ARHGEF19

protein-coding

Rho guanine nucleotide exchange factor 19, the group of Dbl family Rho GEFs

Gene summary

Guanine nucleotide exchange factors (GEFs) such as ARHGEF19 accelerate the GTPase activity of Rho GTPases (see RHOA, MIM 165390).[supplied by OMIM, Dec 2008]

MANE transcript

NM_153213.5

Inheritance

—

ClinVar variants

U:127B:7

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.86

Max pathogenic AF

—

Genomic locus

chr1:16,197,854-16,212,652

External References & Databases

Ensembl (ENSG00000142632)

Transcript & Mutation Effects

hg38 • Region Span ~14.8 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 ARHGEF19 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 122

not providedTotal: 5

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_153213.5. 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			2 clinvar	1 clinvar		3
missense			123 clinvar	6 clinvar		129
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	127	7	0	134

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 22 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_153213.5	RefSeq	NP_694945.2	15	MANE Select
ENST00000270747.8	Ensembl	ENSP00000270747.3	15	MANE Select
ENST00000441785.1	Ensembl	ENSP00000414370.1	2	Standard
ENST00000449495.1	Ensembl	ENSP00000391145.1	6	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
arhgef19	Danio rerio	Structure: periderm Quality: increased size abnormal

Gene / Model

Organism

Observed Phenotype

arhgef19

Danio rerio

Structure: periderm

Quality: increased size

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Signaling by GPCR
Signal Transduction
Rho GTPase cycle
Signaling by Rho GTPases
NRAGE signals death through JNK

Biological Process

G protein-coupled receptor signaling pathway
regulation of actin cytoskeleton organization
regulation of Rho protein signal transduction
wound healing
positive regulation of apoptotic process

Molecular Function

guanyl-nucleotide exchange factor activity
Rho guanyl-nucleotide exchange factor activity
GTPase activator activity
protein binding

Cellular Component

cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000270747
Coding exons: 15
Length: 14756
Individuals with no LoFs: 125666
Homozygous LoFs: 0
Heterozygous LoFs: 81
Defined: 125747
p: 0.000322

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.965	401	459	0.873	0.0000284	5052
Missense (PolyPhen)		125	170.22	0.73435		1802
Synonymous	1.51	162	188	0.860	0.0000105	1694
Loss of Function	0.799	33	38.3	0.861	0.00000200	415

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00054	0.00049	rare
Latino/Admixed American	0.00027	0.00026	rare
Ashkenazi Jewish	0.00030	0.00030	rare
East Asian	0.00016	0.00016	rare
Finnish	0.000098	0.000092	rare
European (Non-Finnish)	0.00041	0.00040	rare
South Asian	0.00030	0.00029	rare
Other	0.00035	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Acts as guanine nucleotide exchange factor (GEF) for RhoA GTPase. {ECO:0000250}.;

Intolerance Scores

LoFtool: 0.846
RVIS EVS: 1
RVIS percentile EVS: 90.72

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.340

Gene Damage Prediction

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