UBE3A

Summary

UBE3A (ubiquitin protein ligase E3A, HGNC:12496) is a protein-coding gene on chromosome 15q11.2, encoding Ubiquitin-protein ligase E3A (Q05086). E3 ubiquitin-protein ligase which accepts ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and transfers it to its substrates. It is haploinsufficient (ClinGen: sufficient evidence).

This gene encodes an E3 ubiquitin-protein ligase, part of the ubiquitin protein degradation system. This imprinted gene is maternally expressed in brain and biallelically expressed in other tissues. Maternally inherited deletion of this gene causes Angelman Syndrome, characterized by severe motor and intellectual retardation, ataxia, hypotonia, epilepsy, absence of speech, and characteristic facies. The protein also interacts with the E6 protein of human papillomavirus types 16 and 18, resulting in ubiquitination and proteolysis of tumor protein p53. Alternative splicing of this gene results in three transcript variants encoding three isoforms with different N-termini. Additional transcript variants have been described, but their full length nature has not been determined.

Source: NCBI Gene 7337 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Angelman syndrome (Definitive, ClinGen)
• GWAS associations: 4
• Clinical variants (ClinVar): 43 total — 8 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 98
• Druggable target: yes
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
• MANE Select transcript: NM_130839

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12496
Approved symbol	UBE3A
Name	ubiquitin protein ligase E3A
Location	15q11.2
Locus type	gene with protein product
Status	Approved
Aliases	AS, ANCR, E6-AP, FLJ26981
Ensembl gene	ENSG00000114062
Ensembl biotype	protein_coding
OMIM	601623
Entrez	7337

Gene structure

Transcript identifiers

Ensembl transcripts: 40 — 31 protein_coding, 5 retained_intron, 4 protein_coding_CDS_not_defined

ENST00000428984, ENST00000438097, ENST00000566215, ENST00000604860, ENST00000625681, ENST00000625778, ENST00000626068, ENST00000626176, ENST00000626589, ENST00000626793, ENST00000627018, ENST00000628267, ENST00000628733, ENST00000628890, ENST00000629252, ENST00000629886, ENST00000630424, ENST00000630607, ENST00000630907, ENST00000631247, ENST00000635914, ENST00000636667, ENST00000637886, ENST00000638011, ENST00000638155, ENST00000648336, ENST00000649550, ENST00000650110, ENST00000675000, ENST00000675038, ENST00000675177, ENST00000675593, ENST00000676452, ENST00000858359, ENST00000858360, ENST00000918482, ENST00000918483, ENST00000970634, ENST00000970635, ENST00000970636

RefSeq mRNA: 28 — MANE Select: NM_130839 NM_000462, NM_001354505, NM_001354506, NM_001354507, NM_001354508, NM_001354509, NM_001354511, NM_001354512, NM_001354513, NM_001354523, NM_001354526, NM_001354538, NM_001354539, NM_001354540, NM_001354541, NM_001354542, NM_001354543, NM_001354544, NM_001354545, NM_001354546, NM_001354547, NM_001354548, NM_001354549, NM_001354550, NM_001354551, NM_001374461, NM_130838, NM_130839

CCDS: CCDS32177, CCDS45191, CCDS45192, CCDS86436, CCDS91966

Canonical transcript exons

ENST00000648336 — 13 exons

Exon	Start	End
ENSE00000778627	25355892	25356056
ENSE00000778628	25356691	25356896
ENSE00000778629	25360383	25360527
ENSE00000815073	25340085	25340228
ENSE00000815075	25354353	25354426
ENSE00000815076	25354528	25354683
ENSE00000815081	25370566	25371812
ENSE00000815082	25375465	25375763
ENSE00001376416	25411908	25411971
ENSE00002454147	25333728	25339257
ENSE00003576935	25409088	25409207
ENSE00003638041	25405461	25405502
ENSE00003840772	25438489	25439024

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 98.20.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 40.9184 / max 229.4964, expressed in 1822 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
149008	39.2146	1822
149009	1.2745	798
149007	0.3109	101
149002	0.1184	34

Top tissues by expression

295 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	98.20	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	98.08	gold quality
calcaneal tendon	UBERON:0003701	97.80	gold quality
male germ cell	CL:0000015	97.75	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	97.75	gold quality
biceps brachii	UBERON:0001507	97.56	gold quality
mucosa of paranasal sinus	UBERON:0005030	97.37	gold quality
nipple	UBERON:0002030	97.25	gold quality
choroid plexus epithelium	UBERON:0003911	97.18	gold quality
vastus lateralis	UBERON:0001379	97.15	gold quality
skeletal muscle tissue	UBERON:0001134	97.14	gold quality
pylorus	UBERON:0001166	97.11	gold quality
cardia of stomach	UBERON:0001162	97.10	gold quality
quadriceps femoris	UBERON:0001377	97.10	gold quality
heart right ventricle	UBERON:0002080	97.09	gold quality
ganglionic eminence	UBERON:0004023	97.09	gold quality
cortical plate	UBERON:0005343	97.01	gold quality
diaphragm	UBERON:0001103	96.88	gold quality
ventricular zone	UBERON:0003053	96.88	gold quality
body of tongue	UBERON:0011876	96.87	gold quality
renal medulla	UBERON:0000362	96.83	gold quality
tibialis anterior	UBERON:0001385	96.81	gold quality
deltoid	UBERON:0001476	96.81	gold quality
dorsal root ganglion	UBERON:0000044	96.78	gold quality
gluteal muscle	UBERON:0002000	96.78	gold quality
endothelial cell	CL:0000115	96.75	gold quality
mammalian vulva	UBERON:0000997	96.64	gold quality
trabecular bone tissue	UBERON:0002483	96.63	gold quality
muscle tissue	UBERON:0002385	96.60	gold quality
corpus callosum	UBERON:0002336	96.44	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-HCAD-25	yes	36.79
E-ANND-3	yes	10.91

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MYC, TFCP2

miRNA regulators (miRDB)

230 targeting UBE3A, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-1229-3P	99.97	66.49	906
HSA-MIR-6888-3P	99.97	65.95	1170
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-557	99.96	70.01	1640
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-218-5P	99.93	72.22	2103

Functional genomics

ClinGen dosage: haploinsufficiency 3 (sufficient evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• evaluation for 22 clinical variables– including growth parameters, acquisition of motor skills, and history of seizures–and molecular and cytogenetic analyses are used to assign a molecular class (I-V) to patients for genotype-phenotype correlations (PMID:11748306)
• A borderline significant association with a 7 bp deletion in UBE3A (P = 0.01) was found. This polymorphism was then evaluated further in a larger series of families with tuberculosis, including 44 Guinean families and 57 families from South Africa. (PMID:12075004)
• Imprinted so that the maternal allele is preferentially expressed. (PMID:12095913)
• VCY2 protein interacts with the HECT domain of ubiquitin-protein ligase E3A (PMID:12207887)
• TIP120A functions as a negative regulator of SCF E3 ubiquitin ligases and may modulate other cullin ligases in a similar fashion. (PMID:12609982)
• degrades p53 in the presence of HPV16 E6 protein (PMID:12620801)
• Inherited mutation at the UBE3A gene (5.4%)in diagnosis of Angelman syndrome. (PMID:12725589)
• By combining our data with those of the literature, we demonstrate statistically that the frequency of UBE3A mutations is significantly higher in the familial than sporadic subsets of AS (angelman syndrome). (PMID:14981718)
• UBE3A gene mutations are associated with Angelman syndrome (PMID:15054837)
• Reduced expression of UBE3A is associated with Rett, Angelman and autism (PMID:15615769)
• E6AP ubiquitin ligase is required for transactivation of the hTERT promoter by the human papillomavirus E6 oncoprotein (PMID:15655249)
• E6AP mediates a broad spectrum of E6 functions, including virtually all functions that impact on the transcriptional program of HPV-positive cell lines. (PMID:15731267)
• E6AP is a component of estrogen receptor degradation via the ubiquitin-proteasome pathway; Ca(2+)/calmodulin modulates this degradation mechanism (PMID:16314411)
• data revealed that E6AP is extensively involved in the ubiquitin-mediated degradation of human papillomavirus E6-dependent substrates as a cellular E3 ubiquitin-protein ligase (PMID:16482544)
• These findings suggest that the silencing of astrin induce a p53-dependent apoptosis and has an additive effect on paclitaxel treatment. (PMID:16546135)
• Telomerase activity at both early and late passages, however, was dependent on E6AP expression, implying a continued reliance on E6 function for telomerase activity (PMID:16708385)
• detected 20 proteins that were differentially regulated by over-expression of human UBE3A in Drosophila (PMID:16905559)
• changes in the cellular milieu initiate E6AP-mediated proteasomal degradation of AIB1 and thus contribute to the control of steady-state levels of this protein in breast cancer cells. (PMID:16951183)
• proteolytic properties of human papillomavirus E6 proteins are mediated by interaction with E6-AP (PMID:17085449)
• A study was done of ubiquitin-dependent proteolysis of TH1L protein by E6-AP. (PMID:17131388)
• Findings indicate that HPV 16 E6 protein is required for the immortalization of tonsil epithelial cells and suggests that a mechanism related to the E6 PDZ motif plays a role in cell transformation of tonsil cells. (PMID:17657785)
• Angelman syndrome is a neurogenetic condition that includes sleep problems. It is caused by lack of expression of the UBE3A gene on the maternal chromosome 15q11-q13. (PMID:17765640)
• binding to E6AP is not necessary for E6 localization to or activation of the hTERT promoter and another activity of E6 is involved in hTERT activation. (PMID:17942561)
• E6-AP not only enhances the degradation of p53 but also regulates the neuronal cell growth. (PMID:18193166)
• E6-AP is a critical mediator of the neuronal response to misfolded polyglutamine proteins and represents a potential therapeutic target in the polyglutamine diseases. (PMID:18201976)
• These data suggest that complex formation between E6, E6AP, and NFX1-91 is a critical step in mediating telomerase activation, which may be one contributing factor to cellular life span extension during human betapapillomavirus infection. (PMID:18256157)
• The degradation of TSC2 is mediated by E6AP ubiquitin ligase. (PMID:18298802)
• We found a novel splice-site mutation of the UBE3A gene in a child with clinical and EEG features of Angelman syndrome. (PMID:18487518)
• Ubiquitin over-expression promotes the destabilization of the ubiquitin protein ligase E6AP, by a mechanism involving self-ubiquitination, and the stabilization of p53. (PMID:18612801)
• oncoprotein E6 inhibits hADA3 in cervical cancer cells and this process is E6AP-dependent. (PMID:19194825)
• Data suggest that E6AP may play a role in controlling the diverse functions of annexin A1 through the ubiquitin-proteasome pathway. (PMID:19204938)
• Novel UBE3A mutations causing Angleman syndrome: different parental origin for single nucleotide changes and multiple nucleotide deletions or insertions. (PMID:19213023)
• Results suggest that E6-AP functions as a cellular quality control ubiquitin ligase and, therefore, can be implicated not only in the pathogenesis of Angelman syndrome but also in the biology of neurodegenerative disorders involving protein aggregation. (PMID:19233847)
• Repression of E6 oncogene results in restoration of p53 and pRb suppressor pathways and induced apoptosis in HPV16-positive oropharyngeal squamous cell cancer cell lines. (PMID:19276448)
• E6AP is the prototype of the subfamily of E3 ligases that covalently bind ubiquitin and are characterized by a C-terminal of homologous to the E6AP C terminus domain. (PMID:19325566)
• Reduction of synaptic vesicle density in the hippocampi of UBE3A deficient mice may be implicated in the pathogenesis of Angelman syndrome. (PMID:19563863)
• These results demonstrate that the stability of E6 of both HPV-16 and HPV-18 is critically dependent upon the presence of E6AP. (PMID:19700180)
• identified in a large Tunisian pedigree a novel UBE3A frameshift mutation in exon 16 coding region, and we expect that the resulting UBE3A truncated protein in our patients is non-functional since the mutation implies the catalytic region of the enzyme (PMID:20034088)
• Regression analysis with a competitive binding model indicates that UbcH7 does not have enhanced affinity for E6AP. (PMID:20039703)
• Findings demonstrate the ability of TTP to act as a tumor suppressor by inhibiting the E6-AP pathway and indicate TTP loss to be a critical event during HPV-mediated cervical cancer carcinogenesis. (PMID:20157568)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	ube3a	ENSDARG00000055737
mus_musculus	Ube3a	ENSMUSG00000025326
rattus_norvegicus	Ube3a	ENSRNOG00000015734
drosophila_melanogaster	Ube3a	FBGN0061469

Paralogs (24): HECW1 (ENSG00000002746), UBE3C (ENSG00000009335), NEDD4L (ENSG00000049759), NEDD4 (ENSG00000069869), ITCH (ENSG00000078747), HACE1 (ENSG00000085382), HUWE1 (ENSG00000086758), HECTD1 (ENSG00000092148), UBR5 (ENSG00000104517), SMURF2 (ENSG00000108854), AREL1 (ENSG00000119682), WWP1 (ENSG00000123124), HERC2 (ENSG00000128731), HECW2 (ENSG00000138411), HERC3 (ENSG00000138641), HERC6 (ENSG00000138642), HERC5 (ENSG00000138646), HERC4 (ENSG00000148634), UBE3B (ENSG00000151148), TRIP12 (ENSG00000153827), HECTD2 (ENSG00000165338), HECTD4 (ENSG00000173064), WWP2 (ENSG00000198373), SMURF1 (ENSG00000198742)

Protein

Protein identifiers

Ubiquitin-protein ligase E3A — Q05086 (reviewed: Q05086)

Alternative names: E6AP ubiquitin-protein ligase, HECT-type ubiquitin transferase E3A, Human papillomavirus E6-associated protein, Oncogenic protein-associated protein E6-AP, Renal carcinoma antigen NY-REN-54

All UniProt accessions (15): A0A0D9SEJ2, A0A0D9SES7, A0A0D9SF91, A0A0D9SFH3, A0A0D9SFU3, A0A0D9SG54, A0A0D9SG63, A0A0D9SG77, A0A0G2JQQ5, A0A1B0GTB3, A0A1B0GVL3, A0A6Q8PHE5, Q05086, Q9H2G0, S4R306

UniProt curated annotations — full annotation on UniProt →

Function. E3 ubiquitin-protein ligase which accepts ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and transfers it to its substrates. Several substrates have been identified including the BMAL1, ARC, LAMTOR1, RAD23A and RAD23B, MCM7 (which is involved in DNA replication), annexin A1, the PML tumor suppressor, and the cell cycle regulator CDKN1B. Additionally, may function as a cellular quality control ubiquitin ligase by helping the degradation of the cytoplasmic misfolded proteins. Finally, UBE3A also promotes its own degradation in vivo. Plays an important role in the regulation of the circadian clock: involved in the ubiquitination of the core clock component BMAL1, leading to its proteasomal degradation. Acts as transcriptional coactivator of progesterone receptor PGR upon progesterone hormone activation. Acts as a regulator of synaptic development by mediating ubiquitination and degradation of ARC. Required for synaptic remodeling in neurons by mediating ubiquitination and degradation of LAMTOR1, thereby limiting mTORC1 signaling and activity-dependent synaptic remodeling. Synergizes with WBP2 in enhancing PGR activity. (Microbial infection) Catalyzes the high-risk human papilloma virus E6-mediated ubiquitination of p53/TP53, contributing to the neoplastic progression of cells infected by these viruses.

Subunit / interactions. The active form is probably a homotrimer. Binds UBQLN1 and UBQLN2. Interacts with the 26S proteasome. Interacts with BPY2. Interacts with HIF1AN, MAPK6 and NEURL4; interaction with MAPK6 may be mediated by NEURL4. Interacts with the proteasomal subunit PSMD4. Interacts with ESR1 and WBP2. Interacts with BMAL1. Interacts with ARC. (Microbial infection) Interacts with HCV core protein and targets it to degradation. (Microbial infection) Interacts with the E6 protein of the cancer-associated human papillomavirus types 16 and 18. The E6/E6-AP complex binds to and targets the p53/TP53 tumor-suppressor protein for ubiquitin-mediated proteolysis.

Subcellular location. Cytoplasm. Nucleus.

Post-translational modifications. Phosphorylation at Tyr-659 by ABL1 impairs E3 ligase activity and protects p53/TP53 from degradation in (HPV)-infected cells.

Disease relevance. Angelman syndrome (AS) [MIM:105830] A neurodevelopmental disorder characterized by severe motor and intellectual retardation, ataxia, frequent jerky limb movements and flapping of the arms and hands, hypotonia, seizures, absence of speech, frequent smiling and episodes of paroxysmal laughter, open-mouthed expression revealing the tongue. The disease is caused by variants affecting the gene represented in this entry.

Pathway. Protein modification; protein ubiquitination.

Miscellaneous. A cysteine residue is required for ubiquitin-thioester formation.

Isoforms (3)

UniProt ID	Names	Canonical?
Q05086-1	II	yes
Q05086-2	I
Q05086-3	III

RefSeq proteins (28): NP_000453, NP_001341434, NP_001341435, NP_001341436, NP_001341437, NP_001341438, NP_001341440, NP_001341441, NP_001341442, NP_001341452, NP_001341455, NP_001341467, NP_001341468, NP_001341469, NP_001341470, NP_001341471, NP_001341472, NP_001341473, NP_001341474, NP_001341475, NP_001341476, NP_001341477, NP_001341478, NP_001341479, NP_001341480, NP_001361390, NP_570853, NP_570854* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000569	HECT_dom	Domain
IPR017134	UBE3A	Family
IPR032353	AZUL	Domain
IPR035983	Hect_E3_ubiquitin_ligase	Homologous_superfamily
IPR042556	AZUL_sf	Homologous_superfamily
IPR044611	E3A/B/C-like	Family

Pfam: PF00632, PF16558

Enzyme classification (BRENDA):

• EC 2.3.2.26 — HECT-type E3 ubiquitin transferase (BRENDA: 14 organisms, 64 substrates, 19 inhibitors, 5 Km, 5 kcat entries)

Substrate kinetics (BRENDA)

1 substrates with measured Km, best-characterized 1. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
[UBC5B]-L-LYSINE	0.0046–0.037	5

UniProt features (121 total): helix 46, sequence variant 29, strand 18, turn 9, sequence conflict 5, region of interest 3, modified residue 2, splice variant 2, compositionally biased region 2, chain 1, domain 1, zinc finger region 1, mutagenesis site 1, active site 1

Structure

Experimental structures (PDB)

25 structures.

PDB	Method	Resolution (Å)
6TGK	X-RAY DIFFRACTION	1.3
6SJV	X-RAY DIFFRACTION	2.03
4XR8	X-RAY DIFFRACTION	2.25
7QPB	X-RAY DIFFRACTION	2.34
4GIZ	X-RAY DIFFRACTION	2.55
9L3L	X-RAY DIFFRACTION	2.59
1C4Z	X-RAY DIFFRACTION	2.6
8JRN	ELECTRON MICROSCOPY	2.6
1D5F	X-RAY DIFFRACTION	2.8
6SLM	X-RAY DIFFRACTION	2.8
8JRO	ELECTRON MICROSCOPY	3.01
7Q41	X-RAY DIFFRACTION	3.01
8GCR	ELECTRON MICROSCOPY	3.38
9CHT	ELECTRON MICROSCOPY	3.54
8JRP	ELECTRON MICROSCOPY	3.58
8R1F	ELECTRON MICROSCOPY	3.67
8R1G	ELECTRON MICROSCOPY	3.99
8JRQ	ELECTRON MICROSCOPY	4.15
8JRR	ELECTRON MICROSCOPY	4.35
1EQX	SOLUTION NMR
2KR1	SOLUTION NMR
6U19	SOLUTION NMR
8ENP	SOLUTION NMR
8EPT	SOLUTION NMR
9VG5	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q05086-F1	81.42	0.52

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1): 843 (glycyl thioester intermediate)

Post-translational modifications (2): 659, 218

Mutagenesis-validated functional residues (1):

Position	Phenotype
750	disrupt trimer formation, 50-fold reduction in e3 ligase activity.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-983168	Antigen processing: Ubiquitination & Proteasome degradation

MSigDB gene sets: 539 (showing top): GOBP_CIRCADIAN_RHYTHM, GOBP_SINGLE_FERTILIZATION, BROWNE_HCMV_INFECTION_4HR_UP, PID_TELOMERASE_PATHWAY, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, GOBP_CELLULAR_RESPONSE_TO_LIPID, REACTOME_CLASS_I_MHC_MEDIATED_ANTIGEN_PROCESSING_PRESENTATION, REACTOME_ANTIGEN_PROCESSING_UBIQUITINATION_PROTEASOME_DEGRADATION, TGCACTT_MIR519C_MIR519B_MIR519A, TTTGTAG_MIR520D, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOBP_GROWTH, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_VESICLE_MEDIATED_TRANSPORT, WONG_PROTEASOME_GENE_MODULE

GO Biological Process (32): protein polyubiquitination (GO:0000209), ovarian follicle development (GO:0001541), proteolysis (GO:0006508), ubiquitin-dependent protein catabolic process (GO:0006511), brain development (GO:0007420), androgen receptor signaling pathway (GO:0030521), positive regulation of protein ubiquitination (GO:0031398), response to progesterone (GO:0032570), sperm entry (GO:0035037), regulation of circadian rhythm (GO:0042752), proteasome-mediated ubiquitin-dependent protein catabolic process (GO:0043161), positive regulation of transcription by RNA polymerase II (GO:0045944), regulation of synaptic plasticity (GO:0048167), rhythmic process (GO:0048511), progesterone receptor signaling pathway (GO:0050847), protein autoubiquitination (GO:0051865), positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0051897), prostate gland growth (GO:0060736), protein K48-linked ubiquitination (GO:0070936), negative regulation of TORC1 signaling (GO:1904262), obsolete positive regulation of Golgi lumen acidification (GO:1905528), regulation of ubiquitin-dependent protein catabolic process (GO:2000058), positive regulation of macromolecule metabolic process (GO:0010604), protein ubiquitination (GO:0016567), nuclear receptor-mediated steroid hormone signaling pathway (GO:0030518), cellular response to nutrient levels (GO:0031669), animal organ development (GO:0048513), system development (GO:0048731), modulation of chemical synaptic transmission (GO:0050804), regulation of primary metabolic process (GO:0080090), positive regulation of protein localization to lysosome (GO:0150032), positive regulation of TORC1 signaling (GO:1904263)

GO Molecular Function (8): transcription coactivator activity (GO:0003713), ubiquitin-protein transferase activity (GO:0004842), zinc ion binding (GO:0008270), ubiquitin protein ligase activity (GO:0061630), protein binding (GO:0005515), transferase activity (GO:0016740), ligase activity (GO:0016874), metal ion binding (GO:0046872)

GO Cellular Component (7): proteasome complex (GO:0000502), nucleus (GO:0005634), cytosol (GO:0005829), synaptic vesicle (GO:0008021), glutamatergic synapse (GO:0098978), postsynaptic cytosol (GO:0099524), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Class I MHC mediated antigen processing & presentation	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein ubiquitination	4
nuclear receptor-mediated steroid hormone signaling pathway	2
positive regulation of DNA-templated transcription	2
catalytic activity	2
cellular anatomical structure	2
female gonad development	1
anatomical structure development	1
protein metabolic process	1
modification-dependent protein catabolic process	1
central nervous system development	1
animal organ development	1
head development	1
regulation of protein ubiquitination	1
positive regulation of protein modification by small protein conjugation or removal	1
response to steroid hormone	1
response to ketone	1
endocytosis	1
single fertilization	1
circadian rhythm	1
regulation of biological process	1
ubiquitin-dependent protein catabolic process	1
proteasomal protein catabolic process	1
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
modulation of chemical synaptic transmission	1
regulation of biological quality	1
biological_process	1
phosphatidylinositol 3-kinase/protein kinase B signal transduction	1
regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	1
positive regulation of intracellular signal transduction	1
developmental process involved in reproduction	1
prostate gland development	1
organ growth	1
protein polyubiquitination	1
negative regulation of TOR signaling	1
TORC1 signaling	1
regulation of TORC1 signaling	1
transcription coregulator activity	1
ubiquitin-like protein transferase activity	1
transition metal ion binding	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

183 interactions, top by confidence:

A	B	Type	Score
E6	UBE3A	psi-mi:“MI:0915”(physical association)	0.950
UBE3A	E6	psi-mi:“MI:0407”(direct interaction)	0.950
E6	UBE3A	psi-mi:“MI:0407”(direct interaction)	0.950
UBE3A	E6	psi-mi:“MI:0915”(physical association)	0.950
HIF1AN	APBA3	psi-mi:“MI:0914”(association)	0.850
UCHL5	PSMD11	psi-mi:“MI:0914”(association)	0.840
TP53	E6	psi-mi:“MI:0407”(direct interaction)	0.810
TP53	E6	psi-mi:“MI:0915”(physical association)	0.810
E6	UBE3A	psi-mi:“MI:0915”(physical association)	0.800
UBE3A	E6	psi-mi:“MI:0915”(physical association)	0.800
UBE3A	E6	psi-mi:“MI:0407”(direct interaction)	0.800
SMARCC2	ARID1A	psi-mi:“MI:0914”(association)	0.790
UBE3A	TP53	psi-mi:“MI:0915”(physical association)	0.770
UBE3A	TP53	psi-mi:“MI:0914”(association)	0.770
PSMD4	PSMD11	psi-mi:“MI:0914”(association)	0.750
PSMD13	PSMD11	psi-mi:“MI:0914”(association)	0.750
PSMD4	UBE3A	psi-mi:“MI:0915”(physical association)	0.730

BioGRID (1014): UBE3A (Reconstituted Complex), UBE2D1 (Reconstituted Complex), UBE3A (Two-hybrid), UBE3A (Two-hybrid), UBE3A (Two-hybrid), AHSP (Two-hybrid), ASAP3 (Two-hybrid), ATG9A (Two-hybrid), KLHL38 (Two-hybrid), UBE2D1 (Reconstituted Complex), UBE2L3 (Reconstituted Complex), UBE2E1 (Reconstituted Complex), UBE3A (Biochemical Activity), UBE3A (Biochemical Activity), UBE3A (Affinity Capture-Western)

ESM2 similar proteins: A0A0G2K344, A0JM23, D3ZBM7, E1C656, F1M386, F1N6G5, F1PBJ0, F8W2M1, O02697, O08759, O14830, O35385, P0CI65, P32871, P42336, P42337, P42338, P48736, Q05086, Q15034, Q28BK1, Q3U0D9, Q3UMR0, Q5GLZ8, Q5PQN1, Q5RD78, Q5REW9, Q5U5R9, Q6AZT7, Q6DCL5, Q6PAV2, Q7TNH6, Q7Z494, Q8BTI9, Q8CDU6, Q8CHG5, Q8CHG7, Q8IVU3, Q8IYU2, Q8K4M9

Diamond homologs: A0A8C0NGY6, A1CQG2, A1D3C5, A2A5Z6, A2QQ28, A9JRZ0, B0XQ72, B8N7E5, D3ZBM7, D6C652, E1B7Q7, E1C656, F1LP64, F1N6G5, F8W2M1, G0S9J5, G5E870, H2LBU8, O00308, O08759, O13834, O14326, O15033, P39940, P40985, P46934, P46935, P46937, P46938, P51593, P53119, Q03280, Q05086, Q08CZ0, Q09291, Q0CCL1, Q14669, Q15034, Q15386, Q1K9C4

SIGNOR signaling

32 interactions.

A	Effect	B	Mechanism
ABL1	“down-regulates activity”	UBE3A	phosphorylation
UBE3A	“down-regulates quantity by destabilization”	PSMB1	ubiquitination
UBE3A	“down-regulates quantity by destabilization”	PSMC2	ubiquitination
UBE3A	“down-regulates quantity by destabilization”	PSMD2	ubiquitination
UBE3A	“down-regulates quantity by destabilization”	PSMD7	ubiquitination
UBE3A	“down-regulates quantity by destabilization”	ALDH1A2	ubiquitination
UBE3A	“down-regulates activity”	“26S Proteasome”	ubiquitination
Ub:E2	“up-regulates activity”	UBE3A	ubiquitination
UBE3A	“down-regulates quantity by destabilization”	TSC2	ubiquitination
UBE3A	“down-regulates quantity by destabilization”	DLG4	ubiquitination
UBE3A	“down-regulates quantity by destabilization”	UBE3A	ubiquitination
UBE3A	“down-regulates quantity by destabilization”	NELFCD	ubiquitination
UBE3A	“down-regulates quantity by destabilization”	SOX9	ubiquitination
UBE3A	“down-regulates quantity by destabilization”	MCM7	polyubiquitination
UBE3A	“down-regulates quantity by destabilization”	TP53	polyubiquitination
UBE3A	“down-regulates quantity by destabilization”	NOL3	ubiquitination
UBE3A	“up-regulates activity”	KCNN2	ubiquitination
UBE3A	“down-regulates quantity”	EEF1E1	ubiquitination
UBE3A	“down-regulates quantity”	TP53	ubiquitination
PRKACA	“down-regulates activity”	UBE3A	phosphorylation
UBE3A	“down-regulates quantity by destabilization”	LAMTOR1	ubiquitination
UBE3A	“down-regulates quantity by destabilization”	RAD23A	polyubiquitination
UBE3A	“down-regulates quantity by destabilization”	RAD23B	polyubiquitination
UBE3A	“down-regulates quantity by destabilization”	SCRIB	polyubiquitination
UBE3A	“down-regulates quantity by destabilization”	SIPA1L1	polyubiquitination
UBE3A	“down-regulates quantity by destabilization”	PSMD4	polyubiquitination

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 154 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Autodegradation of the E3 ubiquitin ligase COP1	12	31.2×	4e-13
Regulation of activated PAK-2p34 by proteasome mediated degradation	11	30.0×	3e-12
AUF1 (hnRNP D0) binds and destabilizes mRNA	12	29.2×	5e-13
FBXL7 down-regulates AURKA during mitotic entry and in early mitosis	12	29.2×	5e-13
Vpu mediated degradation of CD4	11	28.6×	3e-12
Ubiquitin-dependent degradation of Cyclin D	11	28.6×	3e-12
Negative regulation of NOTCH4 signaling	12	28.0×	7e-13
Vif-mediated degradation of APOBEC3G	11	27.4×	5e-12

GO biological processes:

GO term	Partners	Fold	FDR
proteasome-mediated ubiquitin-dependent protein catabolic process	23	8.9×	1e-12
ubiquitin-dependent protein catabolic process	13	7.2×	2e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

43 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	8
Likely pathogenic	1
Uncertain significance	9
Likely benign	8
Benign	13

Top pathogenic / likely-pathogenic (9)

Variant ID	HGVS	Classification
1069013	NC_000015.9:g.(?25584273)(25650609_?)del	Pathogenic
1075074	NC_000015.9:g.(?25584273)(25650609_?)dup	Pathogenic
2427202	NC_000015.9:g.(?25615693)(25650609_?)del	Pathogenic
2427203	NC_000015.9:g.(?25584284)(25585395_?)del	Pathogenic
253397	GRCh37/hg19 15q11.2(chr15:25583931-25685400)x3	Pathogenic
30204	UBE3A, 15-BP DEL/7-BP INS, NT3240	Pathogenic
3243748	NC_000015.9:g.(?25584284)(25650609_?)del	Pathogenic
831131	NC_000015.10:g.(?25339137)(25405462_?)dup	Pathogenic
816549	GRCh37/hg19 15q11.2(chr15:25583840-25611877)x1	Likely pathogenic

SpliceAI

3146 predictions. Top by Δscore:

Variant	Effect	Δscore
15:25339255:AACCT:A	acceptor_loss	1.0000
15:25339256:ACCTA:A	acceptor_loss	1.0000
15:25339258:C:CA	acceptor_loss	1.0000
15:25339259:T:A	acceptor_loss	1.0000
15:25340083:A:AC	donor_gain	1.0000
15:25340084:C:A	donor_loss	1.0000
15:25340084:C:CC	donor_gain	1.0000
15:25340084:CCTTT:C	donor_gain	1.0000
15:25340225:CTCC:C	acceptor_gain	1.0000
15:25340227:CC:C	acceptor_gain	1.0000
15:25340228:CC:C	acceptor_gain	1.0000
15:25340229:C:CC	acceptor_gain	1.0000
15:25340229:CTAAT:C	acceptor_loss	1.0000
15:25340230:T:G	acceptor_loss	1.0000
15:25354423:GATT:G	acceptor_gain	1.0000
15:25354425:TT:T	acceptor_gain	1.0000
15:25354426:TC:T	acceptor_loss	1.0000
15:25354427:C:CC	acceptor_gain	1.0000
15:25354527:CCCGG:C	donor_gain	1.0000
15:25355886:TATTA:T	donor_loss	1.0000
15:25355888:TTAC:T	donor_loss	1.0000
15:25355889:TA:T	donor_loss	1.0000
15:25355890:A:AG	donor_loss	1.0000
15:25355890:ACCTT:A	donor_gain	1.0000
15:25355891:C:CA	donor_loss	1.0000
15:25355891:CCTTC:C	donor_gain	1.0000
15:25355894:T:A	donor_gain	1.0000
15:25355922:A:AC	donor_gain	1.0000
15:25356689:A:AC	donor_gain	1.0000
15:25356690:C:CT	donor_gain	1.0000

AlphaMissense

5800 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:25339149:A:C	F872L	1.000
15:25339149:A:T	F872L	1.000
15:25339150:A:C	F872C	1.000
15:25339150:A:G	F872S	1.000
15:25339151:A:C	F872V	1.000
15:25339151:A:G	F872L	1.000
15:25339151:A:T	F872I	1.000
15:25339153:C:T	G871E	1.000
15:25339154:C:G	G871R	1.000
15:25339154:C:T	G871R	1.000
15:25339171:G:T	A865D	1.000
15:25339172:C:G	A865P	1.000
15:25339192:A:G	L858P	1.000
15:25339219:A:C	L849R	1.000
15:25339219:A:G	L849P	1.000
15:25339219:A:T	L849H	1.000
15:25339225:A:C	L847R	1.000
15:25339225:A:G	L847P	1.000
15:25339225:A:T	L847H	1.000
15:25339230:A:C	N845K	1.000
15:25339230:A:T	N845K	1.000
15:25339233:A:C	F844L	1.000
15:25339233:A:T	F844L	1.000
15:25339234:A:C	F844C	1.000
15:25339234:A:G	F844S	1.000
15:25339235:A:C	F844V	1.000
15:25339235:A:G	F844L	1.000
15:25339235:A:T	F844I	1.000
15:25339236:G:C	C843W	1.000
15:25339237:C:A	C843F	1.000

dbSNP variants (sampled 300 via entrez): RS1000002425 (15:25345979 C>T), RS1000026408 (15:25338431 G>A), RS1000032565 (15:25361571 A>G), RS1000038033 (15:25425526 G>C,T), RS1000060879 (15:25428818 T>A,C), RS1000067015 (15:25385880 AAGTTTTAC>A), RS1000069871 (15:25391359 G>A), RS1000088623 (15:25425227 T>C), RS1000091776 (15:25429047 C>T), RS1000101094 (15:25410082 A>C,G), RS1000127333 (15:25399840 A>G), RS1000177704 (15:25396786 ATT>A,AT,ATTT,ATTTT), RS1000224388 (15:25344337 A>G), RS1000260924 (15:25350712 C>A), RS1000302995 (15:25393073 G>C)

Disease associations

OMIM: gene MIM:601623 | disease phenotypes: MIM:105830

GenCC curated gene-disease

Disease	Classification	Inheritance
Angelman syndrome	Definitive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
Angelman syndrome	Definitive	AD

Mondo (1): Angelman syndrome (MONDO:0007113)

Orphanet (1): Angelman syndrome (Orphanet:72)

HPO phenotypes

98 total (30 of 98 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000154	Wide mouth
HP:0000158	Macroglossia
HP:0000248	Brachycephaly
HP:0000256	Macrocephaly
HP:0000286	Epicanthus
HP:0000298	Mask-like facies
HP:0000303	Mandibular prognathia
HP:0000327	Hypoplasia of the maxilla
HP:0000486	Strabismus
HP:0000490	Deeply set eye
HP:0000494	Downslanted palpebral fissures
HP:0000545	Myopia
HP:0000577	Exotropia
HP:0000635	Blue irides
HP:0000639	Nystagmus
HP:0000687	Widely spaced teeth
HP:0000708	Atypical behavior
HP:0000710	Hyperorality
HP:0000717	Autism
HP:0000722	Compulsive behaviors
HP:0000729	Autistic behavior
HP:0000736	Short attention span
HP:0000748	Inappropriate laughter
HP:0000749	Paroxysmal bursts of laughter
HP:0000750	Delayed speech and language development
HP:0000752	Hyperactivity
HP:0001010	Hypopigmentation of the skin
HP:0001249	Intellectual disability
HP:0001250	Seizure

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST000960_12	Cardiac hypertrophy	2.000000e-07
GCST001762_375	Obesity-related traits	4.000000e-06
GCST002786_1	Gene methylation in lung tissue	3.000000e-08
GCST002786_3	Gene methylation in lung tissue	3.000000e-09

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0002503	cardiac hypertrophy
EFO:0006959	gene methylation measurement

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D017204	Angelman Syndrome	C10.228.662.075; C16.131.077.095; C16.131.260.040; C16.320.180.040; C16.320.447.250
C531619	Happy puppet syndrome (formerly) (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067133 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.17	Kd	6777	nM	CHEMBL3752910
5.16	ED50	6962	nM	CHEMBL3752910

PubChem BioAssay actives

1 with measured affinity, of 2 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149713: Binding affinity to human UBE3A incubated for 45 mins by Kinobead based pull down assay	kd	6.7775	uM

CTD chemical–gene interactions

51 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	3
Tretinoin	decreases expression, increases expression	3
bisphenol S	affects binding, affects folding, decreases reaction, decreases methylation	2
Estradiol	affects binding, increases reaction	2
aristolochic acid I	decreases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	increases abundance, affects cotreatment, decreases expression	1
bisphenol A	affects binding, affects folding, decreases reaction	1
trichostatin A	affects expression	1
beta-lapachone	increases expression	1
arsenite	affects binding, decreases reaction	1
cobaltous chloride	increases expression	1
alpha-cobratoxin	decreases expression, decreases reaction	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
benzo(e)pyrene	decreases methylation	1
methacrylaldehyde	affects cotreatment, decreases expression, increases abundance	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
2-palmitoylglycerol	increases expression	1
7,3’-dihydroxy-4’-methoxyisoflavone	increases expression	1
K 7174	increases expression	1
jinfukang	decreases expression	1
bisphenol AF	decreases reaction, affects binding, affects folding	1
Resveratrol	affects cotreatment, increases expression	1
Temozolomide	decreases expression	1
Arsenic Trioxide	increases expression	1
Acrolein	affects cotreatment, decreases expression, increases abundance	1
Air Pollutants	decreases expression, increases abundance, affects cotreatment	1
Arsenic	affects cotreatment, increases abundance, increases expression	1
Atrazine	decreases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5652755	Binding	Binding affinity to human UBE3A incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Cellosaurus cell lines

10 cell lines: 5 cancer cell line, 3 transformed cell line, 1 induced pluripotent stem cell, 1 telomerase immortalized cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_AY98	GM24206	Transformed cell line	Male
CVCL_AY99	GM24207	Transformed cell line	Female
CVCL_C0J8	WMUi032-A	Induced pluripotent stem cell	Female
CVCL_C3KN	N/Tert-1 UBE3AI	Telomerase immortalized cell line	Male
CVCL_D1UT	Abcam U-87MG UBE3A KO	Cancer cell line	Male
CVCL_D9VA	Ubigene HEK293 UBE3A KO	Transformed cell line	Female
CVCL_E1J0	HyCyte A-549 KO-hUBE3A	Cancer cell line	Male
CVCL_E1M9	HyCyte NCI-H1299 KO-hUBE3A	Cancer cell line	Male
CVCL_TV97	HAP1 UBE3A (-) 1	Cancer cell line	Male
CVCL_XU87	HAP1 UBE3A (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

49 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT02893254	PHASE3	COMPLETED	Efficacy and Safety of IBI303 in Adult Patients With Active Ankylosing Spondylitis
NCT03882918	PHASE3	TERMINATED	An Open-Label Study to Evaluate the Long-Term Safety, Tolerability, and Efficacy of OV101 in Individuals With Angelman Syndrome
NCT06415344	PHASE3	ENROLLING_BY_INVITATION	Long-term Extension of GTX-102 in Angelman Syndrome
NCT06617429	PHASE3	ACTIVE_NOT_RECRUITING	Phase 3 Efficacy and Safety Study of GTX-102 in Pediatric Subjects With Angelman Syndrome (AS)
NCT06914609	PHASE3	RECRUITING	REVEAL: A Phase 3 Study of ION582 in Angelman Syndrome
NCT07605429	PHASE3	NOT_YET_RECRUITING	Phase III Clinical Study of Rugonersen in Angelman Syndrome.
NCT02056665	PHASE2	COMPLETED	Study to Evaluate the Efficacy and Safety of Minocycline in Angelman Syndrome
NCT02996305	PHASE2	COMPLETED	A Study in Adults and Adolescents With Angelman Syndrome (STARS)
NCT05011851	PHASE2	COMPLETED	An Open-Label Study of the Safety, Tolerability, and Pharmacokinetics of Oral NNZ-2591 in Angelman Syndrome
NCT05630066	PHASE2	COMPLETED	A Study to Investigate the Pharmacokinetics (PK) and Safety and to Provide Proof of Mechanism of Alogabat in Children and Adolescents Aged 5-17 Years With Angelman Syndrome (AS) With Deletion Genotype.
NCT07157254	PHASE2	RECRUITING	A Safety and Efficacy Study of GTX-102 in Subjects With Deletion- or Nondeletion-type Angelman Syndrome (AS)
NCT00829439	PHASE1	COMPLETED	Study on Tolerability of Levodopa/Carbidopa in Children With Angelman Syndrome
NCT03109756	PHASE1	COMPLETED	Single Dose Pharmacokinetic (PK) Study
NCT04428281	PHASE1	COMPLETED	A Study to Investigate the Safety, Tolerability, Pharmacokinetics (PK) and Pharmacodynamics (PD) of RO7248824 in Participants With Angelman Syndrome (AS)
NCT04863794	PHASE1	COMPLETED	A Study To Assess Distribution Of RO7248824 In The Central Nervous System Following Single Intrathecal Doses Of [89zr] Labeled RO7248824 In Healthy Male Participants
NCT01281475	PHASE2/PHASE3	COMPLETED	A Trial of Levodopa in Angelman Syndrome
NCT04259281	PHASE1/PHASE2	COMPLETED	A Study of the Safety and Tolerability of GTX-102 in Children With Angelman Syndrome
NCT05127226	PHASE1/PHASE2	RECRUITING	HALOS: A Safety, Tolerability, Pharmacokinetics and Pharmacodynamics Study of Multiple Ascending Doses of ION582 in Participants With Angelman Syndrome
NCT07181837	PHASE1/PHASE2	RECRUITING	A Phase 1/2 Study of the Safety and Efficacy of MVX-220 in Angelman Syndrome
NCT04103333	EARLY_PHASE1	COMPLETED	Angelman Syndrome (AS) Biomarker Study
NCT00004351	Not specified	COMPLETED	Study of Phenotype and Genotype Correlations in Patients With Contiguous Gene Deletion Syndromes
NCT00296764	Not specified	COMPLETED	Characterization of Angelman Syndrome
NCT00348933	Not specified	COMPLETED	Dietary Supplements for the Treatment of Angelman Syndrome
NCT01531582	Not specified	COMPLETED	Minocycline in the Treatment of Angelman Syndrome
NCT02381457	Not specified	COMPLETED	SNP-based Microdeletion and Aneuploidy RegisTry (SMART)
NCT02670694	Not specified	COMPLETED	Sleep Abnormalities in Rare Genetic Disorders: AS, RTT, and PW
NCT03235037	Not specified	COMPLETED	Clinical Trial of Levodopa/Carbidopa ( Sinemet) Therapy in Angel Man Syndrome
NCT03358823	Not specified	COMPLETED	Study on the Brain Network of Angelman Syndrome
NCT03644693	Not specified	COMPLETED	Nutritional Formulation for Angelman Syndrome
NCT03650569	Not specified	COMPLETED	Italian Angelman Syndrome Registry
NCT03655223	Not specified	ENROLLING_BY_INVITATION	Early Check: Expanded Screening in Newborns
NCT03836300	Not specified	ENROLLING_BY_INVITATION	Parent and Infant Inter(X)Action Intervention (PIXI)
NCT04392596	Not specified	COMPLETED	Study of Bone Mineral Density and Trabecular Bone Score in Patients With Ankylosing Spondylitis
NCT04507997	Not specified	RECRUITING	Angelman Syndrome Natural History Study
NCT04768803	Not specified	UNKNOWN	Ghrelin in Patients With a Rare Disease Associated With Intellectual Disability, and Hyperphagia, and/or Overweight, and/or Obesity
NCT05100810	Not specified	UNKNOWN	Angelman Syndrome Natural History Study-FAST UK
NCT05293184	Not specified	RECRUITING	The Global Angelman Syndrome Registry
NCT05637697	Not specified	COMPLETED	Angelman Syndrome Video Assessment (ASVA) Source Material Study
NCT05783791	Not specified	COMPLETED	Development of a Newborn Screening Assay for Angelman Syndrome and Prader-Willi Syndrome
NCT05945576	Not specified	RECRUITING	IDMet (RaDiCo Cohort) (RaDiCo-IDMet)