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    ADAMTS18 ADAM metallopeptidase with thrombospondin type 1 motif 18 [ Homo sapiens (human) ]

    Gene ID: 170692, updated on 2-Nov-2024

    Summary

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    Official Symbol
    ADAMTS18provided by HGNC
    Official Full Name
    ADAM metallopeptidase with thrombospondin type 1 motif 18provided by HGNC
    Primary source
    HGNC:HGNC:17110
    See related
    Ensembl:ENSG00000140873 MIM:607512; AllianceGenome:HGNC:17110
    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
    KNO2; MMCAT; ADAMTS21
    Summary
    This gene encodes a member of the ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) protein family. ADAMTS family members share several distinct protein modules, including a propeptide region, a metalloproteinase domain, a disintegrin-like domain, and a thrombospondin type 1 (TS) motif. Individual members of this family differ in the number of C-terminal TS motifs, and some have unique C-terminal domains. The encoded preproprotein is proteolytically processed to generate the mature protein, which may regulate hemostatic balance and function as a tumor suppressor. Mutations in this gene may be associated with microcornea, myopic chorioretinal atrophy, and telecanthus (MMCAT) and cone-rod dystrophy in human patients. [provided by RefSeq, May 2016]
    Expression
    Biased expression in placenta (RPKM 9.8), endometrium (RPKM 0.6) and 1 other tissue See more
    Orthologs
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    Genomic context

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    See ADAMTS18 in Genome Data Viewer
    Location:
    16q23.1
    Exon count:
    23
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 16 NC_000016.10 (77282128..77435034, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 16 NC_060940.1 (83338334..83491167, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 16 NC_000016.9 (77316025..77468931, complement)

    Chromosome 16 - NC_000016.10Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC124903726 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr16:77246135-77247108 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 11151 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_45200 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_45205 Neighboring gene synaptonemal complex central element protein 1 like Neighboring gene vomeronasal 2 receptor 10, pseudogene Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr16:77322970-77324169 Neighboring gene uncharacterized LOC124903727 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_45289 Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr16:77341323-77342522 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr16:77468627-77469127 Neighboring gene uncharacterized LOC105376775 Neighboring gene NANOG hESC enhancer GRCh37_chr16:77535256-77535757 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr16:77574962-77575540 Neighboring gene long intergenic non-protein coding RNA 2131

    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. Secreted protease ADAMTS18 in development and disease. Nie J, et al. Gene, 2023 Mar 30. PMID 36632911
    2. Epigenetic identification of ADAMTS18 as a novel 16q23.1 tumor suppressor frequently silenced in esophageal, nasopharyngeal and multiple other carcinomas. Jin H, et al. Oncogene, 2007 Nov 22. PMID 17546048, Free PMC Article
    3. High-resolution melting analysis of ADAMTS18 methylation levels in gastric, colorectal and pancreatic cancers. Li Z, et al. Med Oncol, 2010 Sep. PMID 19806480
    4. Mutational and functional analysis reveals ADAMTS18 metalloproteinase as a novel driver in melanoma. Wei X, et al. Mol Cancer Res, 2010 Nov. PMID 21047771, Free PMC Article
    5. The ADAMTS18 gene is responsible for autosomal recessive early onset severe retinal dystrophy. Peluso I, et al. Orphanet J Rare Dis, 2013 Jan 28. PMID 23356391, Free PMC Article

    See all (38) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. [A family with developmental glaucoma and microcornea due to novel ADAMTS18 gene mutations].
      Title: [A family with developmental glaucoma and microcornea due to novel ADAMTS18 gene mutations].
    2. Secreted protease ADAMTS18 in development and disease.
      Title: Secreted protease ADAMTS18 in development and disease.
    3. Aberrant methylation of the 16q23.1 tumor suppressor gene ADAMTS18 promotes tumorigenesis and progression of clear cell renal cell carcinoma.
      Title: Aberrant methylation of the 16q23.1 tumor suppressor gene ADAMTS18 promotes tumorigenesis and progression of clear cell renal cell carcinoma.
    4. Characterization of a functional endothelial super-enhancer that regulates ADAMTS18 and angiogenesis.
      Title: Characterization of a functional endothelial super-enhancer that regulates ADAMTS18 and angiogenesis.
    5. Adamts18 links luminal hormone receptor signaling to basement membrane remodeling and stem cell activation.
      Title: The secreted protease Adamts18 links hormone action to activation of the mammary stem cell niche.
    6. ADAMTS18 promoter methylation is a potential epigenetic biomarker.
      Title: Inactivation of ADAMTS18 by aberrant promoter hypermethylation contribute to lung cancer progression.
    7. study suggests that ADAMTS18 is downregulated in cervical cancer and ADAMTS18 may serve as a potential prognostic biomarker for cervical cancer.
      Title: Downregulation of ADAMTS18 May Serve as a Poor Prognostic Biomarker for Cervical Cancer Patients.
    8. In summary, we demonstrate that ADAMTS18 silencing in breast cancer is significantly correlated with promoter CpG methylation. ADAMTS18 acts as an antagonist of AKT and NF-kappaB signaling, further suppressing EMT and metastasis of breast cancer cells.
      Title: Epigenetic silencing of ADAMTS18 promotes cell migration and invasion of breast cancer through AKT and NF-κB signaling.
    9. This study showed that ADAMTS1, 8, and 18 are highly expressed in GC and its nodal metastases, suggesting important roles of these proteases in carcinogenesis and lymphatic metastasis. The findings from the present study indicate that these proteases may be promising candidates for novel and alternative treatments in GC (gastric cancer)
      Title: Differentially regulated ADAMTS1, 8, and 18 in gastric adenocarcinoma.
    10. Studies suggest that ADAM metallopeptidase with thrombospondin type 1 motif, 18 protein (ADAMTS-18) as a promising diagnostic and therapeutic target.
      Title: ADAMTS-18: a metalloproteinase with multiple functions.
    Submit: New GeneRIF Correction See all GeneRIFs (22)

    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
    Microcornea-myopic chorioretinal atrophy
    MedGen: C3809567 OMIM: 615458 GeneReviews: Not available
    		Compare labs

    EBI GWAS Catalog

    Description
    A genome-wide search for genetic influences and biological pathways related to the brain's white matter integrity.
    EBI GWAS Catalog
    Genome-wide association and follow-up replication studies identified ADAMTS18 and TGFBR3 as bone mass candidate genes in different ethnic groups.
    EBI GWAS Catalog
    Genome-wide association study of chemotherapeutic agent-induced severe neutropenia/leucopenia for patients in Biobank Japan.
    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)

    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables metal ion binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables metalloendopeptidase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    Process Evidence Code Pubs
    involved_in extracellular matrix organization IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in eye development IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    acts_upstream_of_or_within negative regulation of platelet aggregation IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in proteolysis IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in proteolysis IEA
    Inferred from Electronic Annotation
    more info
    		  
    Component Evidence Code Pubs
    is_active_in extracellular matrix IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in extracellular region IEA
    Inferred from Electronic Annotation
    more info
    		  

    General protein information

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    Preferred Names
    A disintegrin and metalloproteinase with thrombospondin motifs 18
    Names
    a disintegrin-like and metalloprotease (reprolysin type) with thrombospondin type 1 motif, 18
    a disintegrin-like and metalloprotease (reprolysin type) with thrombospondin type 1 motif, 21
    disintegrin and metalloprotease-like protein

    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.

    Genomic

    1. NG_031879.2 RefSeqGene

      Range
      5081..157987
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001326358.2 → NP_001313287.1  A disintegrin and metalloproteinase with thrombospondin motifs 18 isoform 3

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) encodes isoform 3. The encoded isoform (3) lacks a predicted signal peptide and a portion of the propeptide compared to isoform 1.
      Source sequence(s)
      AC009139, AC010548, AC025284, BM684970
      Conserved Domains (5) summary
      smart00209
      Location:420 → 471
      TSP1; Thrombospondin type 1 repeats
      cd04273
      Location:121 → 322
      ZnMc_ADAMTS_like; Zinc-dependent metalloprotease, ADAMTS_like subgroup. ADAMs (A Disintegrin And Metalloprotease) are glycoproteins, which play roles in cell signaling, cell fusion, and cell-cell interactions. This particular subfamily represents domain architectures that ...
      pfam01421
      Location:123 → 326
      Reprolysin; Reprolysin (M12B) family zinc metalloprotease
      pfam05986
      Location:577 → 689
      ADAM_spacer1; ADAM-TS Spacer 1
      pfam08686
      Location:1016 → 1046
      PLAC; PLAC (protease and lacunin) domain

    2. NM_199355.4 → NP_955387.1  A disintegrin and metalloproteinase with thrombospondin motifs 18 isoform 1 preproprotein

      See identical proteins and their annotated locations for NP_955387.1

      Status: REVIEWED

      Source sequence(s)
      AC009139, AC010548, AJ311903, AK131403, AY172951, BC063283, BM684970
      Consensus CDS
      CCDS10926.1
      UniProtKB/Swiss-Prot
      Q6P4R5, Q6ZWJ9, Q8TE60
      Related
      ENSP00000282849.5, ENST00000282849.10
      Conserved Domains (6) summary
      smart00209
      Location:592 → 643
      TSP1; Thrombospondin type 1 repeats
      cd04273
      Location:293 → 494
      ZnMc_ADAMTS_like; Zinc-dependent metalloprotease, ADAMTS_like subgroup. ADAMs (A Disintegrin And Metalloprotease) are glycoproteins, which play roles in cell signaling, cell fusion, and cell-cell interactions. This particular subfamily represents domain architectures that ...
      pfam01421
      Location:295 → 498
      Reprolysin; Reprolysin (M12B) family zinc metalloprotease
      pfam01562
      Location:86 → 202
      Pep_M12B_propep; Reprolysin family propeptide
      pfam05986
      Location:749 → 861
      ADAM_spacer1; ADAM-TS Spacer 1
      pfam08686
      Location:1188 → 1218
      PLAC; PLAC (protease and lacunin) domain

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

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

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000016.10 Reference GRCh38.p14 Primary Assembly

      Range
      77282128..77435034 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_047433672.1 → XP_047289628.1  A disintegrin and metalloproteinase with thrombospondin motifs 18 isoform X1

    2. XM_047433673.1 → XP_047289629.1  A disintegrin and metalloproteinase with thrombospondin motifs 18 isoform X2

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060940.1 Alternate T2T-CHM13v2.0

      Range
      83338334..83491167 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054379712.1 → XP_054235687.1  A disintegrin and metalloproteinase with thrombospondin motifs 18 isoform X1

    2. XM_054379713.1 → XP_054235688.1  A disintegrin and metalloproteinase with thrombospondin motifs 18 isoform X2

    Suppressed Reference Sequence(s)

    The following Reference Sequences have been suppressed. Explain

    1. NM_139054.2: Suppressed sequence

      Description
      NM_139054.2: This RefSeq was temporarily suppressed because currently there is not sufficient data to support this transcript.
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q8TE60.3 GenPept UniProtKB/Swiss-Prot:Q8TE60

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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