PLEKHG4B

protein-coding

pleckstrin homology and RhoGEF domain containing G4B, the group of Dbl family Rho GEFs|Pleckstrin homology domain containing

Gene summary

This gene encodes a large protein that contains a pleckstrin homology domain and may function as a guanine nucleotide exchange factor. [provided by RefSeq, May 2017]

MANE transcript

NM_052909.5

Inheritance

—

ClinVar variants

U:277B:35

Top phenotype

Abnormality of neuronal migration

gnomAD constraint

pLI —, LoF o/e 0.97

Max pathogenic AF

—

Genomic locus

chr5:92,168-189,972

External References & Databases

Ensembl (ENSG00000153404)

Transcript & Mutation Effects

hg38 • Region Span ~97.8 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 PLEKHG4B variants in ClinVar

5 Conditions Cataloged

not specifiedTotal: 297

not providedTotal: 7

Abnormality of neuronal migrationTotal: 2

Neurodevelopmental disorderTotal: 1

Prostate cancerTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_052909.5. 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	2 clinvar	2 clinvar	5
missense			274 clinvar	29 clinvar	2 clinvar	305
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	277	31	4	312

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 30 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_052909.5	RefSeq	NP_443141.4	20	MANE Select
ENST00000637938.2	Ensembl	ENSP00000490806.1	20	MANE Select
ENST00000283426.11	Ensembl	ENSP00000283426.6	18	Standard
ENST00000502646.1	Ensembl	ENSP00000422493.1	9	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
protein binding

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000283426
Coding exons: 18
Length: 49713
Individuals with no LoFs: 125612
Homozygous LoFs: 1
Heterozygous LoFs: 135
Defined: 125748
p: 0.000541

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.271	762	741	1.03	0.0000466	8151
Missense (PolyPhen)		186	203.28	0.915		2422
Synonymous	-0.602	332	318	1.04	0.0000210	2620
Loss of Function	0.221	50	51.7	0.967	0.00000289	551

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00033	0.00031	rare
Latino/Admixed American	0.00069	0.00069	rare
Ashkenazi Jewish	0.00010	0.000099	rare
East Asian	0.00039	0.00038	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.00040	0.00039	rare
South Asian	0.0017	0.0016	notable
Other	0.00067	0.00065	rare

dbNSFP Gene Annotations

Source: dbNSFP

Intolerance Scores

LoFtool: 0.609
RVIS EVS: -0.1
RVIS percentile EVS: 45.61

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.140

Gene Damage Prediction

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