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    DDHD1 DDHD domain containing 1 [ Homo sapiens (human) ]

    Gene ID: 80821, updated on 3-Apr-2024

    Summary

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    Official Symbol
    DDHD1provided by HGNC
    Official Full Name
    DDHD domain containing 1provided by HGNC
    Primary source
    HGNC:HGNC:19714
    See related
    Ensembl:ENSG00000100523 MIM:614603; AllianceGenome:HGNC:19714
    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
    SPG28; PAPLA1; iPLA1I; PA-PLA1; iPLA1alpha
    Summary
    This gene is a member of the intracellular phospholipase A1 gene family. The protein encoded by this gene preferentially hydrolyzes phosphatidic acid. It is a cytosolic protein with some mitochondrial localization, and is thought to be involved in the regulation of mitochondrial dynamics. Overexpression of this gene causes fragmentation of the tubular structures in mitochondria, while depletion of the gene results in mitochondrial tubule elongation. Deletion of this gene in male mice caused fertility defects, resulting from disruption in the organization of the mitochondria during spermiogenesis. In humans, mutations in this gene have been associated with hereditary spastic paraplegia (HSP), also known as Strumpell-Lorrain disease, or, familial spastic paraparesis (FSP). This inherited disorder is characterized by progressive weakness and spasticity of the legs. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Aug 2015]
    Expression
    Broad expression in testis (RPKM 6.6), lymph node (RPKM 2.8) and 24 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    Location:
    14q22.1
    Exon count:
    15
    Annotation release Status Assembly Chr Location
    RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 14 NC_000014.9 (53036755..53153323, complement)
    RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 14 NC_060938.1 (47244731..47361295, complement)
    105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 14 NC_000014.8 (53503473..53620041, complement)

    Chromosome 14 - NC_000014.9Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC105370500 Neighboring gene Sharpr-MPRA regulatory region 8176 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr14:53350617-53351142 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr14:53351143-53351668 Neighboring gene FERM domain containing kindlin 2 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 8398 Neighboring gene Sharpr-MPRA regulatory region 10339 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 5751 Neighboring gene H3K27ac hESC enhancer GRCh37_chr14:53418467-53419045 Neighboring gene NADH:ubiquinone oxidoreductase subunit B3 pseudogene 3 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 8399 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 8400 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 8401 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 5752 Neighboring gene uncharacterized LOC105370502 Neighboring gene DDHD1 divergent transcript Neighboring gene ATAC-STARR-seq lymphoblastoid active region 8402 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 8403 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 5753

    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. Mutations in DDHD1, encoding a phospholipase A1, is a novel cause of retinopathy and neurodegeneration with brain iron accumulation. Dard R, et al. Eur J Med Genet, 2017 Dec. PMID 28818478
    2. A novel frameshift mutation of DDHD1 in a Japanese patient with autosomal recessive spastic paraplegia. Miura S, et al. Eur J Med Genet, 2016 Aug. PMID 27216551
    3. Impairment of brain and muscle energy metabolism detected by magnetic resonance spectroscopy in hereditary spastic paraparesis type 28 patients with DDHD1 mutations. Liguori R, et al. J Neurol, 2014 Sep. PMID 24989667
    4. Alteration of fatty-acid-metabolizing enzymes affects mitochondrial form and function in hereditary spastic paraplegia. Tesson C, et al. Am J Hum Genet, 2012 Dec 7. PMID 23176821, Free PMC Article
    5. Mapping of a new form of pure autosomal recessive spastic paraplegia (SPG28). Bouslam N, et al. Ann Neurol, 2005 Apr. PMID 15786464

    See all (36) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Phosphorylation of human phospholipase A1 DDHD1 at newly identified phosphosites affects its subcellular localization.
      Title: Phosphorylation of human phospholipase A1 DDHD1 at newly identified phosphosites affects its subcellular localization.
    2. Expression of Lysophosphatidylinositol Signaling-relevant Molecules in Colorectal Cancer.
      Title: Expression of Lysophosphatidylinositol Signaling-relevant Molecules in Colorectal Cancer.
    3. A novel homozygous mutation in DDHD1 was identified in a patient with hereditary spastic paraplegia, retinal dystrophy and a pattern of neurodegeneration with brain iron accumulation.
      Title: Mutations in DDHD1, encoding a phospholipase A1, is a novel cause of retinopathy and neurodegeneration with brain iron accumulation.
    4. the novel mutation in DDHD1 is the causative variant for the SPG28 patient that is the first record of the disease in Japanese population.
      Title: A novel frameshift mutation of DDHD1 in a Japanese patient with autosomal recessive spastic paraplegia.
    5. Two novel heterozygous mutations in DDHD1 were found in the affected members of one family, with clinical features overlapping the SPG28 subtype.
      Title: Impairment of brain and muscle energy metabolism detected by magnetic resonance spectroscopy in hereditary spastic paraparesis type 28 patients with DDHD1 mutations.
    6. a possible mechanism of PA regulation of the mitochondrial membrane and demonstrate an in vivo function of PA-PLA1 in the organization of mitochondria during spermiogenesis.
      Title: Phosphatidic acid (PA)-preferring phospholipase A1 regulates mitochondrial dynamics.
    7. DDHD1-LPI-GPR55 axis to be involved in functions in the brain.
      Title: Generation of lysophosphatidylinositol by DDHD domain containing 1 (DDHD1): Possible involvement of phospholipase D/phosphatidic acid in the activation of DDHD1.
    Submit: New GeneRIF Correction

    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 28
    MedGen: C1836295 OMIM: 609340 GeneReviews: Not available
    		Compare labs

    EBI GWAS Catalog

    Description
    Identification of 23 new prostate cancer susceptibility loci using the iCOGS custom genotyping array.
    EBI GWAS Catalog

    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

    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

    • FLJ34209, FLJ42555

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables metal ion binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables phospholipase A1 activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables phospholipase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in phosphatidylinositol metabolic process IEA
    Inferred from Electronic Annotation
    more info
    		  
    acts_upstream_of_or_within positive regulation of mitochondrial fission IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Component Evidence Code Pubs
    is_active_in cytoplasm IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in cytosol TAS
    Traceable Author Statement
    more info
    		  

    General protein information

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    Preferred Names
    phospholipase DDHD1
    Names
    intracellular phospholipase A1 alpha
    phosphatidic acid-preferring phospholipase A1 homolog
    phosphatidic acid-preferring phospholipase A1-like protein
    phospholipid sn-1 acylhydrolase
    spastic paraplegia 28 (autosomal recessive)
    NP_001153619.1
    NP_001153620.1
    NP_085140.2
    XP_005268159.1
    XP_005268160.1
    XP_005268162.1
    XP_011535490.1
    XP_011535491.1
    XP_016877157.1
    XP_016877158.1
    XP_054232734.1
    XP_054232735.1
    XP_054232736.1
    XP_054232737.1
    XP_054232738.1
    XP_054232739.1
    XP_054232740.1

    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_042832.1 RefSeqGene

      Range
      5006..121574
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001160147.2 → NP_001153619.1  phospholipase DDHD1 isoform b

      See identical proteins and their annotated locations for NP_001153619.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) includes an alternate in-frame exon in the 5' coding region, compared to variant 1. The encoded isoform (b) is longer than isoform a.
      Source sequence(s)
      AI871726, AK125372, AL352979, BC030703, DA212814
      Consensus CDS
      CCDS53896.1
      UniProtKB/TrEMBL
      Q2PNX9
      Related
      ENSP00000378970.1, ENST00000395606.5
      Conserved Domains (1) summary
      pfam02862
      Location:621 → 864
      DDHD; DDHD domain

    2. NM_001160148.2 → NP_001153620.1  phospholipase DDHD1 isoform c

      See identical proteins and their annotated locations for NP_001153620.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) includes an alternate in-frame coding exon in the 3' coding region, compared to variant 1. The encoded isoform (c) is longer and differs at an amino acid in the C-terminal region compared to isoform a.
      Source sequence(s)
      AI871726, AK125556, AL352979, BC030703, BY796571, DA212814
      Consensus CDS
      CCDS53895.1
      UniProtKB/Swiss-Prot
      G5E9D1, Q8NEL9, Q8WVH3, Q96LL2, Q9C0F8
      UniProtKB/TrEMBL
      D3K5P3
      Related
      ENSP00000500986.2, ENST00000673822.2
      Conserved Domains (1) summary
      pfam02862
      Location:614 → 885
      DDHD; DDHD domain

    3. NM_030637.3 → NP_085140.2  phospholipase DDHD1 isoform a

      See identical proteins and their annotated locations for NP_085140.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the shortest transcript and encodes the shortest isoform (a).
      Source sequence(s)
      AI871726, AK058137, AL352979, BC030703, DA212814
      Consensus CDS
      CCDS9714.1
      UniProtKB/TrEMBL
      Q2PNX9
      Related
      ENSP00000350401.3, ENST00000357758.3
      Conserved Domains (1) summary
      pfam02862
      Location:614 → 857
      DDHD; DDHD domain

    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_000014.9 Reference GRCh38.p14 Primary Assembly

      Range
      53036755..53153323 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_017021669.2 → XP_016877158.1  phospholipase DDHD1 isoform X7

      UniProtKB/TrEMBL
      Q2PNX9

    2. XM_005268105.3 → XP_005268162.1  phospholipase DDHD1 isoform X6

      UniProtKB/TrEMBL
      D3K5P3
      Conserved Domains (1) summary
      pfam02862
      Location:571 → 842
      DDHD; DDHD domain

    3. XM_017021668.2 → XP_016877157.1  phospholipase DDHD1 isoform X5

      UniProtKB/TrEMBL
      Q2PNX9

    4. XM_005268102.3 → XP_005268159.1  phospholipase DDHD1 isoform X2

      UniProtKB/TrEMBL
      D3K5P3
      Conserved Domains (1) summary
      pfam02862
      Location:648 → 919
      DDHD; DDHD domain

    5. XM_005268103.3 → XP_005268160.1  phospholipase DDHD1 isoform X4

      UniProtKB/TrEMBL
      D3K5P3
      Conserved Domains (1) summary
      pfam02862
      Location:621 → 892
      DDHD; DDHD domain

    6. XM_011537189.3 → XP_011535491.1  phospholipase DDHD1 isoform X3

      UniProtKB/TrEMBL
      Q2PNX9
      Conserved Domains (1) summary
      pfam02862
      Location:655 → 898
      DDHD; DDHD domain

    7. XM_011537188.3 → XP_011535490.1  phospholipase DDHD1 isoform X1

      UniProtKB/TrEMBL
      D3K5P3
      Conserved Domains (1) summary
      pfam02862
      Location:655 → 926
      DDHD; DDHD domain

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060938.1 Alternate T2T-CHM13v2.0

      Range
      47244731..47361295 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054376765.1 → XP_054232740.1  phospholipase DDHD1 isoform X7

    2. XM_054376764.1 → XP_054232739.1  phospholipase DDHD1 isoform X6

    3. XM_054376763.1 → XP_054232738.1  phospholipase DDHD1 isoform X5

    4. XM_054376760.1 → XP_054232735.1  phospholipase DDHD1 isoform X2

    5. XM_054376762.1 → XP_054232737.1  phospholipase DDHD1 isoform X4

    6. XM_054376761.1 → XP_054232736.1  phospholipase DDHD1 isoform X3

    7. XM_054376759.1 → XP_054232734.1  phospholipase DDHD1 isoform X1

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q8NEL9.2 GenPept UniProtKB/Swiss-Prot:Q8NEL9

    Gene LinkOut

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

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