Cornelia de Lange syndrome: genes and variants
Cornelia de Lange syndrome is linked to 2 analyzed proteins (RAD21 and BRD4). 5 DNA variants are known to cause it; 84 more are uncertain, and 0 of those already look disease-causing on computable evidence.
Last updated 2026-09-30. Research information, not medical advice.
Also known as: Cornelia de Lange syndrome 1; Cornelia de Lange syndrome 4; Cornelia de Lange syndrome 6
Genes linked to Cornelia de Lange syndrome
RAD21: Double-strand-break repair protein rad21 homolog
It forms part of the cohesin ring that holds replicated chromosomes together and also helps organize three-dimensional chromatin and gene regulation. Haploinsufficiency causes a Cornelia-de-Lange-like developmental syndrome, while somatic mutations occur in myeloid cancers.
4 disease-causing and 81 uncertain variants in RAD21 are linked to Cornelia de Lange syndrome.
BRD4: Bromodomain-containing protein 4
It remains associated with acetylated chromatin and recruits transcriptional elongation machinery to sustain expression of growth and identity genes. Cancer cells can become highly dependent on BRD4-driven transcription, making it a major target of BET inhibitors and protein degraders.
1 disease-causing and 3 uncertain variants in BRD4 are linked to Cornelia de Lange syndrome.
Weakly linked (only a few uncertain records): KMT2A.
Known disease-causing variants in Cornelia de Lange syndrome
| Variant | Position | Protein part | Clinical label |
|---|---|---|---|
| BRD4 Y430C | 430 | Bromo 2 | Disease-causing (★★) |
| RAD21 L603P | 603 | Disease-causing (★) | |
| RAD21 M1I | 1 | Disease-causing (★) | |
| RAD21 D166G | 166 | Interaction with NIPBL | Disease-causing (★) |
| RAD21 I620F | 620 | Disease-causing (★) |
Diseases related to Cornelia de Lange syndrome
- Mungan syndrome, also linked to RAD21
Frequently asked questions
Which genes are linked to Cornelia de Lange syndrome?
In CATVariant, Cornelia de Lange syndrome is linked to 2 analyzed proteins: RAD21 (Double-strand-break repair protein rad21 homolog) and BRD4 (Bromodomain-containing protein 4).
How many genetic variants are linked to Cornelia de Lange syndrome?
122 variants: 5 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 84 are of uncertain significance or have conflicting reports.
Which uncertain variants in Cornelia de Lange syndrome look disease-causing?
None of the uncertain variants currently reaches the likely-pathogenic range on computable evidence alone.
About this data
Variant–disease links come from ClinVar, Open Targets and UniProt, pooled from the latest public CATVariant analysis 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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