DDHD1
Chr 14ARDDHD domain containing 1
Also known as: PA-PLA1, PAPLA1, SPG28, iPLA1I, iPLA1alpha
The protein functions as an intracellular phospholipase A1 that preferentially hydrolyzes phosphatidic acid and regulates mitochondrial dynamics through its cytosolic and mitochondrial localization. Mutations cause autosomal recessive spastic paraplegia 28 (SPG28), characterized by progressive weakness and spasticity of the legs. The pathogenic mechanism involves loss of function leading to disrupted mitochondrial organization and dynamics.
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly LoF-intolerant (top ~10% of genes)
Mild missense constraint
Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.
The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.
ClinVar Variant Classifications
500 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 12 | 0 | 8 | 0 | 20 |
Likely Pathogenic | 5 | 1 | 1 | 0 | 7 |
VUS | 1 | 245 | 11 | 2 | 259 |
Likely Benign | 0 | 9 | 54 | 100 | 163 |
Benign | 0 | 5 | 18 | 4 | 27 |
Conflicting | — | 10 | |||
| Total | 18 | 260 | 92 | 106 | 486 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
DDHD1 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools