EWSR1

EWS RNA binding protein 1, the group of RNA binding motif containing|Zinc fingers RANBP2-type

Basic information

Region (hg38): 22:29268009-29300525

Links

ENSG00000182944NCBI:2130OMIM:133450HGNC:3508Uniprot:Q01844AlphaFoldGenCCjaxSfariGnomADPubmedClinVar

Phenotypes

GenCC

Source: genCC

  • amyotrophic lateral sclerosis (Moderate), mode of inheritance: AD
  • amyotrophic lateral sclerosis (Disputed Evidence), mode of inheritance: Unknown

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the EWSR1 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the EWSR1 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
3
clinvar
3
clinvar
6
missense
21
clinvar
21
nonsense
0
start loss
0
frameshift
0
inframe indel
0
splice donor/acceptor (+/-2bp)
0
splice region
6
6
non coding
1
clinvar
1
clinvar
17
clinvar
19
Total 0 0 22 4 20

Variants in EWSR1

This is a list of pathogenic ClinVar variants found in the EWSR1 region.

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

Position Type Phenotype Significance ClinVar
22-29268334-A-G EWSR1-related disorder Likely benign (May 02, 2019)3037416
22-29268348-G-A EWSR1-related disorder Likely benign (Sep 09, 2019)3040215
22-29268434-G-A Benign (Jun 18, 2021)1246240
22-29272015-C-T Benign (Jun 18, 2021)1220856
22-29272209-C-G Likely benign (Dec 14, 2018)796641
22-29272384-A-G not specified Uncertain significance (Dec 13, 2022)2334412
22-29273659-G-C Benign (Jun 18, 2021)1270867
22-29273704-T-C Benign (Jun 18, 2021)1276860
22-29273723-C-G Benign (Jun 18, 2021)1249698
22-29273778-C-A not specified Uncertain significance (Sep 22, 2023)3090930
22-29273840-A-G not specified Uncertain significance (May 11, 2022)2289055
22-29273848-T-C Likely benign (Mar 01, 2023)2653041
22-29274270-G-A not specified Uncertain significance (Oct 05, 2023)3090934
22-29278031-T-A Likely benign (May 29, 2018)745928
22-29278041-C-A Uncertain significance (Feb 01, 2024)3025886
22-29278047-G-A not specified Uncertain significance (Dec 20, 2022)2400055
22-29278075-A-C not specified Uncertain significance (Mar 30, 2024)3276726
22-29278203-A-G not specified Uncertain significance (Oct 03, 2022)2228234
22-29282413-C-T not specified Uncertain significance (Mar 18, 2024)3276724
22-29282488-G-C not specified Uncertain significance (Oct 13, 2023)3090935
22-29286712-A-T Benign (Jun 18, 2021)1248405
22-29286914-C-G Ewing sarcoma Benign (Dec 31, 2019)773619
22-29286941-G-A Benign (Dec 31, 2019)724658
22-29287056-A-G not specified Uncertain significance (Jun 16, 2023)2604237
22-29287109-A-G EWSR1-related disorder Benign (Mar 28, 2019)3048607

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
EWSR1protein_codingprotein_codingENST00000414183 1832518
pLI Probability
LOF Intolerant
pRec Probability
LOF Recessive
Individuals with
no LOFs
Individuals with
Homozygous LOFs
Individuals with
Heterozygous LOFs
Defined p
1.000.0001951257180301257480.000119
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense2.522563980.6440.00002274236
Missense in Polyphen3256.7780.5636722
Synonymous-1.491561341.160.000007131334
Loss of Function5.44442.00.09520.00000229456

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.0003730.000357
Ashkenazi Jewish0.000.00
East Asian0.00005810.0000544
Finnish0.0001020.0000924
European (Non-Finnish)0.0001530.000149
Middle Eastern0.00005810.0000544
South Asian0.00003270.0000327
Other0.0001630.000163

dbNSFP

Source: dbNSFP

Function
FUNCTION: Might normally function as a transcriptional repressor. EWS-fusion-proteins (EFPS) may play a role in the tumorigenic process. They may disturb gene expression by mimicking, or interfering with the normal function of CTD-POLII within the transcription initiation complex. They may also contribute to an aberrant activation of the fusion protein target genes.;
Disease
DISEASE: Ewing sarcoma (ES) [MIM:612219]: A highly malignant, metastatic, primitive small round cell tumor of bone and soft tissue that affects children and adolescents. It belongs to the Ewing sarcoma family of tumors, a group of morphologically heterogeneous neoplasms that share the same cytogenetic features. They are considered neural tumors derived from cells of the neural crest. Ewing sarcoma represents the less differentiated form of the tumors. {ECO:0000269|PubMed:15044653, ECO:0000269|PubMed:1522903, ECO:0000269|PubMed:7700648, ECO:0000269|PubMed:9121764}. Note=The protein represented in this entry is involved in disease pathogenesis. Chromosomal aberrations involving EWSR1 are found in patients with Ewing sarcoma. Translocation t(11;22)(q24;q12) with FLI1 (PubMed:1522903, PubMed:15044653). Translocation t(7;22)(p22;q12) with ETV1 (PubMed:7700648). Translocation t(21;22)(q22;q21) with ERG (PubMed:15044653). Translocation t(2;21;22)(q23;q22;q12) that forms a EWSR1-FEV fusion protein with potential oncogenic activity (PubMed:9121764). {ECO:0000269|PubMed:15044653, ECO:0000269|PubMed:1522903, ECO:0000269|PubMed:7700648, ECO:0000269|PubMed:9121764}.; DISEASE: Note=A chromosomal aberration involving EWSR1 has been found in extraskeletal myxoid chondrosarcoma. Translocation t(9;22)(q22-31;q11-12) with NR4A3. {ECO:0000269|PubMed:7539287}.; DISEASE: Note=A chromosomal aberration involving EWSR1 is associated with desmoplastic small round cell tumor (DSRCT). Translocation t(11;22)(p13;q12) with WT1. {ECO:0000269|PubMed:7862627}.; DISEASE: Note=A chromosomal aberration involving EWSR1 is associated with malignant melanoma of soft parts (MMSP). Translocation t(12;22)(q13;q12) with ATF1. Malignant melanoma of soft parts, also known as soft tissue clear cell sarcoma, is a rare tumor developing in tendons and aponeuroses. {ECO:0000269|PubMed:8401579}.; DISEASE: Note=A chromosomal aberration involving EWSR1 is associated with small round cell sarcoma. Translocation t(11;22)(p36.1;q12) with PATZ1. {ECO:0000269|PubMed:10949935}.; DISEASE: Angiomatoid fibrous histiocytoma (AFH) [MIM:612160]: A distinct variant of malignant fibrous histiocytoma that typically occurs in children and adolescents and is manifest by nodular subcutaneous growth. Characteristic microscopic features include lobulated sheets of histiocyte-like cells intimately associated with areas of hemorrhage and cystic pseudovascular spaces, as well as a striking cuffing of inflammatory cells, mimicking a lymph node metastasis. {ECO:0000269|PubMed:15884099, ECO:0000269|PubMed:17724745}. Note=The gene represented in this entry is involved in disease pathogenesis. Chromosomal aberrations involving EWSR1 are found in patients with angiomatoid fibrous histiocytoma. Translocation t(12;22)(q13;q12) with ATF1 generates a chimeric EWSR1/ATF1 protein (PubMed:15884099). Translocation t(2;22)(q33;q12) with CREB1 generates a EWSR1/CREB1 fusion gene that is most common genetic abnormality in this tumor type (PubMed:17724745). {ECO:0000269|PubMed:15884099, ECO:0000269|PubMed:17724745}.; DISEASE: Note=EFPS arise due to chromosomal translocations in which EWSR1 is fused to a variety of cellular transcription factors. EFPS are very potent transcriptional activators dependent on the EAD and a C-terminal DNA-binding domain contributed by the fusion partner. The spectrum of malignancies associated with EFPS are thought to arise via EFP-induced transcriptional deregulation, with the tumor phenotype specified by the EWSR1 fusion partner and cell type. Transcriptional repression of the transforming growth factor beta type II receptor (TGF beta RII) is an important target of the EWS-FLI1, EWS-ERG, or EWS-ETV1 oncogene. {ECO:0000305}.;
Pathway
Transcriptional misregulation in cancer - Homo sapiens (human);TGF_beta_Receptor;BARD1 signaling events (Consensus)

Recessive Scores

pRec
0.431

Intolerance Scores

loftool
0.0688
rvis_EVS
-0.78
rvis_percentile_EVS
12.88

Haploinsufficiency Scores

pHI
0.956
hipred
Y
hipred_score
0.783
ghis
0.658

Essentials

essential_gene_CRISPR
N
essential_gene_CRISPR2
E
essential_gene_gene_trap
E
gene_indispensability_pred
E
gene_indispensability_score
0.884

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

Mouse Genome Informatics

Gene name
Ewsr1
Phenotype
adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); endocrine/exocrine gland phenotype; growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); muscle phenotype; immune system phenotype; homeostasis/metabolism phenotype; cellular phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); neoplasm; hematopoietic system phenotype; normal phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); reproductive system phenotype; limbs/digits/tail phenotype; hearing/vestibular/ear phenotype; renal/urinary system phenotype; skeleton phenotype;

Zebrafish Information Network

Gene name
ewsr1a
Affected structure
cell
Phenotype tag
abnormal
Phenotype quality
structure

Gene ontology

Biological process
regulation of transcription, DNA-templated
Cellular component
nucleus;nucleolus;cytoplasm;plasma membrane
Molecular function
RNA binding;protein binding;calmodulin binding;identical protein binding;metal ion binding