ARHGEF5

Rho guanine nucleotide exchange factor 5, the group of Dbl family Rho GEFs

Basic information

Region (hg38): 7:144355287-144380632

Links

ENSG00000050327 ∙ NCBI:7984 ∙ OMIM:600888 ∙ HGNC:13209 ∙ Uniprot:Q12774 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ARHGEF5 gene.

• Inborn genetic diseases (35 variants)
• not provided (5 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ARHGEF5 gene is commonly pathogenic or not.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				4		4
missense			32	4		36
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	32	8	0

Variants in ARHGEF5

This is a list of pathogenic ClinVar variants found in the ARHGEF5 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
7-144362887-A-G		not specified	Uncertain significance (Sep 06, 2023)
7-144362911-A-G		not specified	Uncertain significance (Aug 17, 2022)
7-144362925-G-A		not specified	Uncertain significance (Jun 07, 2023)
7-144363012-C-G		not specified	Uncertain significance (Nov 08, 2022)
7-144363147-A-T		not specified	Uncertain significance (Dec 21, 2023)
7-144363309-G-A		not specified	Uncertain significance (Mar 31, 2023)
7-144363336-C-T		not specified	Uncertain significance (Apr 25, 2023)
7-144363344-G-C		not specified	Uncertain significance (Feb 27, 2024)
7-144363372-C-G		not specified	Uncertain significance (Jul 27, 2022)
7-144363462-G-T		not specified	Uncertain significance (May 05, 2023)
7-144363544-G-A		not specified	Uncertain significance (Mar 17, 2023)
7-144363575-C-T			Likely benign (Jun 01, 2022)
7-144363661-A-G		not specified	Likely benign (May 17, 2023)
7-144363700-A-G		not specified	Uncertain significance (May 23, 2023)
7-144363759-A-G		not specified	Uncertain significance (Mar 16, 2022)
7-144363761-A-C			Likely benign (Jul 01, 2023)
7-144363897-C-G		not specified	Uncertain significance (Oct 05, 2023)
7-144363956-G-A		not specified	Uncertain significance (Jan 26, 2022)
7-144364015-T-C		not specified	Uncertain significance (Jul 05, 2023)
7-144364056-A-G		not specified	Uncertain significance (Aug 14, 2023)
7-144364099-A-G		not specified	Uncertain significance (Jan 17, 2023)
7-144364173-G-T		not specified	Conflicting classifications of pathogenicity (Nov 01, 2022)
7-144364300-G-T		not specified	Uncertain significance (Feb 10, 2022)
7-144364782-C-A		not specified	Uncertain significance (Oct 26, 2022)
7-144365047-C-T		not specified	Uncertain significance (Oct 12, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ARHGEF5	protein_coding	protein_coding	ENST00000056217	14	25345

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
7.59e-14	0.623	125655	2	91	125748	0.000370

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.47	342	427	0.800	0.0000221	9943
Missense in Polyphen		66	103.18	0.63966		2333
Synonymous	2.56	121	162	0.745	0.00000849	3170
Loss of Function	1.63	26	36.7	0.709	0.00000218	692

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000284	0.000274
Ashkenazi Jewish	0.00	0.00
East Asian	0.000165	0.000163
Finnish	0.0000464	0.0000462
European (Non-Finnish)	0.000159	0.000141
Middle Eastern	0.000165	0.000163
South Asian	0.00240	0.00216
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Guanine nucleotide exchange factor which activates Rho GTPases (PubMed:15601624). Strongly activates RHOA (PubMed:15601624). Also strongly activates RHOB, weakly activates RHOC and RHOG and shows no effect on RHOD, RHOV, RHOQ or RAC1 (By similarity). Involved in regulation of cell shape and actin cytoskeletal organization (PubMed:15601624). Plays a role in actin organization by generating a loss of actin stress fibers and the formation of membrane ruffles and filopodia (PubMed:14662653). Required for SRC-induced podosome formation (By similarity). Involved in positive regulation of immature dendritic cell migration (By similarity). {ECO:0000250|UniProtKB:E9Q7D5, ECO:0000269|PubMed:14662653, ECO:0000269|PubMed:15601624}.
• Pathway: Signaling by GPCR;Signal Transduction;pkc-catalyzed phosphorylation of inhibitory phosphoprotein of myosin phosphatase;rho cell motility signaling pathway;rac1 cell motility signaling pathway;Rho GTPase cycle;Signaling by Rho GTPases;EGFR1;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;Regulation of RhoA activity (Consensus)

Recessive Scores

• pRec: 0.0934

Haploinsufficiency Scores

• pHI: 0.0787
• ghis: 0.499

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.346

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Arhgef5
• Phenotype: hematopoietic 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); immune system phenotype

Gene ontology

• Biological process: myeloid dendritic cell chemotaxis;G protein-coupled receptor signaling pathway;actin cytoskeleton organization;regulation of actin cytoskeleton organization;regulation of Rho protein signal transduction;intracellular signal transduction;positive regulation of apoptotic process;regulation of GTPase activity;positive regulation of JUN kinase activity;positive regulation of GTPase activity;regulation of small GTPase mediated signal transduction;positive regulation of DNA-binding transcription factor activity;regulation of cytoskeleton organization;positive regulation of stress fiber assembly;regulation of ERK1 and ERK2 cascade;positive regulation of podosome assembly;positive regulation of protein import
• Cellular component: podosome;nucleus;nucleoplasm;cytoplasm;cytosol;plasma membrane;cell junction;cell projection;cell periphery
• Molecular function: guanyl-nucleotide exchange factor activity;Rho guanyl-nucleotide exchange factor activity;protein binding;GTP binding;lipid binding