ARAP2
protein-codingArfGAP with RhoGAP domain, ankyrin repeat and PH domain 2, the group of Ankyrin repeat domain containing|Pleckstrin homology domain containing|Sterile alpha motif domain containing|ArfGAPs
Gene summary
The protein encoded by this gene contains ARF-GAP, RHO-GAP, ankyrin repeat, RAS-associating, and pleckstrin homology domains. The protein is a phosphatidylinositol (3,4,5)-trisphosphate-dependent Arf6 GAP that binds RhoA-GTP, but it lacks the predicted catalytic arginine in the RHO-GAP domain and does not have RHO-GAP activity. The protein associates with focal adhesions and functions downstream of RhoA to regulate focal adhesion dynamics. [provided by RefSeq, Sep 2008]
- CENTD1
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~296.3 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 ARAP2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_015230.4. 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 | 2 | 2 | ||||
| missense | 263 | 11 | 274 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 9 | 9 | ||||
| Total | 0 | 0 | 272 | 13 | 0 | 285 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_056045.2 | 32 | MANE Select | |
| Ensembl | ENSP00000302895.4 | 32 | MANE Select | |
| Ensembl | ENSP00000422731.1 | 1 | Standard | |
| Ensembl | ENSP00000423886.1 | 2 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Endocytosis - Homo sapiens (human)
- Signal Transduction
- rho cell motility signaling pathway
- t cell receptor signaling pathway
- rac1 cell motility signaling pathway
Biological Process
- signal transduction
- positive regulation of GTPase activity
- regulation of small GTPase mediated signal transduction
Molecular Function
- GTPase activator activity
- phosphatidylinositol-3,4,5-trisphosphate binding
- metal ion binding
Cellular Component
- cytosol
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000303965
- Coding exons
- 32
- Length
- 296289
- Individuals with no LoFs
- 125638
- Homozygous LoFs
- 1
- Heterozygous LoFs
- 109
- Defined
- 125748
- p
- 0.000437
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.820 | 923 | 856 | 1.08 | 0.0000430 | 11223 |
| Missense (PolyPhen) | 183 | 204.86 | 0.89328 | 2817 | ||
| Synonymous | -0.477 | 316 | 305 | 1.03 | 0.0000156 | 3112 |
| Loss of Function | 4.99 | 38 | 88.7 | 0.428 | 0.00000475 | 1138 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00025 | 0.00025 | rare |
| Latino/Admixed American | 0.00055 | 0.00052 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00023 | 0.00022 | rare |
| Finnish | 0.00028 | 0.00028 | rare |
| European (Non-Finnish) | 0.00060 | 0.00057 | rare |
| South Asian | 0.00037 | 0.00036 | rare |
| Other | 0.00034 | 0.00033 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Phosphatidylinositol 3,4,5-trisphosphate-dependent GTPase-activating protein that modulates actin cytoskeleton remodeling by regulating ARF and RHO family members. Is activated by phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3) binding. Can be activated by phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4,5)P2) binding, albeit with lower efficiency (By similarity). {ECO:0000250}.;
Intolerance Scores
- LoFtool
- 0.897
- RVIS EVS
- -0.18
- RVIS percentile EVS
- 40.17
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.162
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |