EXT2

exostosin glycosyltransferase 2, the group of Exostosin glycosyltransferase family

Basic information

Region (hg38): 11:44095648-44251962

Links

ENSG00000151348NCBI:2132OMIM:608210HGNC:3513Uniprot:Q93063AlphaFoldGenCCjaxSfariGnomADPubmedClinVar

Phenotypes

GenCC

Source: genCC

  • exostoses, multiple, type 2 (Definitive), mode of inheritance: AD
  • exostoses, multiple, type 2 (Strong), mode of inheritance: AD
  • exostoses, multiple, type 2 (Definitive), mode of inheritance: AD
  • seizures-scoliosis-macrocephaly syndrome (Limited), mode of inheritance: AR
  • hereditary multiple osteochondromas (Supportive), mode of inheritance: AD
  • seizures-scoliosis-macrocephaly syndrome (Supportive), mode of inheritance: AR
  • exostoses, multiple, type 2 (Strong), mode of inheritance: AD
  • seizures-scoliosis-macrocephaly syndrome (Strong), mode of inheritance: AR
  • exostoses, multiple, type 2 (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Exostoses, multiple, type 2ADOncologicThough data regarding the efficacy of surveillance are lacking, individuals are at risk for the (relatively infrequent) development of malignant change of exostoses, and awareness may allow early detection and managementCraniofacial; Gastrointestinal; Genitourinary; Musculoskeletal; Neurologic; Oncologic7726168; 8782816; 8894688; 9326317; 9463333; 10679937; 11432960; 16879194; 19344451; 20301413; 22258776; 23629877; 23770606; 26246518
Though onset of malignancy is typically described in adulthood, some individuals have been affected at an earlier age; Germline variants have also been implicated in chondrosarcoma

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the EXT2 gene.

  • Exostoses,_multiple,_type_2 (781 variants)
  • not_provided (136 variants)
  • Inborn_genetic_diseases (79 variants)
  • Seizures-scoliosis-macrocephaly_syndrome (62 variants)
  • EXT2-related_disorder (47 variants)
  • not_specified (26 variants)
  • Exostoses,_multiple,_type_1 (11 variants)
  • Ovarian_cancer (7 variants)
  • Multiple_congenital_exostosis (5 variants)
  • Hereditary_cancer-predisposing_syndrome (1 variants)
  • Hereditary_Multiple_Osteochondromatosis (1 variants)
  • Hepatoblastoma (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the EXT2 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000207122.2. Only rare variants are included in the table.

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.

EffectPLPVUSLBBSum
synonymous
2
clinvar
6
clinvar
141
clinvar
8
clinvar
157
missense
6
clinvar
10
clinvar
336
clinvar
46
clinvar
6
clinvar
404
nonsense
55
clinvar
10
clinvar
1
clinvar
66
start loss
1
1
frameshift
81
clinvar
12
clinvar
1
clinvar
94
splice donor/acceptor (+/-2bp)
29
clinvar
13
clinvar
2
clinvar
44
Total 171 47 347 187 14

Highest pathogenic variant AF is 0.0000576229

Loading clinvar variants...

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
EXT2protein_codingprotein_codingENST00000395673 14149881
pLI Probability
LOF Intolerant
pRec Probability
LOF Recessive
Individuals with
no LOFs
Individuals with
Homozygous LOFs
Individuals with
Heterozygous LOFs
Defined p
1.32e-90.9971256950531257480.000211
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense0.6403944310.9130.00002594918
Missense in Polyphen129160.210.805211844
Synonymous-0.2421691651.020.000009811466
Loss of Function2.732139.50.5320.00000216444

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.0006910.000691
Ashkenazi Jewish0.000.00
East Asian0.0001090.000109
Finnish0.00009240.0000924
European (Non-Finnish)0.0001940.000193
Middle Eastern0.0001090.000109
South Asian0.0002940.000261
Other0.0004890.000489

dbNSFP

Source: dbNSFP

Function
FUNCTION: Glycosyltransferase required for the biosynthesis of heparan-sulfate. The EXT1/EXT2 complex possesses substantially higher glycosyltransferase activity than EXT1 or EXT2 alone. Appears to be a tumor suppressor. Required for the exosomal release of SDCBP, CD63 and syndecan (PubMed:22660413). {ECO:0000269|PubMed:22660413}.;
Disease
DISEASE: Potocki-Shaffer syndrome (POSHS) [MIM:601224]: A syndrome characterized by foramina parietalia permagna, multiple exostoses, and craniofacial dysostosis and mental retardation in some cases. Note=The gene represented in this entry is involved in disease pathogenesis.; DISEASE: Seizures, scoliosis, and macrocephaly syndrome (SSMS) [MIM:616682]: An autosomal recessive syndrome characterized by seizures, intellectual disability, hypotonia, scoliosis, macrocephaly, hypertelorism and renal dysfunction. {ECO:0000269|PubMed:26246518}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway
Glycosaminoglycan biosynthesis - heparan sulfate / heparin - Homo sapiens (human);Mesodermal Commitment Pathway;Metabolism of carbohydrates;HS-GAG biosynthesis;Heparan sulfate/heparin (HS-GAG) metabolism;Glycosaminoglycan metabolism;Proteoglycan biosynthesis;heparan sulfate biosynthesis (late stages);heparan sulfate biosynthesis;Metabolism (Consensus)

Recessive Scores

pRec
0.121

Intolerance Scores

loftool
0.0377
rvis_EVS
-0.48
rvis_percentile_EVS
22.75

Haploinsufficiency Scores

pHI
0.116
hipred
Y
hipred_score
0.661
ghis
0.557

Essentials

essential_gene_CRISPR
N
essential_gene_CRISPR2
N
essential_gene_gene_trap
N
gene_indispensability_pred
E
gene_indispensability_score
0.748

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

Mouse Genome Informatics

Gene name
Ext2
Phenotype
skeleton phenotype; embryo 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);

Zebrafish Information Network

Gene name
ext2
Affected structure
retinal ganglion cell
Phenotype tag
abnormal
Phenotype quality
organization quality

Gene ontology

Biological process
ossification;mesoderm formation;glycosaminoglycan biosynthetic process;protein glycosylation;signal transduction;heparan sulfate proteoglycan biosynthetic process;heparan sulfate proteoglycan biosynthetic process, polysaccharide chain biosynthetic process;cell differentiation;cellular polysaccharide biosynthetic process
Cellular component
Golgi membrane;endoplasmic reticulum;endoplasmic reticulum membrane;Golgi apparatus;membrane;integral component of membrane;UDP-N-acetylglucosamine transferase complex;extracellular exosome
Molecular function
protein binding;acetylglucosaminyltransferase activity;glucuronosyltransferase activity;transferase activity, transferring glycosyl groups;heparan sulfate N-acetylglucosaminyltransferase activity;protein homodimerization activity;metal ion binding;protein heterodimerization activity;glucuronosyl-N-acetylglucosaminyl-proteoglycan 4-alpha-N-acetylglucosaminyltransferase activity;N-acetylglucosaminyl-proteoglycan 4-beta-glucuronosyltransferase activity