PLSCR3
protein-codingphospholipid scramblase 3, the group of Phospholipid scramblases
Gene summary
Enables calcium-dependent protein binding activity; metal ion binding activity; and phospholipid scramblase activity. Involved in several processes, including apoptotic process; mitochondrial membrane organization; and regulation of release of cytochrome c from mitochondria. Located in cytosol; mitochondrion; and plasma membrane. [provided by Alliance of Genome Resources, Jul 2025]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~5.1 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 PLSCR3 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_020360.4. 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 | 6 | 6 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 6 | 0 | 1 | 7 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_065093.2 | 7 | MANE Select | |
| Ensembl | ENSP00000483743.2 | 7 | MANE Select | |
| RefSeq | NP_001188505.1 | 7 | Standard | |
| RefSeq | NP_001356336.1 | 7 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- apoptotic process
- plasma membrane phospholipid scrambling
- glucose homeostasis
- cholesterol homeostasis
- cellular response to lipopolysaccharide
Molecular Function
- calcium ion binding
- protein binding
- SH3 domain binding
- phospholipid scramblase activity
- calcium-dependent protein binding
Cellular Component
- mitochondrion
- plasma membrane
- integral component of membrane
- mitochondrial membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000535512
- Coding exons
- 7
- Length
- 14371
- Individuals with no LoFs
- 124783
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 16
- Defined
- 124799
- p
- 0.0000641
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.827 | 136 | 166 | 0.819 | 0.00000996 | 1834 |
| Missense (PolyPhen) | 44 | 69.434 | 0.6337 | 722 | ||
| Synonymous | 0.0573 | 69 | 69.6 | 0.991 | 0.00000393 | 646 |
| Loss of Function | 2.05 | 6 | 14.4 | 0.417 | 8.84e-7 | 148 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000029 | 0.000029 | rare |
| Ashkenazi Jewish | 0.00031 | 0.00030 | rare |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000062 | 0.000062 | rare |
| South Asian | 0.00014 | 0.00013 | rare |
| Other | 0.00017 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: May mediate accelerated ATP-independent bidirectional transbilayer migration of phospholipids upon binding calcium ions that results in a loss of phospholipid asymmetry in the plasma membrane. May play a central role in the initiation of fibrin clot formation, in the activation of mast cells and in the recognition of apoptotic and injured cells by the reticuloendothelial system. Seems to play a role in apoptosis, through translocation of cardiolipin from the inner to the outer mitochondrial membrane which promotes BID recruitment and enhances tBid-induced mitochondrial damages. {ECO:0000269|PubMed:17226776}.;
Recessive Scores
- pRec
- 0.108
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.658