ARHGAP21
protein-codingRho GTPase activating protein 21, the group of Rho GTPase activating proteins|Pleckstrin homology domain containing|PDZ domain containing
Gene summary
ARHGAP21 functions preferentially as a GTPase-activating protein (GAP) for CDC42 (MIM 116952) and regulates the ARP2/3 complex (MIM 604221) and F-actin dynamics at the Golgi through control of CDC42 activity (Dubois et al., 2005 [PubMed 15793564]).[supplied by OMIM, Mar 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~140.3 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 ARHGAP21 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_020824.4. 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 | 4 | 13 | 5 | 22 | ||
| missense | 1 | 277 | 13 | 2 | 293 | |
| nonsense | 5 | 5 | ||||
| start loss | 0 | |||||
| frameshift | 4 | 1 | 5 | |||
| splice donor/acceptor (+/-2bp) | 4 | 4 | ||||
| Total | 0 | 1 | 294 | 27 | 7 | 329 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_065875.3 | 25 | MANE Select | |
| Ensembl | ENSP00000379709.2 | 25 | MANE Select | |
| RefSeq | NP_001354376.1 | 24 | Standard | |
| RefSeq | NP_001354377.1 | 25 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Signal Transduction
- Rho GTPase cycle
- Signaling by Rho GTPases
Biological Process
- Golgi organization
- signal transduction
- positive regulation of GTPase activity
- regulation of small GTPase mediated signal transduction
- establishment of Golgi localization
Molecular Function
- GTPase activator activity
- protein binding
Cellular Component
- Golgi membrane
- Golgi apparatus
- cytosol
- plasma membrane
- actin cytoskeleton
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000396432
- Coding exons
- 25
- Length
- 140060
- Individuals with no LoFs
- 125726
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 22
- Defined
- 125748
- p
- 0.0000875
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.955 | 969 | 1.06e+3 | 0.917 | 0.0000576 | 12776 |
| Missense (PolyPhen) | 291 | 422.96 | 0.68801 | 5110 | ||
| Synonymous | -2.03 | 447 | 396 | 1.13 | 0.0000227 | 3865 |
| Loss of Function | 7.45 | 10 | 83.5 | 0.120 | 0.00000495 | 983 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000064 | 0.000062 | rare |
| Latino/Admixed American | 0.000029 | 0.000029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0.00014 | 0.00014 | rare |
| European (Non-Finnish) | 0.00012 | 0.00011 | rare |
| South Asian | 0.00011 | 0.000098 | rare |
| Other | 0.00016 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Functions as a GTPase-activating protein (GAP) for RHOA and CDC42. Downstream partner of ARF1 which may control Golgi apparatus structure and function. Also required for CTNNA1 recruitment to adherens junctions. {ECO:0000269|PubMed:15793564, ECO:0000269|PubMed:16184169}.;
Recessive Scores
- pRec
- 0.155
Intolerance Scores
- LoFtool
- 0.464
- RVIS EVS
- -0.78
- RVIS percentile EVS
- 12.78
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.748
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |