ARHGAP12

protein-coding

Rho GTPase activating protein 12, the group of Pleckstrin homology domain containing|Rho GTPase activating proteins

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 may be involved in suppressing tumor formation by regulating cell invasion and adhesion. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Jul 2012]

MANE transcript

NM_018287.7

Inheritance

—

ClinVar variants

U:111B:5

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.41

Max pathogenic AF

—

Genomic locus

chr10:31,805,398-31,928,876

External References & Databases

Ensembl (ENSG00000165322)

Transcript & Mutation Effects

hg38 • Region Span ~123.5 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 ARHGAP12 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 99

not providedTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_018287.7. 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			4 clinvar	1 clinvar	1 clinvar	6
missense			101 clinvar	3 clinvar		104
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			5 clinvar			5
Total	0	0	111	4	1	116

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 72 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_018287.7	RefSeq	NP_060757.4	18	MANE Select
ENST00000344936.7	Ensembl	ENSP00000345808.2	18	MANE Select
NM_001270695.1	RefSeq	NP_001257624.1	17	Standard
NM_001270696.2	RefSeq	NP_001257625.1	16	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

morphogenesis of an epithelial sheet
phagocytosis, engulfment
actin filament organization
signal transduction
regulation of GTPase activity

Molecular Function

GTPase activator activity

Cellular Component

phagocytic cup
cytoplasm
cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000344936
Coding exons: 18
Length: 123378
Individuals with no LoFs: 125701
Homozygous LoFs: 0
Heterozygous LoFs: 47
Defined: 125748
p: 0.000187

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.04	387	449	0.862	0.0000231	5603
Missense (PolyPhen)		78	131.54	0.59297		1599
Synonymous	0.115	154	156	0.988	0.00000811	1525
Loss of Function	3.77	19	46.8	0.406	0.00000231	577

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00031	0.00031	rare
Latino/Admixed American	0.00014	0.00014	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00011	0.00011	rare
Finnish	0.000094	0.000092	rare
European (Non-Finnish)	0.00012	0.00011	rare
South Asian	0.00078	0.00065	rare
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. {ECO:0000250}.;

Recessive Scores

pRec: 0.135

Intolerance Scores

LoFtool: 0.667
RVIS EVS: -0.82
RVIS percentile EVS: 11.94

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.121

Gene Damage Prediction

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