01At a glance
02What it is
Angelman syndrome is a neurodevelopmental disorder caused by loss of the maternal UBE3A allele, leaving neurons without UBE3A because the paternal allele is normally silenced by imprinting. It causes severe developmental delay, ataxia, seizures, and a characteristic happy demeanor. The therapeutic frontier is antisense-mediated unsilencing of the intact paternal allele.
03What goes wrong
Haploinsufficiency via imprinting. In neurons, the paternal UBE3A allele is normally silenced by genomic imprinting, so only the maternal allele is expressed. Loss of the maternal allele (deletion, mutation, or paternal uniparental disomy) leaves neurons with no functional UBE3A. This is a loss-of-function, but the fix is NOT to add enzyme — it is to UNSILENCE the intact paternal allele.
04How NIGHTINGALE routes it
Recommended modality: unsilence (reactivate paternal UBE3A — ASO, investigational)
NOT eligible. Angelman is a loss-of-function/haploinsufficiency disease — UBE3A is absent, not accumulated. Degrading any residual UBE3A would worsen the disease. The correct route is to UNSILENCE the intact paternal UBE3A allele (the paternal copy is present but epigenetically off).
05Treatment today
06In the pipeline
- Antisense oligonucleotides to unsilence paternal UBE3A (e.g. targeting UBE3A-ATS antisense transcript — clinical)
- AAV9-UBE3A gene therapy (preclinical)
- Symptomatic: anti-seizure medication (levetiracetam, etc.)
Key reference: PMID 37599585 · PubMed
07Verification
Every line below is the registry's own verification record — what was checked, against which source, and what is still open.
- uniprot: Q05086 = UBE3A (Ubiquitin-protein ligase E3A), 875 aa — VERIFIED via UniProt REST API (live)
- gene mutation: Maternal UBE3A allele loss / imprinting — VERIFIED (OMIM 105830)
- inheritance: Maternal UBE3A loss, paternal imprinted — VERIFIED (OMIM 105830; Orphanet)
- orpha code: 72 = Angelman syndrome (Active) — VERIFIED via Orphanet API (live, 2026-07-02)
- drug mw: No approved therapy — N/A (no small-molecule drug to cite)
- fda date: No FDA-approved disease-modifying therapy — N/A
08Sources
| Fact | Source | Accession | Retrieved |
|---|---|---|---|
| Gene/protein identity | UniProt | Q05086 (UBE3A, 875 aa) | 2026-10-04 |
| Disease classification & definition | Orphanet | ORPHAcode 72 (Angelman syndrome) | 2026-10-04 |
| Inheritance & genetics | OMIM | 105830 (Angelman Syndrome) | 2026-10-04 |
Corrections carried into registry v2 (2)
- VERIFIED (2026-10-04): built fresh. ORPHAcode 72 confirmed live via Orphanet API.
- CLARIFIED: Angelman is HAPLOINSUFFICIENCY via imprinting — the fix is UNSILENCING the paternal allele (ASO), not degradation, not enzyme replacement, not a channel drug.