RIT1
Basic information
Region (hg38): 1:155897808-155911404
Previous symbols: [ "RIT" ]
Links
Phenotypes
GenCC
Source:
- Noonan syndrome 8 (Strong), 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 8 (Definitive), 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 (268 variants)
- Cardiovascular_phenotype (112 variants)
- not_provided (87 variants)
- not_specified (43 variants)
- Noonan_syndrome (23 variants)
- RIT1-related_disorder (23 variants)
- Noonan_syndrome_and_Noonan-related_syndrome (21 variants)
- RASopathy (17 variants)
- Noonan_syndrome_1 (10 variants)
- Inborn_genetic_diseases (3 variants)
- Non-immune_hydrops_fetalis (2 variants)
- Congenital_heart_disease (1 variants)
- Fibrous_dysplasia_of_jaw (1 variants)
- Cardio-facio-cutaneous_syndrome (1 variants)
- Pedal_edema (1 variants)
- Short_stature (1 variants)
- Downslanted_palpebral_fissures (1 variants)
- Hypertelorism (1 variants)
- Megalencephaly-capillary_malformation-polymicrogyria_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. These statistics are base on transcript: NM_000006912.6. 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 | 77 | 79 | ||||
missense | 17 | 21 | 154 | 10 | 202 | |
nonsense | 4 | |||||
start loss | 0 | |||||
frameshift | 8 | |||||
splice donor/acceptor (+/-2bp) | 1 | |||||
Total | 18 | 21 | 165 | 89 | 1 |
Highest pathogenic variant AF is 0.00000656901
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