ROS1

ROS proto-oncogene 1, receptor tyrosine kinase, the group of Fibronectin type III domain containing|Receptor tyrosine kinases

Basic information

Region (hg38): 6:117287352-117425942

Links

ENSG00000047936 ∙ NCBI:6098 ∙ OMIM:165020 ∙ HGNC:10261 ∙ Uniprot:P08922 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• male infertility with azoospermia or oligozoospermia due to single gene mutation (Moderate), mode of inheritance: AR
• breast cancer (Limited), mode of inheritance: AD

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ROS1 gene.

• Inborn genetic diseases (70 variants)
• not provided (49 variants)
• Lung adenocarcinoma (5 variants)
• Squamous cell carcinoma (1 variants)
• not specified (1 variants)
• Abnormal brain morphology (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ROS1 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				11	7	18
missense	1		72	9	12	94
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				1	4	5
non coding			2		4	6
Total	1	0	74	20	23

Highest pathogenic variant AF is 0.000178

Variants in ROS1

This is a list of pathogenic ClinVar variants found in the ROS1 region.

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

Position	Type	Phenotype	Significance	ClinVar
6-117288506-C-T		not specified	Uncertain significance (Sep 16, 2021)
6-117288515-C-T		not specified	Uncertain significance (Jul 20, 2021)
6-117288551-G-C		ROS1-related disorder	Likely benign (Sep 08, 2022)
6-117288553-T-C			Benign (May 03, 2018)
6-117288576-T-G		not specified	Uncertain significance (Aug 02, 2021)
6-117288584-C-T		not specified	Uncertain significance (Oct 26, 2022)
6-117288766-T-C		not specified	Uncertain significance (Apr 25, 2023)
6-117288789-A-C		not specified	Uncertain significance (Feb 12, 2024)
6-117288800-C-T		not specified	Uncertain significance (Dec 14, 2023)
6-117301013-C-T		not specified	Uncertain significance (Jan 30, 2021)
6-117301048-T-A		not specified	Uncertain significance (Sep 28, 2022)
6-117301068-G-T			Likely benign (Nov 01, 2023)
6-117301093-C-A		not specified	Uncertain significance (Aug 04, 2021)
6-117308875-G-C		not specified	Uncertain significance (Dec 18, 2023)
6-117310128-A-G			Likely benign (May 01, 2022)
6-117310138-C-T			Conflicting classifications of pathogenicity (Jul 01, 2023)
6-117310199-C-A		not specified	Uncertain significance (Dec 08, 2023)
6-117310251-G-A			Likely benign (May 31, 2018)
6-117310261-C-T		not specified	Uncertain significance (May 03, 2023)
6-117311093-C-T		not specified	Uncertain significance (Aug 19, 2023)
6-117317154-G-A		not specified	Uncertain significance (Nov 08, 2022)
6-117317179-G-T		not specified	Uncertain significance (Dec 13, 2023)
6-117317181-C-T		Lung sarcomatoid carcinoma	Uncertain significance (-)
6-117317184-C-T		Lung adenocarcinoma	Pathogenic/Likely pathogenic (Dec 26, 2014)
6-117317261-T-C		not specified	Uncertain significance (Sep 20, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ROS1	protein_coding	protein_coding	ENST00000368508	43	137556

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.62e-72	1.47e-10	125158	2	588	125748	0.00235

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.501	1243	1.19e+3	1.04	0.0000585	15335
Missense in Polyphen		357	353.45	1.01		4627
Synonymous	-1.93	478	427	1.12	0.0000212	4463
Loss of Function	0.455	113	118	0.955	0.00000566	1490

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00634	0.00633
Ashkenazi Jewish	0.00	0.00
East Asian	0.00127	0.00125
Finnish	0.00117	0.00116
European (Non-Finnish)	0.00231	0.00230
Middle Eastern	0.00127	0.00125
South Asian	0.00420	0.00409
Other	0.00247	0.00245

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Orphan receptor tyrosine kinase (RTK) that plays a role in epithelial cell differentiation and regionalization of the proximal epididymal epithelium. May activate several downstream signaling pathways related to cell differentiation, proliferation, growth and survival including the PI3 kinase-mTOR signaling pathway. Mediates the phosphorylation of PTPN11, an activator of this pathway. May also phosphorylate and activate the transcription factor STAT3 to control anchorage-independent cell growth. Mediates the phosphorylation and the activation of VAV3, a guanine nucleotide exchange factor regulating cell morphology. May activate other downstream signaling proteins including AKT1, MAPK1, MAPK3, IRS1 and PLCG2. {ECO:0000269|PubMed:11094073, ECO:0000269|PubMed:16885344}.
• Disease: DISEASE: Note=A chromosomal aberration involving ROS1 is found in a glioblastoma multiforme sample. An intra-chromosomal deletion del(6)(q21q21) is responsible for the formation of GOPC-ROS1 chimeric protein which is localized to the Golgi and has a constitutive receptor tyrosine kinase activity. A SLC34A2-ROS1 chimeric protein produced in non-small cell lung cancer cells also retains a constitutive kinase activity. A third type of chimeric protein CD74-ROS1 was also identified in those cells. {ECO:0000269|PubMed:12661006}.
• Pathway: Spinal Cord Injury;NAD metabolism, sirtuins and aging (Consensus)

Recessive Scores

• pRec: 0.247

Intolerance Scores

• loftool: 0.134
• rvis_EVS: -0.03
• rvis_percentile_EVS: 51.41

Haploinsufficiency Scores

• pHI: 0.602
• hipred: N
• hipred_score: 0.325
• ghis: 0.371

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.603

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	High	High	High
Primary Immunodeficiency	High	High	High
Cancer	High	High	High

Mouse Genome Informatics

• Gene name: Ros1
• Phenotype: reproductive system phenotype; cellular phenotype

Gene ontology

• Biological process: regulation of cell growth;columnar/cuboidal epithelial cell development;protein phosphorylation;transmembrane receptor protein tyrosine kinase signaling pathway;spermatogenesis;cell population proliferation;negative regulation of gene expression;regulation of phosphate transport;signal transduction by protein phosphorylation;cell differentiation;regulation of TOR signaling;peptidyl-tyrosine autophosphorylation;regulation of ERK1 and ERK2 cascade
• Cellular component: integral component of plasma membrane;cell surface;membrane;receptor complex;perinuclear region of cytoplasm
• Molecular function: protein tyrosine kinase activity;transmembrane receptor protein tyrosine kinase activity;protein binding;ATP binding;protein phosphatase binding