EXT1

exostosin glycosyltransferase 1, the group of Exostosin glycosyltransferase family

Basic information

Region (hg38): 8:117794490-118111826

Previous symbols: [ "LGCR", "LGS" ]

Links

ENSG00000182197 ∙ NCBI:2131 ∙ OMIM:608177 ∙ HGNC:3512 ∙ Uniprot:Q16394 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• exostoses, multiple, type 1 (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: CGD

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 ClinVar and linked to the EXT1 gene.

• Multiple_congenital_exostosis (947 variants)
• not_provided (155 variants)
• Chondrosarcoma (127 variants)
• Exostoses,_multiple,_type_1 (119 variants)
• Inborn_genetic_diseases (57 variants)
• EXT1-related_disorder (42 variants)
• not_specified (21 variants)
• Ovarian_cancer (8 variants)
• Hereditary_Multiple_Osteochondromatosis (2 variants)
• Exostoses (1 variants)
• Hereditary_cancer (1 variants)
• Microcephaly (1 variants)
• Langer-Giedion_syndrome (1 variants)
• Childhood_neoplasm (1 variants)
• Malignant_tumor_of_breast (1 variants)
• Abnormality_of_the_skeletal_system (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. These statistics are base on transcript: NM_000000127.3. 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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			4	148	9	161
missense	24	30	339	28	6	427
nonsense	127	14	4			145
start loss	2					2
frameshift	241	19	3			263
splice donor/acceptor (+/-2bp)	63	9	5			77
Total	457	72	355	176	15

Highest pathogenic variant AF is 0.000006571079

GnomAD

Source: gnomAD

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
		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: 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: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

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

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