ARHGAP18

protein-coding

Rho GTPase activating protein 18, the group of Rho GTPase activating proteins

Gene summary

Enables GTPase activator activity. Involved in several processes, including regulation of actin filament polymerization; regulation of small GTPase mediated signal transduction; and small GTPase-mediated signal transduction. Located in cytosol. Part of cytoplasmic microtubule and ruffle. Implicated in schizophrenia. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_033515.3

Inheritance

—

ClinVar variants

U:102B:7

Top phenotype

ARHGAP18-related disorder

gnomAD constraint

pLI —, LoF o/e 0.61

Max pathogenic AF

—

Genomic locus

chr6:129,576,132-129,710,177

External References & Databases

Ensembl (ENSG00000146376)

Transcript & Mutation Effects

hg38 • Region Span ~134.0 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 ARHGAP18 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 96

not providedTotal: 3

ARHGAP18-related disorderTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_033515.3. 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			2 clinvar	2 clinvar		4
missense			96 clinvar	4 clinvar	1 clinvar	101
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			3 clinvar			3
Total	0	0	102	6	1	109

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 16 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_033515.3	RefSeq	NP_277050.2	15	MANE Select
ENST00000368149.3	Ensembl	ENSP00000357131.2	15	MANE Select
ENST00000909755.1	Ensembl	ENSP00000579814.1	15	Standard
ENST00000909755.2	Ensembl	ENSP00000579814.1	15	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
arhgap18	Danio rerio	Structure: intersegmental vessel Quality: increased length abnormal

Gene / Model

Organism

Observed Phenotype

arhgap18

Danio rerio

Structure: intersegmental vessel

Quality: increased length

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Signal Transduction
Rho GTPase cycle
Signaling by Rho GTPases

Biological Process

small GTPase mediated signal transduction
regulation of cell shape
regulation of actin filament polymerization
regulation of actin cytoskeleton organization
positive regulation of GTPase activity

Molecular Function

GTPase activator activity
cadherin binding

Cellular Component

cytoplasm
cytosol
plasma membrane
nuclear speck

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000368149
Coding exons: 15
Length: 134094
Individuals with no LoFs: 125693
Homozygous LoFs: 0
Heterozygous LoFs: 55
Defined: 125748
p: 0.000219

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.717	309	347	0.892	0.0000174	4359
Missense (PolyPhen)		55	81.703	0.67317		1008
Synonymous	-0.239	133	130	1.03	0.00000683	1217
Loss of Function	2.26	24	39.3	0.611	0.00000215	449

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.00021	0.00020	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00029	0.00027	rare
Finnish	0.000096	0.000092	rare
European (Non-Finnish)	0.00028	0.00028	rare
South Asian	0.00023	0.00023	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Rho GTPase activating protein that suppresses F-actin polymerization by inhibiting Rho. Rho GTPase activating proteins act by converting Rho-type GTPases to an inactive GDP-bound state (PubMed:21865595). Plays a key role in tissue tension and 3D tissue shape by regulating cortical actomyosin network formation. Acts downstream of YAP1 and inhibits actin polymerization, which in turn reduces nuclear localization of YAP1 (PubMed:25778702). Regulates cell shape, spreading, and migration (PubMed:21865595). {ECO:0000269|PubMed:21865595, ECO:0000269|PubMed:25778702}.;

Recessive Scores

pRec: 0.113

Intolerance Scores

LoFtool: 0.867
RVIS EVS: -0.8
RVIS percentile EVS: 12.49

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.694

Gene Damage Prediction

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