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