PLSCR1

protein-coding

phospholipid scramblase 1, the group of Phospholipid scramblases

Gene summary

This gene encodes a phospholipid scramblase family member. The encoded protein is involved in disruption of the asymmetrical distribution of phospholipids between the inner and outer leaflets of the plasma membrane, resulting in externalization of phosphatidylserine. This cell membrane disruption plays an important role in the blood coagulation cascade as well as macrophage clearing of apoptotic cells. The encoded protein has additionally been implicated in gene regulation and interferon-induced antiviral responses. [provided by RefSeq, May 2022]

MANE transcript

NM_021105.3

Inheritance

—

ClinVar variants

U:37B:1

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.37

Max pathogenic AF

—

Genomic locus

chr3:146,515,180-146,544,856

External References & Databases

Ensembl (ENSG00000188313)

Transcript & Mutation Effects

hg38 • Region Span ~29.7 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 PLSCR1 variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 25

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_021105.3. 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			2 clinvar			2
missense			29 clinvar	1 clinvar		30
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			6 clinvar			6
Total	0	0	37	1	0	38

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 90 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_021105.3	RefSeq	NP_066928.1	8	MANE Select
ENST00000342435.9	Ensembl	ENSP00000345494.4	8	MANE Select
NM_001363872.1	RefSeq	NP_001350801.1	7	Standard
NM_001363874.1	RefSeq	NP_001350803.1	6	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

EGF-EGFR Signaling Pathway
EGFR1

Biological Process

phosphatidylserine biosynthetic process
apoptotic process
acute-phase response
positive regulation of gene expression
plasma membrane phospholipid scrambling

Molecular Function

DNA-binding transcription activator activity, RNA polymerase II-specific
DNA binding
epidermal growth factor receptor binding
calcium ion binding
protein binding

Cellular Component

nucleus
nucleolus
cytoplasm
Golgi apparatus
cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000342435
Coding exons: 8
Length: 29685
Individuals with no LoFs: 125582
Homozygous LoFs: 1
Heterozygous LoFs: 156
Defined: 125739
p: 0.000624

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.866	137	169	0.812	0.00000775	2095
Missense (PolyPhen)		24	28.926	0.82969		398
Synonymous	0.449	54	58.4	0.925	0.00000302	585
Loss of Function	2.35	6	16.2	0.370	7.70e-7	197

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0.013	0.013	notable
East Asian	0.00011	0.00011	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00019	0.00018	rare
South Asian	0.000033	0.000033	rare
Other	0.00083	0.00081	rare

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: 0.136

Intolerance Scores

LoFtool: 0.840
RVIS EVS: 0.39
RVIS percentile EVS: 76.05

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.846

Gene Damage Prediction

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