RRAS

RAS related, the group of RAS type GTPase family

Basic information

Region (hg38): 19:49635291-49640143

Links

ENSG00000126458 ∙ NCBI:6237 ∙ OMIM:165090 ∙ HGNC:10447 ∙ Uniprot:P10301 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Noonan syndrome (Moderate), mode of inheritance: AD
• Noonan syndrome (Limited), mode of inheritance: AD

ClinVar

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

• Noonan syndrome (194 variants)
• Inborn genetic diseases (88 variants)
• not specified (44 variants)
• not provided (33 variants)
• RRAS-related condition (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the RRAS 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				62	1	63
missense			108	3	1	112
nonsense			1			1
start loss			3			3
frameshift			3			3
inframe indel		1				1
splice donor/acceptor (+/-2bp)			1			1
splice region			11	10		21
non coding			7	24	11	42
Total	0	1	123	89	13

Variants in RRAS

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

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

Position	Type	Phenotype	Significance	ClinVar
19-49635346-G-A			Uncertain significance (Feb 04, 2022)
19-49635571-C-T		not specified • RRAS-related disorder	Conflicting classifications of pathogenicity (May 28, 2023)
19-49635572-T-C		not specified • RRAS-related disorder	Benign (Apr 27, 2021)
19-49635581-G-A		Noonan syndrome • not specified	Likely benign (Feb 05, 2023)
19-49635584-G-C		Noonan syndrome	Uncertain significance (Jun 26, 2018)
19-49635587-C-T		Noonan syndrome • not specified	Uncertain significance (Dec 15, 2022)
19-49635588-G-A		Noonan syndrome • RRAS-related disorder • not specified	Likely benign (Jun 14, 2022)
19-49635590-A-G		Noonan syndrome	Uncertain significance (Jul 13, 2022)
19-49635591-G-A		Noonan syndrome • not specified	Likely benign (May 17, 2022)
19-49635602-C-T		Noonan syndrome • not specified	Uncertain significance (Dec 30, 2023)
19-49635603-G-A		Noonan syndrome • RRAS-related disorder • not specified	Likely benign (Oct 17, 2022)
19-49635606-C-A		Noonan syndrome • not specified	Uncertain significance (Jan 07, 2020)
19-49635609-C-T		Noonan syndrome	Likely benign (Nov 01, 2021)
19-49635610-T-C		Noonan syndrome • not specified	Uncertain significance (Nov 04, 2023)
19-49635613-C-T		not specified	Uncertain significance (Nov 05, 2021)
19-49635617-G-A		not specified	Uncertain significance (Jan 22, 2024)
19-49635619-G-A		Noonan syndrome • not specified	Uncertain significance (Jul 14, 2022)
19-49635620-C-T		not specified	Likely benign (Dec 07, 2021)
19-49635623-T-C		Noonan syndrome	Uncertain significance (Aug 05, 2022)
19-49635624-G-A		Noonan syndrome • RRAS-related disorder	Likely benign (Jul 28, 2023)
19-49635633-C-T		Noonan syndrome • not specified • RRAS-related disorder	Benign/Likely benign (Nov 13, 2023)
19-49635634-G-A		Noonan syndrome	Uncertain significance (May 12, 2022)
19-49635635-G-A		Noonan syndrome	Uncertain significance (Aug 22, 2023)
19-49635648-T-C		not specified	Likely benign (Jan 27, 2020)
19-49635657-T-C		Noonan syndrome	Uncertain significance (Feb 11, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
RRAS	protein_coding	protein_coding	ENST00000246792	6	4910

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00466	0.888	125691	0	56	125747	0.000223

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.676	110	132	0.834	0.00000857	1379
Missense in Polyphen		38	46.768	0.81253		487
Synonymous	-0.0423	59	58.6	1.01	0.00000420	450
Loss of Function	1.37	5	9.56	0.523	4.53e-7	110

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000589	0.0000589
Ashkenazi Jewish	0.000102	0.0000992
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.000478	0.000457
Middle Eastern	0.00	0.00
South Asian	0.0000331	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Regulates the organization of the actin cytoskeleton (PubMed:16537651, PubMed:18270267). With OSPBL3, modulates integrin beta-1 (ITGB1) activity (PubMed:18270267). {ECO:0000269|PubMed:16537651, ECO:0000269|PubMed:18270267}.
• Pathway: Autophagy - animal - Homo sapiens (human);HTLV-I infection - Homo sapiens (human);Regulation of actin cytoskeleton - Homo sapiens (human);Mitophagy - animal - Homo sapiens (human);Axon guidance - Homo sapiens (human);cAMP signaling pathway - Homo sapiens (human);Apelin signaling pathway - Homo sapiens (human);C-type lectin receptor signaling pathway - Homo sapiens (human);Rap1 signaling pathway - Homo sapiens (human);Ras signaling pathway - Homo sapiens (human);MAPK signaling pathway - Homo sapiens (human);Phospholipase D signaling pathway - Homo sapiens (human);Proteoglycans in cancer - Homo sapiens (human);Cellular senescence - Homo sapiens (human);EGFR Inhibitor Pathway, Pharmacodynamics;Bisphosphonate Pathway, Pharmacodynamics;Vemurafenib Pathway, Pharmacodynamics;update your name in edit mode;G Protein Signaling Pathways;MAPK Signaling Pathway;Canonical and Non-canonical Notch signaling;MAPK and NFkB Signalling Pathways Inhibited by Yersinia YopJ;T-Cell antigen Receptor (TCR) pathway during Staphylococcus aureus infection;MAPK Cascade;Ras Signaling;Regulation of Actin Cytoskeleton;Developmental Biology;Regulation of Ras family activation;Neuronal System;Sema4D mediated inhibition of cell attachment and migration;Sema4D in semaphorin signaling;SEMA3A-Plexin repulsion signaling by inhibiting Integrin adhesion;Semaphorin interactions;Neurotransmitter receptors and postsynaptic signal transmission;Transmission across Chemical Synapses;Plexin-D1 Signaling;Axon guidance;CREB phosphorylation through the activation of Ras;Post NMDA receptor activation events;Activation of NMDA receptor and postsynaptic events;Signaling events mediated by focal adhesion kinase;EPHB forward signaling (Consensus)

Recessive Scores

• pRec: 0.199

Intolerance Scores

• loftool: 0.435
• rvis_EVS: 0.24
• rvis_percentile_EVS: 69.21

Haploinsufficiency Scores

• pHI: 0.193
• hipred: Y
• hipred_score: 0.756
• ghis: 0.530

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.590

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Rras
• Phenotype: homeostasis/metabolism phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); hematopoietic system phenotype; neoplasm; immune system phenotype

Zebrafish Information Network

• Gene name: rras
• Affected structure: vagal ganglion
• Phenotype tag: abnormal
• Phenotype quality: fused with

Gene ontology

• Biological process: leukocyte differentiation;Ras protein signal transduction;negative regulation of cell migration;positive regulation of angiogenesis;regulation of protein kinase B signaling;face morphogenesis;regulation of ERK1 and ERK2 cascade
• Cellular component: plasma membrane;focal adhesion;extracellular exosome
• Molecular function: GTPase activity;protein binding;GTP binding;GDP binding;protein-containing complex binding