PLSCR4

protein-coding

phospholipid scramblase 4, the group of Phospholipid scramblases

Gene summary

Enables CD4 receptor binding activity; enzyme binding activity; and phospholipid scramblase activity. Involved in calcium activated phosphatidylcholine scrambling and calcium activated phosphatidylserine scrambling. Located in nucleus and plasma membrane. [provided by Alliance of Genome Resources, Jul 2025]

MANE transcript

NM_020353.3

Inheritance

—

ClinVar variants

U:52B:1

Top phenotype

Sensorineural hearing loss disorder

gnomAD constraint

pLI —, LoF o/e 0.7

Max pathogenic AF

—

Genomic locus

chr3:146,192,335-146,251,179

External References & Databases

Ensembl (ENSG00000114698)

Transcript & Mutation Effects

hg38 • Region Span ~58.8 kb

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GenCC 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 PLSCR4 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 46

Sensorineural hearing loss disorderTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_020353.3. 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 clinvar			1
missense			48 clinvar	1 clinvar		49
nonsense						0
start loss			1 clinvar			1
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	52	1	0	53

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 61 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_020353.3	RefSeq	NP_065086.2	8	MANE Select
ENST00000354952.7	Ensembl	ENSP00000347038.2	8	MANE Select
NM_001128304.2	RefSeq	NP_001121776.1	8	Standard
NM_001128305.2	RefSeq	NP_001121777.1	8	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

plasma membrane phospholipid scrambling
cellular response to lipopolysaccharide

Molecular Function

calcium ion binding
protein binding
SH3 domain binding
phospholipid scramblase activity
enzyme binding

Cellular Component

plasma membrane
integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000354952
Coding exons: 8
Length: 58841
Individuals with no LoFs: 125637
Homozygous LoFs: 0
Heterozygous LoFs: 110
Defined: 125747
p: 0.000437

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.431	170	187	0.911	0.00000943	2165
Missense (PolyPhen)		51	58.726	0.86843		687
Synonymous	-0.367	64	60.4	1.06	0.00000298	615
Loss of Function	1.12	11	15.8	0.697	7.51e-7	196

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00034	0.00031	rare
Latino/Admixed American	0.00093	0.00090	rare
Ashkenazi Jewish	0.00031	0.00030	rare
East Asian	0.00064	0.00060	rare
Finnish	0.00053	0.00051	rare
European (Non-Finnish)	0.00033	0.00031	rare
South Asian	0.00026	0.00026	rare
Other	0.0010	0.00098	notable

dbNSFP Gene Annotations

Source: dbNSFP

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.;

Recessive Scores

pRec: 0.0974

Intolerance Scores

LoFtool: 0.910
RVIS EVS: 1.06
RVIS percentile EVS: 91.58

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.902

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium