PLEKHB2

protein-coding

pleckstrin homology domain containing B2, the group of Pleckstrin homology domain containing

Gene summary

Enables phosphatidylinositol-3,4,5-trisphosphate binding activity. Predicted to be involved in regulation of cell differentiation. Predicted to be located in recycling endosome membrane. Predicted to be active in membrane. [provided by Alliance of Genome Resources, Jul 2025]

MANE transcript

NM_001100623.2

Inheritance

—

ClinVar variants

U:39B:2

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.96

Max pathogenic AF

—

Genomic locus

chr2:131,104,847-131,353,709

External References & Databases

Ensembl (ENSG00000115762)

Transcript & Mutation Effects

hg38 • Region Span ~248.9 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 PLEKHB2 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 35

not providedTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001100623.2. 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			33 clinvar	2 clinvar		35
nonsense			2 clinvar			2
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			3 clinvar			3
Total	0	0	39	2	0	41

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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_001100623.2	RefSeq	NP_001094093.1	7	MANE Select
ENST00000693505.1	Ensembl	ENSP00000510611.1	7	MANE Select
NM_001267062.2	RefSeq	NP_001253991.1	8	Standard
NM_001267063.2	RefSeq	NP_001253992.1	8	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

regulation of cell differentiation

Molecular Function

protein binding
phosphatidylinositol-3,4,5-trisphosphate binding

Cellular Component

integral component of membrane
recycling endosome membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000409158
Coding exons: 7
Length: 248863
Individuals with no LoFs: 125576
Homozygous LoFs: 0
Heterozygous LoFs: 171
Defined: 125747
p: 0.000680

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.10	109	146	0.745	0.00000895	1484
Missense (PolyPhen)		32	45.919	0.69688		559
Synonymous	0.291	58	60.9	0.953	0.00000430	449
Loss of Function	0.133	16	16.6	0.965	9.89e-7	159

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00062	0.00043	rare
Latino/Admixed American	0.00012	0.00012	rare
Ashkenazi Jewish	0.0013	0.0013	notable
East Asian	0	0.0	absent
Finnish	0.00014	0.00014	rare
European (Non-Finnish)	0.0012	0.0011	notable
South Asian	0.00020	0.00020	rare
Other	0.0016	0.0015	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Involved in retrograde transport of recycling endosomes. {ECO:0000269|PubMed:21911378, ECO:0000269|PubMed:22281740}.;

Intolerance Scores

LoFtool: 0.442
RVIS EVS: -0.43
RVIS percentile EVS: 25.15

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.325

Gene Damage Prediction

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