Angelman syndrome-like: genes and variants

Genes linked to Angelman syndrome-like

• CDKL5: Cyclin-dependent kinase-like 5

  It phosphorylates neuronal substrates involved in synapse development, cytoskeletal organization, and signaling during early brain maturation. Loss-of-function variants cause CDKL5 deficiency disorder with very early epilepsy and severe developmental impairment.

  41 disease-causing and 154 uncertain variants in CDKL5 are linked to Angelman syndrome-like.

Where Angelman syndrome-like variants cluster

• CDKL5 Protein kinase (positions 13–297): 41 of 41 disease-causing changes, 3.4× more than its size predicts.

Known disease-causing variants in Angelman syndrome-like

Uncertain variants in Angelman syndrome-like that look disease-causing

Which prediction tools work for Angelman syndrome-like

How often each tool ranks a disease-causing variant above a harmless one (AUROC × 100).

• EVE: 99 out of 100
• MutPred2: 98 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• AlphaMissense: 97 out of 100
• PolyPhen-2: 90 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• MetaLR: 88 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• CATVariant: 86 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• SIFT: 78 out of 100

Same protein, different disease

• CDKL5 disorder is also caused by CDKL5 variants; they fall in the same places as the Angelman syndrome-like variants (32 disease-causing).

Diseases related to Angelman syndrome-like

• Rett syndrome, also linked to CDKL5
• CDKL5 disorder, also linked to CDKL5
• Angelman syndrome, also linked to CDKL5
• Autism, also linked to CDKL5
• Infantile spasms, also linked to CDKL5

Frequently asked questions

Which genes are linked to Angelman syndrome-like?

In CATVariant, Angelman syndrome-like is linked to 1 analyzed protein: CDKL5 (Cyclin-dependent kinase-like 5).

How many genetic variants are linked to Angelman syndrome-like?

233 variants: 41 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 154 are of uncertain significance or have conflicting reports.

Which uncertain variants in Angelman syndrome-like look disease-causing?

1 uncertain variants reach the likely-pathogenic range of the ACMG/AMP points scale on computable evidence, for example CDKL5 H133P. These are leads for expert review, not diagnoses.

Which variant effect predictor works best for Angelman syndrome-like?

Among tools not trained on clinical labels, EVE separates this disease's known disease-causing variants from harmless ones best (AUROC 0.99, based on 29 disease-causing and 21 harmless variants).

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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