ARHGEF26

protein-coding

Rho guanine nucleotide exchange factor 26, the group of Dbl family Rho GEFs|Pleckstrin homology domain containing

Gene summary

This gene encodes a member of the Rho-guanine nucleotide exchange factor (Rho-GEF) family. These proteins regulate Rho GTPases by catalyzing the exchange of GDP for GTP. The encoded protein specifically activates RhoG and plays a role in the promotion of macropinocytosis. Underexpression of the encoded protein may be a predictive marker of chemoresistant disease. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Oct 2011]

MANE transcript

NM_015595.4

Inheritance

—

ClinVar variants

P:1U:145B:4

Top phenotype

Marfanoid habitus and intellectual disability

gnomAD constraint

pLI —, LoF o/e 0.72

Max pathogenic AF

—

Genomic locus

chr3:154,121,003-154,257,827

External References & Databases

Ensembl (ENSG00000114790)

Transcript & Mutation Effects

hg38 • Region Span ~136.8 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ARHGEF26 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 138

Marfanoid habitus and intellectual disabilityTotal: 1

Muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B14Total: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_015595.4. 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			3 clinvar			3
missense			137 clinvar	4 clinvar		141
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)		1 clinvar	5 clinvar			6
Total	0	1	145	4	0	150

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 39 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_015595.4	RefSeq	NP_056410.3	14	MANE Select
ENST00000465093.6	Ensembl	ENSP00000423418.1	14	MANE Select
NM_001251962.2	RefSeq	NP_001238891.1	14	Standard
NM_001251963.2	RefSeq	NP_001238892.1	13	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Bacterial invasion of epithelial cells - Homo sapiens (human)
MECP2 and Associated Rett Syndrome
Signaling by GPCR
Signal Transduction
Rho GTPase cycle

Biological Process

endothelial cell morphogenesis
G protein-coupled receptor signaling pathway
regulation of Rho protein signal transduction
positive regulation of apoptotic process
regulation of small GTPase mediated signal transduction

Molecular Function

guanyl-nucleotide exchange factor activity
Rho guanyl-nucleotide exchange factor activity

Cellular Component

ruffle
cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000356448
Coding exons: 14
Length: 136825
Individuals with no LoFs: 124562
Homozygous LoFs: 0
Heterozygous LoFs: 85
Defined: 124647
p: 0.000341

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-1.02	519	458	1.13	0.0000224	5617
Missense (PolyPhen)		110	114.56	0.96019		1452
Synonymous	-2.80	234	186	1.26	0.00000935	1701
Loss of Function	1.60	27	37.6	0.718	0.00000203	467

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00080	0.00077	rare
Latino/Admixed American	0.00041	0.00041	rare
Ashkenazi Jewish	0.00021	0.00020	rare
East Asian	0.00046	0.00045	rare
Finnish	0.00014	0.00014	rare
European (Non-Finnish)	0.00031	0.00029	rare
South Asian	0.00037	0.00036	rare
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Activates RhoG GTPase by promoting the exchange of GDP by GTP. Required for the formation of membrane ruffles during macropinocytosis. Required for the formation of cup-like structures during trans-endothelial migration of leukocytes. In case of Salmonella enterica infection, activated by SopB, which induces cytoskeleton rearrangements and promotes bacterial entry. {ECO:0000269|PubMed:15133129, ECO:0000269|PubMed:17074883, ECO:0000269|PubMed:17875742}.;

Intolerance Scores

RVIS EVS: 0.58
RVIS percentile EVS: 82.31

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): H
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