COMP

Chr 19AD

cartilage oligomeric matrix protein

Also known as: CTS2, EDM1, EPD1, MED, PSACH, THBS5, TSP-5, TSP5

NCBI Gene: 1311 ENSG00000105664 UniProt: P49747 OMIM: 600310

The cartilage oligomeric matrix protein is a pentameric extracellular matrix glycoprotein that maintains structural integrity of cartilage through interactions with collagens, fibronectin, and chondrocyte integrin receptors. Mutations cause autosomal dominant skeletal dysplasias including pseudoachondroplasia and multiple epiphyseal dysplasia, which present in early childhood with short stature, joint pain, and early-onset osteoarthritis. Some mutations also cause carpal tunnel syndrome.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

The protein encoded by this gene is a noncollagenous extracellular matrix (ECM) protein. It consists of five identical glycoprotein subunits, each with EGF-like and calcium-binding (thrombospondin-like) domains. Oligomerization results from formation of a five-stranded coiled coil and disulfides. Binding to other ECM proteins such as collagen appears to depend on divalent cations. Contraction or expansion of a 5 aa aspartate repeat and other mutations can cause pseudochondroplasia (PSACH) and multiple epiphyseal dysplasia (MED). [provided by RefSeq, Jul 2016]

OMIM ResearchGenerating clinical summary…

DNmechanismADLOEUF 0.773 OMIM phenotypes

Clinical Summary— COMP

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Gene-Disease Validity (ClinGen)

COMP-related skeletal dysplasia · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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Clinical Trials

6 active or recruiting trials — potential therapeutic options may be available

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.77LOEUF

pLI 0.000

Z-score 2.73

OE 0.53 (0.38–0.77)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.78Z-score

OE missense 0.77 (0.70–0.84)

348 obs / 454.8 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.53 (0.38–0.77)

0≤0.351.4

Missense OE?0.77 (0.70–0.84)

0≤0.61.4

Synonymous OE?0.95

0≤1.21.6

LoF obs/exp: 21 / 39.5Missense obs/exp: 348 / 454.8Syn Z: 0.56

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

definitiveCOMP-related pseudoachondroplasia and multiple epiphyseal dysplasia spectrumDNAD

This gene — mechanism propensity

0.6162th %ile

GOF

0.6443th %ile

LOF

0.3355th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). The Badonyi & Marsh model scores gain-of-function highest among its predictions, but genomic evidence (constraint, ClinVar variant spectrum, and literature) most strongly supports dominant-negative. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median · 1 literature citation

GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Literature Evidence

DNPSACH growth plate and growth plate chondrocytes studies indicate that COMP mutations have a dominant negative effect with both COMP and type IX collagen being retained in large rER cisternae.1

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

References

1.PMID 15094116 ↗

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

COMP · 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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

Hip Replacement in Osteoarthritis PatientsOsteoarthritis, Hip

Prehabilitation in Older People Undergoing Total Hip Replacement

NOT YET RECRUITING

NCT07048080Phase NAUniversidad de La FronteraStarted 2026-08-02

(P)rehabilitation Progresive Resistance Exercise TrainingPrehabilitation Group Deuterated WaterUsual Care Group Deuterated Water

Hand OsteoarthritisErosive Osteoarthritis

Methotrexate in Erosive Inflammatory Hand Osteoarthritis

ACTIVE NOT RECRUITING

NCT04579848Phase PHASE4Diakonhjemmet HospitalStarted 2021-08-12

Methotrexate TabletsPlaceboFolic Acid 1 MG

Neoplasms

Long-Term Follow-up Protocol for Participants Treated With Gene-Modified T Cells

RECRUITING

NCT03435796Phase PHASE2, PHASE3CelgeneStarted 2018-07-19

Gene-modified (GM) T cell therapy

Locally Advanced or Metastatic Solid Tumor Harboring an NTRK Gene Fusion

Study to Learn More About the Safety and Effectiveness of the Drug VITRAKVI During Routine Use in Patients With TRK Fusion Cancer Which is Locally Advanced or Spread From the Place Where it Started to Other Places in the Body

RECRUITING

NCT04142437BayerStarted 2020-04-03

larotrectinib(Vitrakvi, BAY2757556)

Breast Cancer

NeoadjuVAnt muLti-agENT Chemotherapy or Patritumab Deruxtecan With or Without endocrINE Therapy for High-risk HR+/HER2- Breast Cancer - VALENTINE Trial

ACTIVE NOT RECRUITING

NCT05569811Phase PHASE2SOLTI Breast Cancer Research GroupStarted 2022-11-25

Patritumab deruxtecanChemotherapyLetrozole

Anterior Cruciate Ligament Injuries

Biologic Therapy to Prevent Osteoarthritis After ACL Injury

RECRUITING

NCT03968913Phase EARLY_PHASE1University of California, Los AngelesStarted 2021-09-15

Anakinra injectionsterile saline injection

Clinical Literature

Open Research Assistant →

Landmark / reviewRecent case evidence

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