ARHGEF40

protein-coding

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

Gene summary

This gene encodes a protein similar to guanosine nucleotide exchange factors for Rho GTPases. The encoded protein contains in its C-terminus a GEF domain involved in exchange activity and a pleckstrin homology domain. Alternatively spliced transcripts that encode different proteins have been described. [provided by RefSeq, Mar 2014]

MANE transcript

NM_018071.5

Inheritance

ClinVar variants

U:262B:20

Top phenotype

Prostate cancer

gnomAD constraint

pLI —, LoF o/e 0.37

Max pathogenic AF

—

Genomic locus

chr14:21,070,273-21,090,248

External References & Databases

Ensembl (ENSG00000165801)

Transcript & Mutation Effects

hg38 • Region Span ~20.0 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

neurodevelopmental disorderLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0700092

Submitter: Ambry Genetics

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ARHGEF40 variants in ClinVar

5 Conditions Cataloged

not specifiedTotal: 255

not providedTotal: 9

Prostate cancerTotal: 1

ARHGEF40 related disorderTotal: 1

Myoepithelial tumorTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_018071.5. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			4 clinvar	1 clinvar	2 clinvar	7
missense			253 clinvar	16 clinvar	1 clinvar	270
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			5 clinvar			5
Total	0	0	262	17	3	282

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 106 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_018071.5	RefSeq	NP_060541.3	23	MANE Select
ENST00000298694.9	Ensembl	ENSP00000298694.4	23	MANE Select
NM_001278529.2	RefSeq	NP_001265458.1	14	Standard
NM_001278530.2	RefSeq	NP_001265459.1	13	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Signaling by GPCR
Signal Transduction
Rho GTPase cycle
Signaling by Rho GTPases
NRAGE signals death through JNK

Biological Process

regulation of Rho protein signal transduction

Molecular Function

Rho guanyl-nucleotide exchange factor activity

Cellular Component

cytoplasm

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000298694
Coding exons: 23
Length: 19971
Individuals with no LoFs: 125648
Homozygous LoFs: 0
Heterozygous LoFs: 100
Defined: 125748
p: 0.000398

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.979	815	898	0.908	0.0000557	9480
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00031	0.00031	rare
Latino/Admixed American	0.00047	0.00046	rare
Ashkenazi Jewish	0.00070	0.00069	rare
East Asian	0.00022	0.00022	rare
Finnish	0.00074	0.00074	rare
European (Non-Finnish)	0.00038	0.00035	rare
South Asian	0.00044	0.00036	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

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

Intolerance Scores

RVIS EVS: -0.23
RVIS percentile EVS: 37.13

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.114

Gene Damage Prediction

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