ARHGEF15

Rho guanine nucleotide exchange factor 15, the group of Dbl family Rho GEFs

Basic information

Region (hg38): 17:8310240-8322514

Links

ENSG00000198844 ∙ NCBI:22899 ∙ OMIM:608504 ∙ HGNC:15590 ∙ Uniprot:O94989 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• schizophrenia (No Known Disease Relationship), mode of inheritance: Unknown
• developmental and epileptic encephalopathy (Limited), mode of inheritance: AD

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ARHGEF15 gene.

• Early infantile epileptic encephalopathy with suppression bursts (498 variants)
• Inborn genetic diseases (29 variants)
• not provided (16 variants)
• not specified (3 variants)
• ARHGEF15-related condition (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 ARHGEF15 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	100	16	120
missense			265	12	10	287
nonsense			6			6
start loss						0
frameshift			13			13
inframe indel		1	4			5
splice donor/acceptor (+/-2bp)			3			3
splice region			12	10	2	24
non coding			3	43	4	50
Total	0	1	298	155	30

Variants in ARHGEF15

This is a list of pathogenic ClinVar variants found in the ARHGEF15 region.

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

Position	Type	Phenotype	Significance	ClinVar
17-8312054-C-T		Early infantile epileptic encephalopathy with suppression bursts	Likely benign (Jan 20, 2023)
17-8312055-C-T		not specified	Uncertain significance (Sep 28, 2022)
17-8312071-C-T		Early infantile epileptic encephalopathy with suppression bursts	Uncertain significance (Sep 20, 2021)
17-8312073-C-A		Early infantile epileptic encephalopathy with suppression bursts	Uncertain significance (Jul 12, 2022)
17-8312073-C-G		Early infantile epileptic encephalopathy with suppression bursts	Uncertain significance (Aug 14, 2023)
17-8312075-C-G		Early infantile epileptic encephalopathy with suppression bursts	Likely benign (Aug 02, 2023)
17-8312075-C-T		Early infantile epileptic encephalopathy with suppression bursts	Likely benign (Nov 10, 2022)
17-8312076-A-C		Early infantile epileptic encephalopathy with suppression bursts	Uncertain significance (Mar 22, 2021)
17-8312077-C-G		Early infantile epileptic encephalopathy with suppression bursts	Uncertain significance (Apr 18, 2023)
17-8312077-C-T		Early infantile epileptic encephalopathy with suppression bursts • not specified	Uncertain significance (Dec 12, 2023)
17-8312078-G-A		Early infantile epileptic encephalopathy with suppression bursts	Likely benign (Nov 01, 2021)
17-8312091-C-T		Early infantile epileptic encephalopathy with suppression bursts	Uncertain significance (May 05, 2023)
17-8312092-G-A		Early infantile epileptic encephalopathy with suppression bursts	Uncertain significance (Nov 10, 2023)
17-8312093-G-A		Early infantile epileptic encephalopathy with suppression bursts • ARHGEF15-related disorder	Benign/Likely benign (Dec 27, 2023)
17-8312098-TC-T		Early infantile epileptic encephalopathy with suppression bursts	Uncertain significance (Aug 23, 2022)
17-8312100-C-T		Early infantile epileptic encephalopathy with suppression bursts	Uncertain significance (Mar 20, 2023)
17-8312101-G-A		Early infantile epileptic encephalopathy with suppression bursts	Uncertain significance (Dec 02, 2022)
17-8312102-C-T		Early infantile epileptic encephalopathy with suppression bursts	Likely benign (Dec 09, 2023)
17-8312104-C-T		not specified	Uncertain significance (Nov 15, 2021)
17-8312106-C-T		Early infantile epileptic encephalopathy with suppression bursts • ARHGEF15-related disorder	Benign (Feb 01, 2024)
17-8312107-G-A		Early infantile epileptic encephalopathy with suppression bursts	Uncertain significance (Dec 02, 2022)
17-8312112-C-T		Early infantile epileptic encephalopathy with suppression bursts	Uncertain significance (Jul 06, 2022)
17-8312118-C-T		Early infantile epileptic encephalopathy with suppression bursts	Uncertain significance (Jun 23, 2022)
17-8312119-G-A		Early infantile epileptic encephalopathy with suppression bursts	Uncertain significance (Dec 09, 2023)
17-8312122-C-T		Early infantile epileptic encephalopathy with suppression bursts • not specified	Uncertain significance (Dec 14, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ARHGEF15	protein_coding	protein_coding	ENST00000361926	15	12271

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00000166	1.00	125678	0	66	125744	0.000262

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.715	475	521	0.912	0.0000318	5274
Missense in Polyphen		167	202.66	0.82404		2014
Synonymous	1.04	191	210	0.909	0.0000113	1918
Loss of Function	3.15	16	36.5	0.438	0.00000185	382

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00101	0.000985
Ashkenazi Jewish	0.000141	0.0000992
East Asian	0.000827	0.000816
Finnish	0.0000506	0.0000462
European (Non-Finnish)	0.000194	0.000185
Middle Eastern	0.000827	0.000816
South Asian	0.000145	0.000131
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Specific GEF for RhoA activation. Does not activate RAC1 or CDC42. Regulates vascular smooth muscle contractility. Negatively regulates excitatory synapse development by suppressing the synapse-promoting activity of EPHB2. {ECO:0000269|PubMed:12775584}.
• Pathway: VEGFA-VEGFR2 Signaling 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;EPHA forward signaling;Regulation of RhoA activity (Consensus)

Recessive Scores

• pRec: 0.101

Intolerance Scores

• loftool: 0.372
• rvis_EVS: 0.54
• rvis_percentile_EVS: 81.09

Haploinsufficiency Scores

• pHI: 0.254
• hipred: Y
• hipred_score: 0.687
• ghis: 0.558

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• gene_indispensability_pred: E
• gene_indispensability_score: 0.667

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Arhgef15
• Phenotype: vision/eye 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); 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); reproductive 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); cellular phenotype; homeostasis/metabolism phenotype

Gene ontology

• Biological process: regulation of Rho protein signal transduction;positive regulation of GTPase activity;regulation of catalytic activity;positive regulation of stress fiber assembly;retina vasculature morphogenesis in camera-type eye;negative regulation of synapse maturation
• Cellular component: cytoplasm;dendrite
• Molecular function: Rho guanyl-nucleotide exchange factor activity;GTPase activator activity;protein binding