EXT2

exostosin glycosyltransferase 2, the group of Exostosin glycosyltransferase family

Basic information

Region (hg38): 11:44095648-44251962

Links

ENSG00000151348 ∙ NCBI:2132 ∙ OMIM:608210 ∙ HGNC:3513 ∙ Uniprot:Q93063 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

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

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Exostoses, multiple, type 2	AD	Oncologic	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	Craniofacial; Gastrointestinal; Genitourinary; Musculoskeletal; Neurologic; Oncologic	7726168; 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 (129 variants)
• not provided (32 variants)
• EXT2-related disorder (4 variants)
• Seizures-scoliosis-macrocephaly syndrome;Exostoses, multiple, type 2 (3 variants)
• Inborn genetic diseases (2 variants)
• Seizures-scoliosis-macrocephaly syndrome (1 variants)
• Hereditary cancer-predisposing syndrome (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.

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			8	121	7	136
missense	6	7	279	12	5	309
nonsense	50	7	1			58
start loss						0
frameshift	59	8	1			68
inframe indel			6			6
splice donor/acceptor (+/-2bp)	24	6	2			32
splice region		1	9	9	1	20
non coding			17	71	42	130
Total	139	28	314	204	54

Highest pathogenic variant AF is 0.0000131

Variants in EXT2

This is a list of pathogenic ClinVar variants found in the EXT2 region.

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

Position	Type	Phenotype	Significance	ClinVar
11-44095686-C-G		Exostoses, multiple, type 2	Benign (Jan 13, 2018)
11-44095735-G-A		Exostoses, multiple, type 2	Benign (Jan 13, 2018)
11-44095822-C-G		Exostoses, multiple, type 2	Benign (Jan 13, 2018)
11-44095838-G-T		Exostoses, multiple, type 2	Uncertain significance (Jan 12, 2018)
11-44095859-G-T		Exostoses, multiple, type 2 • not specified	Benign (Jun 25, 2020)
11-44095874-G-A			Benign (Jul 27, 2018)
11-44095894-A-G			Benign (Jul 27, 2018)
11-44095958-C-T			Likely benign (May 12, 2021)
11-44096305-A-G		Exostoses, multiple, type 2	Uncertain significance (May 23, 2022)
11-44096317-A-G		Ovarian cancer	Benign (Jan 01, 2022)
11-44096326-G-A		not specified	Likely benign (Sep 06, 2019)
11-44096348-T-G			Benign (Jul 27, 2018)
11-44096509-G-A			Likely benign (Jan 05, 2021)
11-44107536-A-T			Benign (Jul 27, 2018)
11-44107603-A-C			Likely benign (Jan 22, 2021)
11-44107673-T-A		Multiple congenital exostosis • EXT2-related disorder	Uncertain significance (Mar 17, 2022)
11-44107687-G-T		Exostoses, multiple, type 2 • EXT2-related disorder	Uncertain significance (Jan 12, 2018)
11-44107720-C-T		Exostoses, multiple, type 2	Likely benign (Jan 19, 2024)
11-44107721-G-A		Exostoses, multiple, type 2 • EXT2-related disorder	Likely benign (Aug 12, 2021)
11-44107723-C-T		Exostoses, multiple, type 2 • Seizures-scoliosis-macrocephaly syndrome	Conflicting classifications of pathogenicity (Dec 07, 2023)
11-44107724-G-A		Exostoses, multiple, type 2	Likely benign (Jan 08, 2024)
11-44107730-G-A		Exostoses, multiple, type 2	Likely benign (Jun 01, 2021)
11-44107732-A-G		Exostoses, multiple, type 2	Uncertain significance (Jan 12, 2024)
11-44107734-A-G		Exostoses, multiple, type 2	Uncertain significance (Nov 16, 2023)
11-44107740-C-A		not specified • Exostoses, multiple, type 2 • Exostoses, multiple, type 1	Benign (Feb 01, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
EXT2	protein_coding	protein_coding	ENST00000395673	14	149881

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.32e-9	0.997	125695	0	53	125748	0.000211

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.640	394	431	0.913	0.0000259	4918
Missense in Polyphen		129	160.21	0.80521		1844
Synonymous	-0.242	169	165	1.02	0.00000981	1466
Loss of Function	2.73	21	39.5	0.532	0.00000216	444

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000691	0.000691
Ashkenazi Jewish	0.00	0.00
East Asian	0.000109	0.000109
Finnish	0.0000924	0.0000924
European (Non-Finnish)	0.000194	0.000193
Middle Eastern	0.000109	0.000109
South Asian	0.000294	0.000261
Other	0.000489	0.000489

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

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

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