RAP1A
RAP1A, member of RAS oncogene family, the group of RAS type GTPase family
Basic information
Region (hg38): 1:111542218-111716691
Links
Phenotypes
GenCC
Source:
No genCC data.
ClinVar
This is a list of variants' phenotypes submitted to
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the RAP1A gene is commonly pathogenic or not.
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.
| Variant type | Pathogenic | Likely pathogenic | VUS | Likely benign | Benign | Sum |
|---|---|---|---|---|---|---|
| synonymous | 4 | |||||
| missense | 5 | |||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region | 1 | 1 | ||||
| non coding | 15 | 19 | ||||
| Total | 0 | 0 | 5 | 8 | 15 |
Variants in RAP1A
This is a list of pathogenic ClinVar variants found in the RAP1A region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 1-111691119-T-C | Benign (May 14, 2021) | |||
| 1-111691176-G-A | Benign (May 17, 2021) | |||
| 1-111691365-G-A | not specified | Uncertain significance (Mar 07, 2024) | ||
| 1-111691446-T-A | Benign (Nov 12, 2018) | |||
| 1-111691462-G-T | Benign (May 15, 2021) | |||
| 1-111691593-C-T | Benign (May 17, 2021) | |||
| 1-111695209-A-ATAATAT | Benign (May 14, 2021) | |||
| 1-111695293-A-T | Benign (May 15, 2021) | |||
| 1-111695324-CT-C | RAP1A-related disorder | Likely benign (Feb 17, 2020) | ||
| 1-111695332-T-C | Likely benign (Nov 03, 2017) | |||
| 1-111695352-T-C | Likely benign (May 03, 2018) | |||
| 1-111695594-A-G | Benign (May 16, 2021) | |||
| 1-111697229-C-T | Benign (May 15, 2021) | |||
| 1-111697416-C-CT | Benign (Jun 02, 2021) | |||
| 1-111697430-TG-T | Likely benign (Feb 05, 2018) | |||
| 1-111697431-G-T | Likely benign (Dec 31, 2019) | |||
| 1-111697432-C-G | Likely benign (May 29, 2018) | |||
| 1-111697452-C-T | Likely benign (Jul 26, 2018) | |||
| 1-111697503-G-A | Benign (Dec 31, 2019) | |||
| 1-111703406-C-T | not specified | Uncertain significance (Apr 01, 2024) | ||
| 1-111703469-C-T | not specified | Uncertain significance (Oct 26, 2022) | ||
| 1-111704148-AT-A | Benign (May 14, 2021) | |||
| 1-111704148-A-AT | Benign (Jun 04, 2021) | |||
| 1-111704349-A-G | not specified | Uncertain significance (Jun 10, 2022) | ||
| 1-111704434-G-A | not specified | Uncertain significance (Oct 12, 2022) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| RAP1A | protein_coding | protein_coding | ENST00000369709 | 6 | 174474 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.622 | 0.376 | 125636 | 0 | 6 | 125642 | 0.0000239 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 2.36 | 32 | 97.7 | 0.327 | 0.00000523 | 1199 |
| Missense in Polyphen | 4 | 33.554 | 0.11921 | 442 | ||
| Synonymous | 0.860 | 31 | 37.7 | 0.822 | 0.00000228 | 332 |
| Loss of Function | 2.63 | 2 | 11.7 | 0.171 | 5.78e-7 | 147 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.000116 | 0.000116 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.0000482 | 0.0000462 |
| European (Non-Finnish) | 0.00000881 | 0.00000880 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.00 | 0.00 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Induces morphological reversion of a cell line transformed by a Ras oncogene. Counteracts the mitogenic function of Ras, at least partly because it can interact with Ras GAPs and RAF in a competitive manner. Together with ITGB1BP1, regulates KRIT1 localization to microtubules and membranes. Plays a role in nerve growth factor (NGF)-induced neurite outgrowth. Plays a role in the regulation of embryonic blood vessel formation. Involved in the establishment of basal endothelial barrier function. May be involved in the regulation of the vascular endothelial growth factor receptor KDR expression at endothelial cell-cell junctions. {ECO:0000269|PubMed:17916086, ECO:0000269|PubMed:21840392}.;
- Pathway
- Platelet activation - Homo sapiens (human);Focal adhesion - Homo sapiens (human);Renal cell carcinoma - Homo sapiens (human);Long-term potentiation - Homo sapiens (human);Neurotrophin signaling pathway - Homo sapiens (human);Cushing,s syndrome - Homo sapiens (human);Tight junction - Homo sapiens (human);Chemokine signaling pathway - Homo sapiens (human);cAMP signaling pathway - Homo sapiens (human);Rap1 signaling pathway - Homo sapiens (human);Ras signaling pathway - Homo sapiens (human);Pancreatic secretion - Homo sapiens (human);MAPK signaling pathway - Homo sapiens (human);Leukocyte transendothelial migration - Homo sapiens (human);Bisphosphonate Pathway, Pharmacodynamics;Intracellular Signalling Through Adenosine Receptor A2b and Adenosine;Intracellular Signalling Through Adenosine Receptor A2a and Adenosine;Integrated Breast Cancer Pathway;Integrin-mediated Cell Adhesion;Human Thyroid Stimulating Hormone (TSH) signaling pathway;Androgen Receptor Network in Prostate Cancer;Brain-Derived Neurotrophic Factor (BDNF) signaling pathway;Integrated Lung Cancer Pathway;Common Pathways Underlying Drug Addiction;Focal Adhesion;Signaling of Hepatocyte Growth Factor Receptor;MAPK Signaling Pathway;VEGFA-VEGFR2 Signaling Pathway;Chemokine signaling pathway;MET in type 1 papillary renal cell carcinoma;Ras Signaling;EGF-EGFR Signaling Pathway;Interferon type I signaling pathways;Serotonin HTR1 Group and FOS Pathway;Serotonin Receptor 4-6-7 and NR3C Signaling;MAP2K and MAPK activation;Neutrophil degranulation;Disease;Signal Transduction;GPCR Adenosine A2A receptor;GRB2:SOS provides linkage to MAPK signaling for Integrins ;p130Cas linkage to MAPK signaling for integrins;Integrin alphaIIb beta3 signaling;HGF;TCR;ARMS-mediated activation;Innate Immune System;Immune System;Metabolism;Rap1 signalling;Adaptive Immune System;MET activates RAP1 and RAC1;Glucagon-like Peptide-1 (GLP1) regulates insulin secretion;Regulation of insulin secretion;GPCR signaling-G alpha s Epac and ERK;Platelet Aggregation (Plug Formation);Platelet activation, signaling and aggregation;GPCR signaling-G alpha s PKA and ERK;Frs2-mediated activation;Prolonged ERK activation events;Signalling to ERKs;Signaling by NTRK1 (TRKA);Integrin;Signaling by NTRKs;EGFR1;Integrin signaling;Hemostasis;RAF/MAP kinase cascade;MAPK1/MAPK3 signaling;MAPK family signaling cascades;Signaling events regulated by Ret tyrosine kinase;Class I PI3K signaling events;IFN-gamma pathway;EPO signaling pathway;MET promotes cell motility;Signaling by MET;Signaling by Receptor Tyrosine Kinases;Integration of energy metabolism;Signaling by RAS mutants;Signaling by high-kinase activity BRAF mutants;Signaling by moderate kinase activity BRAF mutants;Paradoxical activation of RAF signaling by kinase inactive BRAF;Nectin adhesion pathway;Neurotrophic factor-mediated Trk receptor signaling;Signaling by BRAF and RAF fusions;Oncogenic MAPK signaling;Diseases of signal transduction;Signaling events mediated by Hepatocyte Growth Factor Receptor (c-Met);Signaling events mediated by focal adhesion kinase;TCR signaling in naïve CD8+ T cells;Reelin signaling pathway;amb2 Integrin signaling;EPHB forward signaling;PDGFR-beta signaling pathway;Trk receptor signaling mediated by the MAPK pathway;TCR signaling in naïve CD4+ T cells;E-cadherin signaling in the nascent adherens junction
(Consensus)
Recessive Scores
- pRec
- 0.281
Intolerance Scores
- loftool
- rvis_EVS
- -0.08
- rvis_percentile_EVS
- 47.79
Haploinsufficiency Scores
- pHI
- 0.552
- hipred
- Y
- hipred_score
- 0.762
- ghis
- 0.616
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.970
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Low | Low | Low |
| Primary Immunodeficiency | Medium | Low | Medium |
| Cancer | Low | Low | Low |
Mouse Genome Informatics
- Gene name
- Rap1a
- Phenotype
- cellular 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); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); hematopoietic system 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); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); immune system phenotype;
Zebrafish Information Network
- Gene name
- rap1aa
- Affected structure
- whole organism
- Phenotype tag
- abnormal
- Phenotype quality
- increased curvature
Gene ontology
- Biological process
- signal transduction;positive regulation of neuron projection development;protein transport;microvillus assembly;Rap protein signal transduction;negative regulation of collagen biosynthetic process;cellular response to drug;nerve growth factor signaling pathway;neutrophil degranulation;positive regulation of GTPase activity;positive regulation of protein kinase activity;positive regulation of glucose import;regulation of insulin secretion;establishment of endothelial barrier;positive regulation of ERK1 and ERK2 cascade;cellular response to cAMP;cellular response to glucose stimulus;response to antineoplastic agent;liver regeneration;regulation of neurotransmitter receptor localization to postsynaptic specialization membrane;regulation of cell junction assembly;positive regulation of Fc-gamma receptor signaling pathway involved in phagocytosis;cellular response to nerve growth factor stimulus;negative regulation of synaptic vesicle exocytosis;positive regulation of vasculogenesis
- Cellular component
- cytoplasm;early endosome;late endosome;cytosol;plasma membrane;cell junction;guanyl-nucleotide exchange factor complex;specific granule membrane;neuron projection;myelin sheath;phagocytic vesicle;perinuclear region of cytoplasm;extracellular exosome;glutamatergic synapse
- Molecular function
- GTPase activity;protein binding;GTP binding;protein transporter activity;Rap guanyl-nucleotide exchange factor activity;protein-containing complex binding