PLCD4
protein-codingphospholipase C delta 4, the group of Phospholipases|C2 domain containing phospholipases|EF-hand domain containing
Gene summary
This gene encodes a member of the delta class of phospholipase C enzymes. Phospholipase C enzymes play a critical role in many cellular processes by hydrolyzing phosphatidylinositol 4,5-bisphosphate into two intracellular second messengers, inositol 1,4,5-trisphosphate and diacylglycerol. Expression of this gene may be a marker for cancer. [provided by RefSeq, Jan 2011]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~29.3 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 PLCD4 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_032726.4. 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 | 7 | 7 | ||||
| missense | 101 | 5 | 106 | |||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 6 | 6 | ||||
| Total | 0 | 0 | 108 | 12 | 0 | 120 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_116115.1 | 15 | MANE Select | |
| Ensembl | ENSP00000388631.2 | 15 | MANE Select | |
| Ensembl | ENSP00000391850.1 | 3 | Standard | |
| Ensembl | ENSP00000396942.1 | 15 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Inositol phosphate metabolism - Homo sapiens (human)
- AGE-RAGE signaling pathway in diabetic complications - Homo sapiens (human)
- Thyroid hormone signaling pathway - Homo sapiens (human)
- Calcium signaling pathway - Homo sapiens (human)
- Phosphatidylinositol signaling system - Homo sapiens (human)
Biological Process
- acrosome reaction
- lipid catabolic process
- inositol trisphosphate biosynthetic process
- intracellular signal transduction
- inositol phosphate metabolic process
Molecular Function
- phosphatidylinositol phospholipase C activity
- calcium ion binding
Cellular Component
- endoplasmic reticulum membrane
- cytosol
- plasma membrane
- nuclear membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000450993
- Coding exons
- 15
- Length
- 29420
- Individuals with no LoFs
- 124334
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 323
- Defined
- 124657
- p
- 0.00130
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.42 | 361 | 445 | 0.810 | 0.0000259 | 5033 |
| Missense (PolyPhen) | 148 | 184.68 | 0.80137 | 2038 | ||
| Synonymous | 1.78 | 138 | 167 | 0.825 | 0.00000887 | 1435 |
| Loss of Function | 2.09 | 27 | 41.5 | 0.651 | 0.00000212 | 453 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.012 | 0.012 | notable |
| Latino/Admixed American | 0.00085 | 0.00084 | rare |
| Ashkenazi Jewish | 0.00020 | 0.00020 | rare |
| East Asian | 0.0014 | 0.0014 | notable |
| Finnish | 0.00014 | 0.00014 | rare |
| European (Non-Finnish) | 0.00047 | 0.00046 | rare |
| South Asian | 0.00079 | 0.00078 | rare |
| Other | 0.00050 | 0.00050 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Hydrolyzes the phosphatidylinositol 4,5-bisphosphate (PIP2) to generate 2 second messenger molecules diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3). DAG mediates the activation of protein kinase C (PKC), while IP3 releases Ca(2+) from intracellular stores. Required for acrosome reaction in sperm during fertilization, probably by acting as an important enzyme for intracellular Ca(2+) mobilization in the zona pellucida- induced acrosome reaction. May play a role in cell growth. Modulates the liver regeneration in cooperation with nuclear PKC. Overexpression up-regulates the Erk signaling pathway and proliferation. {ECO:0000269|PubMed:15140260}.;
Recessive Scores
- pRec
- 0.116
Intolerance Scores
- LoFtool
- 0.801
- RVIS EVS
- -0.93
- RVIS percentile EVS
- 9.68
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.757
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |