ARHGEF18

Rho/Rac guanine nucleotide exchange factor 18, the group of Pleckstrin homology domain containing|Dbl family Rho GEFs

Basic information

Region (hg38): 19:7348937-7472485

Links

ENSG00000104880 ∙ NCBI:23370 ∙ OMIM:616432 ∙ HGNC:17090 ∙ Uniprot:Q6ZSZ5 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• retinitis pigmentosa 78 (Strong), mode of inheritance: AR
• retinitis pigmentosa (Supportive), mode of inheritance: AD
• retinitis pigmentosa 78 (Limited), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Retinitis pigmentosa 78	AR	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	Ophthalmologic	28132693

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ARHGEF18 gene.

• not_provided (921 variants)
• Inborn_genetic_diseases (204 variants)
• ARHGEF18-related_disorder (20 variants)
• Retinitis_pigmentosa_78 (18 variants)
• Retinal_dystrophy (14 variants)
• not_specified (2 variants)
• Optic_atrophy (2 variants)
• Autosomal_recessive_retinitis_pigmentosa (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ARHGEF18 gene is commonly pathogenic or not. These statistics are base on transcript: NM_001367823.1. 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	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			5	269	12	286
missense		1	404	27	9	441
nonsense	8		1			9
start loss						0
frameshift	6	1	1			8
splice donor/acceptor (+/-2bp)		2	1			3
Total	14	4	412	296	21

Highest pathogenic variant AF is 0.0000491522

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ARHGEF18	protein_coding	protein_coding	ENST00000359920	19	77365

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00177	0.998	125704	0	44	125748	0.000175

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.25	568	740	0.767	0.0000516	7544
Missense in Polyphen		175	249.76	0.70068		2556
Synonymous	0.643	319	334	0.955	0.0000259	2378
Loss of Function	4.65	15	50.8	0.296	0.00000243	585

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000854	0.000763
Ashkenazi Jewish	0.000215	0.000198
East Asian	0.000109	0.000109
Finnish	0.000103	0.0000924
European (Non-Finnish)	0.000173	0.000167
Middle Eastern	0.000109	0.000109
South Asian	0.000134	0.000131
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Acts as guanine nucleotide exchange factor (GEF) for RhoA GTPases. Its activation induces formation of actin stress fibers. Also acts as a GEF for RAC1, inducing production of reactive oxygen species (ROS). Does not act as a GEF for CDC42. The G protein beta-gamma (Gbetagamma) subunits of heterotrimeric G proteins act as activators, explaining the integrated effects of LPA and other G-protein coupled receptor agonists on actin stress fiber formation, cell shape change and ROS production. Required for EPB41L4B-mediated regulation of the circumferential actomyosin belt in epithelial cells (PubMed:22006950). {ECO:0000269|PubMed:11085924, ECO:0000269|PubMed:14512443, ECO:0000269|PubMed:15558029, ECO:0000269|PubMed:22006950, ECO:0000269|PubMed:28132693}.
• Pathway: Tight junction - Homo sapiens (human);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;Signaling by TGF-beta Receptor Complex;Signaling by TGF-beta family members;GPCR downstream signalling;Cell death signalling via NRAGE, NRIF and NADE;TGF-beta receptor signaling in EMT (epithelial to mesenchymal transition);Regulation of RhoA activity (Consensus)

Recessive Scores

• pRec: 0.104

Intolerance Scores

• loftool: 0.409
• rvis_EVS: 0.66
• rvis_percentile_EVS: 84.19

Haploinsufficiency Scores

• pHI: 0.109
• hipred: N
• hipred_score: 0.332

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.844

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Arhgef18
• Phenotype: mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span)

Zebrafish Information Network

• Gene name: arhgef18b
• Affected structure: otolith
• Phenotype tag: abnormal
• Phenotype quality: morphology

Gene ontology

• Biological process: transforming growth factor beta receptor signaling pathway;G protein-coupled receptor signaling pathway;small GTPase mediated signal transduction;regulation of cell shape;actin cytoskeleton organization;regulation of Rho protein signal transduction;positive regulation of apoptotic process;regulation of small GTPase mediated signal transduction
• Cellular component: cytosol;cytoskeleton;plasma membrane;apical plasma membrane;cell junction;apical part of cell;extracellular exosome
• Molecular function: nucleic acid binding;guanyl-nucleotide exchange factor activity;Rho guanyl-nucleotide exchange factor activity;metal ion binding