Multiple epiphyseal dysplasia: genes and variants

Genes linked to Multiple epiphyseal dysplasia

• COMP: Cartilage oligomeric matrix protein

  An extracellular-matrix protein that interacts with collagens and other cartilage components to support cartilage structure. Variants can cause pseudoachondroplasia or multiple epiphyseal dysplasia.

  27 ClinVar pathogenic / likely pathogenic and 27 uncertain variants in COMP have source records linked to Multiple epiphyseal dysplasia. Association strength is not clinical gene validity.

• SLC26A2: Sulfate transporter

  A sulfate transporter that supplies chondrocytes with sulfate for cartilage proteoglycan production. Variants cause a spectrum of skeletal disorders, including diastrophic dysplasia.

  12 ClinVar pathogenic / likely pathogenic and 125 uncertain variants in SLC26A2 have source records linked to Multiple epiphyseal dysplasia. Association strength is not clinical gene validity.

• COL2A1: Collagen alpha-1(II) chain

  It provides the principal fibrillar collagen framework of cartilage and is also important in the vitreous and inner ear. Pathogenic variants cause a broad type II collagenopathy spectrum including Stickler syndrome, spondyloepiphyseal dysplasia, and severe skeletal dysplasias.

  1 ClinVar pathogenic / likely pathogenic and 0 uncertain variants in COL2A1 have source records linked to Multiple epiphyseal dysplasia. Association strength is not clinical gene validity.

Where Multiple epiphyseal dysplasia variants cluster

• COMP TSP type-3 6 (positions 419–456): 6 of 27 ClinVar pathogenic / likely pathogenic variants, 4.4× more than its size predicts.
• SLC26A2 Transmembrane (positions 420–440): 3 of 12 ClinVar pathogenic / likely pathogenic variants, 8.8× more than its size predicts.
• COMP TSP type-3 4 (positions 360–395): 4 of 27 ClinVar pathogenic / likely pathogenic variants, 3.1× more than its size predicts.
• COMP TSP type-3 5 (positions 396–418): 3 of 27 ClinVar pathogenic / likely pathogenic variants, 3.7× more than its size predicts.
• COMP TSP type-3 8 (positions 493–528): 3 of 27 ClinVar pathogenic / likely pathogenic variants, 2.3× more than its size predicts.

ClinVar pathogenic and likely pathogenic variants linked to Multiple epiphyseal dysplasia

Uncertain variants prioritized for review in Multiple epiphyseal dysplasia

Which prediction tools work for Multiple epiphyseal dysplasia

Observed separation of ClinVar pathogenic / likely pathogenic from benign / likely benign variants (AUROC × 100). This benchmark is not a clinical recommendation.

• EVE: 100 out of 100
• CATVariant: 95 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• MetaLR: 94 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• REVEL: 94 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• AlphaMissense: 92 out of 100
• SIFT: 91 out of 100
• PolyPhen-2: 91 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• ESM1b (LLR): 89 out of 100
• MutPred2: 83 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• AlphaGenome (regulatory): 78 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• CADD: 74 out of 100
• phyloP: 52 out of 100
• AlphaGenome (splicing): 52 out of 100 (learned from overlapping clinical labels, so this is optimistic)

Same protein, different disease

• Pseudoachondroplastic spondyloepiphyseal dysplasia syndrome also has ClinVar records linked to COMP variants; they fall partly in the same places as the Multiple epiphyseal dysplasia variants (32 pathogenic / likely pathogenic).
• Diastrophic dysplasia also has ClinVar records linked to SLC26A2 variants; they fall mostly in different places as the Multiple epiphyseal dysplasia variants (16 pathogenic / likely pathogenic).
• Achondrogenesis type II also has ClinVar records linked to SLC26A2 variants; they fall mostly in different places as the Multiple epiphyseal dysplasia variants (14 pathogenic / likely pathogenic).
• Atelosteogenesis type II also has ClinVar records linked to SLC26A2 variants; they fall mostly in different places as the Multiple epiphyseal dysplasia variants (11 pathogenic / likely pathogenic).
• Osteochondrodysplasia also has ClinVar records linked to SLC26A2 variants; they fall mostly in different places as the Multiple epiphyseal dysplasia variants (3 pathogenic / likely pathogenic).
• Spondyloepiphyseal dysplasia congenita also has ClinVar records linked to COL2A1 variants; they fall mostly in different places as the Multiple epiphyseal dysplasia variants (38 pathogenic / likely pathogenic).
• Achondrogenesis type II also has ClinVar records linked to COL2A1 variants; they fall mostly in different places as the Multiple epiphyseal dysplasia variants (34 pathogenic / likely pathogenic).
• Stickler syndrome also has ClinVar records linked to COL2A1 variants; they fall mostly in different places as the Multiple epiphyseal dysplasia variants (26 pathogenic / likely pathogenic).
• Spondyloepimetaphyseal dysplasia, Strudwick type also has ClinVar records linked to COL2A1 variants; they fall mostly in different places as the Multiple epiphyseal dysplasia variants (18 pathogenic / likely pathogenic).
• Connective tissue disease also has ClinVar records linked to COL2A1 variants; they fall mostly in different places as the Multiple epiphyseal dysplasia variants (15 pathogenic / likely pathogenic).

Diseases related to Multiple epiphyseal dysplasia

• Connective tissue disease, also linked to COL2A1, COMP and SLC26A2
• Achondrogenesis type II, also linked to COL2A1 and SLC26A2
• Stickler syndrome, also linked to COL2A1
• Spondyloepiphyseal dysplasia congenita, also linked to COL2A1
• Pseudoachondroplastic spondyloepiphyseal dysplasia syndrome, also linked to COMP
• Spondyloepimetaphyseal dysplasia, Strudwick type, also linked to COL2A1
• Atelosteogenesis type II, also linked to SLC26A2
• Diastrophic dysplasia, also linked to SLC26A2
• Type 2 collagenopathy, also linked to COL2A1
• Spondyloperipheral dysplasia, also linked to COL2A1
• Fetal anomalies with a likely genetic cause, also linked to COL2A1
• Carpal tunnel syndrome, also linked to COMP

Frequently asked questions

Which genes have records linked to Multiple epiphyseal dysplasia?

This view contains 3 analyzed proteins: COMP, SLC26A2, COL2A1. Links come from clinical records and association databases. They do not imply that every listed gene is a validated cause, and missing genes may not yet be analyzed.

What do the clinical classifications mean?

Linked records include 40 pathogenic or likely pathogenic variants, 125 variants of uncertain significance and 27 with conflicting classifications. Labels summarize source records; multi-condition records may not make a separate assertion for this disease. Check the original record and review status.

Does the evidence score change a VUS classification?

No. 1 VUS or conflicting variants reach the likely-pathogenic points range on the computable criteria available here. This is a research prioritization signal, not a clinical classification. Patient, family and other required evidence may be missing.

Can I download the variant evidence?

Download the CSV for all 249 variants in the selected disease scope, including clinical labels, review status, evidence criteria, predictor scores, functional measurements and population frequency where available.

About this data

Variant–disease links come from ClinVar, Open Targets and UniProt, pooled from eligible public CATVariant analyses of each human protein. Evidence scores use the ACMG/AMP Bayesian points scale with computable criteria only (position among known disease variants, rarity in gnomAD, calibrated predictors, deep mutational scanning); there is no family or patient data, so they prioritise variants for expert review and never classify them.

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