ARHGAP26
protein-codingRho GTPase activating protein 26, the group of AH/BAR family Rho GTPase activating proteins
Gene summary
Interaction of a cell with the extracellular matrix triggers integrin cell surface receptors to begin signaling cascades that regulate the organization of the actin-cytoskeleton. One of the proteins involved in these cascades is focal adhesion kinase. The protein encoded by this gene is a GTPase activating protein that binds to focal adhesion kinase and mediates the activity of the GTP binding proteins RhoA and Cdc42. Defects in this gene are a cause of juvenile myelomonocytic leukemia (JMML). Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2017]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~458.6 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: Unknown
Disease ID:MONDO:0011908
Submitter: Ambry Genetics
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to ARHGAP26 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001135608.3. 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 | 4 | 2 | 10 | ||
| missense | 67 | 3 | 70 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 5 | 5 | ||||
| Total | 0 | 0 | 77 | 7 | 2 | 86 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001129080.1 | 23 | MANE Select | |
| Ensembl | ENSP00000495131.1 | 23 | MANE Select | |
| RefSeq | NP_001336476.1 | 22 | Standard | |
| RefSeq | NP_055886.1 | 23 | 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
- Signaling events mediated by focal adhesion kinase
Biological Process
- signal transduction
- nervous system development
- actin cytoskeleton organization
- positive regulation of GTPase activity
- regulation of small GTPase mediated signal transduction
Molecular Function
- GTPase activator activity
- protein binding
- phospholipid binding
Cellular Component
- cellular_component
- cytosol
- cytoskeleton
- focal adhesion
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000274498
- Coding exons
- 23
- Length
- 458628
- Individuals with no LoFs
- 125720
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 28
- Defined
- 125748
- p
- 0.000111
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.11 | 329 | 456 | 0.721 | 0.0000250 | 5384 |
| Missense (PolyPhen) | 14 | 40.278 | 0.34758 | 466 | ||
| Synonymous | 1.67 | 144 | 172 | 0.838 | 0.00000985 | 1484 |
| Loss of Function | 5.45 | 7 | 47.6 | 0.147 | 0.00000244 | 565 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000062 | 0.000062 | rare |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0.00010 | 0.000099 | rare |
| East Asian | 0.0010 | 0.0010 | notable |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000063 | 0.000053 | rare |
| South Asian | 0.000033 | 0.000033 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: GTPase-activating protein for RHOA and CDC42.;
- Disease
- DISEASE: Leukemia, juvenile myelomonocytic (JMML) [MIM:607785]: An aggressive pediatric myelodysplastic syndrome/myeloproliferative disorder characterized by malignant transformation in the hematopoietic stem cell compartment with proliferation of differentiated progeny. Patients have splenomegaly, enlarged lymph nodes, rashes, and hemorrhages. Note=The gene represented in this entry is involved in disease pathogenesis. A chromosomal translocation t(5;11)(q31;q23) with KMT2A/MLL1 has been found in leukemic cells from JMML patients, also carrying inactivating mutations on the second allele (PubMed:10908648). {ECO:0000269|PubMed:10908648}.;
Recessive Scores
- pRec
- 0.361
Intolerance Scores
- LoFtool
- 0.452
- RVIS EVS
- -0.87
- RVIS percentile EVS
- 10.73
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.560
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |