ARHGAP42
protein-codingRho GTPase activating protein 42, the group of AH/BAR family Rho GTPase activating proteins
Gene summary
This gene encodes a Rho GTPase-activating protein (RhoGAP), and member of the GRAF or BAR-PH family of proteins. Expression of this gene is enriched in vascular smooth muscle cells and the encoded protein inhibits RhoA activity to regulate vascular tone and control blood pressure. A mutation in the first intron of this gene modulates its expression and is associated with reduced blood pressure in human patients with borderline hypertension. [provided by RefSeq, Jul 2017]
- TMEM133
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~306.7 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0015925
Submitter: PanelApp Australia
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to ARHGAP42 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_152432.4. 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 | 1 | 1 | 2 | |||
| missense | 83 | 2 | 85 | |||
| nonsense | 2 | 2 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 4 | 4 | ||||
| Total | 0 | 0 | 90 | 3 | 0 | 93 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_689645.2 | 24 | MANE Select | |
| Ensembl | ENSP00000298815.7 | 24 | MANE Select | |
| RefSeq | NP_001354874.1 | 22 | Standard | |
| Ensembl | ENSP00000303999.2 | 1 | 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
- EGFR1
Biological Process
- negative regulation of systemic arterial blood pressure
- signal transduction
- negative regulation of Rho protein signal transduction
- activation of GTPase activity
- negative regulation of vascular smooth muscle contraction
Molecular Function
- GTPase activator activity
Cellular Component
- cellular_component
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000298815
- Coding exons
- 24
- Length
- 304285
- Individuals with no LoFs
- 0
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 0
- Defined
- 0
- p
- 0.00
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.96 | 228 | 394 | 0.579 | 0.0000189 | 5715 |
| Missense (PolyPhen) | 54 | 140.11 | 0.3854 | 2048 | ||
| Synonymous | 1.94 | 111 | 140 | 0.791 | 0.00000708 | 1596 |
| Loss of Function | 6.16 | 3 | 50.0 | 0.0600 | 0.00000294 | 658 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0 | 0.0 | absent |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: May influence blood pressure by functioning as a GTPase- activating protein for RHOA in vascular smooth muscle. {ECO:0000269|PubMed:24335996}.;
Intolerance Scores
- RVIS EVS
- 0.08
- RVIS percentile EVS
- 59.76
Essentials
- Essential (CRISPR2)
- S
- Indispensability pred.
- N
- Indispensability score
- 0.114
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |