MRAS

muscle RAS oncogene homolog, the group of RAS type GTPase family

Basic information

Region (hg38): 3:138347647-138405534

Links

ENSG00000158186 ∙ NCBI:22808 ∙ OMIM:608435 ∙ HGNC:7227 ∙ Uniprot:O14807 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Noonan syndrome 11 (Strong), mode of inheritance: AD
• Noonan syndrome 11 (Definitive), mode of inheritance: AD
• Noonan syndrome 11 (Moderate), mode of inheritance: AD
• Noonan syndrome 11 (Strong), mode of inheritance: AD
• Noonan syndrome (Supportive), mode of inheritance: AD
• Noonan syndrome 11 (Strong), mode of inheritance: AD
• Noonan syndrome (Moderate), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Noonan syndrome 11	AD	Cardiovascular	Individuals have been described with cardiac disease, inclduing cardiomyopathy as well as structural cardiac anomalies, and awareness may allow early diagnosis and management (surgical management has been described)	Cardiovascular; Craniofacial; Musculoskeletal; Neurologic	28289718; 31173466

ClinVar

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

• not provided (124 variants)
• Inborn genetic diseases (50 variants)
• not specified (15 variants)
• Noonan syndrome 11 (3 variants)
• RASopathy (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MRAS 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				46	1	47
missense	3	1	50			54
nonsense			1			1
start loss						0
frameshift			1			1
inframe indel						0
splice donor/acceptor (+/-2bp)					1	1
splice region			3	10	2	15
non coding			3	20	7	30
Total	3	1	55	66	9

Variants in MRAS

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

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

Position	Type	Phenotype	Significance	ClinVar
3-138372859-G-T			Benign (May 04, 2021)
3-138372877-G-A		not specified • MRAS-related disorder	Conflicting classifications of pathogenicity (Jun 28, 2021)
3-138372895-C-T		Inborn genetic diseases	Likely benign (Jan 29, 2024)
3-138372896-G-A			Uncertain significance (Aug 10, 2023)
3-138372898-C-T		Inborn genetic diseases	Likely benign (Dec 30, 2023)
3-138372899-G-A		Inborn genetic diseases • not specified	Uncertain significance (Jan 03, 2024)
3-138372905-A-G		Inborn genetic diseases	Conflicting classifications of pathogenicity (Oct 28, 2023)
3-138372906-G-C			Uncertain significance (Nov 08, 2023)
3-138372910-C-A			Uncertain significance (Jul 09, 2022)
3-138372912-A-G		Inborn genetic diseases	Uncertain significance (Oct 08, 2023)
3-138372913-C-T			Likely benign (Feb 22, 2023)
3-138372915-T-C			Uncertain significance (Jun 03, 2022)
3-138372919-C-T			Likely benign (Jul 07, 2023)
3-138372921-C-T			Uncertain significance (Jul 25, 2023)
3-138372922-A-G			Likely benign (Jul 06, 2022)
3-138372925-C-T		Inborn genetic diseases	Likely benign (Jan 03, 2024)
3-138372928-G-A		Inborn genetic diseases	Likely benign (Jan 20, 2023)
3-138372940-G-A			Likely benign (Nov 09, 2021)
3-138372949-G-T		Inborn genetic diseases	Benign/Likely benign (Jan 05, 2024)
3-138372950-G-C		RASopathy	Likely pathogenic (May 15, 2018)
3-138372951-G-T		Noonan syndrome 11 • RASopathy	Pathogenic (Feb 23, 2023)
3-138372963-G-C		Inborn genetic diseases	Uncertain significance (Jan 14, 2020)
3-138372967-C-A			Likely benign (Dec 17, 2022)
3-138372968-C-T			Uncertain significance (Oct 13, 2022)
3-138372997-T-C			Likely benign (Oct 13, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MRAS	protein_coding	protein_coding	ENST00000289104	5	57837

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.921	0.0785	125714	0	8	125722	0.0000318

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.33	56	131	0.428	0.00000816	1393
Missense in Polyphen		12	56.376	0.21286		612
Synonymous	0.594	46	51.4	0.895	0.00000347	375
Loss of Function	2.64	0	8.14	0.00	3.42e-7	109

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000246	0.000246
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000275	0.0000264
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: May serve as an important signal transducer for a novel upstream stimuli in controlling cell proliferation. Weakly activates the MAP kinase pathway. {ECO:0000269|PubMed:16630891}.
• Pathway: Autophagy - animal - Homo sapiens (human);HTLV-I infection - Homo sapiens (human);Regulation of actin cytoskeleton - Homo sapiens (human);Mitophagy - animal - 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;MAPK Signaling Pathway;Ras Signaling;Regulation of Actin Cytoskeleton (Consensus)

Recessive Scores

• pRec: 0.178

Intolerance Scores

• rvis_EVS: -0.14
• rvis_percentile_EVS: 42.88

Haploinsufficiency Scores

• pHI: 0.267
• hipred: Y
• hipred_score: 0.825
• ghis: 0.597

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.902

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Mras
• Phenotype: hematopoietic system phenotype; normal phenotype; immune system phenotype

Gene ontology

• Biological process: Ras protein signal transduction;multicellular organism development;muscle organ development;actin cytoskeleton organization;cellular response to leukemia inhibitory factor
• Cellular component: plasma membrane
• Molecular function: GTPase activity;protein binding;GTP binding;GTP-dependent protein binding