ARHGEF3

Rho guanine nucleotide exchange factor 3, the group of Dbl family Rho GEFs

Basic information

Region (hg38): 3:56727417-57079329

Links

ENSG00000163947 ∙ NCBI:50650 ∙ OMIM:612115 ∙ HGNC:683 ∙ Uniprot:Q9NR81 ∙ 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 ARHGEF3 gene.

• Inborn genetic diseases (20 variants)
• not provided (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ARHGEF3 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				1		1
missense			16			16
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding			4	1		5
Total	0	0	20	2	0

Variants in ARHGEF3

This is a list of pathogenic ClinVar variants found in the ARHGEF3 region.

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

Position	Type	Phenotype	Significance	ClinVar
3-56729275-C-T		not specified	Uncertain significance (Aug 09, 2021)
3-56729276-G-T		not specified	Uncertain significance (Mar 06, 2023)
3-56729362-T-A		not specified	Uncertain significance (Dec 08, 2023)
3-56729363-A-T		not specified	Uncertain significance (Dec 08, 2023)
3-56729449-G-C		not specified	Uncertain significance (Aug 04, 2021)
3-56729460-T-A		not specified	Uncertain significance (Jan 09, 2024)
3-56729485-C-T		not specified	Uncertain significance (Jan 05, 2022)
3-56729518-G-A		not specified	Uncertain significance (Mar 07, 2024)
3-56729546-G-C		not specified	Uncertain significance (Apr 18, 2023)
3-56732259-C-G		not specified	Uncertain significance (Mar 21, 2023)
3-56732340-G-A		not specified	Uncertain significance (Oct 26, 2022)
3-56732402-T-C		not specified	Uncertain significance (Jan 19, 2022)
3-56737187-C-T		not specified	Uncertain significance (Feb 05, 2024)
3-56737195-T-C		not specified	Uncertain significance (Apr 25, 2023)
3-56737214-G-C		not specified	Uncertain significance (Sep 16, 2021)
3-56737255-T-A		not specified	Uncertain significance (Nov 07, 2023)
3-56737285-T-C		not specified	Uncertain significance (Oct 26, 2022)
3-56745350-A-G		not specified	Uncertain significance (Jun 29, 2023)
3-56751090-G-A		not specified	Uncertain significance (Nov 21, 2023)
3-56751346-C-A		not specified	Uncertain significance (Dec 16, 2023)
3-56755022-C-T		not specified	Uncertain significance (Dec 21, 2022)
3-56755070-T-C		not specified	Uncertain significance (Dec 13, 2023)
3-56755082-C-T		not specified	Uncertain significance (Aug 02, 2021)
3-56773715-G-T			Likely benign (Sep 01, 2022)
3-56773716-G-T		not specified	Uncertain significance (Oct 30, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ARHGEF3	protein_coding	protein_coding	ENST00000338458	12	351912

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00405	0.996	125733	0	15	125748	0.0000596

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.08	223	329	0.677	0.0000202	3697
Missense in Polyphen		61	121.4	0.50248		1339
Synonymous	0.0946	124	125	0.989	0.00000767	1038
Loss of Function	3.79	11	35.3	0.311	0.00000230	338

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000275	0.000275
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.0000544	0.0000544
Finnish	0.0000940	0.0000924
European (Non-Finnish)	0.0000264	0.0000264
Middle Eastern	0.0000544	0.0000544
South Asian	0.0000654	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Acts as guanine nucleotide exchange factor (GEF) for RhoA and RhoB GTPases. {ECO:0000269|PubMed:12221096}.
• 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;Regulation of RhoA activity (Consensus)

Recessive Scores

• pRec: 0.124

Intolerance Scores

• loftool: 0.483
• rvis_EVS: -0.29
• rvis_percentile_EVS: 33.34

Haploinsufficiency Scores

• pHI: 0.327
• hipred: Y
• hipred_score: 0.825
• ghis: 0.502

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.678

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Arhgef3
• Phenotype: homeostasis/metabolism phenotype; hematopoietic system phenotype

Zebrafish Information Network

• Gene name: arhgef3
• Affected structure: myeloid cell development
• Phenotype tag: abnormal
• Phenotype quality: absent

Gene ontology

• Biological process: G protein-coupled receptor signaling pathway;Rho protein signal transduction;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;protein binding