ARHGEF1

Rho guanine nucleotide exchange factor 1, the group of Dbl family Rho GEFs

Basic information

Region (hg38): 19:41883173-41930150

Links

ENSG00000076928 ∙ NCBI:9138 ∙ OMIM:601855 ∙ HGNC:681 ∙ Uniprot:Q92888 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• immunodeficiency 62 (Limited), mode of inheritance: Unknown
• immunodeficiency 62 (Limited), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Immunodeficiency 62	AR	Allergy/Immunology/Infectious; Oncologic	The condition can involve early-onset, recurrent, and severe infections and diagnosis may allow preventative measures and early and prompt treatment of infections (for example, with IVIG); Cancer has been described, and awareness of an increased risk may allow early diagnosis and management	Allergy/Immunology/Infectious; Oncologic	30521495

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ARHGEF1 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ARHGEF1 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			3	170	5	178
missense			311	10	2	323
nonsense			1			1
start loss			1			1
frameshift			3			3
inframe indel			2			2
splice donor/acceptor (+/-2bp)			1			1
splice region			30	42	10	82
non coding			4	116	11	131
Total	0	0	326	296	18

Variants in ARHGEF1

This is a list of pathogenic ClinVar variants found in the ARHGEF1 region.

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

Position	Type	Phenotype	Significance	ClinVar
19-41884469-T-A			Uncertain significance (Jan 08, 2025)
19-41884477-C-T			Uncertain significance (Sep 30, 2023)
19-41884481-C-A			Benign (Dec 05, 2024)
19-41884481-C-G		not specified	Uncertain significance (Jan 24, 2024)
19-41884490-G-A			Uncertain significance (Oct 29, 2023)
19-41884490-G-C			Uncertain significance (Aug 08, 2024)
19-41884504-C-A			Likely benign (Aug 31, 2023)
19-41884504-C-T			Likely benign (Jul 29, 2022)
19-41884506-G-A			Likely benign (Apr 25, 2024)
19-41884509-C-T			Likely benign (Mar 31, 2023)
19-41888051-C-G			Likely benign (Jun 24, 2024)
19-41888059-T-C		ARHGEF1-related disorder	Benign (Feb 03, 2025)
19-41888060-C-T			Likely benign (Mar 05, 2024)
19-41888066-C-T			Likely benign (Dec 09, 2024)
19-41888067-T-C			Likely benign (Nov 19, 2023)
19-41888069-C-G			Uncertain significance (May 01, 2023)
19-41888073-G-A			Likely benign (Jan 02, 2024)
19-41888080-G-C			Uncertain significance (Feb 17, 2024)
19-41888082-G-C			Uncertain significance (Aug 14, 2023)
19-41888093-T-C			Uncertain significance (Jun 12, 2024)
19-41888094-C-T			Likely benign (Jan 19, 2025)
19-41888095-G-A			Uncertain significance (Feb 17, 2024)
19-41888099-G-A			Uncertain significance (Oct 25, 2022)
19-41888099-G-C			Uncertain significance (Sep 29, 2024)
19-41888102-G-C			Uncertain significance (Sep 09, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ARHGEF1	protein_coding	protein_coding	ENST00000337665	28	47075

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.768	0.232	125728	0	20	125748	0.0000795

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.83	407	602	0.676	0.0000416	5945
Missense in Polyphen		118	209.8	0.56243		1995
Synonymous	0.701	235	249	0.944	0.0000169	1902
Loss of Function	5.37	11	53.2	0.207	0.00000269	583

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000207	0.000207
Ashkenazi Jewish	0.0000994	0.0000992
East Asian	0.0000544	0.0000544
Finnish	0.000121	0.0000924
European (Non-Finnish)	0.0000628	0.0000615
Middle Eastern	0.0000544	0.0000544
South Asian	0.0000659	0.0000653
Other	0.000174	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Seems to play a role in the regulation of RhoA GTPase by guanine nucleotide-binding alpha-12 (GNA12) and alpha-13 (GNA13) subunits. Acts as GTPase-activating protein (GAP) for GNA12 and GNA13, and as guanine nucleotide exchange factor (GEF) for RhoA GTPase. Activated G alpha 13/GNA13 stimulates the RhoGEF activity through interaction with the RGS-like domain. This GEF activity is inhibited by binding to activated GNA12. Mediates angiotensin-2- induced RhoA activation. {ECO:0000269|PubMed:20098430, ECO:0000269|PubMed:8810315, ECO:0000269|PubMed:9641915, ECO:0000269|PubMed:9641916}.
• Pathway: Platelet activation - Homo sapiens (human);Regulation of actin cytoskeleton - Homo sapiens (human);Vascular smooth muscle contraction - Homo sapiens (human);Proteoglycans in cancer - Homo sapiens (human);Pathways in cancer - Homo sapiens (human);G Protein Signaling Pathways;EGF-EGFR Signaling Pathway;Regulation of Actin Cytoskeleton;G13 Signaling 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;NRAGE signals death through JNK;Thromboxane A2 receptor signaling;Death Receptor Signalling;p75 NTR receptor-mediated signalling;G alpha (12/13) signalling events;GPCR downstream signalling;PAR1-mediated thrombin signaling events;LPA receptor mediated events;Cell death signalling via NRAGE, NRIF and NADE;Regulation of RhoA activity (Consensus)

Recessive Scores

• pRec: 0.150

Intolerance Scores

• loftool: 0.217
• rvis_EVS: -1.84
• rvis_percentile_EVS: 2.07

Haploinsufficiency Scores

• pHI: 0.109
• hipred: Y
• hipred_score: 0.654
• ghis: 0.611

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.960

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Arhgef1
• Phenotype: immune system 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); hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); muscle phenotype; homeostasis/metabolism phenotype

Gene ontology

• Biological process: G protein-coupled receptor signaling pathway;Rho protein signal transduction;cell population proliferation;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: cytoplasm;cytosol;plasma membrane
• Molecular function: G protein-coupled receptor binding;RNA binding;guanyl-nucleotide exchange factor activity;Rho guanyl-nucleotide exchange factor activity;GTPase activator activity;protein binding