DDHD1

Chr 14

DDHD domain containing 1

Also known as: PA-PLA1, PAPLA1, SPG28, iPLA1I, iPLA1alpha

NCBI Gene: 80821ENSG00000100523UniProt: Q8NEL9

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]

GeneReviewsResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtSpastic paraplegia 28, autosomal recessive

Clinical highlights

Gene-disease validity (ClinGen)
hereditary spastic paraplegia · ARDefinitivesufficient evidence for diagnostic panels
Interpreting a novel variant
Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.
0
Active trials
2
Pubs (1 yr)
—
P/LP submissions
—
P/LP missense
0.34
LOEUF· LoF intol.
LOF
Mechanism· G2P
📖
GeneReview available — DDHD1
Authoritative clinical overview · Recommended first read
Open GeneReview ↗
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?
0.34LOEUF
pLI 0.902
Z-score 4.93
OE 0.19 (0.11–0.34)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?
1.18Z-score
OE missense 0.85 (0.79–0.92)
427 obs / 501.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.19 (0.11–0.34)
0≤0.351.4
Missense OE?0.85 (0.79–0.92)
0≤0.61.4
Synonymous OE?1.02
0≤1.21.6
LoF obs/exp: 8 / 42.8Missense obs/exp: 427 / 501.4Syn Z: -0.25

ClinVar Variant Classifications

0 submitted variants in ClinVar

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.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients