ARHGAP22

protein-coding

Rho GTPase activating protein 22, the group of Pleckstrin homology domain containing|Rho GTPase activating proteins

Gene summary

This gene encodes a member of the GTPase activating protein family which activates a GTPase belonging to the RAS superfamily of small GTP-binding proteins. The encoded protein is insulin-responsive, is dependent on the kinase Akt and requires the Akt-dependent 14-3-3 binding protein which binds sequentially to two serine residues. The result of these interactions is regulation of cell motility. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2011]

MANE transcript

NM_021226.4

Inheritance

—

ClinVar variants

U:147B:10

Top phenotype

Long QT syndrome

gnomAD constraint

pLI —, LoF o/e 0.62

Max pathogenic AF

—

Genomic locus

chr10:48,446,036-48,656,265

External References & Databases

Ensembl (ENSG00000128805)

Transcript & Mutation Effects

hg38 • Region Span ~210.2 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 ARHGAP22 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 138

not providedTotal: 9

Long QT syndromeTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_021226.4. 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			5 clinvar	1 clinvar	1 clinvar	7
missense			141 clinvar	7 clinvar	1 clinvar	149
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	147	8	2	157

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 50 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_021226.4	RefSeq	NP_067049.2	10	MANE Select
ENST00000249601.9	Ensembl	ENSP00000249601.4	10	MANE Select
NM_001256024.2	RefSeq	NP_001242953.1	10	Standard
NM_001256025.3	RefSeq	NP_001242954.1	10	Standard

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

angiogenesis
signal transduction
cell differentiation
positive regulation of GTPase activity
regulation of small GTPase mediated signal transduction

Molecular Function

GTPase activator activity
protein binding

Cellular Component

nucleus
cytosol
focal adhesion
glutamatergic synapse

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000417912
Coding exons: 10
Length: 210234
Individuals with no LoFs: 125687
Homozygous LoFs: 0
Heterozygous LoFs: 61
Defined: 125748
p: 0.000243

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.597	413	449	0.921	0.0000309	4541
Missense (PolyPhen)		108	134.82	0.8011		1496
Synonymous	0.474	193	202	0.958	0.0000150	1486
Loss of Function	1.89	18	29.0	0.621	0.00000143	312

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00025	0.00025	rare
Latino/Admixed American	0.00012	0.00012	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00060	0.00060	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.00021	0.00020	rare
South Asian	0.00053	0.00052	rare
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Rho GTPase-activating protein involved in the signal transduction pathway that regulates endothelial cell capillary tube formation during angiogenesis. Acts as a GTPase activator for the RAC1 by converting it to an inactive GDP-bound state. Inhibits RAC1-dependent lamellipodia formation. May also play a role in transcription regulation via its interaction with VEZF1, by regulating activity of the endothelin-1 (EDN1) promoter (By similarity). {ECO:0000250}.;

Recessive Scores

pRec: 0.135

Intolerance Scores

LoFtool: 0.731
RVIS EVS: -0.4
RVIS percentile EVS: 26.98

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.925

Gene Damage Prediction

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