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

ENSG00000129675

∙ NCBI:9459 ∙ OMIM:300267 ∙ HGNC:685 ∙ Uniprot:Q15052 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

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

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Mental retardation, X-linked 46	XL	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Neurologic	9783701; 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.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
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

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ARHGEF6	protein_coding	protein_coding	ENST00000250617	22	116542

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.0000194	125717	2	0	125719	0.00000795

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.35	218	282	0.774	0.0000205	5076
Missense in Polyphen		53	86.554	0.61234		1539
Synonymous	0.826	96	107	0.898	0.00000827	1452
Loss of Function	5.32	1	35.0	0.0286	0.00000259	605

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000244	0.0000176
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

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

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

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