GeneBe

PLEKHG2

pleckstrin homology and RhoGEF domain containing G2, the group of Pleckstrin homology domain containing|Dbl family Rho GEFs

Basic information

Region (hg38): 19:39412669-39428415

Links

ENSG00000090924 ∙ NCBI:64857 ∙ OMIM:611893 ∙ HGNC:29515 ∙ Uniprot:Q9H7P9 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

  • leukodystrophy and acquired microcephaly with or without dystonia; (Limited), mode of inheritance: AR
  • leukodystrophy and acquired microcephaly with or without dystonia; (Strong), mode of inheritance: AR
  • leukodystrophy and acquired microcephaly with or without dystonia; (Limited), mode of inheritance: AR
  • epilepsy (Limited), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Leukodystrophy and acquired microcephaly with or without dystoniaARGeneralGenetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testingNeurologic26573021

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PLEKHG2 gene.

  • not_provided (370 variants)
  • not_specified (210 variants)
  • Leukodystrophy_and_acquired_microcephaly_with_or_without_dystonia%3B (24 variants)
  • PLEKHG2-related_disorder (20 variants)
  • Abnormality_of_neuronal_migration (2 variants)
  • Neurodevelopmental_abnormality (1 variants)
  • Abnormal_brain_morphology (1 variants)
  • Microcephaly (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PLEKHG2 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000022835.3. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
4
clinvar
118
clinvar
7
clinvar
 129
missense
1
clinvar
1
clinvar
307
clinvar
27
clinvar
11
clinvar
 347
nonsense
1
clinvar
4
clinvar
 5
start loss
0
frameshift
6
clinvar
 6
splice donor/acceptor (+/-2bp)
0
Total 1 2 321 145 18

Highest pathogenic variant AF is 0.00022259168

Loading clinvar variants...

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
PLEKHG2protein_codingprotein_codingENST00000409794 1815830
pLI Probability
LOF Intolerant 		pRec Probability
LOF Recessive 		Individuals with
no LOFs 		Individuals with
Homozygous LOFs 		Individuals with
Heterozygous LOFs 		Defined p
1.36e-91.001256800681257480.000270
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense0.8017368000.9200.00004838744
Missense in Polyphen243267.220.909372844
Synonymous0.8943113320.9380.00002023088
Loss of Function3.942557.20.4370.00000340599

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.0007480.000734
Ashkenazi Jewish0.00009940.0000992
East Asian0.0003820.000381
Finnish0.00009260.0000924
European (Non-Finnish)0.0002970.000290
Middle Eastern0.0003820.000381
South Asian0.0002680.000261
Other0.0003290.000326

dbNSFP

Source: dbNSFP

Function
FUNCTION: May be a transforming oncogene with exchange activity for CDC42 (By similarity). May be a guanine-nucleotide exchange factor (GEF) for RAC1 and CDC42. Activated by the binding to subunits beta and gamma of the heterotrimeric guanine nucleotide- binding protein (G protein) (PubMed:18045877). Involved in the regulation of actin polymerization (PubMed:26573021). {ECO:0000250|UniProtKB:Q6KAU7, ECO:0000269|PubMed:18045877, ECO:0000269|PubMed:26573021}.;
Disease
DISEASE: Leukodystrophy and acquired microcephaly with or without dystonia (LDAMD) [MIM:616763]: An autosomal recessive neurologic disorder characterized by profound mental retardation, dystonia, postnatal microcephaly, and white matter abnormalities consistent with leukodystrophy. {ECO:0000269|PubMed:26573021}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway
Signaling by GPCR;Signal Transduction;Rho GTPase cycle;Signaling by Rho GTPases;NRAGE signals death through JNK;Death Receptor Signalling;p75 NTR receptor-mediated signalling;G alpha (12/13) signalling events;GPCR downstream signalling;Cell death signalling via NRAGE, NRIF and NADE (Consensus)

Recessive Scores

pRec
0.0979

Intolerance Scores

loftool
0.407
rvis_EVS
0.51
rvis_percentile_EVS
80.01

Haploinsufficiency Scores

pHI
0.134
hipred
N
hipred_score
0.270
ghis
0.474

Essentials

essential_gene_CRISPR
N
essential_gene_CRISPR2
N
essential_gene_gene_trap
N
gene_indispensability_pred
E
gene_indispensability_score
0.919

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

Mouse Genome Informatics

Gene name
Plekhg2
Phenotype

Gene ontology

Biological process
G protein-coupled receptor signaling pathway;regulation of actin filament polymerization;regulation of Rho protein signal transduction;positive regulation of apoptotic process;regulation of small GTPase mediated signal transduction
Cellular component
cytosol
Molecular function
guanyl-nucleotide exchange factor activity;Rho guanyl-nucleotide exchange factor activity