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GeneBe

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

ENSG00000047936NCBI:6098OMIM:165020HGNC:10261Uniprot:P08922AlphaFoldGenCCjaxSfariGnomADPubmedClinVar

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
clinvar
7
clinvar
18
missense
1
clinvar
72
clinvar
9
clinvar
12
clinvar
94
nonsense
0
start loss
0
frameshift
0
inframe indel
0
splice donor/acceptor (+/-2bp)
0
splice region
1
4
5
non coding
2
clinvar
4
clinvar
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)2251105
6-117288515-C-T not specified Uncertain significance (Jul 20, 2021)2238605
6-117288551-G-C ROS1-related condition Likely benign (Sep 08, 2022)3043741
6-117288553-T-C Benign (May 03, 2018)782476
6-117288576-T-G not specified Uncertain significance (Aug 02, 2021)2390651
6-117288584-C-T not specified Uncertain significance (Oct 26, 2022)2386720
6-117288766-T-C not specified Uncertain significance (Apr 25, 2023)2520402
6-117288789-A-C not specified Uncertain significance (Feb 12, 2024)3155780
6-117288800-C-T not specified Uncertain significance (Dec 14, 2023)3155779
6-117301013-C-T not specified Uncertain significance (Jan 30, 2021)1299379
6-117301048-T-A not specified Uncertain significance (Sep 28, 2022)2407943
6-117301068-G-T Likely benign (Nov 01, 2023)2673077
6-117301093-C-A not specified Uncertain significance (Aug 04, 2021)2257021
6-117308875-G-C not specified Uncertain significance (Dec 18, 2023)3155778
6-117310128-A-G Likely benign (May 01, 2022)2656869
6-117310138-C-T Conflicting classifications of pathogenicity (Jul 01, 2023)709394
6-117310199-C-A not specified Uncertain significance (Dec 08, 2023)3155777
6-117310251-G-A Likely benign (May 31, 2018)712707
6-117310261-C-T not specified Uncertain significance (May 03, 2023)2543434
6-117311093-C-T not specified Uncertain significance (Aug 19, 2023)2599207
6-117317154-G-A not specified Uncertain significance (Nov 08, 2022)2228048
6-117317179-G-T not specified Uncertain significance (Dec 13, 2023)3155776
6-117317181-C-T Lung sarcomatoid carcinoma Uncertain significance (-)2443073
6-117317184-C-T Lung adenocarcinoma Pathogenic/Likely pathogenic (Dec 26, 2014)376139
6-117317261-T-C not specified Uncertain significance (Sep 20, 2023)3155774

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
ROS1protein_codingprotein_codingENST00000368508 43137556
pLI Probability
LOF Intolerant
pRec Probability
LOF Recessive
Individuals with
no LOFs
Individuals with
Homozygous LOFs
Individuals with
Heterozygous LOFs
Defined p
1.62e-721.47e-1012515825881257480.00235
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense-0.50112431.19e+31.040.000058515335
Missense in Polyphen357353.451.014627
Synonymous-1.934784271.120.00002124463
Loss of Function0.4551131180.9550.000005661490

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.006340.00633
Ashkenazi Jewish0.000.00
East Asian0.001270.00125
Finnish0.001170.00116
European (Non-Finnish)0.002310.00230
Middle Eastern0.001270.00125
South Asian0.004200.00409
Other0.002470.00245

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

AllRecessiveDominant
MendelianHighHighHigh
Primary ImmunodeficiencyHighHighHigh
CancerHighHighHigh

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