PLEK

protein-coding

pleckstrin, the group of Pleckstrin homology domain containing

Gene summary

Enables several functions, including phosphatidylinositol-3,4-bisphosphate binding activity; protein homodimerization activity; and protein kinase C binding activity. Involved in several processes, including G protein-coupled receptor signaling pathway; integrin-mediated signaling pathway; and positive regulation of supramolecular fiber organization. Located in cytoplasm and ruffle membrane. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_002664.3

Inheritance

ClinVar variants

U:45B:1

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.43

Max pathogenic AF

—

Genomic locus

chr2:68,365,282-68,397,453

External References & Databases

Ensembl (ENSG00000115956)

Transcript & Mutation Effects

hg38 • Region Span ~32.2 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

autosomal dominant nonsyndromic hearing loss 58LIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0014293

Submitter: PanelApp Australia

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to PLEK variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 40

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_002664.3. 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			43 clinvar		1 clinvar	44
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	45	0	1	46

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 8 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_002664.3	RefSeq	NP_002655.2	9	MANE Select
ENST00000234313.8	Ensembl	ENSP00000234313.7	9	MANE Select
ENST00001049503.1	Ensembl	ENSP00000719320.1	8	Standard
ENST00001095838.1	Ensembl	ENSP00000765644.1	9	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Serotonin and anxiety
Serotonin and anxiety-related events
TYROBP Causal Network
Platelet degranulation
Response to elevated platelet cytosolic Ca2+

Biological Process

hematopoietic progenitor cell differentiation
platelet degranulation
regulation of transcription by RNA polymerase II
vesicle docking involved in exocytosis
integrin-mediated signaling pathway

Molecular Function

DNA-binding transcription factor activity, RNA polymerase II-specific
protein kinase C binding
protein binding
protein homodimerization activity
phosphatidylinositol-3,4-bisphosphate binding

Cellular Component

extracellular region
cytoplasm
cytosol
plasma membrane
membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000234313
Coding exons: 9
Length: 32281
Individuals with no LoFs: 125717
Homozygous LoFs: 0
Heterozygous LoFs: 20
Defined: 125737
p: 0.0000795

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.211	178	186	0.956	0.00000905	2326
Missense (PolyPhen)		54	64.033	0.84332		835
Synonymous	-0.203	69	66.9	1.03	0.00000330	615
Loss of Function	2.27	8	18.6	0.431	8.50e-7	236

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000058	0.000058	rare
Ashkenazi Jewish	0.00010	0.000099	rare
East Asian	0.00027	0.00027	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00011	0.00011	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Major protein kinase C substrate of platelets.;

Recessive Scores

pRec: 0.352

Intolerance Scores

LoFtool: 0.453
RVIS EVS: 0.55
RVIS percentile EVS: 81.48

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.108

Gene Damage Prediction

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