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GeneBe

RIT1

Ras like without CAAX 1, the group of RAS type GTPase family

Basic information

Region (hg38): 1:155897807-155911404

Previous symbols: [ "RIT" ]

Links

ENSG00000143622NCBI:6016OMIM:609591HGNC:10023Uniprot:Q92963AlphaFoldGenCCjaxSfariGnomADPubmed

Phenotypes

GenCC

Source: genCC

  • 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: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Noonan syndrome 8ADCardiovascular; OncologicSurveillance 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 treatmentCardiovascular; Craniofacial; Musculoskeletal; Neurologic; Oncologic23791108; 24939608; 25124994

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the RIT1 gene.

  • 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)link
1-155900379-ATCTTC-A not specified Uncertain significance (Apr 26, 2021)link
1-155900393-TTA-GTG Uncertain significance (Mar 20, 2023)link
1-155900398-G-C Noonan syndrome 8 Uncertain significance (Jun 21, 2022)link
1-155900398-GA-G Noonan syndrome 8 Uncertain significance (May 01, 2022)link
1-155900399-A-AATCTTTCTTCTTCCGGAATGGTGATTTTAGCCTCTTCCATACACTGTTTTTGGGCTTAGATTTTTTCTCCATGGCCAGTACTGCCT not specified Uncertain significance (Apr 20, 2020)link
1-155900400-ATCTT-A Noonan syndrome 8 • Cardiovascular phenotype Conflicting interpretations of pathogenicity (Mar 02, 2023)link
1-155900402-C-T Noonan syndrome 8 • Cardiovascular phenotype Uncertain significance (Apr 11, 2023)link
1-155900402-CT-C Noonan syndrome 8 Uncertain significance (Oct 30, 2022)link
1-155900409-C-T not specified • Noonan syndrome 8 Likely benign (Apr 11, 2023)link
1-155900413-C-T Noonan syndrome and Noonan-related syndrome • Noonan syndrome 8 • Cardiovascular phenotype Uncertain significance (Apr 11, 2023)link
1-155900414-G-A not specified • Noonan syndrome 8 • Noonan syndrome and Noonan-related syndrome • Cardiovascular phenotype Conflicting interpretations of pathogenicity (Sep 28, 2022)link
1-155900430-C-G Noonan syndrome 8 Uncertain significance (Mar 08, 2022)link
1-155900431-C-G Noonan syndrome 8 Uncertain significance (Oct 09, 2022)link
1-155900433-C-A Cardiovascular phenotype Uncertain significance (Oct 02, 2019)link
1-155900439-T-C Cardiovascular phenotype • Noonan syndrome 8 Likely benign (Apr 11, 2023)link
1-155900441-C-T Noonan syndrome 8 Uncertain significance (Apr 11, 2022)link
1-155900444-T-A not specified Uncertain significance (Nov 13, 2015)link
1-155900445-G-A Noonan syndrome 8 Likely benign (Jun 19, 2019)link
1-155900446-T-C Cardiovascular phenotype • Noonan syndrome 8 Conflicting interpretations of pathogenicity (Jun 06, 2022)link
1-155900450-T-G Noonan syndrome 8 Uncertain significance (Jul 12, 2022)link
1-155900454-C-T Noonan syndrome 8 • Cardiovascular phenotype Likely benign (Apr 11, 2023)link
1-155900459-A-G not specified • Noonan syndrome 8 Uncertain significance (Apr 11, 2023)link
1-155900460-T-G Cardiovascular phenotype Uncertain significance (Jan 07, 2020)link
1-155900461-T-G Noonan syndrome 8 Uncertain significance (Sep 23, 2022)link

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
RIT1protein_codingprotein_codingENST00000368322 613597
pLI Probability
LOF Intolerant
pRec Probability
LOF Recessive
Individuals with
no LOFs
Individuals with
Homozygous LOFs
Individuals with
Heterozygous LOFs
Defined p
0.1330.8631257350111257460.0000437
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense2.08751450.5160.000008411550
Missense in Polyphen1456.9920.24565619
Synonymous0.09404545.80.9820.00000212453
Loss of Function2.51414.20.2829.93e-7135

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.0001160.000116
Ashkenazi Jewish0.000.00
East Asian0.000.00
Finnish0.000.00
European (Non-Finnish)0.00004400.0000439
Middle Eastern0.000.00
South Asian0.00003270.0000327
Other0.0001640.000163

dbNSFP

Source: dbNSFP

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

AllRecessiveDominant
MendelianLowLowLow
Primary ImmunodeficiencyMediumLowMedium
CancerLowLowLow

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