ARHGAP32

protein-coding

Rho GTPase activating protein 32, the group of Rho GTPase activating proteins

Gene summary

RICS is a neuron-associated GTPase-activating protein that may regulate dendritic spine morphology and strength by modulating Rho GTPase (see RHOA; MIM 165390) activity (Okabe et al., 2003 [PubMed 12531901]).[supplied by OMIM, Mar 2008]

MANE transcript

NM_001378024.1

Inheritance

—

ClinVar variants

P:2U:266B:53

Top phenotype

ARHGAP32-related disorder

gnomAD constraint

pLI —, LoF o/e 0.16

Max pathogenic AF

—

Genomic locus

chr11:128,965,060-129,279,324

External References & Databases

Ensembl (ENSG00000134909)

Transcript & Mutation Effects

hg38 • Region Span ~314.3 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 ARHGAP32 variants in ClinVar

6 Conditions Cataloged

not specifiedTotal: 263

ARHGAP32-related disorderTotal: 35

not providedTotal: 34

Neurodevelopmental disorderTotal: 1

Global developmental delayTotal: 1

EpendymomaTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001378024.1. 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				27 clinvar	6 clinvar	33
missense	1 clinvar		260 clinvar	15 clinvar	5 clinvar	281
nonsense		1 clinvar	3 clinvar			4
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	1	1	266	42	11	321

Highest pathogenic variant AF is 6.848358e-7

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 24 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001378024.1	RefSeq	NP_001364953.1	23	MANE Select
ENST00000682385.1	Ensembl	ENSP00000507720.1	23	MANE Select
NM_001142685.2	RefSeq	NP_001136157.1	22	Standard
NM_001378025.1	RefSeq	NP_001364954.1	21	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
EGFR1
Neurotrophic factor-mediated Trk receptor signaling

Biological Process

small GTPase mediated signal transduction
positive regulation of GTPase activity
regulation of small GTPase mediated signal transduction

Molecular Function

GTPase activator activity
protein binding
phosphatidylinositol binding

Cellular Component

Golgi membrane
fibrillar center
nucleoplasm
endoplasmic reticulum membrane
Golgi apparatus

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000310343
Coding exons: 22
Length: 314265
Individuals with no LoFs: 125712
Homozygous LoFs: 0
Heterozygous LoFs: 36
Defined: 125748
p: 0.000143

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.81	976	1.15e+3	0.850	0.0000640	13629
Missense (PolyPhen)		316	439.87	0.7184		5035
Synonymous	0.369	427	437	0.978	0.0000251	4185
Loss of Function	7.02	13	81.3	0.160	0.00000447	1019

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.00023	0.00023	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00033	0.00033	rare
Finnish	0.000092	0.000092	rare
European (Non-Finnish)	0.00012	0.00011	rare
South Asian	0.00017	0.00016	rare
Other	0.00017	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: GTPase-activating protein (GAP) promoting GTP hydrolysis on RHOA, CDC42 and RAC1 small GTPases. May be involved in the differentiation of neuronal cells during the formation of neurite extensions. Involved in NMDA receptor activity-dependent actin reorganization in dendritic spines. May mediate cross-talks between Ras- and Rho-regulated signaling pathways in cell growth regulation. Isoform 2 has higher GAP activity (By similarity). {ECO:0000250, ECO:0000269|PubMed:12446789, ECO:0000269|PubMed:12454018, ECO:0000269|PubMed:12531901, ECO:0000269|PubMed:12788081, ECO:0000269|PubMed:12819203, ECO:0000269|PubMed:12857875, ECO:0000269|PubMed:17663722}.;

Intolerance Scores

LoFtool: 0.375
RVIS EVS: -2.15
RVIS percentile EVS: 1.45

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.539

Gene Damage Prediction

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