ARHGEF11
protein-codingRho guanine nucleotide exchange factor 11, the group of MicroRNA protein coding host genes|PDZ domain containing|Dbl family Rho GEFs
Gene summary
Rho GTPases play a fundamental role in numerous cellular processes that are initiated by extracellular stimuli that work through G protein coupled receptors. The encoded protein may form a complex with G proteins and stimulate Rho-dependent signals. A similar protein in rat interacts with glutamate transporter EAAT4 and modulates its glutamate transport activity. Expression of the rat protein induces the reorganization of the actin cytoskeleton and its overexpression induces the formation of membrane ruffling and filopodia. Two alternative transcripts encoding different isoforms have been described. [provided by RefSeq, Jul 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~112.1 kbGenCC 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 ARHGEF11 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_198236.3. 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 | 5 | 3 | 1 | 9 | ||
| missense | 169 | 7 | 176 | |||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 13 | 13 | ||||
| Total | 0 | 0 | 189 | 10 | 1 | 200 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_937879.1 | 41 | MANE Select | |
| Ensembl | ENSP00000357177.3 | 41 | MANE Select | |
| RefSeq | NP_001364347.1 | 41 | Standard | |
| RefSeq | NP_001364348.1 | 40 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| arhgef11 | Danio rerio | Structure: ventricular system Quality: increased size abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Vascular smooth muscle contraction - Homo sapiens (human)
- Pathways in cancer - Homo sapiens (human)
- Developmental Biology
- Signaling by GPCR
- Signal Transduction
Biological Process
- regulation of cell growth
- striated muscle contraction
- G protein-coupled receptor signaling pathway
- Rho protein signal transduction
- establishment of cell polarity
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
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000368194
- Coding exons
- 41
- Length
- 110531
- Individuals with no LoFs
- 125725
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 23
- Defined
- 125748
- p
- 0.0000915
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.63 | 781 | 920 | 0.849 | 0.0000548 | 10092 |
| Missense (PolyPhen) | 206 | 288.83 | 0.71321 | 3129 | ||
| Synonymous | 2.19 | 302 | 354 | 0.852 | 0.0000200 | 3196 |
| Loss of Function | 7.65 | 12 | 90.5 | 0.133 | 0.00000514 | 971 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00012 | 0.00012 | rare |
| Latino/Admixed American | 0.00018 | 0.00014 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000054 | 0.000054 | rare |
| Finnish | 0.000095 | 0.000092 | rare |
| European (Non-Finnish) | 0.000079 | 0.000079 | rare |
| South Asian | 0.00013 | 0.00013 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- 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. Involved in neurotrophin-induced neurite outgrowth. {ECO:0000269|PubMed:21670212}.;
Recessive Scores
- pRec
- 0.151
Intolerance Scores
- LoFtool
- 0.371
- RVIS EVS
- -1.71
- RVIS percentile EVS
- 2.5
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.592
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |