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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
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Genomic context

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See DDHD1 in Genome Data Viewer
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
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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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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

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