ARHGEF10

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

Basic information

Region (hg38): 8:1823926-1958641

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
hereditary peripheral neuropathy (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 (643 variants)
not_specified (261 variants)
Autosomal_dominant_slowed_nerve_conduction_velocity (39 variants)
ARHGEF10-related_disorder (22 variants)
Charcot-Marie-Tooth_disease (3 variants)
Spinal_muscular_atrophy (1 variants)
Myopathy (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. These statistics are base on transcript: NM_000014629.4. Only rare variants are included in the table.

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.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous			8 clinvar	134 clinvar	18 clinvar	160
missense			464 clinvar	45 clinvar	8 clinvar	517
nonsense			11 clinvar			11
start loss						0
frameshift			10 clinvar			10
splice donor/acceptor (+/-2bp)			5 clinvar			5
Total	0	0	498	179	26

Loading clinvar variants...

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
Phenotype

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