PLSCR4 Gene

Name	phospholipid scramblase 4
Description	Enables CD4 receptor binding activity and enzyme binding activity. Predicted to be involved in plasma membrane phospholipid scrambling. Located in plasma membrane. [provided by Alliance of Genome Resources, Mar 2025]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nHuman phospholipid scramblase 4 (hPLSCR4) is a conserved type II transmembrane protein that mediates the bidirectional, Ca²⁺‐dependent translocation of phospholipids across the plasma membrane. Detailed biochemical analyses have shown that hPLSCR4’s activity is activated by divalent cations such as Ca²⁺, Mg²⁺, and Zn²⁺—with critical residues (e.g., Asp290) ensuring proper Ca²⁺ binding and conformational changes that expose hydrophobic regions essential for its scrambling function."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " Moreover, hPLSCR4 harbors a minimal nuclear localization signal that, through exclusive binding to the minor site of importin α1, ensures its active nucleocytoplasmic shuttling. Transcriptional regulation of the hPLSCR4 gene has also been characterized; the Snail transcription factor binds to a specific promoter region to suppress its expression, suggesting that hPLSCR4 levels can be tightly controlled in different cellular contexts."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its core biochemical role, hPLSCR4 participates in intercellular interactions and signaling events that influence disease processes. In the context of infectious disease, secretory leukocyte protease inhibitor (SLPI) has been shown to bind both PLSCR1 and PLSCR4, with these interactions affecting the association of the CD4 receptor on T lymphocytes and thereby modulating HIV-1 entry into host cells."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " Additionally, experimental studies in cancer models have uncovered that non-coding RNAs, such as LINC00641, can function as competing endogenous RNAs to upregulate PLSCR4 expression. In non‐small cell lung cancer (NSCLC) and colorectal cancer (CRC), these regulatory networks—including a miR‑424‑5p/PLSCR4 feedback loop—appear to exert tumor-suppressive effects and impact malignant progression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nhPLSCR4 also plays a role in modulating the biomechanical and signaling properties of cells in other pathological conditions. In sickle cell disease, increased PLSCR4 expression during vaso‑occlusive crisis is linked to alterations in erythrocyte membrane deformability, thereby contributing to hemolysis, enhanced cell adhesion, and thrombosis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " In parallel, studies in adipose progenitor cells have demonstrated that lower levels of PLSCR4 are associated with augmented phosphoinositide 3‑kinase (PI3K)/AKT signaling and increased adipogenesis; conversely, elevated expression of PLSCR4 can dampen lipid accumulation. This suggests that hPLSCR4 is an important regulator in metabolic pathways relevant to PTEN deficiency and lipoma formation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Kaylen Lott, Anshul Bhardwaj, Peter J Sims, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A minimal nuclear localization signal (NLS) in human phospholipid scramblase 4 that binds only the minor NLS-binding site of importin alpha1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M111.228007"}], "href": "https://doi.org/10.1074/jbc.M111.228007"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21690087"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21690087"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Vincent Gerard Francis, Sathyanarayana N Gummadi "}, {"type": "b", "children": [{"type": "t", "text": "Biochemical and functional characterization of human phospholipid scramblase 4 (hPLSCR4)."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biol Chem (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1515/hsz-2012-0129"}], "href": "https://doi.org/10.1515/hsz-2012-0129"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23089641"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23089641"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Janaki Manoja Vinnakota, Sathyanarayana N Gummadi "}, {"type": "b", "children": [{"type": "t", "text": "Snail represses the expression of human phospholipid scramblase 4 gene."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Gene (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.gene.2016.06.050"}], "href": "https://doi.org/10.1016/j.gene.2016.06.050"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27363667"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27363667"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Bénédicte Py, Stéphane Basmaciogullari, Jérôme Bouchet, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The phospholipid scramblases 1 and 4 are cellular receptors for the secretory leukocyte protease inhibitor and interact with CD4 at the plasma membrane."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0005006"}], "href": "https://doi.org/10.1371/journal.pone.0005006"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19333378"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19333378"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Yi Li, Lily Zhao, Pei Zhao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Long non-coding RNA LINC00641 suppresses non-small-cell lung cancer by sponging miR-424-5p to upregulate PLSCR4."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Biomark (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3233/CBM-190142"}], "href": "https://doi.org/10.3233/CBM-190142"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31322545"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31322545"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "D Xue, Y-F Xue, L-J Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "LINC00641 induces the malignant progression of colorectal carcinoma through the miRNA-424-5p/PLSCR4 feedback loop."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Eur Rev Med Pharmacol Sci (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.26355/eurrev_202101_24636"}], "href": "https://doi.org/10.26355/eurrev_202101_24636"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33577029"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33577029"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Hawra Abdulwahab, Muna Aljishi, Ameera Sultan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Whole blood transcriptomic analysis reveals PLSCR4 as a potential marker for vaso-occlusive crises in sickle cell disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41598-021-01702-8"}], "href": "https://doi.org/10.1038/s41598-021-01702-8"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34772994"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34772994"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Lisa A G Barth, Michèle Nebe, Hermann Kalwa, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Phospholipid Scramblase 4 (PLSCR4) Regulates Adipocyte Differentiation via PIP3-Mediated AKT Activation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Mol Sci (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3390/ijms23179787"}], "href": "https://doi.org/10.3390/ijms23179787"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "36077184"}], "href": "https://pubmed.ncbi.nlm.nih.gov/36077184"}]}]}]}
Synonyms	TRA1
Proteins	PLS4_HUMAN
NCBI Gene ID	57088
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

PLSCR4 has 8,423 functional associations with biological entities spanning 9 categories (molecular profile, organism, chemical, functional term, phrase or reference, disease, phenotype or trait, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 109 datasets.

Click the + buttons to view associations for PLSCR4 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

PLSCR4 Gene

Functional Associations

Please acknowledge the Harmonizome in your publications by citing the following reference(s):

	Dataset	Summary
	Achilles Cell Line Gene Essentiality Profiles	cell lines with fitness changed by PLSCR4 gene knockdown relative to other cell lines from the Achilles Cell Line Gene Essentiality Profiles dataset.
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of PLSCR4 gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles	tissues with high or low expression of PLSCR4 gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles	tissue samples with high or low expression of PLSCR4 gene relative to other tissue samples from the Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of PLSCR4 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq	tissue samples with high or low expression of PLSCR4 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq dataset.
	Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of PLSCR4 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of PLSCR4 gene relative to other cell lines from the BioGPS Cell Line Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of PLSCR4 gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	BioGPS Mouse Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of PLSCR4 gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	Carcinogenome Chemical Perturbation Carcinogenicity Signatures	small molecule perturbations changing expression of PLSCR4 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of PLSCR4 gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
	CCLE Cell Line Gene Expression Profiles	cell lines with high or low expression of PLSCR4 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with PLSCR4 gene from the CellMarker Gene-Cell Type Associations dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of PLSCR4 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of PLSCR4 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
	ChEA Transcription Factor Targets 2022	transcription factors binding the promoter of PLSCR4 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	CM4AI KOLF21J CRISPRi Gene Perturbation Atlas	gene perturbations changing expression of PLSCR4 gene from the CM4AI KOLF21J CRISPRi Gene Perturbation Atlas dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of PLSCR4 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing PLSCR4 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing PLSCR4 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with PLSCR4 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025	cellular components co-occuring with PLSCR4 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of PLSCR4 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with PLSCR4 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Disease Associations	diseases associated with PLSCR4 gene/protein from the curated CTD Gene-Disease Associations dataset.
	dbGAP Gene-Trait Associations	traits associated with PLSCR4 gene in GWAS and other genetic association datasets from the dbGAP Gene-Trait Associations dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by PLSCR4 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with PLSCR4 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores 2025	diseases co-occuring with PLSCR4 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
	DisGeNET Gene-Disease Associations	diseases associated with PLSCR4 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with PLSCR4 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at PLSCR4 gene from the ENCODE Histone Modification Site Profiles dataset.
	ENCODE Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of PLSCR4 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of PLSCR4 gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.
	ESCAPE Omics Signatures of Genes and Proteins for Stem Cells	PubMedIDs of publications reporting gene signatures containing PLSCR4 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with PLSCR4 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
	GAD High Level Gene-Disease Associations	diseases associated with PLSCR4 gene in GWAS and other genetic association datasets from the GAD High Level Gene-Disease Associations dataset.
	GDSC Cell Line Gene Expression Profiles	cell lines with high or low expression of PLSCR4 gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with PLSCR4 gene in literature-supported statements describing functions of genes from the GeneRIF Biological Term Annotations dataset.