PLEKHG3

protein-coding

pleckstrin homology and RhoGEF domain containing G3, the group of Pleckstrin homology domain containing|Dbl family Rho GEFs

Gene summary

Enables actin binding activity. Involved in regulation of cell migration and regulation of establishment of cell polarity. Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Jul 2025]

Previous symbols:

KIAA0599

MANE transcript

NM_001308147.2

Inheritance

—

ClinVar variants

U:169B:30

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.45

Max pathogenic AF

—

Genomic locus

chr14:64,704,102-64,750,249

External References & Databases

Ensembl (ENSG00000126822)

Transcript & Mutation Effects

hg38 • Region Span ~46.1 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 PLEKHG3 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 167

not providedTotal: 24

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001308147.2. 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	8 clinvar	2 clinvar	11
missense			157 clinvar	13 clinvar	7 clinvar	177
nonsense			2 clinvar			2
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			9 clinvar			9
Total	0	0	169	21	9	199

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 27 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001308147.2	RefSeq	NP_001295076.1	16	MANE Select
ENST00000247226.13	Ensembl	ENSP00000247226.8	16	MANE Select
ENST00000394691.7	Ensembl	ENSP00000378183.2	14	Standard
ENST00000394691.8	Ensembl	ENSP00000378183.2	14	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

regulation of Rho protein signal transduction

Molecular Function

Rho guanyl-nucleotide exchange factor activity

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000247226
Coding exons: 14
Length: 42791
Individuals with no LoFs: 125704
Homozygous LoFs: 0
Heterozygous LoFs: 44
Defined: 125748
p: 0.000175

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.435	698	731	0.955	0.0000469	7555
Missense (PolyPhen)		189	212.02	0.89144		2194
Synonymous	0.906	283	303	0.934	0.0000193	2396
Loss of Function	3.41	20	44.6	0.448	0.00000231	501

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00032	0.00031	rare
Latino/Admixed American	0.00012	0.00012	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.00022	0.00022	rare
Finnish	0.000098	0.000092	rare
European (Non-Finnish)	0.00022	0.00020	rare
South Asian	0.00014	0.00013	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Recessive Scores

pRec: 0.0913

Intolerance Scores

LoFtool: 0.370
RVIS EVS: -0.21
RVIS percentile EVS: 38.29

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.164

Gene Damage Prediction

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