PLEKHG1

protein-coding

pleckstrin homology and RhoGEF domain containing G1, the group of Dbl family Rho GEFs|Pleckstrin homology domain containing

Gene summary

Predicted to enable guanyl-nucleotide exchange factor activity and small GTPase binding activity. Predicted to be involved in regulation of small GTPase mediated signal transduction. Located in nucleoplasm. [provided by Alliance of Genome Resources, Jul 2025]

MANE transcript

NM_001029884.3

Inheritance

ClinVar variants

U:196B:8

Top phenotype

Prostate cancer

gnomAD constraint

pLI —, LoF o/e 0.27

Max pathogenic AF

—

Genomic locus

chr6:150,599,883-150,843,665

External References & Databases

Ensembl (ENSG00000120278)

Transcript & Mutation Effects

hg38 • Region Span ~243.8 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

periventricular leukomalaciaLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0015742

Submitter: Ambry Genetics

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to PLEKHG1 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 190

not providedTotal: 1

Prostate cancerTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001029884.3. 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				1 clinvar		1
missense			186 clinvar	7 clinvar		193
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			10 clinvar			10
Total	0	0	196	8	0	204

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 31 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001029884.3	RefSeq	NP_001025055.1	15	MANE Select
ENST00000696526.1	Ensembl	ENSP00000512689.1	15	MANE Select
NM_001329798.2	RefSeq	NP_001316727.1	16	Standard
NM_001329799.2	RefSeq	NP_001316728.1	16	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

Cellular Component

nucleus
nucleoplasm

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000367328
Coding exons: 15
Length: 243801
Individuals with no LoFs: 125700
Homozygous LoFs: 0
Heterozygous LoFs: 48
Defined: 125748
p: 0.000191

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.616	733	781	0.938	0.0000451	9160
Missense (PolyPhen)		171	195.76	0.87353		2330
Synonymous	-1.11	343	318	1.08	0.0000199	2672
Loss of Function	5.08	15	56.1	0.268	0.00000290	675

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00037	0.00037	rare
Latino/Admixed American	0.000087	0.000087	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00016	0.00016	rare
Finnish	0.00060	0.00060	rare
European (Non-Finnish)	0.00016	0.00016	rare
South Asian	0.000065	0.000065	rare
Other	0.00049	0.00049	rare

dbNSFP Gene Annotations

Source: dbNSFP

Intolerance Scores

LoFtool: 0.631
RVIS EVS: 0.04
RVIS percentile EVS: 56.93

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Indispensability pred.: N
Indispensability score: 0.105

Gene Damage Prediction

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