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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:Q92963AlphaFoldGenCCjaxSfariGnomADPubmedClinVar

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
  • Noonan syndrome 8 (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 (184 variants)
  • not provided (78 variants)
  • Cardiovascular phenotype (66 variants)
  • not specified (36 variants)
  • Noonan syndrome and Noonan-related syndrome (21 variants)
  • Noonan syndrome (20 variants)
  • Inborn genetic diseases (11 variants)
  • RASopathy (11 variants)
  • Noonan syndrome 1 (10 variants)
  • RIT1-related condition (7 variants)
  • Non-immune hydrops fetalis (2 variants)
  • Congenital heart disease;Noonan syndrome (1 variants)
  • Megalencephaly-capillary malformation-polymicrogyria syndrome;Noonan syndrome 8 (1 variants)
  • Pedal edema;Short stature;Hypertelorism;Downslanted palpebral fissures (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.

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
44
clinvar
1
clinvar
45
missense
16
clinvar
14
clinvar
97
clinvar
127
nonsense
1
clinvar
3
clinvar
4
start loss
0
frameshift
4
clinvar
4
inframe indel
1
clinvar
1
splice donor/acceptor (+/-2bp)
1
clinvar
1
splice region
2
4
2
8
non coding
2
clinvar
33
clinvar
11
clinvar
46
Total 17 14 108 77 12

Highest pathogenic variant AF is 0.00000657

Variants in RIT1

This is a list of pathogenic ClinVar variants found in the RIT1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position Type Phenotype Significance ClinVar
1-155900379-A-G Likely benign (Feb 09, 2023)2429605
1-155900379-ATCTTC-A not specified Uncertain significance (Apr 26, 2021)1098823
1-155900389-C-T Noonan syndrome 8 Likely benign (Sep 08, 2023)2758844
1-155900393-TTA-GTG Uncertain significance (Mar 20, 2023)2580475
1-155900397-T-C Noonan syndrome 8 Likely benign (Sep 10, 2023)2769679
1-155900398-G-C Noonan syndrome 8 Uncertain significance (Jun 21, 2022)2185691
1-155900398-GA-G Noonan syndrome 8 Uncertain significance (Jan 11, 2024)839801
1-155900399-A-AATCTTTCTTCTTCCGGAATGGTGATTTTAGCCTCTTCCATACACTGTTTTTGGGCTTAGATTTTTTCTCCATGGCCAGTACTGCCT not specified Uncertain significance (Apr 20, 2020)917770
1-155900400-ATCTT-A Noonan syndrome 8 • Cardiovascular phenotype Conflicting classifications of pathogenicity (Jan 17, 2024)506383
1-155900402-C-T Noonan syndrome 8 • Cardiovascular phenotype Uncertain significance (May 19, 2023)1354441
1-155900402-CT-C Noonan syndrome 8 Uncertain significance (Dec 13, 2022)1353685
1-155900409-C-T not specified • Noonan syndrome 8 Likely benign (Apr 11, 2023)977724
1-155900409-CT-C Noonan syndrome 8 Uncertain significance (Jan 22, 2024)2891588
1-155900413-C-T Noonan syndrome and Noonan-related syndrome • Noonan syndrome 8 • Cardiovascular phenotype Uncertain significance (May 25, 2023)1334273
1-155900413-CG-C Noonan syndrome 8 Uncertain significance (Jul 14, 2023)2987133
1-155900414-G-A not specified • Noonan syndrome 8 • Noonan syndrome and Noonan-related syndrome • Cardiovascular phenotype Conflicting classifications of pathogenicity (Jan 29, 2024)280150
1-155900430-C-G Noonan syndrome 8 Uncertain significance (Mar 08, 2022)1972860
1-155900431-C-G Noonan syndrome 8 Uncertain significance (Jan 23, 2023)2057517
1-155900431-C-T Noonan syndrome 8 Uncertain significance (Dec 14, 2022)2820648
1-155900433-C-A Cardiovascular phenotype Uncertain significance (Oct 02, 2019)1751944
1-155900439-T-C Cardiovascular phenotype • Noonan syndrome 8 Likely benign (Apr 11, 2023)1751549
1-155900441-C-T Noonan syndrome 8 Uncertain significance (Apr 11, 2022)1958430
1-155900442-ACT-A Noonan syndrome 8 Uncertain significance (Jan 05, 2024)2707741
1-155900444-T-A not specified Uncertain significance (Nov 13, 2015)229202
1-155900445-G-A Noonan syndrome 8 Likely benign (Jun 19, 2019)1141728

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