RIT1
Ras like without CAAX 1, the group of RAS type GTPase family
Basic information
Region (hg38): 1:155897807-155911404
Previous symbols: [ "RIT" ]
Links
Phenotypes
GenCC
Source:
- Noonan syndrome 8 (Strong), mode of inheritance: AD
- Noonan syndrome 8 (Definitive), mode of inheritance: AD
- Noonan syndrome 8 (Strong), mode of inheritance: AD
- Noonan syndrome 8 (Strong), mode of inheritance: AD
- Noonan syndrome (Supportive), mode of inheritance: AD
- Noonan syndrome (Definitive), mode of inheritance: AD
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Noonan syndrome 8 | AD | Cardiovascular; Oncologic | Surveillance and treatment related to manifestations such as cardiac anomalies (which include pulmonic stenosis and hypertrophic cardiomyopathy as well as congenital heart defects ) can be beneficial; Individuals may be at increased risk for malignancy (a child with ALL has been described), and although specific surveillance may not be warranted, awareness may allow prompt detection and treatment | Cardiovascular; Craniofacial; Musculoskeletal; Neurologic; Oncologic | 23791108; 24939608; 25124994 |
ClinVar
This is a list of variants' phenotypes submitted to
- Noonan syndrome 8 (166 variants)
- not provided (75 variants)
- Cardiovascular phenotype (53 variants)
- not specified (34 variants)
- Noonan syndrome (23 variants)
- Noonan syndrome and Noonan-related syndrome (21 variants)
- Inborn genetic diseases (10 variants)
- RASopathy (9 variants)
- Noonan syndrome 1 (7 variants)
- Non-immune hydrops fetalis (2 variants)
- Noonan syndrome 8;Megalencephaly-capillary malformation-polymicrogyria syndrome (1 variants)
- Downslanted palpebral fissures;Hypertelorism;Pedal edema;Short stature (1 variants)
- Fibrous dysplasia of jaw (1 variants)
- Cardio-facio-cutaneous syndrome (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the RIT1 gene is commonly pathogenic or not.
| Variant type | Pathogenic | Likely pathogenic | VUS | Likely benign | Benign | Sum |
|---|---|---|---|---|---|---|
| synonymous | 40 | 1 | 41 | |||
| missense | 18 | 16 | 89 | 7 | 1 | 131 |
| nonsense | 2 | 3 | 5 | |||
| start loss | 0 | |||||
| frameshift | 3 | 1 | 4 | |||
| inframe indel | 1 | 1 | ||||
| splice variant | 3 | 6 | 2 | 11 | ||
| non coding | 28 | 10 | 38 | |||
| Total | 20 | 16 | 99 | 82 | 14 |
Highest pathogenic variant AF is 0.00000657
Variants in RIT1
This is a list of pathogenic ClinVar variants found in the RIT1 region.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 1-155900379-A-G | Likely benign (Feb 09, 2023) | |||
| 1-155900379-ATCTTC-A | not specified | Uncertain significance (Apr 26, 2021) | ||
| 1-155900393-TTA-GTG | Uncertain significance (Mar 20, 2023) | |||
| 1-155900398-G-C | Noonan syndrome 8 | Uncertain significance (Jun 21, 2022) | ||
| 1-155900398-GA-G | Noonan syndrome 8 | Uncertain significance (May 01, 2022) | ||
| 1-155900399-A-AATCTTTCTTCTTCCGGAATGGTGATTTTAGCCTCTTCCATACACTGTTTTTGGGCTTAGATTTTTTCTCCATGGCCAGTACTGCCT | not specified | Uncertain significance (Apr 20, 2020) | ||
| 1-155900400-ATCTT-A | Noonan syndrome 8 • Cardiovascular phenotype | Conflicting interpretations of pathogenicity (Mar 02, 2023) | ||
| 1-155900402-C-T | Noonan syndrome 8 • Cardiovascular phenotype | Uncertain significance (Apr 11, 2023) | ||
| 1-155900402-CT-C | Noonan syndrome 8 | Uncertain significance (Oct 30, 2022) | ||
| 1-155900409-C-T | not specified • Noonan syndrome 8 | Likely benign (Apr 11, 2023) | ||
| 1-155900413-C-T | Noonan syndrome and Noonan-related syndrome • Noonan syndrome 8 • Cardiovascular phenotype | Uncertain significance (Apr 11, 2023) | ||
| 1-155900414-G-A | not specified • Noonan syndrome 8 • Noonan syndrome and Noonan-related syndrome • Cardiovascular phenotype | Conflicting interpretations of pathogenicity (Sep 28, 2022) | ||
| 1-155900430-C-G | Noonan syndrome 8 | Uncertain significance (Mar 08, 2022) | ||
| 1-155900431-C-G | Noonan syndrome 8 | Uncertain significance (Oct 09, 2022) | ||
| 1-155900433-C-A | Cardiovascular phenotype | Uncertain significance (Oct 02, 2019) | ||
| 1-155900439-T-C | Cardiovascular phenotype • Noonan syndrome 8 | Likely benign (Apr 11, 2023) | ||
| 1-155900441-C-T | Noonan syndrome 8 | Uncertain significance (Apr 11, 2022) | ||
| 1-155900444-T-A | not specified | Uncertain significance (Nov 13, 2015) | ||
| 1-155900445-G-A | Noonan syndrome 8 | Likely benign (Jun 19, 2019) | ||
| 1-155900446-T-C | Cardiovascular phenotype • Noonan syndrome 8 | Conflicting interpretations of pathogenicity (Jun 06, 2022) | ||
| 1-155900450-T-G | Noonan syndrome 8 | Uncertain significance (Jul 12, 2022) | ||
| 1-155900454-C-T | Noonan syndrome 8 • Cardiovascular phenotype | Likely benign (Apr 11, 2023) | ||
| 1-155900459-A-G | not specified • Noonan syndrome 8 | Uncertain significance (Apr 11, 2023) | ||
| 1-155900460-T-G | Cardiovascular phenotype | Uncertain significance (Jan 07, 2020) | ||
| 1-155900461-T-G | Noonan syndrome 8 | Uncertain significance (Sep 23, 2022) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| RIT1 | protein_coding | protein_coding | ENST00000368322 | 6 | 13597 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.133 | 0.863 | 125735 | 0 | 11 | 125746 | 0.0000437 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 2.08 | 75 | 145 | 0.516 | 0.00000841 | 1550 |
| Missense in Polyphen | 14 | 56.992 | 0.24565 | 619 | ||
| Synonymous | 0.0940 | 45 | 45.8 | 0.982 | 0.00000212 | 453 |
| Loss of Function | 2.51 | 4 | 14.2 | 0.282 | 9.93e-7 | 135 |
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 | 0.00 | 0.00 |
| European (Non-Finnish) | 0.0000440 | 0.0000439 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.0000327 | 0.0000327 |
| Other | 0.000164 | 0.000163 |
dbNSFP
Source:
- Function
- FUNCTION: Plays a crucial role in coupling NGF stimulation to the activation of both EPHB2 and MAPK14 signaling pathways and in NGF- dependent neuronal differentiation. Involved in ELK1 transactivation through the Ras-MAPK signaling cascade that mediates a wide variety of cellular functions, including cell proliferation, survival, and differentiation. {ECO:0000269|PubMed:15632082, ECO:0000269|PubMed:23791108}.;
- Pathway
- Ectoderm Differentiation;Signal Transduction;Signalling to p38 via RIT and RIN;Signalling to ERKs;Signaling by NTRK1 (TRKA);Signaling by NTRKs;Signaling by Receptor Tyrosine Kinases;Neurotrophic factor-mediated Trk receptor signaling;Trk receptor signaling mediated by the MAPK pathway
(Consensus)
Recessive Scores
- pRec
- 0.212
Intolerance Scores
- loftool
- 0.351
- rvis_EVS
- -0.19
- rvis_percentile_EVS
- 39.68
Haploinsufficiency Scores
- pHI
- 0.122
- hipred
- Y
- hipred_score
- 0.711
- ghis
- 0.629
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- N
- gene_indispensability_score
- 0.442
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Low | Low | Low |
| Primary Immunodeficiency | Medium | Low | Medium |
| Cancer | Low | Low | Low |
Mouse Genome Informatics
- Gene name
- Rit1
- Phenotype
- cellular phenotype;
Gene ontology
- Biological process
- signal transduction;Ras protein signal transduction
- Cellular component
- plasma membrane
- Molecular function
- GTPase activity;protein binding;calmodulin binding;GTP binding