ACAN (aggrecan)

Gene

• Entrez ID: 176
• Gene name: Aggrecan
• Gene symbol: ACAN
• Synonyms: AGC1, AGCAN, CSPG1, CSPGCP, MSK16, SEDK, SSOAOD
• Chromosome: 15
• Chromosome location: 15q26.1
• 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

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs121913568	G>A	Pathogenic	Missense variant, coding sequence variant
rs150555123	G>A,C	Conflicting-interpretations-of-pathogenicity	Missense variant, coding sequence variant
rs267604368	G>A,T	Likely-pathogenic	Coding sequence variant, missense variant, stop gained
rs267606625	G>A	Pathogenic	Coding sequence variant, missense variant
rs368979713	G>A	Conflicting-interpretations-of-pathogenicity	Coding sequence variant, synonymous variant
rs371065660	C>T	Likely-pathogenic	Coding sequence variant, missense variant
rs387906534	->C	Pathogenic	Coding sequence variant, frameshift variant
rs576947078	C>T	Conflicting-interpretations-of-pathogenicity	Coding sequence variant, synonymous variant
rs577419060	T>C	Conflicting-interpretations-of-pathogenicity	Coding sequence variant, missense variant
rs758892087	G>A,T	Likely-pathogenic	Missense variant, stop gained, coding sequence variant
rs773948197	C>G,T	Likely-pathogenic	Stop gained, coding sequence variant, missense variant
rs1555453695	T>C	Pathogenic	Missense variant, coding sequence variant
rs1555453708	A>-	Pathogenic	Coding sequence variant, frameshift variant
rs1555454630	A>-	Pathogenic	Coding sequence variant, frameshift variant
rs1555455057	T>-	Pathogenic	Coding sequence variant, frameshift variant
rs1555455127	G>A	Pathogenic	Splice donor variant
rs1555455284	C>-	Likely-pathogenic	Stop gained, coding sequence variant
rs1555455969	T>-	Pathogenic	Coding sequence variant, frameshift variant
rs1555456128	G>T	Pathogenic	Stop gained, coding sequence variant
rs1555456230	G>-	Pathogenic	Coding sequence variant, frameshift variant
rs1555457492	T>C	Likely-pathogenic	Missense variant, coding sequence variant
rs1555457513	T>C	Pathogenic	Missense variant, coding sequence variant
rs1555457525	C>T	Pathogenic	Stop gained, coding sequence variant
rs1555457632	G>A	Pathogenic	Stop gained, coding sequence variant
rs1555457638	ACGAGAAGGGC>-	Likely-pathogenic	Coding sequence variant, frameshift variant
rs1567185220	G>T	Pathogenic	Coding sequence variant, missense variant
rs1567186585	T>A	Pathogenic	Coding sequence variant, missense variant
rs1596128699	A>T	Likely-pathogenic	Splice acceptor variant
rs1596136784	G>-	Pathogenic	Coding sequence variant, frameshift variant
rs1596144242	C>-	Pathogenic	Coding sequence variant, frameshift variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT053690	hsa-miR-181a-5p	Microarray	22942087
MIRT1921421	hsa-miR-4667-3p	CLIP-seq
MIRT1921421	hsa-miR-4667-3p	CLIP-seq
MIRT1921421	hsa-miR-4667-3p	CLIP-seq
MIRT2165851	hsa-miR-4254	CLIP-seq
MIRT2165852	hsa-miR-4469	CLIP-seq
MIRT1921421	hsa-miR-4667-3p	CLIP-seq

Transcription factors

Transcription factor	Regulation	Reference
SHOX	Unknown	24421874
SHOX2	Unknown	24421874
SIRT1	Activation	21337390
SP1	Unknown	12081893

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0001501	Process	Skeletal system development	IBA	21873635
GO:0001501	Process	Skeletal system development	NAS	1569188
GO:0005201	Function	Extracellular matrix structural constituent	TAS	1569188
GO:0005515	Function	Protein binding	IPI	17588949, 32814053
GO:0005540	Function	Hyaluronic acid binding	IEA
GO:0005576	Component	Extracellular region	TAS
GO:0005796	Component	Golgi lumen	TAS
GO:0006508	Process	Proteolysis	NAS	1569188
GO:0007155	Process	Cell adhesion	IEA
GO:0007417	Process	Central nervous system development	IBA	21873635
GO:0018146	Process	Keratan sulfate biosynthetic process	TAS
GO:0030021	Function	Extracellular matrix structural constituent conferring compression resistance	RCA	20551380, 27068509
GO:0030198	Process	Extracellular matrix organization	TAS
GO:0030246	Function	Carbohydrate binding	IEA
GO:0031012	Component	Extracellular matrix	IBA	21873635
GO:0042340	Process	Keratan sulfate catabolic process	TAS
GO:0043202	Component	Lysosomal lumen	TAS
GO:0046872	Function	Metal ion binding	IEA
GO:0062023	Component	Collagen-containing extracellular matrix	HDA	27068509
GO:0062023	Component	Collagen-containing extracellular matrix	HDA	20551380

Other IDs

• MIM: 155760
• HGNC: 319
• e!Ensembl: ENSG00000157766

Protein

• UniProt ID: P16112
• Protein name: Aggrecan core protein (Cartilage-specific proteoglycan core protein) (CSPCP) (Chondroitin sulfate proteoglycan core protein 1) (Chondroitin sulfate proteoglycan 1) [Cleaved into: Aggrecan core protein 2]
• Protein function: This proteoglycan is a major component of extracellular matrix of cartilagenous tissues. A major function of this protein is to resist compression in cartilage. It binds avidly to hyaluronic acid via an N-terminal globular region.
• PDB: 4MD4, 7RDV
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF07686	V-set	34 → 151	Immunoglobulin V-set domain	Domain
  PF00193	Xlink	153 → 247	Extracellular link domain	Domain
  PF00193	Xlink	254 → 349	Extracellular link domain	Domain
  PF00193	Xlink	478 → 572	Extracellular link domain	Domain
  PF00193	Xlink	579 → 674	Extracellular link domain	Domain
  PF00059	Lectin_C	2337 → 2442	Lectin C-type domain	Domain
  PF00084	Sushi	2447 → 2503	Sushi repeat (SCR repeat)	Domain

• Sequence:

  MTTLLWVFVTLRVITAAVTVETSDHDNSLSVSIPQPSPLRVLLGTSLTIPCYFIDPMHPV
  TTAPSTAPLAPRIKWSRVSKEKEVVLLVATEGRVRVNSAYQDKVSLPNYPAIPSDATLEV
  QSLRSNDSGVYRCEVMHGIEDSEATLEVVVKGIVFHYRAISTRYTLDFDRAQRACLQNSA
  IIATPEQLQAAYEDGFHQCDAGWLADQTVRYPIHTPREGCYGDKDEFPGVRTYGIRDTNE
  TYDVYCFAEEMEGEVFYATSPEKFTFQEAANECRRLGARLATTGQLYLAWQAGMDMCSAG
  WLADRSVRYPISKARPNCGGNLLGVRTVYVHANQTGYPDPSSRYDAICYTGEDFVDIPEN
  FFGVGGEEDITVQTVTWPDMELPLPRNITEGEARGSVILTVKPIFEVSPSPLEPEEPFTF
  APEIGATAFAEVENETGEATRPWGFPTPGLGPATAFTSEDLVVQVTAVPGQPHLPGGVVF
  HYRPGPTRYSLTFEEAQQACLRTGAVIASPEQLQAAYEAGYEQCDAGWLRDQTVRYPIVS
  PRTPCVGDKDSSPGVRTYGVRPSTETYDVYCFVDRLEGEVFFATRLEQFTFQEALEFCES
  HNATLATTGQLYAAWSRGLDKCYAGWLADGSLRYPIVTPRPACGGDKPGVRTVYLYPNQT
  GLPDPLSRHHAFCFRGISAVPSPGEEEGGTPTSPSGVEEWIVTQVVPGVAAVPVEEETTA
  VPSGETTAILEFTTEPENQTEWEPAYTPVGTSPLPGILPTWPPTGAATEESTEGPSATEV
  PSASEEPSPSEVPFPSEEPSPSEEPFPSVRPFPSVELFPSEEPFPSKEPSPSEEPSASEE
  PYTPSPPVPSWTELPSSGEESGAPDVSGDFTGSGDVSGHLDFSGQLSGDRASGLPSGDLD
  SSGLTSTVGSGLPVESGLPSGDEERIEWPSTPTVGELPSGAEILEGSASGVGDLSGLPSG
  EVLETSASGVGDLSGLPSGEVLETTAPGVEDISGLPSGEVLETTAPGVEDISGLPSGEVL
  ETTAPGVEDISGLPSGEVLETTAPGVEDISGLPSGEVLETTAPGVEDISGLPSGEVLETT
  APGVEDISGLPSGEVLETAAPGVEDISGLPSGEVLETAAPGVEDISGLPSGEVLETAAPG
  VEDISGLPSGEVLETAAPGVEDISGLPSGEVLETAAPGVEDISGLPSGEVLETAAPGVED
  ISGLPSGEVLETAAPGVEDISGLPSGEVLETAAPGVEDISGLPSGEVLETAAPGVEDISG
  LPSGEVLETAAPGVEDISGLPSGEVLETAAPGVEDISGLPSGEVLETAAPGVEDISGLPS
  GEVLETAAPGVEDISGLPSGEVLETAAPGVEDISGLPSGEVLETAAPGVEDISGLPSGEV
  LETAAPGVEDISGLPSGEVLETTAPGVEEISGLPSGEVLETTAPGVDEISGLPSGEVLET
  TAPGVEEISGLPSGEVLETSTSAVGDLSGLPSGGEVLEISVSGVEDISGLPSGEVVETSA
  SGIEDVSELPSGEGLETSASGVEDLSRLPSGEEVLEISASGFGDLSGLPSGGEGLETSAS
  EVGTDLSGLPSGREGLETSASGAEDLSGLPSGKEDLVGSASGDLDLGKLPSGTLGSGQAP
  ETSGLPSGFSGEYSGVDLGSGPPSGLPDFSGLPSGFPTVSLVDSTLVEVVTASTASELEG
  RGTIGISGAGEISGLPSSELDISGRASGLPSGTELSGQASGSPDVSGEIPGLFGVSGQPS
  GFPDTSGETSGVTELSGLSSGQPGISGEASGVLYGTSQPFGITDLSGETSGVPDLSGQPS
  GLPGFSGATSGVPDLVSGTTSGSGESSGITFVDTSLVEVAPTTFKEEEGLGSVELSGLPS
  GEADLSGKSGMVDVSGQFSGTVDSSGFTSQTPEFSGLPSGIAEVSGESSRAEIGSSLPSG
  AYYGSGTPSSFPTVSLVDRTLVESVTQAPTAQEAGEGPSGILELSGAHSGAPDMSGEHSG
  FLDLSGLQSGLIEPSGEPPGTPYFSGDFASTTNVSGESSVAMGTSGEASGLPEVTLITSE
  FVEGVTEPTISQELGQRPPVTHTPQLFESSGKVSTAGDISGATPVLPGSGVEVSSVPESS
  SETSAYPEAGFGASAAPEASREDSGSPDLSETTSAFHEANLERSSGLGVSGSTLTFQEGE
  ASAAPEVSGESTTTSDVGTEAPGLPSATPTASGDRTEISGDLSGHTSQLGVVISTSIPES
  EWTQQTQRPAETHLEIESSSLLYSGEETHTVETATSPTDASIPASPEWKRESESTAAAPA
  RSCAEEPCGAGTCKETEGHVICLCPPGYTGEHCNIDQEVCEEGWNKYQGHCYRHFPDRET
  WVDAERRCREQQSHLSSIVTPEEQEFVNNNAQDYQWIGLNDRTIEGDFRWSDGHPMQFEN
  WRPNQPDNFFAAGEDCVVMIWHEKGEWNDVPCNYHLPFTCKKGTVACGEPPVVEHARTFG
  QKKDRYEINSLVRYQCTEGFVQRHMPTIRCQPSGHWEEPQITCTDPTTYKRRLQKRSSRH
  PRRSRPSTAH

• Sequence length: 2530

Pathways

Reactome:

Degradation of the extracellular matrix
Keratan sulfate biosynthesis
Keratan sulfate degradation
ECM proteoglycans
Defective CHST6 causes MCDC1
Defective ST3GAL3 causes MCT12 and EIEE15
Defective B4GALT1 causes B4GALT1-CDG (CDG-2d)

Associated diseases

Causal
Disease name	Disease term	dbSNP ID	References
Arthritis	Degenerative polyarthritis	rs1594890601, rs1594882933, rs184370809, rs776489319, rs1594883470
Brachydactyly	Brachydactyly	rs121908949, rs28937580, rs121909082, rs104894122, rs863223289, rs863223290, rs104894121, rs1587657302, rs863223292, rs74315386, rs74315387, rs28936397, rs753691079, rs121909348, rs121917852, rs121917853, rs121917854, rs121917855, rs121917859, rs121917861, rs267606873, rs267606872, rs267606985, rs267606986, rs267606987, rs267606988, rs28933082, rs397514519, rs869025613, rs869025614, rs886039878, rs1553540620, rs1057518333, rs1948841937, rs1948868228, rs1948842030, rs1948842142
Facioscapulohumeral muscular dystrophy	Muscular Dystrophy, Facioscapulohumeral	rs387907319, rs397514623, rs1057519614, rs1598416221, rs886041918, rs886042417, rs1057519644, rs1245372794, rs1555642277, rs1555644339, rs1555647265, rs886044369, rs1568350731, rs377471712, rs2075161300, rs2075566961, rs2075161499	12868502
Macrocephaly	Relative macrocephaly	rs786204854, rs764333096, rs1557739557
Multiple congenital anomalies	Multiple congenital anomalies	rs1057517732	24762113, 1978986, 12626230, 21948754, 16080123, 27870580, 19110214, 20137779, 18226555, 17317784, 12205105
Osteochondritis dissecans	Osteochondritis Dissecans, Familial Osteochondritis Dissecans	rs1596128699, rs1596144242	27870580, 20137779, 24762113
Rheumatoid arthritis	Rheumatoid Arthritis	rs3766379, rs3792876, rs2071592, rs3087456, rs587776843, rs1566328963, rs2240340, rs1557787212	15292528
Spondyloepimetaphyseal dysplasia	Spondyloepimetaphyseal disorder	rs121909497, rs121909499, rs879255602, rs878853267, rs779218846, rs878852980, rs878852981, rs1325869434, rs1565256477, rs1597675888, rs1597675890, rs1597676540, rs369033671
Spondyloepiphyseal dysplasia	Spondyloepiphyseal Dysplasia, Spondyloepiphyseal Dysplasia, Kimberley Type, Spondyloepimetaphyseal Dysplasia, Aggrecan Type	rs72555367, rs121908950, rs121908951, rs121908952, rs104893637, rs104893639, rs387906534, rs121913568, rs606231241, rs606231242, rs786200933, rs606231243, rs786200934, rs397515546, rs797045099, rs869312907, rs886041895, rs760093841, rs374379931, rs1471554906, rs1567185220, rs1567186585, rs1592198747, rs1239366051, rs1592197682	16080123, 27870580, 24762113, 19110214, 27870580

Unknown
Disease name	Disease term	dbSNP ID	References
Bronchospasm	Bronchospasm
Dwarfism	Dwarfism
Dysmorphic features	Dysmorphic features		27870580, 21948754, 16080123, 17317784, 1978986, 20137779, 24762113, 18226555, 19110214, 12626230, 12205105
Frontal bossing	Frontal bossing
Hypoplasia of thumb	Hypoplasia of thumb
Malocclusion	Class III malocclusion
Mesomelia	Mesomelia
Micromelia	Micromelia
Osteoarthritis of hip	Osteoarthritis of hip
Rhizomelia	Rhizomelia
Short stature-advanced bone age osteoarthritis syndrome	Short stature-advanced bone age-early-onset osteoarthritis syndrome