ARHGEF10

Rho guanine nucleotide exchange factor 10, the group of Dbl family Rho GEFs

Basic information

Region (hg38): 8:1823925-1958641

Links

ENSG00000104728 ∙ NCBI:9639 ∙ OMIM:608136 ∙ HGNC:14103 ∙ Uniprot:O15013 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autosomal dominant slowed nerve conduction velocity (Supportive), mode of inheritance: AD
• peripheral neuropathy (Limited), mode of inheritance: AD
• autosomal dominant slowed nerve conduction velocity (Limited), mode of inheritance: Unknown
• autosomal dominant slowed nerve conduction velocity (Limited), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Slowed nerve conduction velocity, autosomal dominant (Hereditary motor and sensory neuropathy)	AD	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	Neurologic	9678704; 14508709

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ARHGEF10 gene.

• not provided (497 variants)
• Inborn genetic diseases (72 variants)
• Autosomal dominant slowed nerve conduction velocity (32 variants)
• not specified (17 variants)
• Charcot-Marie-Tooth disease (3 variants)
• Peripheral axonal neuropathy (1 variants)
• Myopathy;Spinal muscular atrophy (1 variants)
• ARHGEF10-related condition (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ARHGEF10 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			6	74	25	105
missense			236	21	12	269
nonsense		1	6			7
start loss						0
frameshift			6			6
inframe indel			3			3
splice donor/acceptor (+/-2bp)			5			5
splice region			10	11	12	33
non coding			10	38	83	131
Total	0	1	272	133	120

Variants in ARHGEF10

This is a list of pathogenic ClinVar variants found in the ARHGEF10 region.

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

Position	Type	Phenotype	Significance	ClinVar
8-1843267-C-T			Benign (May 10, 2021)
8-1843424-C-A			Uncertain significance (Jul 22, 2022)
8-1843441-C-T		ARHGEF10-related disorder	Likely benign (Mar 28, 2019)
8-1843472-T-G			Benign (May 10, 2021)
8-1843496-C-T			Benign (May 11, 2021)
8-1843497-G-A			Benign (May 10, 2021)
8-1843506-C-T			Benign (May 10, 2021)
8-1843519-A-G			Benign (May 10, 2021)
8-1857814-T-C			Benign (May 10, 2021)
8-1857870-AGATC-A			Benign (May 10, 2021)
8-1857875-GATCGATCT-G			Benign (May 11, 2021)
8-1857875-GATCGATCTATCT-G			Benign (May 21, 2021)
8-1857875-G-GATCT			Benign (May 10, 2021)
8-1857879-G-T			Benign (May 10, 2021)
8-1857879-GATCT-G			Benign (May 19, 2021)
8-1857879-G-GATCT			Benign (May 10, 2021)
8-1857947-TTTTTC-T		ARHGEF10-related disorder	Benign (Jan 24, 2024)
8-1857950-T-C		Autosomal dominant slowed nerve conduction velocity • not specified	Benign/Likely benign (Jan 21, 2024)
8-1857951-T-A			Likely benign (Oct 30, 2023)
8-1857972-A-G			Uncertain significance (Jan 15, 2024)
8-1857977-G-T			Uncertain significance (Jul 26, 2022)
8-1857996-A-G			Uncertain significance (Oct 03, 2023)
8-1857998-G-C		not specified	Uncertain significance (Sep 23, 2023)
8-1858005-G-C			Uncertain significance (Jun 06, 2023)
8-1858015-C-T			Likely benign (Sep 01, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ARHGEF10	protein_coding	protein_coding	ENST00000349830	28	134666

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
6.77e-30	0.0301	125611	0	137	125748	0.000545

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-2.72	1013	797	1.27	0.0000515	8822
Missense in Polyphen		355	327.32	1.0846		3595
Synonymous	-5.54	471	341	1.38	0.0000270	2598
Loss of Function	1.72	54	69.4	0.778	0.00000369	808

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00107	0.00107
Ashkenazi Jewish	0.00	0.00
East Asian	0.000381	0.000381
Finnish	0.000603	0.000601
European (Non-Finnish)	0.000555	0.000554
Middle Eastern	0.000381	0.000381
South Asian	0.000753	0.000752
Other	0.000489	0.000489

dbNSFP

Source: dbNSFP

• Function: FUNCTION: May play a role in developmental myelination of peripheral nerves. {ECO:0000269|PubMed:14508709}.
• Disease: DISEASE: Slowed nerve conduction velocity (SNCV) [MIM:608236]: Affected individuals present a reduction in nerve conduction velocities without any clinical signs of peripheral or central nervous system dysfunction. SNCV inheritance is autosomal dominant. {ECO:0000269|PubMed:14508709}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• 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)

Intolerance Scores

• loftool: 0.799
• rvis_EVS: -1.02
• rvis_percentile_EVS: 8.11

Haploinsufficiency Scores

• pHI: 0.220
• hipred: Y
• hipred_score: 0.540
• ghis: 0.542

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.657

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Arhgef10

Gene ontology

• Biological process: myelination in peripheral nervous system;actin cytoskeleton organization;regulation of Rho protein signal transduction;centrosome duplication;positive regulation of stress fiber assembly;mitotic spindle assembly;activation of GTPase activity
• Cellular component: centrosome;cytosol
• Molecular function: guanyl-nucleotide exchange factor activity;Rho guanyl-nucleotide exchange factor activity;protein binding;kinesin binding