ACAN Gene: Aggrecan – Cartilage Proteoglycan Core Protein
Essential structural component of cartilage extracellular matrix; mutations cause skeletal dysplasias and osteoarthritis.
Gene Information Card
| Symbol | ACAN |
|---|---|
| Full Name | Aggrecan |
| Gene Type | Protein coding |
| Chromosomal Location | 15q26.1 |
| NCBI Gene ID | 176 ncbi.nlm.nih.gov/gene/176 |
| Ensembl ID | ENSG00000157766 |
| UniProt ID | P16112 |
| OMIM ID | 155760 |
| HGNC ID | 319 |
| Aliases | AGC1, AGCAN, CSPG1, CSPGCP, MSK16, SEDK |
Description
The ACAN gene encodes aggrecan, a large proteoglycan that is a major structural component of cartilage extracellular matrix. Aggrecan provides cartilage with its compressive resistance by forming large aggregates with hyaluronan. Mutations in ACAN lead to various skeletal dysplasias, including spondyloepiphyseal dysplasia, Kimberley type, and familial osteochondritis dissecans, as well as increased risk of osteoarthritis and short stature.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Spondyloepiphyseal dysplasia, Kimberley type | Loss-of-function mutations in ACAN disrupt cartilage matrix integrity, leading to disproportionate short stature and skeletal abnormalities. | OMIM #608361 |
| Familial osteochondritis dissecans | Dominant negative mutations affect aggrecan function, causing joint cartilage fragmentation and early osteoarthritis. | OMIM #165800 |
| Osteoarthritis susceptibility | Common variants in ACAN are associated with altered aggrecan expression and increased risk of osteoarthritis. | ClinVar, PMID: 24879434 |
| Short stature, idiopathic | Heterozygous loss-of-function mutations in ACAN cause mild to moderate short stature without major skeletal dysplasia. | OMIM #165800, PMID: 28166811 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Cartilage | High (nTPM: 1000+) | High |
| Bone | Moderate (nTPM: 100-500) | Moderate |
| Adipose tissue | Low (nTPM: 10-50) | Low |
| Brain | Not detected | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Chondrocytes (primary) | High | Major site of aggrecan synthesis |
| SW1353 (chondrosarcoma) | Moderate | Used in cartilage research |
| HeLa | Not detected | Non-cartilage cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.7274delC (p.Pro2425Leufs*47) | Frameshift | Rare | Loss of function; causes spondyloepiphyseal dysplasia |
| c.6802C>T (p.Arg2268*) | Nonsense | Rare | Premature stop; loss of function |
| c.1003G>A (p.Gly335Arg) | Missense | Rare | Dominant negative; associated with osteochondritis dissecans |
| c.1A>G (p.Met1?) | Start loss | Rare | Complete loss of protein; severe skeletal dysplasia |
Mutation functional classification
Loss of Function (LOF)
Frameshift, nonsense, and start-loss mutations lead to truncated or absent aggrecan, impairing cartilage structure and causing skeletal dysplasias.
Gain of Function (GOF)
No gain-of-function mutations reported for ACAN.
Dominant Negative (DN)
Missense mutations (e.g., p.Gly335Arg) produce abnormal aggrecan that interferes with normal protein function, leading to familial osteochondritis dissecans.
View complete mutation data：
Gene Ontology (GO)
| • GO:0005576 – extracellular region | • GO:0031012 – extracellular matrix |
| • GO:0005201 – extracellular matrix structural constituent | • GO:0005539 – glycosaminoglycan binding |
| • GO:0001501 – skeletal system development | • GO:0007155 – cell adhesion |
Pathways
• ECM-receptor interaction (KEGG: hsa04512)
• Proteoglycans in cancer (KEGG: hsa05205)
• Aggrecan degradation in osteoarthritis (Reactome: R-HSA-2022090)
Protein Summary
Aggrecan is a large proteoglycan (core protein ~250 kDa) heavily modified with chondroitin sulfate and keratan sulfate glycosaminoglycan chains. It forms aggregates with hyaluronan via link protein, providing cartilage with its ability to resist compressive loads. The protein contains an N-terminal G1 domain (hyaluronan binding), a central glycosaminoglycan attachment region, and a C-terminal G3 domain (lectin-like). Mutations affecting any domain can disrupt cartilage integrity.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ACAN Knockout HEK293 Cell Line | EDJ-KQ2172 | Human | 176 | Details Get a Quote |
| ACAN Knockout HeLa Cell Line | EDJ-KQ52578 | Human | 176 | Details Get a Quote |
| ACAN Knockout A-549 Cell Line | EDJ-KQ61056 | Human | 176 | Details Get a Quote |
| ACAN Knockout HCT 116 Cell Line | EDJ-KQ69537 | Human | 176 | Details Get a Quote |
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