Menu
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:P08922AlphaFoldGenCCjaxSfariGnomADPubmed

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 (45 variants)
  • not provided (42 variants)
  • Lung adenocarcinoma (6 variants)
  • not specified (3 variants)
  • Short stature (2 variants)
  • Squamous cell carcinoma (1 variants)
  • Abnormality of 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.

Variant type Pathogenic Likely pathogenic VUS Likely benign Benign Sum
synonymous 7 9 16
missense 1 1 50 7 14 73
nonsense 0
start loss 0
frameshift 1 1
inframe indel 0
splice variant 1 3 4
non coding 2 3 5
Total 2 1 52 15 29

Highest pathogenic variant AF is 0.000178

Variants in ROS1

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

Position Type Phenotype Significance ClinVar
6-117288506-C-T Inborn genetic diseases Uncertain significance (Sep 16, 2021)link
6-117288515-C-T Inborn genetic diseases Uncertain significance (Jul 20, 2021)link
6-117288553-T-C Benign (May 03, 2018)link
6-117288576-T-G Inborn genetic diseases Uncertain significance (Aug 02, 2021)link
6-117288584-C-T Inborn genetic diseases Uncertain significance (Oct 26, 2022)link
6-117288766-T-C Inborn genetic diseases Uncertain significance (Apr 25, 2023)link
6-117301013-C-T not specified Uncertain significance (Jan 30, 2021)link
6-117301048-T-A Inborn genetic diseases Uncertain significance (Sep 28, 2022)link
6-117301093-C-A Inborn genetic diseases Uncertain significance (Aug 04, 2021)link
6-117310138-C-T Benign (Jul 12, 2018)link
6-117310251-G-A Likely benign (May 31, 2018)link
6-117310261-C-T Inborn genetic diseases Uncertain significance (May 03, 2023)link
6-117311093-C-T Inborn genetic diseases Uncertain significance (Aug 19, 2023)link
6-117317154-G-A Inborn genetic diseases Uncertain significance (Nov 08, 2022)link
6-117317181-C-T Lung sarcomatoid carcinoma Uncertain significance (-)link
6-117317184-C-T Lung adenocarcinoma Pathogenic/Likely pathogenic (Dec 26, 2014)link
6-117318226-C-A Inborn genetic diseases Uncertain significance (Mar 24, 2023)link
6-117319897-C-T Inborn genetic diseases Uncertain significance (Dec 06, 2021)link
6-117319899-A-T Inborn genetic diseases Uncertain significance (Oct 29, 2021)link
6-117321332-C-T Benign (Jul 27, 2018)link
6-117321368-T-C Likely benign (Jul 23, 2018)link
6-117321388-T-C Inborn genetic diseases Uncertain significance (Jun 18, 2021)link
6-117329320-C-T Benign (Mar 30, 2018)link
6-117329351-T-G Inborn genetic diseases Uncertain significance (Apr 07, 2023)link
6-117329360-A-G Inborn genetic diseases Uncertain significance (Jun 24, 2022)link

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