EXT1
exostosin glycosyltransferase 1, the group of Exostosin glycosyltransferase family
Basic information
Region (hg38): 8:117794489-118111826
Previous symbols: [ "LGCR", "LGS" ]
Links
Phenotypes
GenCC
Source:
- exostoses, multiple, type 1 (Definitive), mode of inheritance: AD
- trichorhinophalangeal syndrome type II (Definitive), mode of inheritance: AD
- chondrosarcoma (Strong), mode of inheritance: AD
- exostoses, multiple, type 1 (Strong), mode of inheritance: AD
- hereditary multiple osteochondromas (Supportive), mode of inheritance: AD
- exostoses, multiple, type 1 (Definitive), mode of inheritance: AD
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Exostoses, multiple, type 1; Chondrosarcoma | AD | Oncologic | In Exostoses, multiple, type 1, though 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 management; In Chondrosarcoma, individuals may be at risk of chondrosarcoma, and awareness may allow early diagnosis and management | Musculoskeletal; Oncologic | 7550340; 8981950; 9326317; 9521425; 9463333; 10679937; 11432960; 11170095; 15253765; 16879194; 19344451; 20301413; 22258776; 23629877; 23770606 |
| 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
- Multiple congenital exostosis (702 variants)
- not provided (143 variants)
- Chondrosarcoma (73 variants)
- Exostoses, multiple, type 1 (50 variants)
- not specified (18 variants)
- Inborn genetic diseases (14 variants)
- EXT1-related condition (11 variants)
- Ovarian cancer (8 variants)
- Hereditary Multiple Osteochondromatosis (5 variants)
- Chondrosarcoma;Exostoses, multiple, type 1 (3 variants)
- Langer-Giedion syndrome (2 variants)
- Abnormality of the skeletal system (1 variants)
- Microcephaly (1 variants)
- Malignant tumor of breast (1 variants)
- Exostoses, multiple, type 1;Chondrosarcoma (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the EXT1 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 | 87 | 13 | 104 | |||
| missense | 18 | 18 | 215 | 264 | ||
| nonsense | 101 | 10 | 113 | |||
| start loss | 1 | |||||
| frameshift | 164 | 173 | ||||
| inframe indel | 10 | |||||
| splice donor/acceptor (+/-2bp) | 49 | 58 | ||||
| splice region ? | 1 | 2 | 11 | 9 | 2 | 25 |
| non coding ? | 18 | 37 | 26 | 81 | ||
| Total | 335 | 45 | 248 | 132 | 44 |
Highest pathogenic variant AF is 0.00000657
Variants in EXT1
This is a list of pathogenic ClinVar variants found in the EXT1 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| EXT1 | protein_coding | protein_coding | ENST00000378204 | 11 | 317364 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.997 | 0.00268 | 125741 | 0 | 7 | 125748 | 0.0000278 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 1.67 | 317 | 412 | 0.769 | 0.0000223 | 4940 |
| Missense in Polyphen | 90 | 171.94 | 0.52344 | 2147 | ||
| Synonymous | -0.729 | 171 | 159 | 1.07 | 0.00000924 | 1399 |
| Loss of Function | 4.86 | 4 | 35.0 | 0.114 | 0.00000161 | 420 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.00 | 0.00 |
| Ashkenazi Jewish | 0.0000997 | 0.0000992 |
| East Asian | 0.000109 | 0.000109 |
| Finnish | 0.0000465 | 0.0000462 |
| European (Non-Finnish) | 0.0000264 | 0.0000264 |
| Middle Eastern | 0.000109 | 0.000109 |
| South Asian | 0.00 | 0.00 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- 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:11518722, ECO:0000269|PubMed:22660413}.;
- Disease
- DISEASE: Tricho-rhino-phalangeal syndrome 2 (TRPS2) [MIM:150230]: A syndrome that combines the clinical features of tricho-rhino- phalangeal syndrome type 1 and multiple exostoses type 1. Affected individuals manifest multiple dysmorphic facial features including large, laterally protruding ears, a bulbous nose, an elongated upper lip, as well as sparse scalp hair, winged scapulae, multiple cartilaginous exostoses, redundant skin, and mental retardation. Note=The gene represented in this entry is involved in disease pathogenesis. A chromosomal aberration resulting in the loss of functional copies of TRPS1 and EXT1 has been found in TRPS2 patients.; DISEASE: Chondrosarcoma (CHDSA) [MIM:215300]: A malignant neoplasm derived from cartilage cells. Chondrosarcomas range from slow- growing non-metastasizing lesions to highly aggressive metastasizing sarcomas. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- Glycosaminoglycan biosynthesis - heparan sulfate / heparin - Homo sapiens (human);Endoderm Differentiation;Mesodermal Commitment Pathway;Olfactory bulb development and olfactory learning;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
- 0.268
Intolerance Scores
- loftool
- 0.00765
- rvis_EVS
- -1.13
- rvis_percentile_EVS
- 6.43
Haploinsufficiency Scores
- pHI
- 0.736
- hipred
- Y
- hipred_score
- 0.851
- ghis
- 0.626
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.819
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Ext1
- 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); growth/size/body region phenotype; craniofacial phenotype; cellular phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); embryo phenotype; neoplasm; 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); normal phenotype; vision/eye phenotype; hearing/vestibular/ear phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); limbs/digits/tail phenotype; digestive/alimentary phenotype; skeleton phenotype;
Gene ontology
- Biological process
- skeletal system development;ossification;glycosaminoglycan biosynthetic process;protein glycosylation;signal transduction;gastrulation;axon guidance;endoderm development;mesoderm development;heparan sulfate proteoglycan biosynthetic process;heparan sulfate proteoglycan biosynthetic process, polysaccharide chain biosynthetic process;olfactory bulb development;cellular polysaccharide biosynthetic process;embryonic skeletal joint development
- Cellular component
- Golgi membrane;endoplasmic reticulum;endoplasmic reticulum membrane;Golgi apparatus;integral component of membrane;integral component of endoplasmic reticulum membrane
- Molecular function
- 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