PLEKHG4

protein-coding

pleckstrin homology and RhoGEF domain containing G4, the group of Pleckstrin homology domain containing|Dbl family Rho GEFs

Gene summary

The protein encoded by this gene can function as a guanine nucleotide exchange factor (GEF) and may play a role in intracellular signaling and cytoskeleton dynamics at the Golgi apparatus. Polymorphisms in the region of this gene have been found to be associated with spinocerebellar ataxia in some study populations. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2015]

Previous symbols:

SCA4

MANE transcript

NM_001129729.3

Inheritance

—

ClinVar variants

U:140B:15

Top phenotype

PLEKHG4-related disorder

gnomAD constraint

pLI —, LoF o/e 0.58

Max pathogenic AF

—

Genomic locus

chr16:67,277,510-67,289,499

External References & Databases

Ensembl (ENSG00000196155)

Transcript & Mutation Effects

hg38 • Region Span ~12.0 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 PLEKHG4 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 137

not providedTotal: 10

PLEKHG4-related disorderTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001129729.3. 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			3 clinvar	2 clinvar		5
missense			134 clinvar	8 clinvar	4 clinvar	146
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			3 clinvar	1 clinvar		4
Total	0	0	140	11	4	155

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 50 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001129729.3	RefSeq	NP_001123201.1	21	MANE Select
ENST00000379344.8	Ensembl	ENSP00000368649.3	21	MANE Select
NM_001129727.3	RefSeq	NP_001123199.1	21	Standard
NM_001129728.2	RefSeq	NP_001123200.1	21	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

regulation of Rho protein signal transduction
activation of GTPase activity

Molecular Function

Rho guanyl-nucleotide exchange factor activity
protein binding

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000360461
Coding exons: 21
Length: 11990
Individuals with no LoFs: 125532
Homozygous LoFs: 1
Heterozygous LoFs: 215
Defined: 125748
p: 0.000859

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.30	578	673	0.859	0.0000435	7591
Missense (PolyPhen)		132	164.13	0.80422		1941
Synonymous	0.953	273	294	0.929	0.0000182	2558
Loss of Function	3.06	36	62.0	0.580	0.00000375	615

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00025	0.00025	rare
Latino/Admixed American	0.00061	0.00061	rare
Ashkenazi Jewish	0.00069	0.00069	rare
East Asian	0.00038	0.00038	rare
Finnish	0.00023	0.00023	rare
European (Non-Finnish)	0.0012	0.0012	notable
South Asian	0.0011	0.0011	notable
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Possible role in intracellular signaling and cytoskeleton dynamics at the Golgi.;

Recessive Scores

pRec: 0.166

Intolerance Scores

LoFtool: 0.936
RVIS EVS: 0.57
RVIS percentile EVS: 81.75

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): K
Indispensability pred.: N
Indispensability score: 0.312

Gene Damage Prediction

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