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    EXTL3 exostosin like glycosyltransferase 3 [ Homo sapiens (human) ]

    Gene ID: 2137, updated on 3-Apr-2024

    Summary

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    Official Symbol
    EXTL3provided by HGNC
    Official Full Name
    exostosin like glycosyltransferase 3provided by HGNC
    Primary source
    HGNC:HGNC:3518
    See related
    Ensembl:ENSG00000012232 MIM:605744; AllianceGenome:HGNC:3518
    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
    RPR; BOTV; REGR; EXTR1; ISDNA; EXTL1L
    Summary
    This gene encodes a single-pass membrane protein which functions as a glycosyltransferase. The encoded protein catalyzes the transfer of N-acetylglucosamine to glycosaminoglycan chains. This reaction is important in heparin and heparan sulfate synthesis. Alternative splicing results in the multiple transcript variants. [provided by RefSeq, Nov 2012]
    Expression
    Ubiquitous expression in heart (RPKM 14.3), brain (RPKM 13.9) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    Location:
    8p21.1
    Exon count:
    12
    Annotation release Status Assembly Chr Location
    RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 8 NC_000008.11 (28607736..28755599)
    RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 8 NC_060932.1 (28885904..29033822)
    105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 8 NC_000008.10 (28559018..28613116)

    Chromosome 8 - NC_000008.11Genomic Context describing neighboring genes Neighboring gene VISTA enhancer hs1329 Neighboring gene microRNA 4288 Neighboring gene frizzled class receptor 3 Neighboring gene RNA, 5S ribosomal pseudogene 259 Neighboring gene ReSE screen-validated silencer GRCh37_chr8:28415895-28416077 Neighboring gene NANOG hESC enhancer GRCh37_chr8:28419252-28419778 Neighboring gene ReSE screen-validated silencer GRCh37_chr8:28479657-28480093 Neighboring gene Sharpr-MPRA regulatory region 11135 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 19062 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 19064 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 19063 Neighboring gene EXTL3 antisense RNA 1 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr8:28583611-28584110 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr8:28609290-28610234 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr8:28610235-28611177 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 19065 Neighboring gene uncharacterized LOC124902104 Neighboring gene H3K27ac hESC enhancer GRCh37_chr8:28647439-28647939 Neighboring gene integrator complex subunit 9 Neighboring gene ribosomal protein L36a pseudogene 32

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • 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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    Related articles in PubMed

    1. Spondyloepimetaphyseal dysplasia EXTL3-deficient type: Long-term follow-up and review of the literature. Akalın A, et al. Am J Med Genet A, 2021 Oct. PMID 34089299
    2. EXTL3-interacting endometriosis-specific serum factors induce colony formation of endometrial stromal cells. Aints A, et al. Sci Rep, 2019 Aug 29. PMID 31467315, Free PMC Article
    3. Structural and Biophysical Characterization of Human EXTL3: Domain Organization, Glycosylation, and Solution Structure. Awad W, et al. Biochemistry, 2018 Feb 20. PMID 29346724
    4. Expanding the spectrum of skeletal dysplasia with immunodeficiency: a commentary on identification of biallelic EXTL3 mutations in a novel type of spondylo-epi-metaphyseal dysplasia. Notarangelo LD. J Hum Genet, 2017 Aug. PMID 28446799, Free PMC Article
    5. Identification of biallelic EXTL3 mutations in a novel type of spondylo-epi-metaphyseal dysplasia. Guo L, et al. J Hum Genet, 2017 Aug. PMID 28331220, Free PMC Article

    See all (52) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Glycosyltransferases EXTL2 and EXTL3 cellular balance dictates heparan sulfate biosynthesis and shapes gastric cancer cell motility and invasion.
      Title: Glycosyltransferases EXTL2 and EXTL3 cellular balance dictates heparan sulfate biosynthesis and shapes gastric cancer cell motility and invasion.
    2. Spondyloepimetaphyseal dysplasia EXTL3-deficient type: Long-term follow-up and review of the literature.
      Title: Spondyloepimetaphyseal dysplasia EXTL3-deficient type: Long-term follow-up and review of the literature.
    3. REG3A/REG3B promotes acinar to ductal metaplasia through binding to EXTL3 and activating the RAS-RAF-MEK-ERK signaling pathway.
      Title: REG3A/REG3B promotes acinar to ductal metaplasia through binding to EXTL3 and activating the RAS-RAF-MEK-ERK signaling pathway.
    4. EXTL3-interacting endometriosis-specific serum factors induce colony formation of endometrial stromal cells.
      Title: EXTL3-interacting endometriosis-specific serum factors induce colony formation of endometrial stromal cells.
    5. EXTL3 mutations are associated with spondylo-epi-metaphyseal dysplasia with immunodeficiency.
      Title: Expanding the spectrum of skeletal dysplasia with immunodeficiency: a commentary on identification of biallelic EXTL3 mutations in a novel type of spondylo-epi-metaphyseal dysplasia.
    6. Human lumenal N-glycosylated EXTL3 (EXTL3DeltaN) was cloned, expressed in human embryonic kidney cells, and purified. Various biophysical and biochemical approaches were then employed to elucidate the N-glycosylation sites and the function of their attached N-glycans.
      Title: Structural and Biophysical Characterization of Human EXTL3: Domain Organization, Glycosylation, and Solution Structure.
    7. EXTL3 missense mutation is associated with spondylo-epi-metaphyseal dysplasia.
      Title: Identification of biallelic EXTL3 mutations in a novel type of spondylo-epi-metaphyseal dysplasia.
    8. EXTL3 mutations as a novel cause of severe immune deficiency with skeletal dysplasia and developmental delay and underline a crucial role of HS in thymopoiesis and skeletal and brain development.
      Title: EXTL3 mutations cause skeletal dysplasia, immune deficiency, and developmental delay.
    9. We show that biallelic mutations in EXTL3 disturb glycosaminoglycan synthesis and thus lead to a recognizable syndrome characterized by variable expression of skeletal, neurological, and immunological abnormalities.
      Title: Mutations in EXTL3 Cause Neuro-immuno-skeletal Dysplasia Syndrome.
    10. Recombinant EXTL2 showed weak ability to transfer N-acetylgalactosamine to heparan sulfate precursor molecules but also, that EXTL2 exhibited much stronger in vitro N-acetylglucosamine-transferase activity related to elongation of heparan sulfate chains.
      Title: Reduced Expression of EXTL2, a Member of the Exostosin (EXT) Family of Glycosyltransferases, in Human Embryonic Kidney 293 Cells Results in Longer Heparan Sulfate Chains.
    Submit: New GeneRIF Correction See all GeneRIFs (16)

    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
    Immunoskeletal dysplasia with neurodevelopmental abnormalities
    MedGen: C4479452 OMIM: 617425 GeneReviews: Not available
    		Compare labs

    EBI GWAS Catalog

    Description
    Meta-analysis of genome-wide association studies of adult height in East Asians identifies 17 novel loci.
    EBI GWAS Catalog

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Genotypes

    HIV-1 interactions

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    Protein interactions

    Protein Gene Interaction Pubs
    Envelope surface glycoprotein gp160, precursor env HIV-1 gp160 interacts with EXTL3; predicted interaction to be within the endoplasmic reticulum PubMed

    Go to the HIV-1, Human Interaction Database

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Clone Names

    • FLJ42628, KIAA0519, DKFZp686C2342

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables glucuronyl-galactosyl-proteoglycan 4-alpha-N-acetylglucosaminyltransferase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables glycosyltransferase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables glycosyltransferase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables magnesium ion binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables protein-hormone receptor activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables protein-hormone receptor activity ISS
    Inferred from Sequence or Structural Similarity
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in heparan sulfate proteoglycan biosynthetic process IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in heparan sulfate proteoglycan biosynthetic process IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in negative regulation of cytokine production involved in inflammatory response ISS
    Inferred from Sequence or Structural Similarity
    more info
    		 PubMed 
    involved_in negative regulation of inflammatory response ISS
    Inferred from Sequence or Structural Similarity
    more info
    		 PubMed 
    involved_in negative regulation of inflammatory response to wounding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in negative regulation of keratinocyte differentiation IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in positive regulation of cell growth IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in positive regulation of detection of glucose ISS
    Inferred from Sequence or Structural Similarity
    more info
    		 PubMed 
    involved_in positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in protein glycosylation IEA
    Inferred from Electronic Annotation
    more info
    		  
    Component Evidence Code Pubs
    is_active_in Golgi apparatus IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in Golgi apparatus IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in endoplasmic reticulum IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in endoplasmic reticulum membrane TAS
    Traceable Author Statement
    more info
    		  
    located_in nucleus IEA
    Inferred from Electronic Annotation
    more info
    		  
    is_active_in plasma membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 

    General protein information

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    Preferred Names
    exostosin-like 3
    Names
    EXT-related 1
    epididymis secretory sperm binding protein
    exostoses (multiple)-like 3
    exostosin tumor-like 3
    glucuronyl-galactosyl-proteoglycan 4-alpha-N-acetylglucosaminyltransferase
    hereditary multiple exostoses gene isolog
    putative tumor suppressor protein EXTL3
    reg receptor
    NP_001431.1
    XP_011542742.1
    XP_024302862.1
    XP_024302864.1
    XP_047277470.1
    XP_047277471.1
    XP_047277472.1
    XP_047277473.1
    XP_047277474.1
    XP_054216003.1
    XP_054216004.1
    XP_054216005.1
    XP_054216006.1
    XP_054216007.1
    XP_054216008.1
    XP_054216009.1
    XP_054216010.1

    NCBI Reference Sequences (RefSeq)

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    NEW Try the new Transcript table

    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.

    mRNA and Protein(s)

    1. NM_001440.4 → NP_001431.1  exostosin-like 3

      See identical proteins and their annotated locations for NP_001431.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longest transcript and encodes the functional protein.
      Source sequence(s)
      AB011091, AC131969, AW105691, DA757362
      Consensus CDS
      CCDS6070.1
      UniProtKB/Swiss-Prot
      D3DST8, O00225, O43909, Q53XT3
      UniProtKB/TrEMBL
      A0A384NPY9, A0A8Q3SIF4
      Related
      ENSP00000220562.4, ENST00000220562.9
      Conserved Domains (3) summary
      pfam03016
      Location:190 → 500
      Exostosin; Exostosin family
      pfam07926
      Location:71 → 150
      TPR_MLP1_2; TPR/MLP1/MLP2-like protein
      pfam09258
      Location:663 → 900
      Glyco_transf_64; Glycosyl transferase family 64 domain

    RNA

    1. NR_073468.2 RNA Sequence

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) lacks two internal exons, compared to variant 1. This variant is represented as non-coding because it lacks a large portion of the coding region, including the translational start codon, found in variant 1.
      Source sequence(s)
      AB011091, AC131969, AW105691, DA222815, DA757362
      Related
      ENST00000696182.1

    2. NR_073469.2 RNA Sequence

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) has multiple differences compared to variant 1. This variant is represented as non-coding because it lacks a large portion of the coding region found in variant 1.
      Source sequence(s)
      AF029231, AW105691, BI911162, DA757362

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

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

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000008.11 Reference GRCh38.p14 Primary Assembly

      Range
      28607736..28755599
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_024447096.2 → XP_024302864.1  exostosin-like 3 isoform X1

      UniProtKB/Swiss-Prot
      D3DST8, O00225, O43909, Q53XT3
      UniProtKB/TrEMBL
      A0A384NPY9, A0A8Q3SIF4
      Conserved Domains (3) summary
      pfam03016
      Location:190 → 500
      Exostosin; Exostosin family
      pfam07926
      Location:71 → 150
      TPR_MLP1_2; TPR/MLP1/MLP2-like protein
      pfam09258
      Location:663 → 900
      Glyco_transf_64; Glycosyl transferase family 64 domain

    2. XM_047421516.1 → XP_047277472.1  exostosin-like 3 isoform X1

      UniProtKB/Swiss-Prot
      D3DST8, O00225, O43909, Q53XT3
      UniProtKB/TrEMBL
      A0A384NPY9

    3. XM_047421518.1 → XP_047277474.1  exostosin-like 3 isoform X1

      UniProtKB/Swiss-Prot
      D3DST8, O00225, O43909, Q53XT3
      UniProtKB/TrEMBL
      A0A384NPY9

    4. XM_047421514.1 → XP_047277470.1  exostosin-like 3 isoform X1

      UniProtKB/Swiss-Prot
      D3DST8, O00225, O43909, Q53XT3
      UniProtKB/TrEMBL
      A0A384NPY9

    5. XM_024447094.2 → XP_024302862.1  exostosin-like 3 isoform X1

      UniProtKB/Swiss-Prot
      D3DST8, O00225, O43909, Q53XT3
      UniProtKB/TrEMBL
      A0A384NPY9, A0A8Q3SIF4
      Related
      ENSP00000512468.1, ENST00000696178.1
      Conserved Domains (3) summary
      pfam03016
      Location:190 → 500
      Exostosin; Exostosin family
      pfam07926
      Location:71 → 150
      TPR_MLP1_2; TPR/MLP1/MLP2-like protein
      pfam09258
      Location:663 → 900
      Glyco_transf_64; Glycosyl transferase family 64 domain

    6. XM_047421515.1 → XP_047277471.1  exostosin-like 3 isoform X1

      UniProtKB/Swiss-Prot
      D3DST8, O00225, O43909, Q53XT3
      UniProtKB/TrEMBL
      A0A384NPY9

    7. XM_047421517.1 → XP_047277473.1  exostosin-like 3 isoform X1

      UniProtKB/Swiss-Prot
      D3DST8, O00225, O43909, Q53XT3
      UniProtKB/TrEMBL
      A0A384NPY9

    8. XM_011544440.4 → XP_011542742.1  exostosin-like 3 isoform X1

      See identical proteins and their annotated locations for XP_011542742.1

      UniProtKB/Swiss-Prot
      D3DST8, O00225, O43909, Q53XT3
      UniProtKB/TrEMBL
      A0A384NPY9, A0A8Q3SIF4
      Related
      ENSP00000512474.1, ENST00000696186.1
      Conserved Domains (3) summary
      pfam03016
      Location:190 → 500
      Exostosin; Exostosin family
      pfam07926
      Location:71 → 150
      TPR_MLP1_2; TPR/MLP1/MLP2-like protein
      pfam09258
      Location:663 → 900
      Glyco_transf_64; Glycosyl transferase family 64 domain

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060932.1 Alternate T2T-CHM13v2.0

      Range
      28885904..29033822
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054360030.1 → XP_054216005.1  exostosin-like 3 isoform X1

      UniProtKB/Swiss-Prot
      D3DST8, O00225, O43909, Q53XT3
      UniProtKB/TrEMBL
      A0A384NPY9

    2. XM_054360032.1 → XP_054216007.1  exostosin-like 3 isoform X1

      UniProtKB/Swiss-Prot
      D3DST8, O00225, O43909, Q53XT3
      UniProtKB/TrEMBL
      A0A384NPY9

    3. XM_054360033.1 → XP_054216008.1  exostosin-like 3 isoform X1

      UniProtKB/Swiss-Prot
      D3DST8, O00225, O43909, Q53XT3
      UniProtKB/TrEMBL
      A0A384NPY9

    4. XM_054360034.1 → XP_054216009.1  exostosin-like 3 isoform X1

      UniProtKB/Swiss-Prot
      D3DST8, O00225, O43909, Q53XT3
      UniProtKB/TrEMBL
      A0A384NPY9

    5. XM_054360035.1 → XP_054216010.1  exostosin-like 3 isoform X1

      UniProtKB/Swiss-Prot
      D3DST8, O00225, O43909, Q53XT3
      UniProtKB/TrEMBL
      A0A384NPY9

    6. XM_054360028.1 → XP_054216003.1  exostosin-like 3 isoform X1

      UniProtKB/Swiss-Prot
      D3DST8, O00225, O43909, Q53XT3
      UniProtKB/TrEMBL
      A0A384NPY9

    7. XM_054360029.1 → XP_054216004.1  exostosin-like 3 isoform X1

      UniProtKB/Swiss-Prot
      D3DST8, O00225, O43909, Q53XT3
      UniProtKB/TrEMBL
      A0A384NPY9

    8. XM_054360031.1 → XP_054216006.1  exostosin-like 3 isoform X1

      UniProtKB/Swiss-Prot
      D3DST8, O00225, O43909, Q53XT3
      UniProtKB/TrEMBL
      A0A384NPY9
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    O43909.1 GenPept UniProtKB/Swiss-Prot:O43909

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