ARHGAP4

protein-coding

Rho GTPase activating protein 4, the group of AH/BAR family Rho GTPase activating proteins|F-BAR domain containing

Gene summary

This gene encodes a member of the rhoGAP family of proteins which play a role in the regulation of small GTP-binding proteins belonging to the RAS superfamily. The protein encoded by the orthologous gene in rat is localized to the Golgi complex and can redistribute to microtubules. The rat protein stimulates the activity of some Rho GTPases in vitro. Genomic deletions of this gene and a neighboring gene have been found in patients with nephrogenic diabetes insipidus. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2009]

MANE transcript

NM_001666.5

Inheritance

ClinVar variants

P:1U:196B:25

Top phenotype

Diabetes insipidus, nephrogenic, X-linked

gnomAD constraint

pLI —, LoF o/e 0.15

Max pathogenic AF

—

Genomic locus

chrX:153,907,367-153,934,999

External References & Databases

Ensembl (ENSG00000089820)

Transcript & Mutation Effects

hg38 • Region Span ~27.6 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

intellectual disabilityLIMITED

Inheritance Pattern: XL

Disease ID:MONDO:0001071

Submitter: Ambry Genetics

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ARHGAP4 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 140

not providedTotal: 25

Diabetes insipidus, nephrogenic, X-linkedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001666.5. 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			9 clinvar	9 clinvar	3 clinvar	21
missense			162 clinvar	13 clinvar		175
nonsense			4 clinvar			4
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)	1 clinvar		21 clinvar			22
Total	1	0	196	22	3	222

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 38 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001666.5	RefSeq	NP_001657.3	22	MANE Select
ENST00000350060.10	Ensembl	ENSP00000203786.8	22	MANE Select
NM_001164741.2	RefSeq	NP_001158213.1	23	Standard
ENST00000370016.5	Ensembl	ENSP00000359033.1	21	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Signal Transduction
rho cell motility signaling pathway
t cell receptor signaling pathway
rac1 cell motility signaling pathway
Rho GTPase cycle

Biological Process

cytoskeleton organization
Rho protein signal transduction
positive regulation of signal transduction
negative regulation of fibroblast migration
negative regulation of cell migration

Molecular Function

SH3/SH2 adaptor activity
GTPase activator activity
protein binding
Rac GTPase binding

Cellular Component

cytoplasm
Golgi apparatus
cytosol
microtubule
growth cone

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000370028
Coding exons: 23
Length: 27632
Individuals with no LoFs: 125605
Homozygous LoFs: 4
Heterozygous LoFs: 4
Defined: 125613
p: 0.0000318

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.687	394	434	0.907	0.0000406	6256
Missense (PolyPhen)		97	147.08	0.65949		2079
Synonymous	-2.33	231	190	1.22	0.0000176	2057
Loss of Function	4.57	5	33.6	0.149	0.00000238	557

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000037	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000076	0.000054	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000062	0.000044	rare
South Asian	0	0.0	absent
Other	0.00022	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Inhibitory effect on stress fiber organization. May down-regulate Rho-like GTPase in hematopoietic cells.;

Recessive Scores

pRec: 0.233

Intolerance Scores

LoFtool: 0.0857
RVIS EVS: 0.16
RVIS percentile EVS: 64.92

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.508

Gene Damage Prediction

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