RIT1

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

Basic information

Region (hg38): 1:155897807-155911404

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 (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 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 (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	1	45
missense	16	14	97			127
nonsense	1		3			4
start loss						0
frameshift			4			4
inframe indel			1			1
splice donor/acceptor (+/-2bp)			1			1
splice region			2	4	2	8
non coding			2	33	11	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)
1-155900379-ATCTTC-A		not specified	Uncertain significance (Apr 26, 2021)
1-155900389-C-T		Noonan syndrome 8	Likely benign (Sep 08, 2023)
1-155900393-TTA-GTG			Uncertain significance (Mar 20, 2023)
1-155900397-T-C		Noonan syndrome 8	Likely benign (Sep 10, 2023)
1-155900398-G-C		Noonan syndrome 8	Uncertain significance (Jun 21, 2022)
1-155900398-GA-G		Noonan syndrome 8	Uncertain significance (Jan 11, 2024)
1-155900399-A-AATCTTTCTTCTTCCGGAATGGTGATTTTAGCCTCTTCCATACACTGTTTTTGGGCTTAGATTTTTTCTCCATGGCCAGTACTGCCT		not specified	Uncertain significance (Apr 20, 2020)
1-155900400-ATCTT-A		Noonan syndrome 8 • Cardiovascular phenotype	Conflicting classifications of pathogenicity (Jan 17, 2024)
1-155900402-C-T		Noonan syndrome 8 • Cardiovascular phenotype	Uncertain significance (May 19, 2023)
1-155900402-CT-C		Noonan syndrome 8	Uncertain significance (Dec 13, 2022)
1-155900409-C-T		not specified • Noonan syndrome 8	Likely benign (Apr 11, 2023)
1-155900409-CT-C		Noonan syndrome 8	Uncertain significance (Jan 22, 2024)
1-155900413-C-T		Noonan syndrome and Noonan-related syndrome • Noonan syndrome 8 • Cardiovascular phenotype	Uncertain significance (May 25, 2023)
1-155900413-CG-C		Noonan syndrome 8	Uncertain significance (Jul 14, 2023)
1-155900414-G-A		Noonan syndrome 8 • not specified • Noonan syndrome and Noonan-related syndrome • Cardiovascular phenotype	Conflicting classifications of pathogenicity (Jan 29, 2024)
1-155900430-C-G		Noonan syndrome 8	Uncertain significance (Mar 08, 2022)
1-155900431-C-G		Noonan syndrome 8	Uncertain significance (Jan 23, 2023)
1-155900431-C-T		Noonan syndrome 8	Uncertain significance (Dec 14, 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)
1-155900442-ACT-A		Noonan syndrome 8	Uncertain significance (Jan 05, 2024)
1-155900444-T-A		not specified	Uncertain significance (Nov 13, 2015)
1-155900445-G-A		Noonan syndrome 8	Likely benign (Jun 19, 2019)

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