GPLD1
protein-codingglycosylphosphatidylinositol specific phospholipase D1
Gene summary
Many proteins are tethered to the extracellular face of eukaryotic plasma membranes by a glycosylphosphatidylinositol (GPI) anchor. The GPI-anchor is a glycolipid found on many blood cells. The protein encoded by this gene is a GPI degrading enzyme. Glycosylphosphatidylinositol specific phospholipase D1 hydrolyzes the inositol phosphate linkage in proteins anchored by phosphatidylinositol glycans, thereby releasing the attached protein from the plasma membrane. [provided by RefSeq, Jul 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~70.6 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to GPLD1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001503.4. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 1 | ||||
| missense | 128 | 6 | 134 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 128 | 7 | 1 | 136 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001494.2 | 25 | MANE Select | |
| Ensembl | ENSP00000230036.1 | 25 | MANE Select | |
| Ensembl | ENSP00000561994.1 | 23 | Standard | |
| Ensembl | ENSP00000561994.1 | 23 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Glycosylphosphatidylinositol (GPI)-anchor biosynthesis - Homo sapiens (human)
- Post-translational modification: synthesis of GPI-anchored proteins
- Post-translational protein modification
- Metabolism of proteins
- adp-ribosylation factor
Biological Process
- ossification
- cell migration involved in sprouting angiogenesis
- chondrocyte differentiation
- complement receptor mediated signaling pathway
- C-terminal protein lipidation
Molecular Function
- glycosylphosphatidylinositol phospholipase D activity
- phospholipase D activity
- sodium channel regulator activity
Cellular Component
- extracellular region
- extracellular space
- cytoplasm
- lysosomal membrane
- extracellular matrix
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000230036
- Coding exons
- 25
- Length
- 70641
- Individuals with no LoFs
- 124426
- Homozygous LoFs
- 8
- Heterozygous LoFs
- 1314
- Defined
- 125748
- p
- 0.00527
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.296 | 505 | 487 | 1.04 | 0.0000272 | 5455 |
| Missense (PolyPhen) | 178 | 174.36 | 1.0209 | 1949 | ||
| Synonymous | 0.104 | 198 | 200 | 0.991 | 0.0000132 | 1651 |
| Loss of Function | 2.53 | 32 | 51.6 | 0.620 | 0.00000270 | 583 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.0014 | 0.0014 | notable |
| Latino/Admixed American | 0.0019 | 0.0019 | notable |
| Ashkenazi Jewish | 0.0036 | 0.0036 | notable |
| East Asian | 0.00060 | 0.00060 | rare |
| Finnish | 0.022 | 0.022 | notable |
| European (Non-Finnish) | 0.0058 | 0.0058 | notable |
| South Asian | 0.0015 | 0.0015 | notable |
| Other | 0.0041 | 0.0039 | notable |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: This protein hydrolyzes the inositol phosphate linkage in proteins anchored by phosphatidylinositol glycans (GPI-anchor) thus releasing these proteins from the membrane.;
Recessive Scores
- pRec
- 0.118
Intolerance Scores
- LoFtool
- 0.962
- RVIS EVS
- 0.28
- RVIS percentile EVS
- 70.78
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.633
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |