ARHGEF5
protein-codingRho guanine nucleotide exchange factor 5, the group of Dbl family Rho GEFs
Gene summary
Rho GTPases play a fundamental role in numerous cellular processes 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. This protein may be involved in the control of cytoskeletal organization. [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 ~25.3 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 ARHGEF5 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_005435.4. 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 | 8 | 8 | ||||
| missense | 127 | 8 | 135 | |||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 128 | 17 | 0 | 145 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_005426.2 | 14 | MANE Select | |
| Ensembl | ENSP00000056217.5 | 14 | MANE Select | |
| Ensembl | ENSP00000418227.1 | 12 | Standard | |
| Ensembl | ENSP00000418745.1 | 13 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Signaling by GPCR
- Signal Transduction
- pkc-catalyzed phosphorylation of inhibitory phosphoprotein of myosin phosphatase
- rho cell motility signaling pathway
- rac1 cell motility signaling pathway
Biological Process
- myeloid dendritic cell chemotaxis
- G protein-coupled receptor signaling pathway
- actin cytoskeleton organization
- regulation of actin cytoskeleton organization
- regulation of Rho protein signal transduction
Molecular Function
- guanyl-nucleotide exchange factor activity
- Rho guanyl-nucleotide exchange factor activity
- protein binding
- GTP binding
- lipid binding
Cellular Component
- podosome
- nucleus
- nucleoplasm
- cytoplasm
- cytosol
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000056217
- Coding exons
- 14
- Length
- 25345
- Individuals with no LoFs
- 125655
- Homozygous LoFs
- 2
- Heterozygous LoFs
- 91
- Defined
- 125748
- p
- 0.000370
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.47 | 342 | 427 | 0.800 | 0.0000221 | 9943 |
| Missense (PolyPhen) | 66 | 103.18 | 0.63966 | 2333 | ||
| Synonymous | 2.56 | 121 | 162 | 0.745 | 0.00000849 | 3170 |
| Loss of Function | 1.63 | 26 | 36.7 | 0.709 | 0.00000218 | 692 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00013 | 0.00012 | rare |
| Latino/Admixed American | 0.00015 | 0.00014 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00017 | 0.00016 | rare |
| Finnish | 0.000046 | 0.000046 | rare |
| European (Non-Finnish) | 0.00016 | 0.00014 | rare |
| South Asian | 0.0024 | 0.0022 | notable |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Guanine nucleotide exchange factor which activates Rho GTPases (PubMed:15601624). Strongly activates RHOA (PubMed:15601624). Also strongly activates RHOB, weakly activates RHOC and RHOG and shows no effect on RHOD, RHOV, RHOQ or RAC1 (By similarity). Involved in regulation of cell shape and actin cytoskeletal organization (PubMed:15601624). Plays a role in actin organization by generating a loss of actin stress fibers and the formation of membrane ruffles and filopodia (PubMed:14662653). Required for SRC-induced podosome formation (By similarity). Involved in positive regulation of immature dendritic cell migration (By similarity). {ECO:0000250|UniProtKB:E9Q7D5, ECO:0000269|PubMed:14662653, ECO:0000269|PubMed:15601624}.;
Recessive Scores
- pRec
- 0.0934
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.346
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |