U.S. flag

An official website of the United States government

Format

Send to:

Choose Destination

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

Gene ID: 23259, updated on 3-Apr-2024

Summary

Go to the top of the page Help
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
NEW
Try the new Gene table
Try the new Transcript table

Genomic context

Go to the top of the page Help
Location:
8p11.23
Exon count:
21
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 8 NC_000008.11 (38231585..38273647)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 8 NC_060932.1 (38508534..38550602)
105.20220307 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

Go to the top of the page Help

Go to nucleotide: Graphics FASTA GenBank

Expression

Go to the top of the page Help
  • 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

Go to the top of the pageHelp

Related articles in PubMed

  1. Genome-wide landscape of RNA-binding protein target site dysregulation reveals a major impact on psychiatric disorder risk. Park CY, et al. Nat Genet, 2021 Feb. PMID 33462483, Free PMC Article
  2. Common genetic risk variants identified in the SPARK cohort support DDHD2 as a candidate risk gene for autism. Matoba N, et al. Transl Psychiatry, 2020 Aug 3. PMID 32747698, Free PMC Article
  3. Defining the clinical-genetic and neuroradiological features in SPG54: description of eight additional cases and nine novel DDHD2 variants. Nicita F, et al. J Neurol, 2019 Nov. PMID 31302745
  4. 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
  5. 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

See all (45) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. 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.
  2. 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.
  3. 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.
  4. 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.
  5. 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.
  6. 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.
  7. 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.
  8. 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.
  9. Truncating mutation has been found in the DDHD2 gene in a large consanguineous family with hereditary spastic paraplegia and intellectual disability.
    Title: Truncating mutation in intracellular phospholipase A₁ gene (DDHD2) in hereditary spastic paraplegia with intellectual disability (SPG54).
  10. Our results provide an extensive genome wide set of targets for miR-503, miR-103, and miR-494, and suggest that miR-503 may act as a tumor suppressor in breast cancer by its direct non-canonical targeting of DDHD2.
    Title: miR-503 represses human cell proliferation and directly targets the oncogene DDHD2 by non-canonical target pairing.
Submit: New GeneRIF Correction See all GeneRIFs (18)

Phenotypes

Go to the top of the page Help

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
Compare labs

Variation

Go to the top of the page Help

See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

Pathways from PubChem

Go to the top of the page

Interactions

Go to the top of the page Help
Products Interactant Other Gene Complex Source Pubs Description

General gene information

Go to the top of the page Help

Markers

Homology

Clone Names

  • KIAA0725

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables metal ion binding IEA
Inferred from Electronic Annotation
more info
  
enables triglyceride 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
  
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

Go to the top of the page Help
Preferred Names
phospholipase DDHD2
Names
PA-PLA1 like
SAM, WWE and DDHD domain-containing protein 1
intracellular phospholipase A1gamma
sec23p-interacting protein p125-like phosphatidic acid-preferring phospholipase A1

NCBI Reference Sequences (RefSeq)

Go to the top of the page Help

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  phospholipase 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  phospholipase 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  phospholipase 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  phospholipase 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  phospholipase 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  phospholipase 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  phospholipase 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_2023_10

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

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

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

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

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

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

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

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

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

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

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.

Chemical Information
Molecular Biology Databases
Research Materials
Tools
Miscellaneous