondrion 2
peroxisome 2
cytoskeleton 1
endoplasmic reticulum 1
lysosome 1

Subcellular locations from the

Human Protein Atlas (HPA)

Gene Ontology (GO) - Cellular Components for NAPEPLD Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000139 Golgi membrane IEA --
GO:0005634 nucleus IEA --
GO:0005635 nuclear envelope ISS --
GO:0005654 nucleoplasm ISS --
GO:0005737 cytoplasm IBA 21873635
genes like me logo Genes that share ontologies with NAPEPLD: view

Pathways & Interactions for NAPEPLD Gene

genes like me logo Genes that share pathways with NAPEPLD: view

Pathways by source for NAPEPLD Gene

1 GeneGo (Thomson Reuters) pathway for NAPEPLD Gene
  • Anandamide biosynthesis and metabolism

Interacting Proteins for NAPEPLD Gene

Gene Ontology (GO) - Biological Process for NAPEPLD Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001523 retinoid metabolic process TAS --
GO:0001659 temperature homeostasis ISS --
GO:0006629 lipid metabolic process IEA --
GO:0006644 phospholipid metabolic process IEA --
GO:0007568 aging IEA --
genes like me logo Genes that share ontologies with NAPEPLD: view

No data available for SIGNOR curated interactions for NAPEPLD Gene

Drugs & Compounds for NAPEPLD Gene

(4) Drugs for NAPEPLD Gene - From: DrugBank and HMDB

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Water Approved Pharma 0
Medical Cannabis Experimental, Investigational Pharma Target, inhibitor 0
PE(16:0/16:0) Experimental Pharma 0
Anandamide Pharma Pore Blocker, Antagonist, Agonist, Partial agonist, Allosteric regulator, Potentiation, Full agonist, Inhibitor, Channel blocker, Activator 0

(16) Additional Compounds for NAPEPLD Gene - From: HMDB

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
PA(16:0/16:0)
  • 1,2-Dipalmitoyl-3-sn-phosphatidic acid
  • 1,2-Dipalmitoyl-sn-glycerol-3-phosphate
  • 1,2-Dipalmitoyl-sn-glycerol-3-phosphoric acid
  • Dipalmitoyl phosphatidic acid
  • PA(32:0)
7091-44-3
PA(16:0/18:1(11Z))
  • 1-Hexadecanoyl-2-(11Z-octadecenoyl)-sn-phosphatidic acid
  • 1-Palmitoyl-2-vaccenoyl-sn-glycero-3-phosphate
  • PA(16:0/18:1)
  • PA(16:0/18:1N7)
  • PA(16:0/18:1W7)
PA(16:0/18:1(9Z))
  • (2R)-1-(Palmitoyloxy)-3-(phosphonooxy)propan-2-yl (9Z)-octadec-9-enoate
  • 1-Hexadecanoyl-2-(9Z-octadecenoyl)-sn-glycero-3-phosphate
  • 1-Hexadecanoyl-2-(9Z-octadecenoyl)-sn-glycerol 3-phosphate
  • 1-Hexadecanoyl-2-(9Z-octadecenoyl)-sn-phosphatidic acid
  • PA(16:0/18:1)
PA(16:0/18:2(9Z,12Z))
  • 1-16:0-2-18:2-Phosphatidic acid
  • 1-Palmitoyl-2-linoleoyl-sn-glycero-3-phosphate
  • 16:0-18:2-PA
  • 2-Linoleoyl-1-palmitoyl-sn-glycero-3-phosphate
  • PA(16:0/18:2)
PA(16:0e/18:0)
  • 2-Octadecanoyl-1-hexadecyl-sn-glycero-3-phosphate
  • PA(O-16:0/18:0)
genes like me logo Genes that share compounds with NAPEPLD: view

Transcripts for NAPEPLD Gene

mRNA/cDNA for NAPEPLD Gene

2 REFSEQ mRNAs :
9 NCBI additional mRNA sequence :
10 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for NAPEPLD

Alternative Splicing Database (ASD) splice patterns (SP) for NAPEPLD Gene

ExUns: 1 ^ 2a · 2b · 2c ^ 3 ^ 4a · 4b · 4c ^ 5 ^ 6
SP1:
SP2: - - -
SP3: -

Relevant External Links for NAPEPLD Gene

GeneLoc Exon Structure for
NAPEPLD

Expression for NAPEPLD Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for NAPEPLD Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Protein differential expression in normal tissues from HIPED for NAPEPLD Gene

This gene is overexpressed in Frontal cortex (28.0), Bone marrow mesenchymal stem cell (12.6), Brain (8.3), and Adipocyte (6.4).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB and MOPED for NAPEPLD Gene



Protein tissue co-expression partners for NAPEPLD Gene

- Elite partner

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for NAPEPLD

SOURCE GeneReport for Unigene cluster for NAPEPLD Gene:

Hs.324271

mRNA Expression by UniProt/SwissProt for NAPEPLD Gene:

Q6IQ20-NAPEP_HUMAN
Tissue specificity: Widely expressed. Highest expression in brain, kidney and testis (at protein level). Expressed in adipose tissue (at protein level).

Evidence on tissue expression from TISSUES for NAPEPLD Gene

  • Nervous system(4.8)
  • Intestine(2.5)
  • Kidney(2.2)
  • Liver(2)
  • Skin(2)
genes like me logo Genes that share expression patterns with NAPEPLD: view

No data available for mRNA differential expression in normal tissues and Phenotype-based relationships between genes and organs from Gene ORGANizer for NAPEPLD Gene

Orthologs for NAPEPLD Gene

This gene was present in the common ancestor of animals and fungi.

Orthologs for NAPEPLD Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia NAPEPLD 30 31
  • 99.41 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia NAPEPLD 30 31
  • 88.29 (n)
OneToOne
Mouse
(Mus musculus)
Mammalia Napepld 30 17 31
  • 83.97 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Napepld 30
  • 83.97 (n)
Dog
(Canis familiaris)
Mammalia NAPEPLD 30 31
  • 79.55 (n)
OneToOne
Oppossum
(Monodelphis domestica)
Mammalia NAPEPLD 31
  • 73 (a)
OneToOne
Platypus
(Ornithorhynchus anatinus)
Mammalia NAPEPLD 31
  • 60 (a)
OneToOne
Chicken
(Gallus gallus)
Aves NAPEPLD 30 31
  • 76.78 (n)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia NAPEPLD 31
  • 78 (a)
OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia napepld 30
  • 72.96 (n)
Str.17648 30
African clawed frog
(Xenopus laevis)
Amphibia Xl.33958 30
Zebrafish
(Danio rerio)
Actinopterygii napepld 30 31
  • 64.1 (n)
OneToOne
wufc56b11 30
Worm
(Caenorhabditis elegans)
Secernentea nape-2 30 31
  • 51.5 (n)
OneToMany
nape-1 31
  • 41 (a)
OneToMany
Baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes FMP30 31 33
  • 26 (a)
OneToOne
Bread mold
(Neurospora crassa)
Ascomycetes NCU07271 30
  • 48.96 (n)
Species where no ortholog for NAPEPLD was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Fruit Fly (Drosophila melanogaster)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Squirt (Ciona savignyi)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Thale Cress (Arabidopsis thaliana)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Wheat (Triticum aestivum)

Evolution for NAPEPLD Gene

ENSEMBL:
Gene Tree for NAPEPLD (if available)
TreeFam:
Gene Tree for NAPEPLD (if available)
Aminode:
Evolutionary constrained regions (ECRs) for NAPEPLD: view image

Paralogs for NAPEPLD Gene

Pseudogenes.org Pseudogenes for NAPEPLD Gene

genes like me logo Genes that share paralogs with NAPEPLD: view

No data available for Paralogs for NAPEPLD Gene

Variants for NAPEPLD Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for NAPEPLD Gene

SNP ID Clinical significance and condition Chr 07 pos Variation AA Info Type
768191 Benign: not provided 103,119,720(-) T/C SYNONYMOUS_VARIANT
787861 Benign: not provided 103,128,629(-) G/A SYNONYMOUS_VARIANT
rs12540583 - p.Ser152Ala
rs3181009 - p.Asp389Asn

Additional dbSNP identifiers (rs#s) for NAPEPLD Gene

Structural Variations from Database of Genomic Variants (DGV) for NAPEPLD Gene

Variant ID Type Subtype PubMed ID
esv2674575 CNV deletion 23128226
esv2752138 CNV loss 17911159
esv3614368 CNV loss 21293372
esv3614369 CNV loss 21293372
nsv5882 CNV insertion 18451855
nsv831084 CNV gain 17160897
nsv970565 CNV duplication 23825009
nsv981565 CNV duplication 23825009

Variation tolerance for NAPEPLD Gene

Residual Variation Intolerance Score: 48.9% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 6.38; 76.99% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for NAPEPLD Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
NAPEPLD

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for NAPEPLD Gene

Disorders for NAPEPLD Gene

MalaCards: The human disease database

(2) MalaCards diseases for NAPEPLD Gene - From: DISEASES

Disorder Aliases PubMed IDs
cannabis abuse
  • marijuana abuse
hallucinogen dependence
- elite association - COSMIC cancer census association via MalaCards

Additional Disease Information for NAPEPLD

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
genes like me logo Genes that share disorders with NAPEPLD: view

No data available for UniProtKB/Swiss-Prot and Genatlas for NAPEPLD Gene

Publications for NAPEPLD Gene

  1. Isolation and analysis of candidate myeloid tumor suppressor genes from a commonly deleted segment of 7q22. (PMID: 15820312) Curtiss NP … Shannon KM (Genomics 2005) 2 3 4
  2. Molecular characterization of a phospholipase D generating anandamide and its congeners. (PMID: 14634025) Okamoto Y … Ueda N (The Journal of biological chemistry 2004) 2 3 4
  3. Structure of human N-acylphosphatidylethanolamine-hydrolyzing phospholipase D: regulation of fatty acid ethanolamide biosynthesis by bile acids. (PMID: 25684574) Magotti P … Garau G (Structure (London, England : 1993) 2015) 3 4
  4. Localization of N-acyl phosphatidylethanolamine phospholipase D (NAPE-PLD) expression in mouse brain: A new perspective on N-acylethanolamines as neural signaling molecules. (PMID: 18067139) Egertová M … Elphick MR (The Journal of comparative neurology 2008) 2 3
  5. NAPE-PLD controls OEA synthesis and fat absorption by regulating lipoprotein synthesis in an in vitro model of intestinal epithelial cells. (PMID: 30399323) Igarashi M … Kubota N (FASEB journal : official publication of the Federation of American Societies for Experimental Biology 2019) 3

Products for NAPEPLD Gene

Sources for NAPEPLD Gene