RRAS
RAS related, the group of RAS type GTPase family
Basic information
Region (hg38): 19:49635291-49640143
Links
Phenotypes
GenCC
Source:
- Noonan syndrome (Moderate), mode of inheritance: AD
- Noonan syndrome (Limited), mode of inheritance: AD
ClinVar
This is a list of variants' phenotypes submitted to
- Noonan syndrome (182 variants)
- Inborn genetic diseases (69 variants)
- not specified (39 variants)
- not provided (32 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the RRAS gene is commonly pathogenic or not.
| Variant type | Pathogenic | Likely pathogenic | VUS | Likely benign | Benign | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 57 | 1 | 59 | ||
| missense | 96 | 7 | 1 | 104 | ||
| nonsense | 3 | 3 | ||||
| start loss | 0 | |||||
| frameshift | 1 | 2 | 3 | |||
| inframe indel | 0 | |||||
| splice variant | 12 | 11 | 23 | |||
| non coding | 6 | 22 | 10 | 38 | ||
| Total | 0 | 1 | 120 | 97 | 12 |
Variants in RRAS
This is a list of pathogenic ClinVar variants found in the RRAS region.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 19-49635346-G-A | Uncertain significance (Feb 04, 2022) | |||
| 19-49635571-C-T | not specified | Uncertain significance (May 28, 2023) | ||
| 19-49635572-T-C | not specified | Benign (Apr 27, 2021) | ||
| 19-49635581-G-A | Noonan syndrome • Inborn genetic diseases | Likely benign (Feb 05, 2023) | ||
| 19-49635584-G-C | Noonan syndrome | Uncertain significance (Aug 30, 2021) | ||
| 19-49635587-C-T | Noonan syndrome • Inborn genetic diseases | Uncertain significance (Dec 15, 2022) | ||
| 19-49635588-G-A | Noonan syndrome • Inborn genetic diseases | Likely benign (Jun 14, 2022) | ||
| 19-49635590-A-G | Noonan syndrome | Uncertain significance (Jul 13, 2022) | ||
| 19-49635591-G-A | Inborn genetic diseases • Noonan syndrome | Likely benign (May 17, 2022) | ||
| 19-49635602-C-T | Noonan syndrome • not specified | Uncertain significance (Aug 06, 2022) | ||
| 19-49635603-G-A | Inborn genetic diseases • Noonan syndrome | Likely benign (Oct 17, 2022) | ||
| 19-49635606-C-A | Noonan syndrome • not specified | Uncertain significance (Jan 07, 2020) | ||
| 19-49635609-C-T | Noonan syndrome | Likely benign (Nov 01, 2021) | ||
| 19-49635610-T-C | Noonan syndrome | Uncertain significance (Sep 25, 2022) | ||
| 19-49635613-C-T | Inborn genetic diseases | Uncertain significance (Nov 05, 2021) | ||
| 19-49635619-G-A | Noonan syndrome • Inborn genetic diseases | Uncertain significance (Jul 14, 2022) | ||
| 19-49635620-C-T | Inborn genetic diseases | Likely benign (Dec 07, 2021) | ||
| 19-49635623-T-C | Noonan syndrome | Uncertain significance (Aug 05, 2022) | ||
| 19-49635633-C-T | Noonan syndrome • not specified • Inborn genetic diseases | Benign/Likely benign (Sep 03, 2022) | ||
| 19-49635634-G-A | Noonan syndrome | Uncertain significance (May 12, 2022) | ||
| 19-49635635-G-A | Noonan syndrome | Uncertain significance (Aug 27, 2022) | ||
| 19-49635648-T-C | Inborn genetic diseases | Likely benign (Jan 27, 2020) | ||
| 19-49635664-T-G | not specified | Uncertain significance (Dec 04, 2021) | ||
| 19-49635672-C-T | Noonan syndrome | Benign/Likely benign (Oct 25, 2022) | ||
| 19-49635673-G-A | Noonan syndrome | Likely benign (Jul 25, 2022) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| RRAS | protein_coding | protein_coding | ENST00000246792 | 6 | 4910 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.00466 | 0.888 | 125691 | 0 | 56 | 125747 | 0.000223 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 0.676 | 110 | 132 | 0.834 | 0.00000857 | 1379 |
| Missense in Polyphen | 38 | 46.768 | 0.81253 | 487 | ||
| Synonymous | -0.0423 | 59 | 58.6 | 1.01 | 0.00000420 | 450 |
| Loss of Function | 1.37 | 5 | 9.56 | 0.523 | 4.53e-7 | 110 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.0000589 | 0.0000589 |
| Ashkenazi Jewish | 0.000102 | 0.0000992 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.000478 | 0.000457 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.0000331 | 0.0000327 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Regulates the organization of the actin cytoskeleton (PubMed:16537651, PubMed:18270267). With OSPBL3, modulates integrin beta-1 (ITGB1) activity (PubMed:18270267). {ECO:0000269|PubMed:16537651, ECO:0000269|PubMed:18270267}.;
- Pathway
- Autophagy - animal - Homo sapiens (human);HTLV-I infection - Homo sapiens (human);Regulation of actin cytoskeleton - Homo sapiens (human);Mitophagy - animal - Homo sapiens (human);Axon guidance - Homo sapiens (human);cAMP signaling pathway - Homo sapiens (human);Apelin signaling pathway - Homo sapiens (human);C-type lectin receptor signaling pathway - Homo sapiens (human);Rap1 signaling pathway - Homo sapiens (human);Ras signaling pathway - Homo sapiens (human);MAPK signaling pathway - Homo sapiens (human);Phospholipase D signaling pathway - Homo sapiens (human);Proteoglycans in cancer - Homo sapiens (human);Cellular senescence - Homo sapiens (human);EGFR Inhibitor Pathway, Pharmacodynamics;Bisphosphonate Pathway, Pharmacodynamics;Vemurafenib Pathway, Pharmacodynamics;update your name in edit mode;G Protein Signaling Pathways;MAPK Signaling Pathway;Canonical and Non-canonical Notch signaling;MAPK and NFkB Signalling Pathways Inhibited by Yersinia YopJ;T-Cell antigen Receptor (TCR) pathway during Staphylococcus aureus infection;MAPK Cascade;Ras Signaling;Regulation of Actin Cytoskeleton;Developmental Biology;Regulation of Ras family activation;Neuronal System;Sema4D mediated inhibition of cell attachment and migration;Sema4D in semaphorin signaling;SEMA3A-Plexin repulsion signaling by inhibiting Integrin adhesion;Semaphorin interactions;Neurotransmitter receptors and postsynaptic signal transmission;Transmission across Chemical Synapses;Plexin-D1 Signaling;Axon guidance;CREB phosphorylation through the activation of Ras;Post NMDA receptor activation events;Activation of NMDA receptor and postsynaptic events;Signaling events mediated by focal adhesion kinase;EPHB forward signaling
(Consensus)
Recessive Scores
- pRec
- 0.199
Intolerance Scores
- loftool
- 0.435
- rvis_EVS
- 0.24
- rvis_percentile_EVS
- 69.21
Haploinsufficiency Scores
- pHI
- 0.193
- hipred
- Y
- hipred_score
- 0.756
- ghis
- 0.530
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.590
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Rras
- Phenotype
- homeostasis/metabolism phenotype; 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; neoplasm; immune system phenotype;
Zebrafish Information Network
- Gene name
- rras
- Affected structure
- vagal ganglion
- Phenotype tag
- abnormal
- Phenotype quality
- fused with
Gene ontology
- Biological process
- leukocyte differentiation;Ras protein signal transduction;negative regulation of cell migration;positive regulation of angiogenesis;regulation of protein kinase B signaling;face morphogenesis;regulation of ERK1 and ERK2 cascade
- Cellular component
- plasma membrane;focal adhesion;extracellular exosome
- Molecular function
- GTPase activity;protein binding;GTP binding;GDP binding;protein-containing complex binding