ARHGAP35
Rho GTPase activating protein 35, the group of Rho GTPase activating proteins
Basic information
Region (hg38): 19:46860997-47005077
Previous symbols: [ "GRLF1" ]
Links
Phenotypes
GenCC
Source:
- complex neurodevelopmental disorder (Limited), mode of inheritance: AD
- neurodevelopmental disorder (Definitive), mode of inheritance: AD
- neurodevelopmental disorder (Moderate), mode of inheritance: AD
- multiple congenital anomalies/dysmorphic syndrome (Limited), mode of inheritance: AD
ClinVar
This is a list of variants' phenotypes submitted to
- not_specified (104 variants)
- Martsolf_syndrome_1 (17 variants)
- not_provided (5 variants)
- Neurodevelopmental_disorder (2 variants)
- ARHGAP35-related_condition (2 variants)
- Bilateral_microphthalmos (1 variants)
- Irido-corneo-trabecular_dysgenesis (1 variants)
- Anophthalmia (1 variants)
- Unilateral_microphthalmos (1 variants)
- Breast_ductal_adenocarcinoma (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the ARHGAP35 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000004491.5. Only rare variants are included in the table.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 3 | |||||
| missense | 111 | 118 | ||||
| nonsense | 8 | |||||
| start loss | 0 | |||||
| frameshift | 8 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 6 | 11 | 112 | 5 | 3 |
Highest pathogenic variant AF is 0.00000657263
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| ARHGAP35 | protein_coding | protein_coding | ENST00000404338 | 6 | 86402 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 1.00 | 6.33e-9 | 124634 | 0 | 4 | 124638 | 0.0000160 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 4.16 | 510 | 852 | 0.599 | 0.0000497 | 9949 |
| Missense in Polyphen | 136 | 356.04 | 0.38197 | 4119 | ||
| Synonymous | 0.153 | 334 | 338 | 0.989 | 0.0000206 | 2906 |
| Loss of Function | 6.68 | 0 | 52.0 | 0.00 | 0.00000310 | 609 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.0000290 | 0.0000290 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.0000266 | 0.0000265 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.00 | 0.00 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Rho GTPase-activating protein (GAP) (PubMed:19673492, PubMed:28894085). Binds several acidic phospholipids which inhibits the Rho GAP activity to promote the Rac GAP activity (PubMed:19673492). This binding is inhibited by phosphorylation by PRKCA (PubMed:19673492). Involved in cell differentiation as well as cell adhesion and migration, plays an important role in retinal tissue morphogenesis, neural tube fusion, midline fusion of the cerebral hemispheres and mammary gland branching morphogenesis (By similarity). Transduces signals from p21-ras to the nucleus, acting via the ras GTPase-activating protein (GAP) (By similarity). Transduces SRC-dependent signals from cell-surface adhesion molecules, such as laminin, to promote neurite outgrowth. Regulates axon outgrowth, guidance and fasciculation (By similarity). Modulates Rho GTPase-dependent F-actin polymerization, organization and assembly, is involved in polarized cell migration and in the positive regulation of ciliogenesis and cilia elongation (By similarity). During mammary gland development, is required in both the epithelial and stromal compartments for ductal outgrowth (By similarity). Represses transcription of the glucocorticoid receptor by binding to the cis-acting regulatory sequence 5'-GAGAAAAGAAACTGGAGAAACTC-3'; this function is however unclear and would need additional experimental evidences (PubMed:1894621). {ECO:0000250|UniProtKB:P81128, ECO:0000250|UniProtKB:Q91YM2, ECO:0000269|PubMed:1894621, ECO:0000269|PubMed:19673492, ECO:0000269|PubMed:28894085}.;
- Pathway
- Platelet activation - Homo sapiens (human);Focal adhesion - Homo sapiens (human);Regulation of actin cytoskeleton - Homo sapiens (human);Leukocyte transendothelial migration - Homo sapiens (human);Focal Adhesion;Regulation of Actin Cytoskeleton;Developmental Biology;Signaling by PTK6;Signal Transduction;TCR;Rho GTPase cycle;Signaling by Rho GTPases;Sema4D mediated inhibition of cell attachment and migration;EGFR1;SHP2 signaling;Sema4D in semaphorin signaling;Semaphorin interactions;PTK6 Regulates RHO GTPases, RAS GTPase and MAP kinases;Signaling by Non-Receptor Tyrosine Kinases;Axon guidance;Signaling events mediated by focal adhesion kinase;PDGFR-beta signaling pathway;EPHA2 forward signaling;Regulation of RhoA activity
(Consensus)
Recessive Scores
- pRec
- 0.167
Intolerance Scores
- loftool
- rvis_EVS
- -1.81
- rvis_percentile_EVS
- 2.17
Haploinsufficiency Scores
- pHI
- 0.635
- hipred
- Y
- hipred_score
- 0.768
- ghis
- 0.619
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- N
- gene_indispensability_score
- 0.114
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Arhgap35
- Phenotype
- cellular phenotype; growth/size/body region phenotype; embryo phenotype; renal/urinary system phenotype; vision/eye phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); pigmentation phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span);
Gene ontology
- Biological process
- negative regulation of transcription by RNA polymerase II;neural tube closure;transcription, DNA-templated;signal transduction;axon guidance;axonal fasciculation;regulation of actin polymerization or depolymerization;regulation of cell shape;positive regulation of neuron projection development;cell migration;central nervous system neuron axonogenesis;mammary gland development;forebrain development;establishment or maintenance of actin cytoskeleton polarity;cellular response to extracellular stimulus;regulation of actin cytoskeleton organization;negative regulation of Rho protein signal transduction;camera-type eye development;negative regulation of vascular permeability;positive regulation of GTPase activity;wound healing, spreading of cells;positive regulation of cilium assembly;negative regulation of transcription, DNA-templated;regulation of axonogenesis;regulation of small GTPase mediated signal transduction;neuron projection guidance
- Cellular component
- nucleus;cytosol;plasma membrane;actin cytoskeleton;ciliary basal body
- Molecular function
- RNA polymerase II regulatory region sequence-specific DNA binding;DNA-binding transcription repressor activity, RNA polymerase II-specific;DNA binding;transcription corepressor activity;GTPase activity;GTPase activator activity;GTP binding;phospholipid binding