PLEK2

protein-coding

pleckstrin 2, the group of Pleckstrin homology domain containing

Gene summary

The protein encoded by this gene associates with membrane-bound phosphatidylinositols generated by phosphatidylinositol 3-kinase. The encoded protein then interacts with the actin cytoskeleton to induce cell spreading. In conjunction with complement component 1, q subcomponent, B chain (C1QB), this gene shows an increase in expression in melanoma cells and may serve as an accurate biomarker for the disease. [provided by RefSeq, Dec 2015]

MANE transcript

NM_016445.3

Inheritance

—

ClinVar variants

U:56B:2

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.78

Max pathogenic AF

—

Genomic locus

chr14:67,386,984-67,412,167

External References & Databases

Ensembl (ENSG00000100558)

Transcript & Mutation Effects

hg38 • Region Span ~25.2 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 PLEK2 variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 57

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_016445.3. 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						0
missense			56 clinvar	2 clinvar		58
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	56	2	0	58

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 15 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_016445.3	RefSeq	NP_057529.1	9	MANE Select
ENST00000216446.9	Ensembl	ENSP00000216446.4	9	MANE Select
ENST00000553387.1	Ensembl	ENSP00000451023.1	3	Standard
ENST00000554395.1	Ensembl	ENSP00000450892.1	6	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

actin cytoskeleton reorganization
intracellular signal transduction
positive regulation of plasma membrane bounded cell projection assembly

Molecular Function

phosphatidylinositol-3-phosphate binding
phosphatidylinositol-3,4-bisphosphate binding
phosphatidylinositol-3,5-bisphosphate binding

Cellular Component

cytoplasm
cytoskeleton
plasma membrane
lamellipodium membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000216446
Coding exons: 9
Length: 25218
Individuals with no LoFs: 125659
Homozygous LoFs: 0
Heterozygous LoFs: 89
Defined: 125748
p: 0.000354

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.824	175	208	0.839	0.0000123	2301
Missense (PolyPhen)		69	87.724	0.78655		983
Synonymous	0.00134	82	82.0	1.00	0.00000481	691
Loss of Function	0.888	15	19.2	0.781	0.00000110	210

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00068	0.00068	rare
Latino/Admixed American	0.00023	0.00023	rare
Ashkenazi Jewish	0.0010	0.00099	notable
East Asian	0.0013	0.0013	notable
Finnish	0.000092	0.000092	rare
European (Non-Finnish)	0.00023	0.00023	rare
South Asian	0.00020	0.00020	rare
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May help orchestrate cytoskeletal arrangement. Contribute to lamellipodia formation.;

Recessive Scores

pRec: 0.109

Intolerance Scores

LoFtool: 0.535
RVIS EVS: -0.34
RVIS percentile EVS: 30.56

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.322

Gene Damage Prediction

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