ARHGEF12

protein-coding

Rho guanine nucleotide exchange factor 12, the group of Dbl family Rho GEFs|PDZ domain containing

Gene summary

Rho GTPases play a fundamental role in numerous cellular processes that are initiated by extracellular stimuli working through G protein-coupled receptors. The encoded protein may form a complex with G proteins and stimulate Rho-dependent signals. This protein has been observed to form a myeloid/lymphoid fusion partner in acute myeloid leukemia. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2014]

MANE transcript

NM_015313.3

Inheritance

—

ClinVar variants

U:168B:12

Top phenotype

Glaucoma

gnomAD constraint

pLI —, LoF o/e 0.11

Max pathogenic AF

—

Genomic locus

chr11:120,336,413-120,489,937

External References & Databases

Ensembl (ENSG00000196914)

Transcript & Mutation Effects

hg38 • Region Span ~153.5 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 ARHGEF12 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 147

not providedTotal: 11

GlaucomaTotal: 1

Syndromic microphthalmiaTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_015313.3. 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			2 clinvar	3 clinvar	2 clinvar	7
missense			151 clinvar	6 clinvar	1 clinvar	158
nonsense			2 clinvar			2
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			12 clinvar			12
Total	0	0	168	9	3	180

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 47 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_015313.3	RefSeq	NP_056128.1	41	MANE Select
ENST00000397843.7	Ensembl	ENSP00000380942.2	41	MANE Select
NM_001198665.2	RefSeq	NP_001185594.1	40	Standard
NM_001301084.2	RefSeq	NP_001288013.1	36	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Platelet activation - Homo sapiens (human)
Regulation of actin cytoskeleton - Homo sapiens (human)
Axon guidance - Homo sapiens (human)
Vascular smooth muscle contraction - Homo sapiens (human)
C-type lectin receptor signaling pathway - Homo sapiens (human)

Biological Process

G protein-coupled receptor signaling pathway
Rho protein signal transduction
regulation of Rho protein signal transduction
positive regulation of apoptotic process
positive regulation of GTPase activity

Molecular Function

G protein-coupled receptor binding
guanyl-nucleotide exchange factor activity
Rho guanyl-nucleotide exchange factor activity
GTPase activator activity
protein binding

Cellular Component

cytoplasm
cytosol
membrane
extracellular exosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000397843
Coding exons: 41
Length: 152859
Individuals with no LoFs: 124776
Homozygous LoFs: 0
Heterozygous LoFs: 20
Defined: 124796
p: 0.0000801

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	3.25	572	836	0.684	0.0000456	10095
Missense (PolyPhen)		94	221.36	0.42464		2610
Synonymous	1.50	258	291	0.888	0.0000149	2916
Loss of Function	8.08	10	94.9	0.105	0.00000517	1131

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00013	0.00013	rare
Latino/Admixed American	0.00012	0.00012	rare
Ashkenazi Jewish	0.00010	0.000099	rare
East Asian	0.00022	0.00022	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000062	0.000062	rare
South Asian	0.000065	0.000065	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May play a role in the regulation of RhoA GTPase by guanine nucleotide-binding alpha-12 (GNA12) and alpha-13 (GNA13). Acts as guanine nucleotide exchange factor (GEF) for RhoA GTPase and may act as GTPase-activating protein (GAP) for GNA12 and GNA13. {ECO:0000269|PubMed:11094164}.;

Intolerance Scores

LoFtool: 0.241
RVIS EVS: -0.32
RVIS percentile EVS: 30.94

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): H
Indispensability pred.: E
Indispensability score: 1.00

Gene Damage Prediction

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