ARAP3
protein-codingArfGAP with RhoGAP domain, ankyrin repeat and PH domain 3, the group of Ankyrin repeat domain containing|Pleckstrin homology domain containing|Sterile alpha motif domain containing|ArfGAPs
Gene summary
This gene encodes a phosphoinositide binding protein containing ARF-GAP, RHO-GAP, RAS-associating, and pleckstrin homology domains. The ARF-GAP and RHO-GAP domains cooperate in mediating rearrangements in the cell cytoskeleton and cell shape. It is a specific PtdIns(3,4,5)P3/PtdIns(3,4)P2-stimulated Arf6-GAP protein. An alternatively spliced transcript has been found for this gene, but its biological validity has not been determined. [provided by RefSeq, Sep 2015]
- CENTD3
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~28.8 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AD
Disease ID:MONDO:0019297
Submitter: PanelApp Australia
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to ARAP3 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_022481.6. 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 | 1 | 1 | 2 | |||
| missense | 213 | 13 | 226 | |||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 14 | 14 | ||||
| Total | 0 | 0 | 229 | 14 | 0 | 243 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_071926.4 | 32 | MANE Select | |
| Ensembl | ENSP00000239440.4 | 32 | MANE Select | |
| Ensembl | ENSP00000421148.1 | 9 | Standard | |
| Ensembl | ENSP00000421826.1 | 31 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Endocytosis - Homo sapiens (human)
- cAMP signaling pathway - Homo sapiens (human)
- Rap1 signaling pathway - Homo sapiens (human)
- Signal Transduction
- Rho GTPase cycle
Biological Process
- cytoskeleton organization
- signal transduction
- regulation of cell shape
- vesicle-mediated transport
- negative regulation of cell migration
Molecular Function
- GTPase activator activity
- protein binding
- phosphatidylinositol-3,4,5-trisphosphate binding
- phosphatidylinositol-3,4-bisphosphate binding
- metal ion binding
Cellular Component
- ruffle
- cytoplasm
- cytosol
- cytoskeleton
- plasma membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000239440
- Coding exons
- 32
- Length
- 28821
- Individuals with no LoFs
- 125675
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 73
- Defined
- 125748
- p
- 0.000290
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.82 | 769 | 925 | 0.832 | 0.0000578 | 9859 |
| Missense (PolyPhen) | 285 | 378.48 | 0.75301 | 3975 | ||
| Synonymous | 1.05 | 340 | 366 | 0.930 | 0.0000207 | 3292 |
| Loss of Function | 5.66 | 24 | 77.9 | 0.308 | 0.00000423 | 831 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00078 | 0.00074 | rare |
| Latino/Admixed American | 0.000058 | 0.000058 | rare |
| Ashkenazi Jewish | 0.00020 | 0.00020 | rare |
| East Asian | 0.00033 | 0.00033 | rare |
| Finnish | 0.00042 | 0.00042 | rare |
| European (Non-Finnish) | 0.00027 | 0.00026 | rare |
| South Asian | 0.00033 | 0.00033 | rare |
| Other | 0.00033 | 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. Acts on ARF6, RAC1, RHOA and CDC42. Plays a role in the internalization of anthrax toxin. {ECO:0000269|PubMed:11804589, ECO:0000269|PubMed:15569923}.;
Recessive Scores
- pRec
- 0.126
Intolerance Scores
- LoFtool
- 0.566
- RVIS EVS
- -0.71
- RVIS percentile EVS
- 14.41
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.185
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |