ARHGEF6

Rac/Cdc42 guanine nucleotide exchange factor 6, the group of Pleckstrin homology domain containing|Dbl family Rho GEFs

Basic information

Region (hg38): X:136665547-136780932

Previous symbols: [ "MRX46" ]

Links

ENSG00000129675NCBI:9459OMIM:300267HGNC:685Uniprot:Q15052AlphaFoldGenCCjaxSfariGnomADPubmedClinVar

Phenotypes

GenCC

Source: genCC

  • non-syndromic X-linked intellectual disability (Limited), mode of inheritance: XL
  • non-syndromic X-linked intellectual disability (Supportive), mode of inheritance: XL
  • complex neurodevelopmental disorder (Limited), mode of inheritance: AD
  • intellectual disability, X-linked 46 (Limited), mode of inheritance: XL
  • intellectual disability, X-linked 46 (Limited), mode of inheritance: XL
  • non-syndromic X-linked intellectual disability (Disputed Evidence), mode of inheritance: XL
  • X-linked intellectual disability (Limited), mode of inheritance: XL
  • congenital anomaly of kidney and urinary tract (Limited), mode of inheritance: XL

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Mental retardation, X-linked 46XLGeneralGenetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testingNeurologic9783701; 11017088; 23871722
The evidence of variants as related to disease causation has been questioned due to subsequent population-based studies

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ARHGEF6 gene.

  • not_specified (69 variants)
  • not_provided (39 variants)
  • ARHGEF6-related_disorder (13 variants)
  • Intellectual_disability,_X-linked_46 (6 variants)
  • Intellectual_disability (2 variants)
  • ARHGEF6-associated_Neurodevelopmental_disorder (1 variants)
  • Vanishing_white_matter_disease (1 variants)
  • History_of_neurodevelopmental_disorder (1 variants)
  • Genetic_developmental_and_epileptic_encephalopathy (1 variants)
  • Non-syndromic_X-linked_intellectual_disability (1 variants)
  • See_cases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ARHGEF6 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000004840.3. 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
3
clinvar
6
clinvar
4
clinvar
13
missense
67
clinvar
12
clinvar
79
nonsense
0
start loss
0
frameshift
1
clinvar
1
splice donor/acceptor (+/-2bp)
0
Total 0 0 71 18 4
Loading clinvar variants...

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
ARHGEF6protein_codingprotein_codingENST00000250617 22116542
pLI Probability
LOF Intolerant
pRec Probability
LOF Recessive
Individuals with
no LOFs
Individuals with
Homozygous LOFs
Individuals with
Heterozygous LOFs
Defined p
1.000.0000194125717201257190.00000795
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense1.352182820.7740.00002055076
Missense in Polyphen5386.5540.612341539
Synonymous0.826961070.8980.000008271452
Loss of Function5.32135.00.02860.00000259605

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.000.00
Ashkenazi Jewish0.000.00
East Asian0.000.00
Finnish0.000.00
European (Non-Finnish)0.00002440.0000176
Middle Eastern0.000.00
South Asian0.000.00
Other0.000.00

dbNSFP

Source: dbNSFP

Function
FUNCTION: Acts as a RAC1 guanine nucleotide exchange factor (GEF).;
Pathway
Regulation of actin cytoskeleton - Homo sapiens (human);Pancreatic cancer - Homo sapiens (human);Regulation of Actin Cytoskeleton;Signaling by GPCR;Signal Transduction;TCR;Rho GTPase cycle;Signaling by Rho GTPases;Integrin;agrin in postsynaptic differentiation;Regulation of RAC1 activity;NRAGE signals death through JNK;PDGF;Death Receptor Signalling;p75 NTR receptor-mediated signalling;G alpha (12/13) signalling events;Integrin-linked kinase signaling;Regulation of cytoskeletal remodeling and cell spreading by IPP complex components;Cell-extracellular matrix interactions;Cell junction organization;Cell-Cell communication;GPCR downstream signalling;Regulation of CDC42 activity;CDC42 signaling events;Cell death signalling via NRAGE, NRIF and NADE (Consensus)

Recessive Scores

pRec
0.266

Intolerance Scores

loftool
0.241
rvis_EVS
0.64
rvis_percentile_EVS
83.98

Haploinsufficiency Scores

pHI
0.332
hipred
Y
hipred_score
0.825
ghis
0.422

Essentials

essential_gene_CRISPR
N
essential_gene_CRISPR2
N
essential_gene_gene_trap
N
gene_indispensability_pred
N
gene_indispensability_score
0.497

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

Mouse Genome Informatics

Gene name
Arhgef6
Phenotype
behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); immune system phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); hematopoietic system phenotype;

Gene ontology

Biological process
apoptotic process;G protein-coupled receptor signaling pathway;JNK cascade;lamellipodium assembly;regulation of Rho protein signal transduction;positive regulation of apoptotic process;positive regulation of GTPase activity;regulation of small GTPase mediated signal transduction
Cellular component
cytosol;lamellipodium
Molecular function
guanyl-nucleotide exchange factor activity;Rho guanyl-nucleotide exchange factor activity;GTPase activator activity;protein binding