ARHGAP6

protein-coding

Rho GTPase activating protein 6, the group of Rho GTPase activating proteins|MicroRNA protein coding host genes

Gene summary

This gene encodes a member of the rhoGAP family of proteins which play a role in the regulation of actin polymerization at the plasma membrane during several cellular processes. This protein is thought to have two independent functions, one as a GTPase-activating protein with specificity for RhoA, and another as a cytoskeletal protein that promotes actin remodeling. Multiple alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

MANE transcript

NM_013427.3

Inheritance

—

ClinVar variants

U:208B:24

Top phenotype

Amelogenesis imperfecta type 1E

gnomAD constraint

pLI —, LoF o/e 0.07

Max pathogenic AF

—

Genomic locus

chrX:11,117,651-11,665,920

External References & Databases

Ensembl (ENSG00000047648)

Transcript & Mutation Effects

hg38 • Region Span ~548.3 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 ARHGAP6 variants in ClinVar

9 Conditions Cataloged

not specifiedTotal: 113

not providedTotal: 38

Amelogenesis imperfecta type 1ETotal: 18

AMELX-related disorderTotal: 16

Inborn genetic diseasesTotal: 15

ARHGAP6-related disorderTotal: 5

Amelogenesis imperfectaTotal: 3

X-linked amelogenesis imperfecta hypoplastic/hypomaturation 2Total: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_013427.3. 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			16 clinvar	7 clinvar	7 clinvar	30
missense			157 clinvar	8 clinvar	2 clinvar	167
nonsense			12 clinvar			12
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			23 clinvar			23
Total	0	0	208	15	9	232

Highest pathogenic variant AF is 0.0000127526155

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 13 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_013427.3	RefSeq	NP_038286.2	13	MANE Select
ENST00000337414.9	Ensembl	ENSP00000338967.4	13	MANE Select
NM_001287242.2	RefSeq	NP_001274171.1	13	Standard
NM_006125.3	RefSeq	NP_006116.2	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

Rho protein signal transduction
positive regulation of signal transduction
actin filament polymerization
positive regulation of GTPase activity
focal adhesion assembly

Molecular Function

SH3/SH2 adaptor activity
GTPase activator activity
SH3 domain binding

Cellular Component

cytoplasm
cytosol
actin filament
actin cytoskeleton

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000337414
Coding exons: 13
Length: 547583
Individuals with no LoFs: 125742
Homozygous LoFs: 1
Heterozygous LoFs: 5
Defined: 125748
p: 0.0000239

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.82	282	382	0.738	0.0000308	6233
Missense (PolyPhen)		43	98.18	0.43797		1723
Synonymous	0.636	167	178	0.939	0.0000158	2008
Loss of Function	4.52	2	27.7	0.0723	0.00000193	489

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0.00013	0.000099	rare
East Asian	0	0.0	absent
Finnish	0.000062	0.000046	rare
European (Non-Finnish)	0.000051	0.000035	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: GTPase activator for the Rho-type GTPases by converting them to an inactive GDP-bound state. Could regulate the interactions of signaling molecules with the actin cytoskeleton. Promotes continuous elongation of cytoplasmic processes during cell motility and simultaneous retraction of the cell body changing the cell morphology. {ECO:0000269|PubMed:10699171}.;

Recessive Scores

pRec: 0.140

Intolerance Scores

LoFtool: 0.326
RVIS EVS: -0.56
RVIS percentile EVS: 19.73

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.123

Gene Damage Prediction

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