ARHGEF40

Rho guanine nucleotide exchange factor 40, the group of Dbl family Rho GEFs

Basic information

Region (hg38): 14:21070273-21090248

Links

ENSG00000165801 ∙ NCBI:55701 ∙ OMIM:610018 ∙ HGNC:25516 ∙ Uniprot:Q8TER5 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• neurodevelopmental disorder (Limited), mode of inheritance: AD

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ARHGEF40 gene.

• not_specified (221 variants)
• not_provided (7 variants)
• Prostate_cancer (1 variants)
• ARHGEF40_related_disorder (1 variants)
• Myoepithelial_tumor (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ARHGEF40 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000018071.5. 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	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				1	2	3
missense			209	15	1	225
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	209	16	3

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ARHGEF40	protein_coding	protein_coding	ENST00000298694	23	19971

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
6.63e-9	1.00	125648	0	100	125748	0.000398

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.979	815	898	0.908	0.0000557	9480
Missense in Polyphen		303	360.77	0.83987		3823
Synonymous	-0.550	376	363	1.04	0.0000198	3416
Loss of Function	5.22	29	79.1	0.367	0.00000522	745

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000777	0.000774
Ashkenazi Jewish	0.000697	0.000695
East Asian	0.000221	0.000217
Finnish	0.000743	0.000739
European (Non-Finnish)	0.000376	0.000352
Middle Eastern	0.000221	0.000217
South Asian	0.000440	0.000359
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: May act as a guanine nucleotide exchange factor (GEF). {ECO:0000250}.
• 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 (Consensus)

Intolerance Scores

• rvis_EVS: -0.23
• rvis_percentile_EVS: 37.13

Haploinsufficiency Scores

• hipred: N
• hipred_score: 0.385
• ghis: 0.435

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.114

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Arhgef40

Gene ontology

• Biological process: regulation of Rho protein signal transduction
• Cellular component: cytoplasm
• Molecular function: Rho guanyl-nucleotide exchange factor activity