ARHGAP1

protein-coding

Rho GTPase activating protein 1, the group of Rho GTPase activating proteins|BCH domain containing

Gene summary

This gene encodes a member of a large family of proteins that activate Rho-type guanosine triphosphate (GTP) metabolizing enzymes. The encoded protein contains a SRC homology 3 domain and interacts with Bcl-2-associated protein family members. [provided by RefSeq, Aug 2012]

MANE transcript

NM_004308.5

Inheritance

—

ClinVar variants

U:53B:9

Top phenotype

ARHGAP1-related condition

gnomAD constraint

pLI —, LoF o/e 0.18

Max pathogenic AF

—

Genomic locus

chr11:46,677,080-46,700,619

External References & Databases

Ensembl (ENSG00000175220)

Transcript & Mutation Effects

hg38 • Region Span ~23.5 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 ARHGAP1 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 49

not providedTotal: 8

ARHGAP1-related conditionTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_004308.5. 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			1 clinvar	4 clinvar	2 clinvar	7
missense			49 clinvar	2 clinvar	1 clinvar	52
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			3 clinvar			3
Total	0	0	53	6	3	62

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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_004308.5	RefSeq	NP_004299.1	12	MANE Select
ENST00000311956.9	Ensembl	ENSP00000310491.4	12	MANE Select
ENST00000525488.1	Ensembl	ENSP00000432794.1	6	Standard
ENST00000528837.5	Ensembl	ENSP00000434883.1	11	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

small GTPase mediated signal transduction
Rho protein signal transduction
positive regulation of signal transduction
endosomal transport
transferrin transport

Molecular Function

SH3/SH2 adaptor activity
GTPase activator activity
protein binding
SH3 domain binding
Rab GTPase binding

Cellular Component

cytoplasm
cytosol
endosome membrane
perinuclear region of cytoplasm
extracellular exosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000311956
Coding exons: 12
Length: 23536
Individuals with no LoFs: 125738
Homozygous LoFs: 0
Heterozygous LoFs: 9
Defined: 125747
p: 0.0000358

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.25	207	264	0.783	0.0000157	2896
Missense (PolyPhen)		61	92.884	0.65673		1045
Synonymous	0.817	102	113	0.902	0.00000727	837
Loss of Function	3.60	4	22.4	0.179	9.52e-7	265

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.000062	0.000062	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: GTPase activator for the Rho, Rac and Cdc42 proteins, converting them to the putatively inactive GDP-bound state. Cdc42 seems to be the preferred substrate.;

Recessive Scores

pRec: 0.308

Intolerance Scores

RVIS EVS: -0.14
RVIS percentile EVS: 43.57

Essentials

Essential (CRISPR): E
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.944

Gene Damage Prediction

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