EXT2 exostosin glycosyltransferase 2 [Homo sapiens (human)] - Gene

Summary

Official Symbol: EXT2provided by HGNC
Official Full Name: exostosin glycosyltransferase 2provided by HGNC
Primary source: HGNC:HGNC:3513
See related: Ensembl:ENSG00000151348 MIM:608210
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: SOTV; SSMS
Summary: This gene encodes one of two glycosyltransferases involved in the chain elongation step of heparan sulfate biosynthesis. Mutations in this gene cause the type II form of multiple exostoses. Alternatively spliced transcript variants encoding different isoforms have been noted for this gene. [provided by RefSeq, Jul 2008]
Expression: Ubiquitous expression in placenta (RPKM 29.3), endometrium (RPKM 20.5) and 25 other tissues See more
Orthologs: mouse all

Genomic context

Location:: 11p11.2

Exon count:: 18

Annotation release	Status	Assembly	Chr	Location
109.20190905	current	GRCh38.p13 (GCF_000001405.39)	11	NC_000011.10 (44095549..44251981)
105	previous assembly	GRCh37.p13 (GCF_000001405.25)	11	NC_000011.9 (44117099..44266980)

Chromosome 11 - NC_000011.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

identification of mutations in EXT1 and EXT2 in Cypriot patients with a clinical diagnosis of hereditary multiple osteochondromas (HMO); five patients, representing the first report of genetic screening of HMO affected individuals in the Cypriot population are described
Title: Genetic screening of EXT1 and EXT2 in Cypriot families with hereditary multiple osteochondromas.
Mutations of the EXT1 and EXT2 genes probably underlie the hereditary multiple exostosis in both pedigrees
Title: [Analysis of EXT1 and EXT2 gene mutations in two Chinese pedigrees affected with hereditary multiple exostosis].
A novel EXT2 mutation was identified in a family with severe developmental delay, microcephaly, seizures, feeding difficulties, and osteopenia.
Title: A novel EXT2 mutation in a consanguineous family with severe developmental delay, microcephaly, seizures, feeding difficulties, and osteopenia extends the phenotypic spectrum of autosomal recessive EXT2-related syndrome (AREXT2).
The present study identified pathogenic mutations in 93% (68/73) of unrelated hereditary multiple osteochondromasprobands from 73 pedigrees. Mutations in EXT1 and EXT2 were identified in 53% (39/73) and 40% (29/73) of families.
Title: Heterogeneous spectrum of EXT gene mutations in Chinese patients with hereditary multiple osteochondromas.
Exons and flanking regions of the EXT1 and EXT2 genes were analyzed from the genomic DNA of 153 patients in 114 families with multiple osteochondromas. We identified 33 variants in EXT1 (13 frameshift, 11 nonsense, 5 missense, 2 splice site mutation, and 2 large deletions) in and 17 (6 frameshift, 6 splice site mutation, 3 nonsense, 1 missense, and 1 large deletion) in EXT2 gene. Of all 50 variants, 31 (62%) were novel.
Title: Analysis of mutations in EXT1 and EXT2 in Brazilian patients with multiple osteochondromas.
RT-PCR analysis showed that the overall transcriptional activity of the main Heparan Sulfate biosynthesis-involved genes (EXT1, EXT2, NDST1, NDST2, GLCE, HS2ST1, HS3ST1, HS3ST2, HS6ST1, HS6ST2, SULF1, SULF2, HPSE) was decreased by 1.5-2-fold in Grade II-III glioma.
Title: Heparan Sulfate Biosynthetic System Is Inhibited in Human Glioma Due to EXT1/2 and HS6ST1/2 Down-Regulation.
The nine mutations identified by targeted next-generation sequencing include two missense mutations (EXT1: c.1088G>A and c.2120C>T), one splicing mutation (EXT2: c.744-1G>T)
Title: Targeted Next-Generation Sequencing Newly Identifies Mutations in Exostosin-1 and Exostosin-2 Genes of Patients with Multiple Osteochondromas.
Let-7b-mediated suppression of initiation codon depends on the length of 5'-UTR of EXT2 mRNA and its suppression is inhibited in the presence of polyamines.
Title: Polyamines release the let-7b-mediated suppression of initiation codon recognition during the protein synthesis of EXT2.
the present study identified a novel missense mutation (c.1385G>A) in exon 8 and a splicing mutation (c.725+1G>C) in intron 3 of the EXT2 gene, which are responsible for MO in certain Chinese patients. The findings are useful for expanding the database of known EXT2 mutations and understanding the genetic basis of MO in Chinese patients, which may improve genetic counseling and the prenatal diagnosis of MO.
Title: Identification of mutations in EXT1 and EXT2 genes in six Chinese families with multiple osteochondromas.
Germline EXT2 mutation is associated with chondrosarcoma.
Title: Familial solitary chondrosarcoma resulting from germline EXT2 mutation.

Submit: New GeneRIF Correction See all GeneRIFs (65)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Multiple exostoses type 2 MedGen: C1851413 OMIM: 133701 GeneReviews: Hereditary Multiple Osteochondromas	Compare labs
Seizures, scoliosis, and macrocephaly syndrome MedGen: C4225248 OMIM: 616682 GeneReviews: Not available	Compare labs

Copy number response

Description
Copy number response Triplosensitivity No evidence available (Last evaluated (2012-03-08) ClinGen Genome Curation Page Haploinsufficency Sufficient evidence for dosage pathogenicity (Last evaluated (2012-03-08) ClinGen Genome Curation PagePubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Pathways from BioSystems

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Glycosaminoglycan biosynthesis - heparan sulfate / heparin, organism-specific biosystem (from KEGG)
Glycosaminoglycan biosynthesis - heparan sulfate / heparin, organism-specific biosystemHeparan sulfate (HS) and heparin (Hep) are glycosaminoglycans with repeating disaccharide units that consist of alternating residues of alpha-D-glucosamine (GlcN) and uronic acid, the latter being ei...
Glycosaminoglycan biosynthesis - heparan sulfate / heparin, conserved biosystem (from KEGG)
Glycosaminoglycan biosynthesis - heparan sulfate / heparin, conserved biosystemHeparan sulfate (HS) and heparin (Hep) are glycosaminoglycans with repeating disaccharide units that consist of alternating residues of alpha-D-glucosamine (GlcN) and uronic acid, the latter being ei...
Glycosaminoglycan biosynthesis, heparan sulfate backbone, organism-specific biosystem (from KEGG)
Glycosaminoglycan biosynthesis, heparan sulfate backbone, organism-specific biosystemPathway module; Carbohydrate and lipid metabolism; Glycosaminoglycan metabolism
Glycosaminoglycan biosynthesis, heparan sulfate backbone, conserved biosystem (from KEGG)
Glycosaminoglycan biosynthesis, heparan sulfate backbone, conserved biosystemPathway module; Carbohydrate and lipid metabolism; Glycosaminoglycan metabolism
Glycosaminoglycan metabolism, organism-specific biosystem (from REACTOME)
Glycosaminoglycan metabolism, organism-specific biosystemGlycosaminoglycans (GAGs) are long, unbranched polysaccharides containing a repeating disaccharide unit composed of a hexosamine (either N-acetylgalactosamine (GalNAc) or N-acetylglucosamine (GlcNAc)...
HS-GAG biosynthesis, organism-specific biosystem (from REACTOME)
HS-GAG biosynthesis, organism-specific biosystemHeparan sulfate (HS) and heparin (sometimes collectively called HS-GAG) consist of the disaccharide unit GlcNAc-GlcA (N-acetylglucosamine-glucuronic acid) connected by a beta1,4 linkage. Heparin is e...
Heparan sulfate/heparin (HS-GAG) metabolism, organism-specific biosystem (from REACTOME)
Heparan sulfate/heparin (HS-GAG) metabolism, organism-specific biosystemThe acronym HS-GAG is used to describe both heparin and heparan sulfate. HS-GAG is a member of the glycosaminoglycan family and consists of a variably sulfated repeating disaccharide unit, the most ...
Mesodermal Commitment Pathway, organism-specific biosystem (from WikiPathways)
Mesodermal Commitment Pathway, organism-specific biosystemModel depicting mesodermal specification based on the literature and highly enriched gene expression profiles via comparison across dozens of independent induced and embryonic pluripotent stem cell l...
Metabolic pathways, organism-specific biosystem (from KEGG)
Metabolic pathways, organism-specific biosystem
Metabolic pathways
Metabolism, organism-specific biosystem (from REACTOME)
Metabolism, organism-specific biosystemMetabolic processes in human cells generate energy through the oxidation of molecules consumed in the diet and mediate the synthesis of diverse essential molecules not taken in the diet as well as th...
Metabolism of carbohydrates, organism-specific biosystem (from REACTOME)
Metabolism of carbohydrates, organism-specific biosystemThese pathways together are responsible for: 1) the extraction of energy and carbon skeletons for biosyntheses from dietary sugars and related molecules; 2) the short-term storage of glucose in the b...
heparan sulfate biosynthesis, conserved biosystem (from BIOCYC)
heparan sulfate biosynthesis, conserved biosystemBackground |FRAME: Heparan-Sulfate "Heparan sulfate"| is a linear polysaccharide found in all animal tissues. It occurs as a proteoglycan in which two or three heparan sulfate chains are attached to...
heparan sulfate biosynthesis (late stages), conserved biosystem (from BIOCYC)
heparan sulfate biosynthesis (late stages), conserved biosystemBackground |FRAME: Heparan-Sulfate "Heparan sulfate"| is a linear polysaccharide found in all animal tissues. It occurs as a proteoglycan in which two or three heparan sulfate chains are attached to...

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

HSC1YH092 (e-PCR)
- UniSTS:80896

D11S2263E (e-PCR)
- UniSTS:78861

RH45722 (e-PCR)
- UniSTS:48141

D11S4650 (e-PCR)
- UniSTS:37912

D11S903 (e-PCR), detects polymorphism
- UniSTS:2601

RH121355 (e-PCR)
- UniSTS:134201

WI-20248 (e-PCR)
- UniSTS:72780

SHGC-149810 (e-PCR)
- UniSTS:177234

D11S3975 (e-PCR)
- UniSTS:74589

D11S903 (e-PCR), detects polymorphism
- UniSTS:14215

RH98305 (e-PCR)
- UniSTS:84618

STS-N22755 (e-PCR)
- UniSTS:47793

D11S3805 (e-PCR)
- UniSTS:153035

GDB:313855 (e-PCR)
- UniSTS:56811

Homology

Homologs of the EXT2 gene: The EXT2 gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, chicken, zebrafish, fruit fly, mosquito, and frog.
Orthologs from Annotation Pipeline: 279 organisms have orthologs with human gene EXT2
Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
N-acetylglucosaminyl-proteoglycan 4-beta-glucuronosyltransferase activity	IBA Inferred from Biological aspect of Ancestor more info	PubMed
N-acetylglucosaminyl-proteoglycan 4-beta-glucuronosyltransferase activity	NAS Non-traceable Author Statement more info	PubMed
acetylglucosaminyltransferase activity	IBA Inferred from Biological aspect of Ancestor more info	PubMed
contributes_to acetylglucosaminyltransferase activity	IDA Inferred from Direct Assay more info	PubMed
glucuronosyl-N-acetylglucosaminyl-proteoglycan 4-alpha-N-acetylglucosaminyltransferase activity	IEA Inferred from Electronic Annotation more info
glucuronosyltransferase activity	IDA Inferred from Direct Assay more info	PubMed
heparan sulfate N-acetylglucosaminyltransferase activity	NAS Non-traceable Author Statement more info	PubMed
metal ion binding	IEA Inferred from Electronic Annotation more info
protein binding	IPI Inferred from Physical Interaction more info	PubMed
protein heterodimerization activity	IPI Inferred from Physical Interaction more info	PubMed
NOT protein homodimerization activity	IDA Inferred from Direct Assay more info	PubMed
transferase activity, transferring glycosyl groups	IBA Inferred from Biological aspect of Ancestor more info	PubMed
transferase activity, transferring glycosyl groups	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
cell differentiation	IEA Inferred from Electronic Annotation more info
cellular polysaccharide biosynthetic process	IDA Inferred from Direct Assay more info	PubMed
glycosaminoglycan biosynthetic process	IBA Inferred from Biological aspect of Ancestor more info	PubMed
glycosaminoglycan biosynthetic process	IDA Inferred from Direct Assay more info	PubMed
glycosaminoglycan biosynthetic process	TAS Traceable Author Statement more info
heparan sulfate proteoglycan biosynthetic process	IMP Inferred from Mutant Phenotype more info	PubMed
heparan sulfate proteoglycan biosynthetic process, polysaccharide chain biosynthetic process	IBA Inferred from Biological aspect of Ancestor more info	PubMed
heparan sulfate proteoglycan biosynthetic process, polysaccharide chain biosynthetic process	IMP Inferred from Mutant Phenotype more info	PubMed
mesoderm formation	IEA Inferred from Electronic Annotation more info
ossification	IMP Inferred from Mutant Phenotype more info	PubMed
protein glycosylation	IEA Inferred from Electronic Annotation more info
signal transduction	TAS Traceable Author Statement more info	PubMed

Component	Evidence Code	Pubs
Golgi apparatus	IBA Inferred from Biological aspect of Ancestor more info	PubMed
Golgi apparatus	IDA Inferred from Direct Assay more info
Golgi apparatus	ISS Inferred from Sequence or Structural Similarity more info
Golgi membrane	TAS Traceable Author Statement more info
UDP-N-acetylglucosamine transferase complex	IDA Inferred from Direct Assay more info	PubMed
endoplasmic reticulum	IBA Inferred from Biological aspect of Ancestor more info	PubMed
endoplasmic reticulum	ISS Inferred from Sequence or Structural Similarity more info
endoplasmic reticulum membrane	TAS Traceable Author Statement more info	PubMed
extracellular exosome	HDA more info	PubMed
integral component of membrane	IEA Inferred from Electronic Annotation more info
membrane	HDA more info	PubMed

General protein information

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Preferred Names: exostosin-2

Names: N-acetylglucosaminyl-proteoglycan 4-beta-glucuronosyltransferase; glucuronosyl-N-acetylglucosaminyl-proteoglycan/N-acetylglucosaminyl-proteoglycan 4-alpha-N-acetylglucosaminyltransferase; multiple exostoses protein 2; multiple exostosis 2; putative tumor suppressor protein EXT2

NP_000392.3

EC 2.4.1.224

EC 2.4.1.225

NP_001171554.1

EC 2.4.1.224

EC 2.4.1.225

NP_997005.1

EC 2.4.1.224

EC 2.4.1.225

XP_011518252.1

EC 2.4.1.224

EC 2.4.1.225

XP_011518253.1

EC 2.4.1.224

EC 2.4.1.225

XP_024304151.1

EC 2.4.1.224

EC 2.4.1.225

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_007560.1 RefSeqGene

Range

5001..154882

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_494

mRNA and Protein(s)

NM_000401.3 → NP_000392.3 exostosin-2 isoform 1

See identical proteins and their annotated locations for NP_000392.3

Status: REVIEWED

Description

Transcript Variant: This variant (1) encodes the longer isoform (1).

Source sequence(s)

AC068457, AC103854, BE348865, BX648142, DA738392

Consensus CDS

CCDS53618.1

UniProtKB/Swiss-Prot

Q93063

Related

ENSP00000379032.3, ENST00000395673.7

Conserved Domains (2) summary

pfam03016
Location:133 → 413

Exostosin; Exostosin family

pfam09258
Location:489 → 723

Glyco_transf_64; Glycosyl transferase family 64 domain
NM_001178083.2 → NP_001171554.1 exostosin-2 isoform 3

See identical proteins and their annotated locations for NP_001171554.1

Status: REVIEWED

Description

Transcript Variant: This variant (3) has multiple differences, compared to variant 1. These differences result in a distinct 5' UTR and cause translation initiation at a downstream start codon, compared to variant 1. The encoded protein (isoform 3) is shorter than isoform 1.

Source sequence(s)

AC068457, AC103854, BE348865, BX648142, U62740, U72263

Consensus CDS

CCDS53619.1

UniProtKB/Swiss-Prot

Q93063

Related

ENSP00000351509.4, ENST00000358681.8

Conserved Domains (2) summary

pfam03016
Location:100 → 380

Exostosin; Exostosin family

pfam09258
Location:466 → 700

Glyco_transf_64; Glycosyl transferase family 64 domain
NM_207122.1 → NP_997005.1 exostosin-2 isoform 2

See identical proteins and their annotated locations for NP_997005.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) is the predominant transcript and differs in the 5' UTR and coding region, compared to variant 1. These differences causes translation initiation at a downstream start codon and result in isoform (2) which has a shorter N-terminus, compared to isoform 1.

Source sequence(s)

BM997250, U62740

Consensus CDS

CCDS7908.1

UniProtKB/Swiss-Prot

Q93063

Related

ENSP00000431173.1, ENST00000533608.6

Conserved Domains (2) summary

pfam03016
Location:100 → 380

Exostosin; Exostosin family

pfam09258
Location:456 → 697

Glyco_transf_64; Glycosyl transferase family 64 domain

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 109 details...

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p13 Primary Assembly

Genomic

NC_000011.10 Reference GRCh38.p13 Primary Assembly

Range

44095549..44251981

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_011519951.1 → XP_011518253.1 exostosin-2 isoform X2

See identical proteins and their annotated locations for XP_011518253.1

UniProtKB/TrEMBL

D3DR24

Conserved Domains (2) summary

pfam03016
Location:113 → 393

Exostosin; Exostosin family

pfam09258
Location:469 → 703

Glyco_transf_64; Glycosyl transferase family 64 domain
XM_011519950.1 → XP_011518252.1 exostosin-2 isoform X1

Conserved Domains (2) summary

pfam03016
Location:146 → 426

Exostosin; Exostosin family

pfam09258
Location:502 → 736

Glyco_transf_64; Glycosyl transferase family 64 domain
XM_024448383.1 → XP_024304151.1 exostosin-2 isoform X3

Conserved Domains (1) summary

pfam03016
Location:146 → 426

Exostosin; Exostosin family