ARHGEF16

protein-coding

Rho guanine nucleotide exchange factor 16, the group of Dbl family Rho GEFs|Pleckstrin homology domain containing

Gene summary

Although the specific function of this protein is not known yet, it is thought to be involved in protein-protein and protein-lipid interactions. [provided by RefSeq, Jul 2008]

MANE transcript

NM_014448.4

Inheritance

—

ClinVar variants

U:125B:11

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.72

Max pathogenic AF

—

Genomic locus

chr1:3,454,665-3,481,113

External References & Databases

Ensembl (ENSG00000130762)

Transcript & Mutation Effects

hg38 • Region Span ~26.4 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 ARHGEF16 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 119

not providedTotal: 6

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_014448.4. 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	1 clinvar	6
missense			114 clinvar	6 clinvar	1 clinvar	121
nonsense						0
start loss						0
frameshift			3 clinvar			3
splice donor/acceptor (+/-2bp)			6 clinvar			6
Total	0	0	125	9	2	136

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 37 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_014448.4	RefSeq	NP_055263.2	14	MANE Select
ENST00000378378.9	Ensembl	ENSP00000367629.4	14	MANE Select
ENST00000378371.6	Ensembl	ENSP00000367622.2	10	Standard
ENST00000378371.7	Ensembl	ENSP00000367622.2	10	Standard

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 Rho protein signal transduction
positive regulation of apoptotic process
regulation of small GTPase mediated signal transduction
cell chemotaxis

Molecular Function

guanyl-nucleotide exchange factor activity
Rho guanyl-nucleotide exchange factor activity
protein binding
Rho GTPase binding
PDZ domain binding

Cellular Component

cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000378378
Coding exons: 14
Length: 26688
Individuals with no LoFs: 125393
Homozygous LoFs: 0
Heterozygous LoFs: 113
Defined: 125506
p: 0.000450

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.456	411	438	0.939	0.0000302	4618
Missense (PolyPhen)		159	176.61	0.90028		1665
Synonymous	-0.337	195	189	1.03	0.0000136	1432
Loss of Function	1.47	24	33.1	0.724	0.00000166	364

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00013	0.00012	rare
Latino/Admixed American	0.00073	0.00072	rare
Ashkenazi Jewish	0.0024	0.0024	notable
East Asian	0.00038	0.00038	rare
Finnish	0.000047	0.000046	rare
European (Non-Finnish)	0.00037	0.00036	rare
South Asian	0.00033	0.00033	rare
Other	0.00049	0.00049	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Guanyl-nucleotide exchange factor of the RHOG GTPase stimulating the exchange of RHOG-associated GDP for GTP. May play a role in chemotactic cell migration by mediating the activation of RAC1 by EPHA2. May also activate CDC42 and mediate activation of CDC42 by the viral protein HPV16 E6. {ECO:0000269|PubMed:20679435}.;

Recessive Scores

pRec: 0.141

Intolerance Scores

LoFtool: 0.808
RVIS EVS: 0.25
RVIS percentile EVS: 69.57

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.755

Gene Damage Prediction

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