ARHGAP9
protein-codingRho GTPase activating protein 9, the group of Pleckstrin homology domain containing|Rho GTPase activating proteins
Gene summary
This gene encodes a member of the Rho-GAP family of GTPase activating proteins. The protein has substantial GAP activity towards several Rho-family GTPases in vitro, converting them to an inactive GDP-bound state. It is implicated in regulating adhesion of hematopoietic cells to the extracellular matrix. Multiple transcript variants encoding different isoforms have been found for this gene. [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 ~16.6 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 ARHGAP9 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_032496.4. 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 | 3 | 1 | 1 | 5 | ||
| missense | 71 | 3 | 74 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 4 | 4 | ||||
| Total | 0 | 0 | 78 | 4 | 1 | 83 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_115885.2 | 17 | MANE Select | |
| Ensembl | ENSP00000377380.3 | 17 | MANE Select | |
| RefSeq | NP_001073625.1 | 15 | Standard | |
| RefSeq | NP_001073626.1 | 16 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Neutrophil degranulation
- Signal Transduction
- Innate Immune System
- Immune System
- Rho GTPase cycle
Biological Process
- signal transduction
- regulation of GTPase activity
- neutrophil degranulation
- positive regulation of GTPase activity
- regulation of small GTPase mediated signal transduction
Molecular Function
- GTPase activator activity
- protein binding
- phosphatidylinositol-3,4,5-trisphosphate binding
Cellular Component
- extracellular region
- cytoplasm
- cytosol
- secretory granule lumen
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000393791
- Coding exons
- 17
- Length
- 16560
- Individuals with no LoFs
- 125629
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 119
- Defined
- 125748
- p
- 0.000473
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.414 | 414 | 438 | 0.944 | 0.0000257 | 4633 |
| Missense (PolyPhen) | 141 | 184.03 | 0.76617 | 1944 | ||
| Synonymous | 1.05 | 162 | 180 | 0.900 | 0.00000982 | 1577 |
| Loss of Function | 2.37 | 23 | 39.0 | 0.590 | 0.00000199 | 411 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00071 | 0.00068 | rare |
| Latino/Admixed American | 0.00076 | 0.00075 | rare |
| Ashkenazi Jewish | 0.00020 | 0.00020 | rare |
| East Asian | 0.00076 | 0.00076 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00053 | 0.00052 | rare |
| South Asian | 0.00023 | 0.00023 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: GTPase activator for the Rho-type GTPases by converting them to an inactive GDP-bound state. Has a substantial GAP activity toward CDC42 and RAC1 and less toward RHOA. Has a role in regulating adhesion of hematopoietic cells to the extracellular matrix. Binds phosphoinositides, and has the highest affinity for phosphatidylinositol 3,4,5-trisphosphate, followed by phosphatidylinositol 3,4-bisphosphate and phosphatidylinositol 4,5-bisphosphate. {ECO:0000269|PubMed:11396949}.;
Recessive Scores
- pRec
- 0.213
Intolerance Scores
- LoFtool
- 0.930
- RVIS EVS
- -0.33
- RVIS percentile EVS
- 30.9
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.356
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |