ARHGEF7
protein-codingRho guanine nucleotide exchange factor 7, the group of Pleckstrin homology domain containing|Dbl family Rho GEFs
Gene summary
This gene encodes a protein that belongs to a family of cytoplasmic proteins that activate the Ras-like family of Rho proteins by exchanging bound GDP for GTP. It forms a complex with the small GTP binding protein Rac1 and recruits Rac1 to membrane ruffles and to focal adhesions. Multiple alternatively spliced transcript variants encoding different isoforms have been observed for this gene. [provided by RefSeq, Mar 2016]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~191.2 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 ARHGEF7 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001354046.2. 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 | 3 | 11 | 16 | ||
| missense | 81 | 4 | 85 | |||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 5 | 5 | ||||
| Total | 0 | 0 | 88 | 8 | 11 | 107 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001340975.1 | 22 | MANE Select | |
| Ensembl | ENSP00000495631.1 | 22 | MANE Select | |
| RefSeq | NP_001106983.1 | 20 | Standard | |
| RefSeq | NP_001106984.1 | 18 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| arhgef7b | Danio rerio | Structure: leukocyte Quality: accumulation abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Regulation of actin cytoskeleton - Homo sapiens (human)
- Intracellular Signalling Through Adenosine Receptor A2b and Adenosine
- Intracellular Signalling Through Adenosine Receptor A2a and Adenosine
- Integrin-mediated Cell Adhesion
- Regulation of Actin Cytoskeleton
Biological Process
- hematopoietic progenitor cell differentiation
- Golgi organization
- signal transduction
- G protein-coupled receptor signaling pathway
- nervous system development
Molecular Function
- guanyl-nucleotide exchange factor activity
- Rho guanyl-nucleotide exchange factor activity
- protein binding
- protein kinase binding
Cellular Component
- storage vacuole
- ruffle
- cytosol
- plasma membrane
- focal adhesion
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000375741
- Coding exons
- 20
- Length
- 191179
- Individuals with no LoFs
- 125742
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 6
- Defined
- 125748
- p
- 0.0000239
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.57 | 313 | 470 | 0.666 | 0.0000278 | 5214 |
| Missense (PolyPhen) | 90 | 174.92 | 0.51452 | 1863 | ||
| Synonymous | 0.197 | 186 | 189 | 0.982 | 0.0000120 | 1550 |
| Loss of Function | 5.54 | 3 | 41.5 | 0.0723 | 0.00000184 | 527 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000029 | 0.000029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000055 | 0.000054 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000036 | 0.000035 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Acts as a RAC1 guanine nucleotide exchange factor (GEF) and can induce membrane ruffling. Functions in cell migration, attachment and cell spreading. Promotes targeting of RAC1 to focal adhesions (By similarity). May function as a positive regulator of apoptosis. Downstream of NMDA receptors and CaMKK-CaMK1 signaling cascade, promotes the formation of spines and synapses in hippocampal neurons. {ECO:0000250, ECO:0000269|PubMed:18184567, ECO:0000269|PubMed:18716323, ECO:0000269|PubMed:19041750}.;
Recessive Scores
- pRec
- 0.624
Intolerance Scores
- LoFtool
- 0.444
- RVIS EVS
- -1.04
- RVIS percentile EVS
- 7.8
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.894
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |