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    ACAN aggrecan [ Homo sapiens (human) ]

    Gene ID: 176, updated on 2-Nov-2024

    Summary

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    Official Symbol
    ACANprovided by HGNC
    Official Full Name
    aggrecanprovided by HGNC
    Primary source
    HGNC:HGNC:319
    See related
    Ensembl:ENSG00000157766 MIM:155760; AllianceGenome:HGNC:319
    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
    AGC1; SEDK; AGCAN; CSPG1; MSK16; CSPGCP; SSOAOD
    Summary
    This gene is a member of the aggrecan/versican proteoglycan family. The encoded protein is an integral part of the extracellular matrix in cartilagenous tissue and it withstands compression in cartilage. Mutations in this gene may be involved in skeletal dysplasia and spinal degeneration. Multiple alternatively spliced transcript variants that encode different protein isoforms have been observed in this gene. [provided by RefSeq, Jul 2008]
    Expression
    Broad expression in testis (RPKM 1.8), urinary bladder (RPKM 1.4) and 17 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See ACAN in Genome Data Viewer
    Location:
    15q26.1
    Exon count:
    20
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 15 NC_000015.10 (88803436..88875353)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 15 NC_060939.1 (86558075..86629996)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 15 NC_000015.9 (89346667..89418584)

    Chromosome 15 - NC_000015.10Genomic Context describing neighboring genes Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr15:89156265-89156949 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr15:89163779-89164452 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr15:89164453-89165126 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr15:89166102-89167301 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr15:89169771-89170314 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 10029 Neighboring gene microRNA 3529 Neighboring gene Sharpr-MPRA regulatory region 1748 Neighboring gene microRNA 7-2 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr15:89181184-89182162 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr15:89182163-89183141 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 10033 Neighboring gene apoptosis enhancing nuclease Neighboring gene H3K4me1 hESC enhancer GRCh37_chr15:89191225-89191986 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 10034 Neighboring gene interferon stimulated exonuclease gene 20 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 10035 Neighboring gene uncharacterized LOC105370960 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr15:89390146-89390646 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr15:89390647-89391147 Neighboring gene ReSE screen-validated silencer GRCh37_chr15:89391205-89391372 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr15:89421781-89422356 Neighboring gene H3K27ac hESC enhancer GRCh37_chr15:89428493-89429204 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr15:89438001-89438612 Neighboring gene Sharpr-MPRA regulatory region 11373 Neighboring gene hyaluronan and proteoglycan link protein 3 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 6792 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr15:89450127-89451112 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr15:89455820-89456351 Neighboring gene milk fat globule EGF and factor V/VIII domain containing

    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 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. Identification of a locus for a form of spondyloepiphyseal dysplasia on chromosome 15q26.1: exclusion of aggrecan as a candidate gene. Eyre S, et al. J Med Genet, 2002 Sep. PMID 12205105, Free PMC Article
    2. Aggrecan turnover in human intervertebral disc as determined by the racemization of aspartic acid. Sivan SS, et al. J Biol Chem, 2006 May 12. PMID 16537531
    3. Short aggrecan gene repetitive alleles associated with lumbar degenerative disc disease in Turkish patients. Eser O, et al. Genet Mol Res, 2011 Aug 30. PMID 21948754
    4. The involvement of aggrecan polymorphism in degeneration of human intervertebral disc and articular cartilage. Roughley P, et al. Eur Cell Mater, 2006 Jan 18. PMID 16425147
    5. Genetic variability in the extracellular matrix protein as a determinant of risk for developing HTLV-I-associated neurological disease. Nobuhara Y, et al. Immunogenetics, 2006 Jan. PMID 16402214

    See all (176) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Genotype and phenotype in patients with ACAN gene variants: Three cases and literature review.
      Title: Genotype and phenotype in patients with ACAN gene variants: Three cases and literature review.
    2. Brachyury positively regulates extracellular matrix synthesis via directly promoting aggrecan transcription in nucleus pulposus.
      Title: Brachyury positively regulates extracellular matrix synthesis via directly promoting aggrecan transcription in nucleus pulposus.
    3. The relationship between the aggrecan VNTR polymorphism and its content in lumbar intervertebral discs.
      Title: The relationship between the aggrecan VNTR polymorphism and its content in lumbar intervertebral discs.
    4. [Analysis of a Chinese pedigree affected with familial short stature due to 15q25.3q26.1 deletion involving the ACAN gene].
      Title: [Analysis of a Chinese pedigree affected with familial short stature due to 15q25.3q26.1 deletion involving the ACAN gene].
    5. Downregulation of ACAN is Associated with the Growth hormone pathway and Induces short stature.
      Title: Downregulation of ACAN is Associated with the Growth hormone pathway and Induces short stature.
    6. Identification of variants in ACAN and PAPSS2 leading to spondyloepi(meta)physeal dysplasias in four Chinese families.
      Title: Identification of variants in ACAN and PAPSS2 leading to spondyloepi(meta)physeal dysplasias in four Chinese families.
    7. Novel missense ACAN gene variants linked to familial osteochondritis dissecans cluster in the C-terminal globular domain of aggrecan.
      Title: Novel missense ACAN gene variants linked to familial osteochondritis dissecans cluster in the C-terminal globular domain of aggrecan.
    8. Identification of novel ACAN mutations in two Chinese families and genotype-phenotype correlation in patients with 74 pathogenic ACAN variations.
      Title: Identification of novel ACAN mutations in two Chinese families and genotype-phenotype correlation in patients with 74 pathogenic ACAN variations.
    9. Altered Expression of Aggrecan, FAM20B, B3GALT6, and EXTL2 in Patients with Osteoarthritis and Kashin-Beck Disease.
      Title: Altered Expression of Aggrecan, FAM20B, B3GALT6, and EXTL2 in Patients with Osteoarthritis and Kashin-Beck Disease.
    10. Blood and urine biomarkers in osteoarthritis - an update on cartilage associated type II collagen and aggrecan markers.
      Title: Blood and urine biomarkers in osteoarthritis - an update on cartilage associated type II collagen and aggrecan markers.
    Submit: New GeneRIF Correction See all GeneRIFs (125)

    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
    Short stature and advanced bone age, with or without early-onset osteoarthritis and/or osteochondritis dissecans
    MedGen: C3665488 OMIM: 165800 GeneReviews: Not available
    		not available
    Spondyloepimetaphyseal dysplasia, aggrecan type
    MedGen: C2748544 OMIM: 612813 GeneReviews: Not available
    		not available
    Spondyloepiphyseal dysplasia, Kimberley type
    MedGen: C1842149 OMIM: 608361 GeneReviews: Not available
    		not available

    EBI GWAS Catalog

    Description
    A novel common variant in DCST2 is associated with length in early life and height in adulthood.
    EBI GWAS Catalog
    Genome-wide association analysis identifies 20 loci that influence adult height.
    EBI GWAS Catalog
    Genome-wide association studies and heritability estimates of body mass index related phenotypes in bangladeshi adults.
    EBI GWAS Catalog
    Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture.
    EBI GWAS Catalog
    Hundreds of variants clustered in genomic loci and biological pathways affect human height.
    EBI GWAS Catalog
    Identification, replication, and fine-mapping of Loci associated with adult height in individuals of african ancestry.
    EBI GWAS Catalog
    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
    Tat tat HIV-Tat peptide interferes with polyamine uptake via competition for proteoglycan binding sites rather than a putative downstream transporter in human carcinoma cells 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

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables carbohydrate binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables extracellular matrix structural constituent TAS
    Traceable Author Statement
    more info
    		 PubMed 
    enables extracellular matrix structural constituent conferring compression resistance RCA
    inferred from Reviewed Computational Analysis
    more info
    		 PubMed 
    enables hyaluronic acid binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables metal ion binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in cell adhesion IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in central nervous system development IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in glial cell differentiation IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in positive regulation of neuroblast proliferation IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in proteolysis NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    involved_in skeletal system development IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in skeletal system development NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    Component Evidence Code Pubs
    located_in Golgi lumen TAS
    Traceable Author Statement
    more info
    		  
    colocalizes_with collagen-containing extracellular matrix HDA PubMed 
    located_in collagen-containing extracellular matrix HDA PubMed 
    located_in extracellular region TAS
    Traceable Author Statement
    more info
    		  
    is_active_in extracellular space IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in lysosomal lumen TAS
    Traceable Author Statement
    more info
    		  
    is_active_in perineuronal net IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    is_active_in synapse IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  

    General protein information

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    Preferred Names
    aggrecan core protein
    Names
    cartilage-specific proteoglycan core protein
    chondroitin sulfate proteoglycan core protein 1
    large aggregating proteoglycan

    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_012794.1 RefSeqGene

      Range
      4994..76911
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001135.4 → NP_001126.3  aggrecan core protein isoform 1 precursor

      See identical proteins and their annotated locations for NP_001126.3

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) lacks three alternate in-frame exons in the 3' CDS, compared to variant 3. It encodes isoform 1, which lacks two internal segments, and is shorter, compared to isoform 3.
      Source sequence(s)
      AC103982
      Consensus CDS
      CCDS53971.1
      UniProtKB/TrEMBL
      E7ENV9
      Related
      ENSP00000341615.7, ENST00000352105.11
      Conserved Domains (7) summary
      cd03588
      Location:2282 → 2405
      CLECT_CSPGs; C-type lectin-like domain (CTLD) of the type found in chondroitin sulfate proteoglycan core proteins
      PRK15387
      Location:1433 → 1614
      PRK15387; type III secretion system effector E3 ubiquitin transferase SspH2
      TIGR00864
      Location:2115 → 2403
      PCC; polycystin cation channel protein
      smart00409
      Location:36 → 150
      IG; Immunoglobulin
      PHA03307
      Location:716 → 975
      PHA03307; transcriptional regulator ICP4; Provisional
      cd03517
      Location:153 → 247
      Link_domain_CSPGs_modules_1_3; this extracellular link domain is found in the first and third link modules of the chondroitin sulfate proteoglycan core protein (CSPG) aggrecan. In addition, it is found in the first link module of three other CSPGs: versican, neurocan, and brevican. ...
      cd03520
      Location:254 → 349
      Link_domain_CSPGs_modules_2_4; this link domain is found in the second and fourth link modules of the chondroitin sulfate proteoglycan core protein (CSPG) aggrecan and, in the second link module of three other CSPGs: versican, neurocan, and brevican. The link domain is a hyaluronan ...

    2. NM_001369268.1 → NP_001356197.1  aggrecan core protein isoform 3 precursor

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) represents the longest transcript and encodes the longest isoform (3).
      Source sequence(s)
      AC103982
      Consensus CDS
      CCDS92054.1
      UniProtKB/TrEMBL
      H0YMF1
      Related
      ENSP00000453581.2, ENST00000560601.4
      Conserved Domains (8) summary
      cd05900
      Location:43 → 154
      Ig_Aggrecan; Immunoglobulin (Ig)-like domain of the chondroitin sulfate proteoglycan core protein (CSPG), aggrecan
      cd00033
      Location:2485 → 2541
      CCP; Complement control protein (CCP) modules (aka short consensus repeats SCRs or SUSHI repeats) have been identified in several proteins of the complement system
      cd03588
      Location:2358 → 2481
      CLECT_CSPGs; C-type lectin-like domain (CTLD) of the type found in chondroitin sulfate proteoglycan core proteins
      PRK15387
      Location:1433 → 1614
      PRK15387; E3 ubiquitin-protein ligase SspH2; Provisional
      PHA03307
      Location:716 → 975
      PHA03307; transcriptional regulator ICP4; Provisional
      cd00054
      Location:2316 → 2352
      EGF_CA; Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular (mostly animal) proteins. Many of these proteins require calcium for their biological function and calcium-binding sites have been found to be located at the ...
      cd03517
      Location:153 → 247
      Link_domain_CSPGs_modules_1_3; this extracellular link domain is found in the first and third link modules of the chondroitin sulfate proteoglycan core protein (CSPG) aggrecan. In addition, it is found in the first link module of three other CSPGs: versican, neurocan, and brevican. ...
      cd03520
      Location:254 → 349
      Link_domain_CSPGs_modules_2_4; this link domain is found in the second and fourth link modules of the chondroitin sulfate proteoglycan core protein (CSPG) aggrecan and, in the second link module of three other CSPGs: versican, neurocan, and brevican. The link domain is a hyaluronan ...

    3. NM_001411096.1 → NP_001398025.1  aggrecan core protein isoform 4 precursor

      Status: REVIEWED

      Source sequence(s)
      AC103982
      Consensus CDS
      CCDS92056.1
      Related
      ENSP00000453499.1, ENST00000559004.5

    4. NM_001411097.1 → NP_001398026.1  aggrecan core protein isoform 5 precursor

      Status: REVIEWED

      Source sequence(s)
      AC103982
      Consensus CDS
      CCDS92055.1
      UniProtKB/TrEMBL
      A0A5K1VW97
      Related
      ENSP00000453342.3, ENST00000561243.7

    5. NM_013227.4 → NP_037359.3  aggrecan core protein isoform 2 precursor

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) lacks an alternate in-frame exon in the 3' CDS, compared to variant 3. It encodes isoform 2, which lacks an internal segment, and is shorter, compared to isoform 3.
      Source sequence(s)
      AC103982
      Consensus CDS
      CCDS53970.1
      UniProtKB/Swiss-Prot
      B9EK55, E7ENV9, E7EX88, H0YM81, P16112, Q13650, Q9UCD3, Q9UCP4, Q9UCP5, Q9UDE0
      Related
      ENSP00000387356.2, ENST00000439576.7
      Conserved Domains (8) summary
      cd05900
      Location:43 → 154
      Ig_Aggrecan; Immunoglobulin (Ig)-like domain of the chondroitin sulfate proteoglycan core protein (CSPG), aggrecan
      cd00033
      Location:2447 → 2503
      CCP; Complement control protein (CCP) modules (aka short consensus repeats SCRs or SUSHI repeats) have been identified in several proteins of the complement system
      cd03588
      Location:2320 → 2443
      CLECT_CSPGs; C-type lectin-like domain (CTLD) of the type found in chondroitin sulfate proteoglycan core proteins
      cd00054
      Location:2283 → 2313
      EGF_CA; Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular (mostly animal) proteins. Many of these proteins require calcium for their biological function and calcium-binding sites have been found to be located at the ...
      cd03517
      Location:153 → 247
      Link_domain_CSPGs_modules_1_3; Link_domain_CSPGs_modules_1_3; this extracellular link domain is found in the first and third link modules of the chondroitin sulfate proteoglycan core protein (CSPG) aggrecan. In addition, it is found in the first link module of three other CSPGs: ...
      cd03520
      Location:254 → 349
      Link_domain_CSPGs_modules_2_4; Link_domain_CSPGs_modules_2_4; this link domain is found in the second and fourth link modules of the chondroitin sulfate proteoglycan core protein (CSPG) aggrecan and, in the second link module of three other CSPGs: versican, neurocan, and brevican. The ...
      cl26018
      Location:1433 → 1614
      NEL; C-terminal novel E3 ligase, LRR-interacting
      cl28033
      Location:716 → 975
      Herpes_ICP4_C; Herpesvirus ICP4-like protein C-terminal region

    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_000015.10 Reference GRCh38.p14 Primary Assembly

      Range
      88803436..88875353
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_047432214.1 → XP_047288170.1  aggrecan core protein isoform X1

    2. XM_047432216.1 → XP_047288172.1  aggrecan core protein isoform X3

    3. XM_047432215.1 → XP_047288171.1  aggrecan core protein isoform X2

    4. XM_047432217.1 → XP_047288173.1  aggrecan core protein isoform X3

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060939.1 Alternate T2T-CHM13v2.0

      Range
      86558075..86629996
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054377434.1 → XP_054233409.1  aggrecan core protein isoform X1

    2. XM_054377436.1 → XP_054233411.1  aggrecan core protein isoform X3

    3. XM_054377435.1 → XP_054233410.1  aggrecan core protein isoform X2

    4. XM_054377437.1 → XP_054233412.1  aggrecan core protein isoform X3

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    P16112.3 GenPept UniProtKB/Swiss-Prot:P16112

    Gene LinkOut

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

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