RIT1

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

Basic information

Region (hg38): 1:155897808-155911404

Previous symbols: [ "RIT" ]

Links

ENSG00000143622

∙ NCBI:6016 ∙ OMIM:609591 ∙ HGNC:10023 ∙ Uniprot:Q92963 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

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: CGD

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 ClinVar and linked to the RIT1 gene.

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			1 clinvar	77 clinvar	1 clinvar	79
missense	17 clinvar	21 clinvar	154 clinvar	10 clinvar		202
nonsense	1 clinvar		2 clinvar	1 clinvar		4
start loss						0
frameshift			7 clinvar	1 clinvar		8
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	18	21	165	89	1

Highest pathogenic variant AF is 0.00000656901

Loading clinvar variants...

GnomAD

Source: gnomAD

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: 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

	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