DDHD1 Gene
DDHD Domain Containing 1: A Phospholipase A1 Involved in Lipid Metabolism and Neurodevelopment
Gene Information Card
| Symbol | DDHD1 |
|---|---|
| Full Name | DDHD domain containing 1 |
| Gene Type | Protein-coding |
| Chromosomal Location | 14q22.1 |
| NCBI Gene ID | 80821 ncbi.nlm.nih.gov/gene/80821 |
| Ensembl ID | ENSG00000100526 |
| UniProt ID | Q8TBJ3 |
| OMIM ID | 614603 |
| HGNC ID | 19706 |
| Aliases | PA-PLA1, PAPLA1, SPG28, iPLA1-alpha |
Description
DDHD1 encodes a phospholipase A1 enzyme that catalyzes the hydrolysis of phosphatidic acid to lysophosphatidic acid, playing a key role in lipid metabolism, membrane trafficking, and axonal development. Mutations in DDHD1 are associated with hereditary spastic paraplegia type 28 (SPG28), a neurodegenerative disorder characterized by progressive spasticity and weakness of the lower limbs.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Hereditary Spastic Paraplegia 28 (SPG28) | Loss-of-function mutations in DDHD1 impair phospholipase A1 activity, disrupting lipid signaling and axonal transport in corticospinal motor neurons. | OMIM #614603; ClinVar; multiple case reports |
| Complex Hereditary Spastic Paraplegia with Cerebellar Ataxia | Biallelic DDHD1 variants lead to additional cerebellar involvement, possibly due to altered lysophosphatidic acid signaling. | ClinVar; literature review |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 10.2 | Medium |
| Testis | 8.5 | Medium |
| Adipose Tissue | 6.1 | Low |
| Liver | 5.3 | Low |
| Skeletal Muscle | 4.7 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 12.3 | Neuronal model |
| HeLa (cervical carcinoma) | 9.8 | Epithelial |
| HepG2 (hepatocellular carcinoma) | 7.1 | Hepatic |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1741C>T (p.Arg581*) | Nonsense | Rare | Premature stop; loss of phospholipase A1 activity |
| c.2077C>T (p.Arg693Cys) | Missense | Rare | Reduced catalytic activity; associated with SPG28 |
| c.1222G>A (p.Gly408Arg) | Missense | Rare | Impaired protein stability; pathogenic in ClinVar |
Mutation functional classification
Loss of Function (LOF)
Biallelic loss-of-function mutations (nonsense, frameshift) cause hereditary spastic paraplegia 28 (SPG28) by abolishing phospholipase A1 activity.
Gain of Function (GOF)
No gain-of-function mutations reported for DDHD1.
Dominant Negative (DN)
No dominant-negative mutations reported; inheritance is autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Phospholipid metabolism (Reactome: R-HSA-1483206)
• Glycerophospholipid biosynthesis (KEGG: map00564)
• Lysophosphatidic acid signaling (Reactome: R-HSA-428157)
Protein Summary
DDHD1 (PA-PLA1) is a 1006-amino acid phospholipase A1 that localizes to the Golgi and plasma membrane. It specifically hydrolyzes phosphatidic acid to produce lysophosphatidic acid (LPA), a bioactive lipid involved in cell proliferation, migration, and neuronal development. The protein contains a DDHD domain (named after conserved residues) and a lipase motif. Mutations in DDHD1 lead to reduced LPA production, impairing axonal membrane dynamics and causing hereditary spastic paraplegia.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| DDHD1 Knockout HEK293 Cell Line | EDJ-KQ9581 | Human | 80821 | Details Get a Quote |
| DDHD1 Knockout HeLa Cell Line | EDJ-KQ35143 | Human | 80821 | Details Get a Quote |
| DDHD1 Knockout A-549 Cell Line | EDJ-KQ36405 | Human | 80821 | Details Get a Quote |
| DDHD1 Knockout HCT 116 Cell Line | EDJ-KQ36406 | Human | 80821 | Details Get a Quote |
