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    DDHD2 DDHD domain containing 2 [ Homo sapiens (human) ]

    Gene ID: 23259, updated on 10-Dec-2024

    Summary

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    Official Symbol
    DDHD2provided by HGNC
    Official Full Name
    DDHD domain containing 2provided by HGNC
    Primary source
    HGNC:HGNC:29106
    See related
    Ensembl:ENSG00000085788 MIM:615003; AllianceGenome:HGNC:29106
    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
    SPG54; p125B; SAMWD1; iPLA1A; iPLA1gamma; iPLA(1)gamma
    Summary
    This gene encodes a phospholipase enzyme containing sterile-alpha-motif (SAM), WWE, and DDHD domains. This protein participates in membrane trafficking between the endoplastic reticulum and the Golgi body. Mutations in this gene can cause autosomal recessive spastic paraplegia 54. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2013]
    Expression
    Ubiquitous expression in brain (RPKM 15.7), fat (RPKM 12.4) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See DDHD2 in Genome Data Viewer
    Location:
    8p11.23
    Exon count:
    21
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 8 NC_000008.11 (38231585..38273647)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 8 NC_060932.1 (38508534..38550602)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 8 NC_000008.10 (38089103..38120354)

    Chromosome 8 - NC_000008.11Genomic Context describing neighboring genes Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr8:38032979-38033836 Neighboring gene H3K27ac hESC enhancer GRCh37_chr8:38033837-38034694 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 27245 Neighboring gene RNA, U6 small nuclear 323, pseudogene Neighboring gene ATAC-STARR-seq lymphoblastoid active region 27246 Neighboring gene LSM1 homolog, mRNA degradation associated Neighboring gene BAG cochaperone 4 Neighboring gene Sharpr-MPRA regulatory region 4585 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 19117 Neighboring gene H3K27ac hESC enhancer GRCh37_chr8:38089405-38089904 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 19119 Neighboring gene phospholipid phosphatase 5 Neighboring gene nuclear receptor binding SET domain protein 3 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 19120 Neighboring gene NUP98-NSD3 recombination region Neighboring gene ATAC-STARR-seq lymphoblastoid active region 27247 Neighboring gene OCT4 hESC enhancer GRCh37_chr8:38235530-38236031 Neighboring gene OCT4 hESC enhancer GRCh37_chr8:38238312-38238846 Neighboring gene H3K27ac hESC enhancer GRCh37_chr8:38239137-38239927 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 19122 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 19123 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr8:38242638-38243268 Neighboring gene OCT4-NANOG-H3K4me1 hESC enhancer GRCh37_chr8:38243269-38243898 Neighboring gene OCT4 hESC enhancer GRCh37_chr8:38244052-38244553 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 19125 Neighboring gene OCT4 hESC enhancer GRCh37_chr8:38247000-38247501 Neighboring gene OCT4 hESC enhancer GRCh37_chr8:38248280-38248781 Neighboring gene OCT4 hESC enhancer GRCh37_chr8:38257600-38258101 Neighboring gene uncharacterized LOC102723716 Neighboring gene OCT4-H3K4me1 hESC enhancer GRCh37_chr8:38261681-38262180 Neighboring gene OCT4 hESC enhancer GRCh37_chr8:38262831-38263332 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 19126 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr8:38269931-38270603 Neighboring gene leucine zipper and EF-hand containing transmembrane protein 2 Neighboring gene OCT4-H3K4me1 hESC enhancer GRCh37_chr8:38270604-38271277 Neighboring gene OCT4-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr8:38272896-38273666 Neighboring gene OCT4-H3K27ac hESC enhancer GRCh37_chr8:38274107-38274772 Neighboring gene OCT4 hESC enhancer GRCh37_chr8:38275681-38276444 Neighboring gene OCT4 hESC enhancer GRCh37_chr8:38277305-38277806 Neighboring gene OCT4-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr8:38277908-38278453 Neighboring gene OCT4-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr8:38278454-38278998 Neighboring gene OCT4-H3K4me1 hESC enhancer GRCh37_chr8:38278999-38279544 Neighboring gene OCT4-H3K4me1 hESC enhancer GRCh37_chr8:38279545-38280088 Neighboring gene OCT4-H3K27ac hESC enhancer GRCh37_chr8:38280202-38280702 Neighboring gene OCT4-H3K27ac hESC enhancer GRCh37_chr8:38280703-38281203 Neighboring gene OCT4-H3K4me1 hESC enhancer GRCh37_chr8:38282951-38283642 Neighboring gene OCT4-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr8:38285189-38286186 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr8:38287183-38288180 Neighboring gene OCT4-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr8:38289284-38289961 Neighboring gene OCT4-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr8:38289962-38290638 Neighboring gene OCT4-H3K27ac hESC enhancer GRCh37_chr8:38292133-38292640 Neighboring gene fibroblast growth factor receptor 1 Neighboring gene ribosomal protein S20 pseudogene 22

    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. Roles of SAM and DDHD domains in mammalian intracellular phospholipase A1 KIAA0725p. Inoue H, et al. Biochim Biophys Acta, 2012 Apr. PMID 22922100
    2. Late-onset spastic ataxia phenotype in a patient with a homozygous DDHD2 mutation. Doi H, et al. Sci Rep, 2014 Nov 24. PMID 25417924, Free PMC Article
    3. Truncating mutation in intracellular phospholipase A₁ gene (DDHD2) in hereditary spastic paraplegia with intellectual disability (SPG54). Alrayes N, et al. BMC Res Notes, 2015 Jun 27. PMID 26113134, Free PMC Article
    4. Further evidence that DDHD2 gene mutations cause autosomal recessive hereditary spastic paraplegia with thin corpus callosum. Magariello A, et al. Eur J Neurol, 2014 Mar. PMID 24517879
    5. Mutations in phospholipase DDHD2 cause autosomal recessive hereditary spastic paraplegia (SPG54). Gonzalez M, et al. Eur J Hum Genet, 2013 Nov. PMID 23486545, Free PMC Article

    See all (49) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Radiation-Induced Endothelial Ferroptosis Accelerates Atherosclerosis via the DDHD2-Mediated Nrf2/GPX4 Pathway.
      Title: Radiation-Induced Endothelial Ferroptosis Accelerates Atherosclerosis via the DDHD2-Mediated Nrf2/GPX4 Pathway.
    2. Panoramic variation analysis of a family with neurodevelopmental disorders caused by biallelic loss-of-function variants in TMEM141, DDHD2, and LHFPL5.
      Title: Panoramic variation analysis of a family with neurodevelopmental disorders caused by biallelic loss-of-function variants in TMEM141, DDHD2, and LHFPL5.
    3. DDHD2, whose mutations cause spastic paraplegia type 54, enhances lipophagy via engaging ATG8 family proteins.
      Title: DDHD2, whose mutations cause spastic paraplegia type 54, enhances lipophagy via engaging ATG8 family proteins.
    4. Biallelic DDHD2 mutations in patients with adult-onset complex hereditary spastic paraplegia.
      Title: Biallelic DDHD2 mutations in patients with adult-onset complex hereditary spastic paraplegia.
    5. Circular RNA circRUNX1 promotes papillary thyroid cancer progression and metastasis by sponging MiR-296-3p and regulating DDHD2 expression.
      Title: Circular RNA circRUNX1 promotes papillary thyroid cancer progression and metastasis by sponging MiR-296-3p and regulating DDHD2 expression.
    6. Common genetic risk variants identified in the SPARK cohort support DDHD2 as a candidate risk gene for autism.
      Title: Common genetic risk variants identified in the SPARK cohort support DDHD2 as a candidate risk gene for autism.
    7. Genome-wide landscape of RNA-binding protein target site dysregulation reveals a major impact on psychiatric disorder risk.
      Title: Genome-wide landscape of RNA-binding protein target site dysregulation reveals a major impact on psychiatric disorder risk.
    8. The identification of nine novel variants expands the molecular spectrum of DDHD2-related hereditary spastic paraplegia
      Title: Defining the clinical-genetic and neuroradiological features in SPG54: description of eight additional cases and nine novel DDHD2 variants.
    9. The protective role of DDHD2 for mitochondrial integrity and provide a clue to the pathogenic mechanism of SPG54.
      Title: Loss of DDHD2, whose mutation causes spastic paraplegia, promotes reactive oxygen species generation and apoptosis.
    10. A set of HSP-related mutations in DDHD2 disrupt triglyceride hydrolase activity in vitro and impair the capacity of DDHD2 to protect cells from lipid droplet accumulation after exposure to free fatty acid.Genetic inactivation of DDHD2 from HSP-associated mutations perturbs lipid homeostasis and the formation and content of LDs. DDHD2 plays a role in triglyceride metabolism for normal CNS function.
      Title: Functional Contribution of the Spastic Paraplegia-Related Triglyceride Hydrolase DDHD2 to the Formation and Content of Lipid Droplets.
    Submit: New GeneRIF Correction See all GeneRIFs (20)

    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
    Hereditary spastic paraplegia 54
    MedGen: C3539495 OMIM: 615033 GeneReviews: Not available
    		not available

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    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

    • KIAA0725

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables diacylglycerol lipase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables metal ion binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables phospholipase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables triacylglycerol lipase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    Process Evidence Code Pubs
    involved_in lipid droplet organization IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in locomotory behavior IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in mitochondrial fission IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in positive regulation of mitochondrial fission IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in triglyceride catabolic process IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in visual learning IEA
    Inferred from Electronic Annotation
    more info
    		  
    Component Evidence Code Pubs
    is_active_in COPII-coated ER to Golgi transport vesicle IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in Golgi apparatus IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in centriolar satellite IDA
    Inferred from Direct Assay
    more info
    		  
    is_active_in cytoplasm IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in cytosol IDA
    Inferred from Direct Assay
    more info
    		  
    located_in cytosol TAS
    Traceable Author Statement
    more info
    		  
    located_in endoplasmic reticulum-Golgi intermediate compartment IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in membrane IEA
    Inferred from Electronic Annotation
    more info
    		  

    General protein information

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    Preferred Names
    triacylglycerol hydrolase DDHD2; phospholipase DDHD2
    Names
    PA-PLA1 like
    SAM, WWE and DDHD domain-containing protein 1
    TAG hydrolase
    intracellular phospholipase A1gamma
    sec23p-interacting protein p125-like phosphatidic acid-preferring phospholipase A1
    triglyceride hydrolase DDHD2
    triglyceride lipase
    NP_001157704.1
    NP_001157706.1
    NP_001349840.1
    NP_001349841.1
    NP_001349842.1
    NP_001349843.1
    NP_056029.2
    XP_011542758.1
    XP_047277570.1
    XP_047277571.1
    XP_047277572.1
    XP_047277573.1
    XP_054216159.1
    XP_054216160.1
    XP_054216161.1
    XP_054216162.1
    XP_054216163.1

    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_033875.2 RefSeqGene

      Range
      5002..36253
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001164232.2 → NP_001157704.1  triacylglycerol hydrolase DDHD2 isoform 1

      See identical proteins and their annotated locations for NP_001157704.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) differs in the 5' UTR compared to variant 1. Both variants 1 and 2 encode the same isoform (1).
      Source sequence(s)
      AB018268, AC087362, AK125904, BM510691
      Consensus CDS
      CCDS34883.1
      UniProtKB/Swiss-Prot
      B3KWV2, B3KXB5, O94830, Q9H8X7
      UniProtKB/TrEMBL
      B3KPM6
      Related
      ENSP00000429932.2, ENST00000520272.6
      Conserved Domains (3) summary
      cd09585
      Location:379 → 447
      SAM_DDHD2; SAM domain of DDHD2
      pfam02825
      Location:42 → 112
      WWE; WWE domain
      pfam02862
      Location:498 → 699
      DDHD; DDHD domain

    2. NM_001164234.2 → NP_001157706.1  triacylglycerol hydrolase DDHD2 isoform 2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) lacks multiple 3' coding exons and its 3' terminal exon extends past a splice junction that is used in variant 1, resulting in a different 3' coding region and 3' UTR. It encodes isoform 2, which has a shorter and distinct C-terminus compared to isoform 1.
      Source sequence(s)
      AC084024, BI789108, DA333302
      UniProtKB/TrEMBL
      E9PKE6
      Related
      ENST00000519857.5
      Conserved Domains (1) summary
      pfam02825
      Location:42 → 99
      WWE; WWE domain

    3. NM_001362911.2 → NP_001349840.1  triacylglycerol hydrolase DDHD2 isoform 1

      Status: REVIEWED

      Source sequence(s)
      AB018268, AK056525, AK125904, BM510691, DA412370
      Consensus CDS
      CCDS34883.1
      UniProtKB/Swiss-Prot
      B3KWV2, B3KXB5, O94830, Q9H8X7
      UniProtKB/TrEMBL
      B3KPM6
      Conserved Domains (3) summary
      cd09585
      Location:379 → 447
      SAM_DDHD2; SAM domain of DDHD2
      pfam02825
      Location:42 → 112
      WWE; WWE domain
      pfam02862
      Location:498 → 699
      DDHD; DDHD domain

    4. NM_001362912.2 → NP_001349841.1  triacylglycerol hydrolase DDHD2 isoform 1

      Status: REVIEWED

      Source sequence(s)
      AB018268, AK056525, AK125904, BM510691, BM698122, DA412370, DA531740
      Consensus CDS
      CCDS34883.1
      UniProtKB/Swiss-Prot
      B3KWV2, B3KXB5, O94830, Q9H8X7
      UniProtKB/TrEMBL
      B3KPM6
      Conserved Domains (3) summary
      cd09585
      Location:379 → 447
      SAM_DDHD2; SAM domain of DDHD2
      pfam02825
      Location:42 → 112
      WWE; WWE domain
      pfam02862
      Location:498 → 699
      DDHD; DDHD domain

    5. NM_001362913.2 → NP_001349842.1  triacylglycerol hydrolase DDHD2 isoform 3

      Status: REVIEWED

      Source sequence(s)
      AB018268, AC087362, AK056525, AK125904, BM510691, DA412370, DN989297
      UniProtKB/TrEMBL
      B3KPM6
      Conserved Domains (3) summary
      cd09585
      Location:349 → 417
      SAM_DDHD2; SAM domain of DDHD2
      pfam02825
      Location:42 → 112
      WWE; WWE domain
      pfam02862
      Location:468 → 669
      DDHD; DDHD domain

    6. NM_001362914.2 → NP_001349843.1  triacylglycerol hydrolase DDHD2 isoform 1

      Status: REVIEWED

      Source sequence(s)
      AB018268, AC084024, AC087362, AK056525, AK125904, BM510691
      Consensus CDS
      CCDS34883.1
      UniProtKB/Swiss-Prot
      B3KWV2, B3KXB5, O94830, Q9H8X7
      UniProtKB/TrEMBL
      B3KPM6
      Conserved Domains (3) summary
      cd09585
      Location:379 → 447
      SAM_DDHD2; SAM domain of DDHD2
      pfam02825
      Location:42 → 112
      WWE; WWE domain
      pfam02862
      Location:498 → 699
      DDHD; DDHD domain

    7. NM_015214.3 → NP_056029.2  triacylglycerol hydrolase DDHD2 isoform 1

      See identical proteins and their annotated locations for NP_056029.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longest transcript and encodes the longer isoform (1). Both variants 1 and 2 encode the same isoform (1).
      Source sequence(s)
      AB018268, AC087362, AK056525, AK125904, BM510691, DA412370
      Consensus CDS
      CCDS34883.1
      UniProtKB/Swiss-Prot
      B3KWV2, B3KXB5, O94830, Q9H8X7
      UniProtKB/TrEMBL
      B3KPM6
      Related
      ENSP00000380352.2, ENST00000397166.7
      Conserved Domains (3) summary
      cd09585
      Location:379 → 447
      SAM_DDHD2; SAM domain of DDHD2
      pfam02825
      Location:42 → 112
      WWE; WWE domain
      pfam02862
      Location:498 → 699
      DDHD; DDHD domain

    RNA

    1. NR_156416.2 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      AB018268, AC087362, AK056525, AK125904, BM510691, BM684667, DA412370, DA758753

    2. NR_156417.2 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      AB018268, AK056525, AK125904, BM510691, DA412370, DA758753

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000008.11 Reference GRCh38.p14 Primary Assembly

      Range
      38231585..38273647
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_011544456.3 → XP_011542758.1  phospholipase DDHD2 isoform X1

      See identical proteins and their annotated locations for XP_011542758.1

      UniProtKB/Swiss-Prot
      B3KWV2, B3KXB5, O94830, Q9H8X7
      UniProtKB/TrEMBL
      B3KPM6
      Conserved Domains (3) summary
      cd09585
      Location:379 → 447
      SAM_DDHD2; SAM domain of DDHD2
      pfam02825
      Location:42 → 112
      WWE; WWE domain
      pfam02862
      Location:498 → 699
      DDHD; DDHD domain

    2. XM_047421614.1 → XP_047277570.1  phospholipase DDHD2 isoform X1

      UniProtKB/Swiss-Prot
      B3KWV2, B3KXB5, O94830, Q9H8X7
      UniProtKB/TrEMBL
      B3KPM6

    3. XM_047421615.1 → XP_047277571.1  phospholipase DDHD2 isoform X2

      UniProtKB/TrEMBL
      B3KPM6

    4. XM_047421616.1 → XP_047277572.1  phospholipase DDHD2 isoform X2

      UniProtKB/TrEMBL
      B3KPM6

    5. XM_047421617.1 → XP_047277573.1  phospholipase DDHD2 isoform X2

      UniProtKB/TrEMBL
      B3KPM6

    RNA

    1. XR_007060723.1 RNA Sequence

    2. XR_007060724.1 RNA Sequence

    3. XR_001745504.3 RNA Sequence

    4. XR_007060726.1 RNA Sequence

    5. XR_007060725.1 RNA Sequence

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060932.1 Alternate T2T-CHM13v2.0

      Range
      38508534..38550602
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054360184.1 → XP_054216159.1  phospholipase DDHD2 isoform X1

      UniProtKB/Swiss-Prot
      B3KWV2, B3KXB5, O94830, Q9H8X7
      UniProtKB/TrEMBL
      B3KPM6

    2. XM_054360185.1 → XP_054216160.1  phospholipase DDHD2 isoform X1

      UniProtKB/Swiss-Prot
      B3KWV2, B3KXB5, O94830, Q9H8X7
      UniProtKB/TrEMBL
      B3KPM6

    3. XM_054360186.1 → XP_054216161.1  phospholipase DDHD2 isoform X2

      UniProtKB/TrEMBL
      B3KPM6

    4. XM_054360187.1 → XP_054216162.1  phospholipase DDHD2 isoform X2

      UniProtKB/TrEMBL
      B3KPM6

    5. XM_054360188.1 → XP_054216163.1  phospholipase DDHD2 isoform X2

      UniProtKB/TrEMBL
      B3KPM6

    RNA

    1. XR_008487830.1 RNA Sequence

    2. XR_008487831.1 RNA Sequence

    3. XR_008487833.1 RNA Sequence

    4. XR_008487829.1 RNA Sequence

    5. XR_008487832.1 RNA Sequence

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    O94830.2 GenPept UniProtKB/Swiss-Prot:O94830

    Gene LinkOut

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

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