ACAN

Chr 15

aggrecan

Also known as: AGC1, AGCAN, CSPG1, CSPGCP, MSK16, SEDK, SSOAOD

NCBI Gene: 176ENSG00000157766UniProt: P16112

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]

GeneReviewsResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtSpondyloepiphyseal dysplasia type Kimberley
UniProtSpondyloepimetaphyseal dysplasia, aggrecan type
UniProtShort stature and advanced bone age, with or without early-onset osteoarthritis and/or osteochondritis dissecans

Clinical highlights

Gene-disease validity (ClinGen)
ACAN-related short stature spectrum · ADDefinitivesufficient evidence for diagnostic panels
Interpreting a novel variant
Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.
2
Active trials
334
Pubs (1 yr)
—
P/LP submissions
—
P/LP missense
0.18
LOEUF· LoF intol.
LOF
Mechanism· G2P
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GeneReview available — ACAN
Authoritative clinical overview · Recommended first read
Open GeneReview ↗
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?
0.18LOEUF
pLI 1.000
Z-score 7.08
OE 0.10 (0.05–0.18)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?
0.21Z-score
OE missense 0.98 (0.94–1.03)
1197 obs / 1217.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.10 (0.05–0.18)
0≤0.351.4
Missense OE?0.98 (0.94–1.03)
0≤0.61.4
Synonymous OE?0.98
0≤1.21.6
LoF obs/exp: 7 / 71.7Missense obs/exp: 1197 / 1217.3Syn Z: 0.29

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

ACAN · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients