DDHD Domain-Containing Protein 2

Alternative Names

  • DDHD2
  • KIAA0725
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OMIM Number


Gene Map Locus


The DDHD2 gene belongs to the mammalian intracellular phospholipase A1 (iPLA1) family, and its encoded protein/enzyme comprises a sterile-alpha-motif (SAM), WWE, and DDHD domains. This phospholipase hydrolyzes sn-1 ester bonds of phospholipids, producing 2-acyl-lysophospholipids and fatty acids. The enzyme DDHD2 has a preference for phosphatidic acid as substrate, and is involved in organelle biogenesis and membrane trafficking between the endoplasmic reticulum and the Golgi apparatus. 

Molecular Genetics

The DDHD2 gene is highly expressed in multiple human brain regions, including the cerebellum, cortex, hippocampus, and thalamus. High levels of expression were also detected in several other human tissues; e.g. heart, brain, skeletal muscle, and testis. The DDHD2 gene has multiple transcript variants through alternative splicing. At least two transcripts were observed in humans; a major transcript of 5.4 kb and a minor transcript of 2.8 kb. The full-length protein is calculated to be 711 amino-acid long with a molecular mass of 81 kD.  

DDHD2 mutations were implicated in autosomal recessive spastic paraplegia 54 (SPG54). These mutations include deletions, duplications and insertions mainly affecting the DDHD domain, which is required for the phospholipase activity. The role of the latter domain was elucidated by studies on DDHD-knockdown Drosophila model, which exhibited a reduced number of active zones at synaptic terminals. The manifestations of SPG54 in humans seem to mirror that abovementioned phenotype in Drosophila. 

Epidemiology in the Arab World

View Map
Variant NameCountryGenomic LocationClinvar Clinical SignificanceCTGA Clinical Significance Condition(s)HGVS ExpressionsdbSNPClinvar
NM_015214.2:c.1249_1891delSaudi ArabiaNC_000008.11:g.38249709_38253128delLikely PathogenicLikely PathogenicSpastic Paraplegia 54, Autosomal RecessiveNG_033875.1:g.23219_26638del; NM_015214.2:c.1249_1891del183317
NM_015214.3:c.1546C>TOmanNC_000008.11:g.38252216C>TPathogenicPathogenicSpastic Paraplegia 54, Autosomal RecessiveNG_033875.1:g.25726C>T; NM_015214.3:c.1546C>T; NP_056029.2:p.Arg516Ter37385611939680
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