ARHGAP24

protein-coding

Rho GTPase activating protein 24, the group of Pleckstrin homology domain containing|MicroRNA protein coding host genes|Rho GTPase activating proteins

Gene summary

This gene encodes a Rho-GTPase activating protein, which is specific for the small GTPase family member Rac. Binding of the encoded protein by filamin A targets it to sites of membrane protrusion, where it antognizes Rac. This results in suppression of lamellae formation and promotion of retraction to regulate cell polarity. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2016]

MANE transcript

NM_001025616.3

Inheritance

ClinVar variants

U:160B:94

Top phenotype

familial idiopathic steroid-resistant nephrotic syndrome

gnomAD constraint

pLI —, LoF o/e 0.58

Max pathogenic AF

—

Genomic locus

chr4:85,475,150-86,002,668

External References & Databases

Ensembl (ENSG00000138639)

Transcript & Mutation Effects

hg38 • Region Span ~527.5 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

inherited focal segmental glomerulosclerosisLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0005363

Submitter: PanelApp Australia

familial idiopathic steroid-resistant nephrotic syndromeSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0019006

Submitter: Orphanet

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ARHGAP24 variants in ClinVar

6 Conditions Cataloged

not providedTotal: 209

not specifiedTotal: 125

ARHGAP24-related disorderTotal: 36

Nephrotic syndromeTotal: 1

Focal segmental glomerulosclerosis 1Total: 1

Focal segmental glomerulosclerosisTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001025616.3. 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				52 clinvar	6 clinvar	58
missense			155 clinvar	33 clinvar	3 clinvar	191
nonsense			3 clinvar			3
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	160	85	9	254

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 21 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001025616.3	RefSeq	NP_001020787.2	9	MANE Select
ENST00000395184.6	Ensembl	ENSP00000378611.1	9	MANE Select
NM_001042669.2	RefSeq	NP_001036134.1	7	Standard
NM_001287805.2	RefSeq	NP_001274734.1	8	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

cytosol
cytoskeleton
focal adhesion
cell projection

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000395184
Coding exons: 9
Length: 527557
Individuals with no LoFs: 125679
Homozygous LoFs: 0
Heterozygous LoFs: 69
Defined: 125748
p: 0.000274

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.153	397	406	0.979	0.0000218	5030
Missense (PolyPhen)		93	115.43	0.80571		1400
Synonymous	-0.453	156	149	1.05	0.00000812	1355
Loss of Function	2.35	21	36.3	0.579	0.00000236	375

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00018	0.00018	rare
Latino/Admixed American	0.00014	0.00014	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.00027	0.00027	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.00040	0.00040	rare
South Asian	0.00023	0.00023	rare
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Rho GTPase-activating protein involved in cell polarity, cell morphology and cytoskeletal organization. Acts as a GTPase activator for the Rac-type GTPase by converting it to an inactive GDP-bound state. Controls actin remodeling by inactivating Rac downstream of Rho leading to suppress leading edge protrusion and promotes cell retraction to achieve cellular polarity. Able to suppress RAC1 and CDC42 activity in vitro. Overexpression induces cell rounding with partial or complete disruption of actin stress fibers and formation of membrane ruffles, lamellipodia, and filopodia. Isoform 2 is a vascular cell-specific GAP involved in modulation of angiogenesis. {ECO:0000269|PubMed:15302923, ECO:0000269|PubMed:15611138, ECO:0000269|PubMed:16862148}.;

Recessive Scores

pRec: 0.124

Intolerance Scores

LoFtool: 0.783
RVIS EVS: -0.62
RVIS percentile EVS: 17.45

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.486

Gene Damage Prediction

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