ARHGEF25

protein-coding

Rho guanine nucleotide exchange factor 25, the group of Dbl family Rho GEFs

Gene summary

Rho GTPases alternate between an inactive GDP-bound state and an active GTP-bound state, and GEFs facilitate GDP/GTP exchange. This gene encodes a guanine nucleotide exchange factor (GEF) which interacts with Rho GTPases involved in contraction of vascular smooth muscles, regulation of responses to angiotensin II and lens cell differentiation. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2012]

MANE transcript

NM_182947.4

Inheritance

—

ClinVar variants

P:1U:69B:1

Top phenotype

Prostate cancer

gnomAD constraint

pLI —, LoF o/e 0.59

Max pathogenic AF

—

Genomic locus

chr12:57,610,180-57,617,245

External References & Databases

Ensembl (ENSG00000240771)

Transcript & Mutation Effects

hg38 • Region Span ~7.1 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 ARHGEF25 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 64

not providedTotal: 1

Prostate cancerTotal: 1

Moyamoya angiopathyTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_182947.4. 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			4 clinvar	1 clinvar		5
missense		1 clinvar	64 clinvar			65
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	1	69	1	0	71

Highest pathogenic variant AF is 0.000009576958

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 15 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_182947.4	RefSeq	NP_891992.3	15	MANE Select
ENST00000286494.9	Ensembl	ENSP00000286494.4	15	MANE Select
NM_001111270.3	RefSeq	NP_001104740.2	16	Standard
NM_001347933.2	RefSeq	NP_001334862.2	14	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Signaling by GPCR
Signal Transduction
Regulation of RAC1 activity
G alpha (q) signalling events
GPCR downstream signalling

Biological Process

G protein-coupled receptor signaling pathway
regulation of Rho protein signal transduction

Molecular Function

Rho guanyl-nucleotide exchange factor activity

Cellular Component

cytosol
plasma membrane
myofibril
sarcomere

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000333972
Coding exons: 16
Length: 9200
Individuals with no LoFs: 125678
Homozygous LoFs: 0
Heterozygous LoFs: 70
Defined: 125748
p: 0.000278

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.933	302	351	0.860	0.0000189	3957
Missense (PolyPhen)		117	151.33	0.77314		1699
Synonymous	0.370	132	138	0.960	0.00000727	1261
Loss of Function	2.26	21	35.5	0.591	0.00000182	396

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00074	0.00062	rare
Latino/Admixed American	0.00017	0.00017	rare
Ashkenazi Jewish	0.00010	0.000099	rare
East Asian	0.00060	0.00049	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00026	0.00025	rare
South Asian	0.00042	0.00042	rare
Other	0.00035	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May play a role in actin cytoskeleton reorganization in different tissues since its activation induces formation of actin stress fibers. It works as a guanine nucleotide exchange factor for Rho family of small GTPases. Links specifically G alpha q/11- coupled receptors to RHOA activation. May be an important regulator of processes involved in axon and dendrite formation. In neurons seems to be an exchange factor primarily for RAC1. Involved in skeletal myogenesis (By similarity). {ECO:0000250, ECO:0000269|PubMed:11861769, ECO:0000269|PubMed:12547822, ECO:0000269|PubMed:15069594, ECO:0000269|PubMed:15632174, ECO:0000269|PubMed:16314529, ECO:0000269|PubMed:17606614}.;

Intolerance Scores

RVIS EVS: -0.02
RVIS percentile EVS: 52.15

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