NEDD4

Summary

NEDD4 (NEDD4 E3 ubiquitin protein ligase, HGNC:7727) is a protein-coding gene on chromosome 15q21.3, encoding E3 ubiquitin-protein ligase NEDD4 (P46934). E3 ubiquitin-protein ligase which accepts ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfers the ubiquitin to targeted substrates.

This gene is the founding member of the NEDD4 family of HECT ubiquitin ligases that function in the ubiquitin proteasome system of protein degradation. The encoded protein contains an N-terminal calcium and phospholipid binding C2 domain followed by multiple tryptophan-rich WW domains and, a C-terminal HECT ubiquitin ligase catalytic domain. It plays critical role in the regulation of a number of membrane receptors, endocytic machinery components and the tumor suppressor PTEN.

Source: NCBI Gene 4734 — RefSeq curated summary.

At a glance

• GWAS associations: 11
• Clinical variants (ClinVar): 237 total
• Phenotypes (HPO): 1
• Druggable target: yes
• MANE Select transcript: NM_006154

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7727
Approved symbol	NEDD4
Name	NEDD4 E3 ubiquitin protein ligase
Location	15q21.3
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0093, MGC176705, NEDD4-1, RPF1
Ensembl gene	ENSG00000069869
Ensembl biotype	protein_coding
OMIM	602278
Entrez	4734

Gene structure

Transcript identifiers

Ensembl transcripts: 21 — 13 protein_coding, 4 nonsense_mediated_decay, 3 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000338963, ENST00000435532, ENST00000502612, ENST00000503468, ENST00000506154, ENST00000507063, ENST00000508075, ENST00000508342, ENST00000508871, ENST00000513957, ENST00000514893, ENST00000557845, ENST00000648451, ENST00000911094, ENST00000911095, ENST00000911096, ENST00000911097, ENST00000911098, ENST00000932730, ENST00000954479, ENST00000954480

RefSeq mRNA: 6 — MANE Select: NM_006154 NM_001284338, NM_001284339, NM_001284340, NM_001329212, NM_006154, NM_198400

CCDS: CCDS10156, CCDS45265, CCDS61643, CCDS61644

Canonical transcript exons

ENST00000435532 — 29 exons

Exon	Start	End
ENSE00000941938	55837789	55837849
ENSE00001249088	55834227	55834286
ENSE00001652747	55993511	55993612
ENSE00003484195	55862913	55863079
ENSE00003486630	55860407	55860574
ENSE00003516424	55826922	55829999
ENSE00003524967	55860661	55860778
ENSE00003533197	55872415	55872476
ENSE00003556885	55951376	55951414
ENSE00003577303	55924646	55924699
ENSE00003585173	55966473	55966546
ENSE00003587049	55852424	55852543
ENSE00003591517	55833008	55833104
ENSE00003601016	55841934	55842163
ENSE00003603773	55840606	55840727
ENSE00003611181	55838509	55838604
ENSE00003612245	55830514	55830586
ENSE00003613308	55850542	55850742
ENSE00003624333	55840447	55840517
ENSE00003624713	55838107	55838180
ENSE00003630808	55873958	55874008
ENSE00003634649	55951511	55951589
ENSE00003636910	55856131	55856196
ENSE00003644461	55846969	55847034
ENSE00003656295	55834038	55834145
ENSE00003670211	55848521	55848575
ENSE00003682689	55848372	55848430
ENSE00003691036	55848806	55848886
ENSE00003692255	55869579	55869681

Expression profiles

Bgee: expression breadth ubiquitous, 248 present calls, max score 98.63.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 17.3347 / max 496.5268, expressed in 1747 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
150150	12.9142	1738
150142	2.1772	550
150147	1.4443	495
150143	0.6032	281
150146	0.0895	42
150145	0.0417	15
150149	0.0362	11
150148	0.0284	9

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	98.63	gold quality
colonic epithelium	UBERON:0000397	98.52	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	97.12	gold quality
calcaneal tendon	UBERON:0003701	96.47	gold quality
biceps brachii	UBERON:0001507	96.27	gold quality
vastus lateralis	UBERON:0001379	96.07	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	95.71	gold quality
quadriceps femoris	UBERON:0001377	95.37	gold quality
diaphragm	UBERON:0001103	94.41	gold quality
skeletal muscle tissue	UBERON:0001134	94.32	gold quality
gluteal muscle	UBERON:0002000	94.29	gold quality
gastrocnemius	UBERON:0001388	94.26	gold quality
muscle organ	UBERON:0001630	94.16	gold quality
muscle of leg	UBERON:0001383	93.80	gold quality
hindlimb stylopod muscle	UBERON:0004252	92.60	gold quality
triceps brachii	UBERON:0001509	92.57	gold quality
bone marrow cell	CL:0002092	92.17	gold quality
deltoid	UBERON:0001476	91.82	gold quality
adrenal tissue	UBERON:0018303	91.79	gold quality
muscle tissue	UBERON:0002385	90.94	gold quality
stromal cell of endometrium	CL:0002255	87.44	gold quality
tibialis anterior	UBERON:0001385	87.20	gold quality
placenta	UBERON:0001987	86.99	gold quality
liver	UBERON:0002107	86.56	gold quality
ventricular zone	UBERON:0003053	86.01	gold quality
mucosa of stomach	UBERON:0001199	85.22	gold quality
tendon	UBERON:0000043	85.20	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	84.90	gold quality
sural nerve	UBERON:0015488	84.72	gold quality
right lobe of liver	UBERON:0001114	84.27	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-GEOD-89232	yes	3114.03
E-MTAB-11011	yes	838.05
E-MTAB-5061	yes	15.56
E-GEOD-137537	yes	15.30
E-ANND-3	yes	5.93
E-ENAD-27	no	3.90

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): APP, AR, FOXM1, MYC, SIRT2

miRNA regulators (miRDB)

134 targeting NEDD4, 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-5011-5P	100.00	83.46	5820
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-8075	99.97	67.20	962
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163

Literature-anchored findings (GeneRIF, showing 40)

• Endogenous Nedd4-2, but not Nedd4, negatively regulates the epithelial Na+ channel (ENaC) and is a component of a signaling pathway by which steroid hormones regulate ENaC. (PMID:14645220)
• Nedd4-mediated vascular endothelial growth factor receptor-2 degradation is prevented by Grb10 (PMID:15060076)
• Nedd4.1 and Tsg101 act successively in the assembly process of HTLV-1 to ensure proper Gag trafficking through the endocytic pathway up to late endosomes where the late steps of retroviral release occur (PMID:15126635)
• Nedd4-2 acts on Na(v)1.5 by decreasing the channel density at the cell surface. the effect of Nedd4-2 requires the PY-motif of Nav1.5. (PMID:15217910)
• N4WBP5A acts as an adaptor to recruit Nedd4 family ubiquitin-protein ligases to the protein trafficking machinery (PMID:15252135)
• Data show that WWP2 and Nedd4-2 both bind to the cardiac sodium channel Na(v)1.5, but only Nedd4-2 robustly ubiquitinated and downregulated Na(v)1.5. (PMID:15548568)
• Both NEDD4 and ubiquitin protein ligase ubiquitin protein ligase Itch participate in the degradation of Melan-A (PMID:15703212)
• Gamma-adaptin, a novel ubiquitin-interacting adaptor, and Nedd4 ubiquitin ligase control hepatitis B virus maturation (PMID:16867982)
• A new mechanistic model of DAT endocytosis is proposed whereby the PKC-induced ubiquitination of DAT mediated by Nedd4-2 leads to interaction of DAT with adaptor proteins. (PMID:16885233)
• These results demonstrate a novel mechanism by which the ubiquitin-ligase Nedd4, via interactions with GGA3 and cargo (LAPTM5), regulates cargo trafficking to the lysosome without requiring cargo ubiquitination. (PMID:17116753)
• NEDD4-1 is a potential proto-oncogene that negatively regulates PTEN via ubiquitination, a paradigm analogous to that of Mdm2 and p53. (PMID:17218260)
• G-protein-coupled receptor kinase 2 interacts not only with epithelial Na(+) channels, but also with both Nedd4 and Nedd4-2 (PMID:17544362)
• Nedd4 is an E3 ligase that associates with and ubiquitylates RNAPII in response to UV-induced DNA damage in human cells. (PMID:17996703)
• Nedd4-2 reduces ENaC surface expression by altering its trafficking at two distinct sites in the endocytic pathway, inducing endocytosis of cleaved channels and targeting them for degradation. (PMID:18174164)
• a mechanistically novel function of ISG15 in the enhancement of the innate anti-viral response through specific inhibition of Nedd4 Ub-E3 activity (PMID:18287095)
• These data provide evidence of antiviral activity of ISG15 against Ebola virus and suggest a mechanism of action involving disruption of Nedd4 function and subsequent ubiquitination of VP40. (PMID:18305167)
• Results discuss the role of PTEN upon the E3 ubquitin ligase Nedd4 as a negative feedback regulator as well as a substrate. (PMID:18307411)
• UL56 regulates Nedd4 in HSV-2-infected cells, although deletion of UL56 had no apparent effect on viral growth in v (PMID:18353951)
• degradative fate of the beta(2)AR in the lysosomal compartments is dependent upon beta-arrestin2-mediated recruitment of Nedd4 to the activated receptor and Nedd4-catalyzed ubiquitination (PMID:18544533)
• decreased PMEPA1 expression frequently noted in prostate cancers may lead to increased AR functions and strengthen the biological role of the NEDD4-binding protein PMEPA1 in prostate cancers (PMID:18703514)
• The ubiquitin ligase Nedd4 mediates oxidized low-density lipoprotein-induced downregulation of insulin-like growth factor-1 receptor. (PMID:18723765)
• C2 domain of Nedd4 is ubiquitinated itself and as such is recruited by the ubiquitin-interacting motif of gamma2-adaptin for subsequent ubiquitin conjugation (PMID:18772139)
• Our results suggest human Nedd4 ligase inhibits yeast cell growth by disturbing the actin cytoskeleton, in part by increasing Las17p level, and that Nedd4 ubiquitination targets may include actin cytoskeleton-associated proteins conserved in evolution. (PMID:18804462)
• The increased expression of NEDD4-1 in malignant gastric and colorectal cells compared to their normal epithelial cells suggests that NEDD4-1 expression may play a role in colorectal and gastric cancer development. (PMID:19024597)
• NEDD4 is capable of binding to Spy1A and the dominant negative forms and knockdown of Nedd4 reduce ubiquitination and further degradation of Spy1A (PMID:19054764)
• Data found that hMTMR4 (human MTMR4) and Nedd4 co-immunoprecipitated and co-localized to late endosomes. (PMID:19125695)
• the Nedd4/proSP-C tandem is part of a larger protein complex containing a ubiquitinated component that further directs its transport (PMID:19366705)
• Nedd4-2 phosphorylation is emerging as a central convergence point for the regulation of epithelial Na(+) transport [REVIEW] (PMID:19602703)
• A low-energy barrier exists between different macrostates from the ubiquitin ligase Nedd4 fourth tryptophan (WW4) domain, placing it at the frontier of cooperative folding. (PMID:19670909)
• Here, the authors report that Vps4B and Nedd4.1 play critical roles in Marburg virus VP40-mediated budding. (PMID:19812267)
• These data suggest that UL56 regulates Nedd4 and functions to facilitate the cytoplasmic transport of virions from trans-Golgi network to the plasma membrane and/or release of virions from the cell surface. (PMID:19835589)
• Spry1 and Spry2, but not Spry3 or Spry4, associate with the HECT domain family E3 ubiquitin ligase, Nedd4. (PMID:19864419)
• Although several substrates were recognized by both Nedd4-1 and Nedd4-2, others were specific to only one, with several Tyr kinases preferred by Nedd4-1 and some ion channels by Nedd4- (PMID:19953087)
• NEDD4 gene polymorphisms are not associated with hypertension in Kazak Chinese population. (PMID:20078934)
• These findings suggest an essential role of Nedd4-1 in regulation of EGFR degradation through interaction with and ubiquitination of ACK. (PMID:20086093)
• calcium-mediated membrane translocation through the C2 domain might be an activation mechanism of Nedd4 (PMID:20172859)
• Results showed that overexpression of FoxM1B upregulated NEDD4-1, an E3 ligase that mediates the degradation and downregulation of phosphatase and tensin homologue (PTEN) in multiple cell lines. (PMID:20332230)
• Together these data support a model in which Alix recruits Nedd4-1 to facilitate HIV-1 release mediated through the LYPX(n)L/Alix budding pathway via a mechanism that involves Alix ubiquitination. (PMID:20519395)
• Nedd4-2 interacts with Na(v)1.6 via a Pro-Ser-Tyr(1945) motif in the C terminus of the channel and reduces Na(v)1.6 current density, and this regulation requires both the Pro-Gly-Ser-Pro motif in L1 and the Pro-Ser-Tyr motif in the C terminus (PMID:20530479)
• Data show that ARRDC3 interacts with NEDD4 through two conserved PPXY motifs and recruits NEDD4 to the activated beta2-adrenergic receptor. (PMID:20559325)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	nedd4a	ENSDARG00000099843
mus_musculus	Nedd4	ENSMUSG00000032216
rattus_norvegicus	Nedd4	ENSRNOG00000058898

Paralogs (24): HECW1 (ENSG00000002746), UBE3C (ENSG00000009335), NEDD4L (ENSG00000049759), ITCH (ENSG00000078747), HACE1 (ENSG00000085382), HUWE1 (ENSG00000086758), HECTD1 (ENSG00000092148), UBR5 (ENSG00000104517), SMURF2 (ENSG00000108854), UBE3A (ENSG00000114062), 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

E3 ubiquitin-protein ligase NEDD4 — P46934 (reviewed: P46934)

Alternative names: Cell proliferation-inducing gene 53 protein, HECT-type E3 ubiquitin transferase NEDD4, Neural precursor cell expressed developmentally down-regulated protein 4

All UniProt accessions (6): P46934, A0A3B3IUC1, H0Y8H4, H0Y8X6, H0Y9L1, H0YA37

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 then directly transfers the ubiquitin to targeted substrates. Specifically ubiquitinates ‘Lys-63’ in target proteins. Involved in the pathway leading to the degradation of VEGFR-2/KDFR, independently of its ubiquitin-ligase activity. Monoubiquitinates IGF1R at multiple sites, thus leading to receptor internalization and degradation in lysosomes. Ubiquitinates FGFR1, leading to receptor internalization and degradation in lysosomes. Promotes ubiquitination of RAPGEF2. According to PubMed:18562292 the direct link between NEDD4 and PTEN regulation through polyubiquitination described in PubMed:17218260 is questionable. Involved in ubiquitination of ERBB4 intracellular domain E4ICD. Part of a signaling complex composed of NEDD4, RAP2A and TNIK which regulates neuronal dendrite extension and arborization during development. Ubiquitinates TNK2 and regulates EGF-induced degradation of EGFR and TNF2. Ubiquitinates BRAT1 and this ubiquitination is enhanced in the presence of NDFIP1. Ubiquitinates DAZAP2, leading to its proteasomal degradation. Ubiquitinates POLR2A. Functions as a platform to recruit USP13 to form an NEDD4-USP13 deubiquitination complex that plays a critical role in cleaving the ‘Lys-48’-linked ubiquitin chains of VPS34 and then stabilizing VPS34, thus promoting the formation of autophagosomes. (Microbial infection) Involved in the ubiquitination of Ebola virus protein VP40 which plays a role in viral budding.

Subunit / interactions. Binds, in vitro, through the WW2 and WW3 domains, to neural isoforms of ENAH that contain the PPSY motif. Interacts with BEAN1, LITAF, RNF11, WBP1, WBP2, PMEPAI and PRRG2. Interacts with NDFIP1 and NDFIP2; this interaction activates the E3 ubiquitin-protein ligase and may induce its recruitment to exosomes. Interacts with UBE2D2. Interaction with PTEN is questionable according to PubMed:18562292. Interacts (via C2 domain) with GRB10 (via SH2 domain). Interacts with ERBB4. Interacts with TNIK; the interaction is direct, allows the TNIK-dependent recruitment of RAP2A and its ubiquitination by NEDD4. Interacts (via WW3 domain) with TNK2; EGF promotes this interaction. Interacts (via WW3 domain) with FGFR1 (via C-terminus). Interacts with OTUD7B. Interacts with ISG15. Interacts (via WW domain) with RAPGEF2; this interaction leads to ubiquitination and degradation via the proteasome pathway. Interacts (via WW domains) with ARRDC3 (via PPXY motifs). Interacts with LAPTM4B; may play a role in the lysosomal sorting of LAPTM4B. Interacts (via WW domains) with ARRDC1, ARRDC2 and ARRDC3. Interacts with ZBTB7B. Interacts with PRRG4 (via cytoplasmic domain). Interacts directly with LDLRAD3; this interaction promotes NEDD4 auto-ubiquitination. Interacts with ADRB2. Interacts (via WW domains) with DAZAP2 (via PPAY motif). Interacts with USP13. (Microbial infection) Interacts with viral proteins that contain a late-budding motif P-P-P-Y. This interaction is essential for viral particle budding of many retroviruses, like HTLV-1 Gag and MLV Gag. Interacts with Herpes simplex virus 2 (HHV-2) protein UL56; this interaction induces NEDD4 degradation. Interacts with Ebola virus protein VP40.

Subcellular location. Cytoplasm. Nucleus. Cell membrane.

Post-translational modifications. Undergoes ‘Lys-29’-linked auto-ubiquitination at Lys-1279 and serves as a scaffold for recruiting USP13 to form an NEDD4-USP13 deubiquitination complex.

Activity regulation. Activated by NDFIP1- and NDFIP2-binding.

Domain organisation. WW domains are involved in recognizing PPxY motifs in substrate proteins. The WW domains mediate interaction with LITAF, RNF11, WBP1, WBP2, PMEPAI, NDFIP1 and PRRG2.

Pathway. Protein modification; protein ubiquitination.

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

Isoforms (4)

UniProt ID	Names	Canonical?
P46934-1	1	yes
P46934-2	2
P46934-3	3
P46934-4	4

RefSeq proteins (6): NP_001271267, NP_001271268, NP_001271269, NP_001316141, NP_006145, NP_940682 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000569	HECT_dom	Domain
IPR001202	WW_dom	Domain
IPR035892	C2_domain_sf	Homologous_superfamily
IPR035983	Hect_E3_ubiquitin_ligase	Homologous_superfamily
IPR036020	WW_dom_sf	Homologous_superfamily
IPR050409	E3_ubiq-protein_ligase	Family

Pfam: PF00397, PF00632

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 (92 total): helix 24, strand 22, modified residue 6, sequence conflict 6, domain 5, mutagenesis site 5, splice variant 4, sequence variant 4, turn 4, region of interest 4, compositionally biased region 3, chain 1, short sequence motif 1, active site 1, cross-link 1, initiator methionine 1

Structure

Experimental structures (PDB)

15 structures.

PDB	Method	Resolution (Å)
4N7F	X-RAY DIFFRACTION	1.1
4N7H	X-RAY DIFFRACTION	1.7
3B7Y	X-RAY DIFFRACTION	1.8
9H9O	X-RAY DIFFRACTION	2.12
9H9T	X-RAY DIFFRACTION	2.17
5C91	X-RAY DIFFRACTION	2.44
2XBF	X-RAY DIFFRACTION	2.5
4BBN	X-RAY DIFFRACTION	2.51
2XBB	X-RAY DIFFRACTION	2.68
4BE8	X-RAY DIFFRACTION	3
5C7J	X-RAY DIFFRACTION	3
2KPZ	SOLUTION NMR
2KQ0	SOLUTION NMR
2M3O	SOLUTION NMR
5AHT	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P46934-F1	54.86	0.14

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): 1286 (glycyl thioester intermediate)

Post-translational modifications (7): 576, 648, 670, 742, 747, 1279, 2

Mutagenesis-validated functional residues (5):

Position	Phenotype
724–726	increased nuclear localization.
795	abolishes interaction with arrdc3; when associated with a-868 and a-920.
868	abolishes interaction with arrdc3; when associated with a-795 and a-920.
920	abolishes interaction with arrdc3; when associated with a-795 and a-868.
1286	abolishes ubiquitination of dazap2.

Function

Pathways and Gene Ontology

Reactome pathways

17 pathways

ID	Pathway
R-HSA-1169408	ISG15 antiviral mechanism
R-HSA-1253288	Downregulation of ERBB4 signaling
R-HSA-8948747	Regulation of PTEN localization
R-HSA-8948751	Regulation of PTEN stability and activity
R-HSA-983168	Antigen processing: Ubiquitination & Proteasome degradation
R-HSA-1169410	Antimicrobial mechanism of IFN-stimulated genes
R-HSA-1236394	Signaling by ERBB4
R-HSA-1257604	PIP3 activates AKT signaling
R-HSA-1280215	Cytokine Signaling in Immune system
R-HSA-1280218	Adaptive Immune System
R-HSA-162582	Signal Transduction
R-HSA-168256	Immune System
R-HSA-6807070	PTEN Regulation
R-HSA-9006925	Intracellular signaling by second messengers
R-HSA-9006934	Signaling by Receptor Tyrosine Kinases
R-HSA-913531	Interferon Signaling
R-HSA-983169	Class I MHC mediated antigen processing & presentation

MSigDB gene sets: 610 (showing top): GOBP_POTASSIUM_ION_TRANSPORT, GOBP_NEUROMUSCULAR_JUNCTION_DEVELOPMENT, GOBP_DENDRITE_DEVELOPMENT, VERHAAK_AML_WITH_NPM1_MUTATED_DN, GOBP_RIBOSOME_BIOGENESIS, GOBP_NEGATIVE_REGULATION_OF_TRANSMEMBRANE_TRANSPORT, GOBP_REGULATION_OF_CELLULAR_RESPONSE_TO_GROWTH_FACTOR_STIMULUS, GOBP_REGULATION_OF_AUTOPHAGY, GOBP_LYSOSOMAL_TRANSPORT, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, GOBP_NEGATIVE_REGULATION_OF_SODIUM_ION_TRANSPORT, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_CELLULAR_RESPONSE_TO_UV

GO Biological Process (44): negative regulation of transcription by RNA polymerase II (GO:0000122), adaptive immune response (GO:0002250), outflow tract morphogenesis (GO:0003151), endocardial cushion development (GO:0003197), ubiquitin-dependent protein catabolic process (GO:0006511), protein monoubiquitination (GO:0006513), protein targeting to lysosome (GO:0006622), sodium ion transport (GO:0006814), DNA damage response (GO:0006974), lysosomal transport (GO:0007041), neuromuscular junction development (GO:0007528), negative regulation of sodium ion transport (GO:0010766), regulation of macroautophagy (GO:0016241), protein ubiquitination (GO:0016567), negative regulation of vascular endothelial growth factor receptor signaling pathway (GO:0030948), neuron projection development (GO:0031175), receptor internalization (GO:0031623), receptor catabolic process (GO:0032801), cellular response to UV (GO:0034644), T cell activation (GO:0042110), regulation of membrane potential (GO:0042391), nuclear receptor-mediated glucocorticoid signaling pathway (GO:0042921), ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway (GO:0043162), formation of structure involved in a symbiotic process (GO:0044111), positive regulation of protein catabolic process (GO:0045732), viral budding (GO:0046755), positive regulation of nucleocytoplasmic transport (GO:0046824), blood vessel morphogenesis (GO:0048514), regulation of dendrite morphogenesis (GO:0048814), regulation of synapse organization (GO:0050807), progesterone receptor signaling pathway (GO:0050847), response to calcium ion (GO:0051592), positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0051897), protein K63-linked ubiquitination (GO:0070534), negative regulation of potassium ion export across plasma membrane (GO:1903765), transcription by RNA polymerase II (GO:0006366), immune response (GO:0006955), nervous system development (GO:0007399), regulation of cell communication (GO:0010646), regulation of signaling (GO:0023051)

GO Molecular Function (17): ubiquitin-protein transferase activity (GO:0004842), channel inhibitor activity (GO:0016248), potassium channel inhibitor activity (GO:0019870), sodium channel inhibitor activity (GO:0019871), enzyme binding (GO:0019899), protein domain specific binding (GO:0019904), beta-2 adrenergic receptor binding (GO:0031698), ionotropic glutamate receptor binding (GO:0035255), ubiquitin binding (GO:0043130), transmembrane transporter binding (GO:0044325), phosphoserine residue binding (GO:0050815), phosphothreonine residue binding (GO:0050816), ubiquitin protein ligase activity (GO:0061630), RNA polymerase binding (GO:0070063), proline-rich region binding (GO:0070064), protein binding (GO:0005515), transferase activity (GO:0016740)

GO Cellular Component (16): ubiquitin ligase complex (GO:0000151), chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), Golgi apparatus (GO:0005794), cytosol (GO:0005829), plasma membrane (GO:0005886), cell cortex (GO:0005938), apicolateral plasma membrane (GO:0016327), protein-containing complex (GO:0032991), perinuclear region of cytoplasm (GO:0048471), extracellular exosome (GO:0070062), glutamatergic synapse (GO:0098978), postsynaptic cytosol (GO:0099524), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-12 pathways:

Category	Pathways
PTEN Regulation	2
Immune System	2
Signal Transduction	2
Antimicrobial mechanism of IFN-stimulated genes	1
Signaling by ERBB4	1
Class I MHC mediated antigen processing & presentation	1
Interferon Signaling	1
Signaling by Receptor Tyrosine Kinases	1
Intracellular signaling by second messengers	1
PIP3 activates AKT signaling	1
Cytokine Signaling in Immune system	1
Adaptive Immune System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	6
protein binding	4
cytoplasm	4
protein ubiquitination	2
ion channel inhibitor activity	2
protein phosphorylated amino acid binding	2
intracellular membrane-bounded organelle	2
cell periphery	2
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription	1
immune response	1
heart morphogenesis	1
anatomical structure morphogenesis	1
heart development	1
mesenchyme development	1
modification-dependent protein catabolic process	1
protein targeting to vacuole	1
lysosomal transport	1
protein localization to lysosome	1
metal ion transport	1
cellular response to stress	1
vacuolar transport	1
synapse organization	1
regulation of sodium ion transport	1
sodium ion transport	1
negative regulation of monoatomic ion transport	1
regulation of autophagy	1
macroautophagy	1
protein modification by small protein conjugation	1
negative regulation of signal transduction	1
regulation of vascular endothelial growth factor receptor signaling pathway	1
vascular endothelial growth factor receptor signaling pathway	1
negative regulation of cellular response to growth factor stimulus	1
neuron development	1
plasma membrane bounded cell projection organization	1
receptor-mediated endocytosis	1
macromolecule catabolic process	1
receptor metabolic process	1
response to UV	1

Protein interactions and networks

STRING

3204 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NEDD4	NDFIP1	Q9BT67	999
NEDD4	NDFIP2	Q9NV92	988
NEDD4	ARRDC3	Q96B67	945
NEDD4	PMEPA1	Q969W9	899
NEDD4	SCNN1B	P51168	898
NEDD4	SCNN1G	P51170	888
NEDD4	ARRB2	P32121	874
NEDD4	TSG101	Q99816	810
NEDD4	SCNN1A	P37088	795
NEDD4	AP1G2	O75843	791
NEDD4	N4BP1	O75113	762
NEDD4	GRB10	Q13322	747
NEDD4	PTEN	P60484	742
NEDD4	CBL	P22681	734
NEDD4	UBE2D1	P51668	708

IntAct

264 interactions, top by confidence:

A	B	Type	Score
ARRDC1	WWP2	psi-mi:“MI:0914”(association)	0.850
ENTREP1	WWP2	psi-mi:“MI:0914”(association)	0.850
PRRG4	NEDD4	psi-mi:“MI:0407”(direct interaction)	0.820
PRRG4	NEDD4	psi-mi:“MI:0915”(physical association)	0.820
NEDD4	PRRG4	psi-mi:“MI:0407”(direct interaction)	0.820
NEDD4	SCNN1B	psi-mi:“MI:0407”(direct interaction)	0.810
ARRDC3	NEDD4	psi-mi:“MI:0403”(colocalization)	0.790
LITAF	NEDD4	psi-mi:“MI:0915”(physical association)	0.790
LITAF	NEDD4	psi-mi:“MI:0407”(direct interaction)	0.790
RNF11	NEDD4	psi-mi:“MI:0407”(direct interaction)	0.790
NEDD4	RNF11	psi-mi:“MI:0407”(direct interaction)	0.790
ARRDC3	WWP2	psi-mi:“MI:0914”(association)	0.770
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
GABARAPL2	IPO5	psi-mi:“MI:0914”(association)	0.690
NEDD4	LDLRAD4	psi-mi:“MI:0407”(direct interaction)	0.690
NEDD4	ENTREP1	psi-mi:“MI:0407”(direct interaction)	0.690
ENTREP1	NEDD4	psi-mi:“MI:0914”(association)	0.690
LDLRAD4	NEDD4	psi-mi:“MI:0914”(association)	0.690
NEDD4	SCNN1A	psi-mi:“MI:0407”(direct interaction)	0.680
ARRDC1	NEDD4	psi-mi:“MI:0914”(association)	0.640
NEDD4	MAP1LC3B	psi-mi:“MI:0407”(direct interaction)	0.620
NEDD4	TP73	psi-mi:“MI:0407”(direct interaction)	0.620

BioGRID (1155): NEDD4 (Affinity Capture-Western), SPT23 (Affinity Capture-Western), NEDD4 (Affinity Capture-Western), RNF7 (Affinity Capture-Western), CUL5 (Affinity Capture-Western), RNF7 (Biochemical Activity), UBE2D3 (Reconstituted Complex), NEDD4 (Affinity Capture-Western), SRC (Affinity Capture-Western), NEDD4 (Reconstituted Complex), NEDD4 (Biochemical Activity), NEDD4 (Biochemical Activity), UBE2L3 (Reconstituted Complex), NEDD4 (Reconstituted Complex), NEDD4 (Reconstituted Complex)

ESM2 similar proteins: A0A1L8FZ84, A0A1S4GMU2, A0A2K1J5A5, A0A2K1JJ00, A0A2R6X6S3, A2AWL7, A2BIL8, A4IGV6, A9RNY0, B4GBA9, D3Z3C6, F4HYG2, F4J6F6, P10243, P24433, P46012, P46934, P51960, Q03237, Q05935, Q06616, Q06813, Q08729, Q0P4S0, Q290S5, Q5RD08, Q5T5U3, Q62417, Q69Z38, Q6DFB0, Q6DFV3, Q6P6I6, Q8IWI9, Q91018, Q949U2, Q96GY3, Q96RV3, Q9D722, Q9GSR1, Q9H792

Diamond homologs: A0A8C0NGY6, A0A8I3PQN6, A1A5G4, A1CQG2, A1D3C5, A2QQ28, A4IIJ3, B0XQ72, B3LWS4, B3P3M8, B4HEJ6, B4K6I9, B4M5X4, B4NAD3, B4PSQ2, B8N7E5, D6C652, G0S9J5, H2LBU8, O14326, O88382, P39940, P46934, P46935, P46936, P46937, P46938, Q0CCL1, Q19404, Q1L8J7, Q2EJA0, Q2UBP1, Q32NJ6, Q45VV3, Q4L1J4, Q4WTF3, Q54T86, Q5BDP1, Q5F488, Q5RBF2

SIGNOR signaling

37 interactions.

A	Effect	B	Mechanism
SIRT2	“down-regulates quantity by repression”	NEDD4	“transcriptional regulation”
NDFIP2	“down-regulates activity”	NEDD4	relocalization
NDFIP2	“up-regulates activity”	NEDD4	relocalization
NDFIP1	“up-regulates activity”	NEDD4	relocalization
NEDD4	“down-regulates quantity by destabilization”	KCNH2	ubiquitination
Ub:E2	“up-regulates activity”	NEDD4	ubiquitination
NEDD4	“down-regulates quantity by destabilization”	SPRY2	polyubiquitination
NEDD4	“down-regulates quantity by destabilization”	LYN	polyubiquitination
NEDD4	“down-regulates quantity by destabilization”	SYK	polyubiquitination
NEDD4	“up-regulates activity”	N4BP1	monoubiquitination
NEDD4	“up-regulates activity”	AP1G2	monoubiquitination
NEDD4	“up-regulates activity”	AP1G2	polyubiquitination
AP1G2	“up-regulates activity”	NEDD4	binding
NEDD4	“up-regulates quantity”	DCUN1D1	monoubiquitination
NEDD4	“down-regulates quantity by destabilization”	SAG	polyubiquitination
NEDD4	“down-regulates quantity by destabilization”	GUCD1	polyubiquitination
NEDD4	“down-regulates quantity by destabilization”	KIF26B	polyubiquitination
NEDD4	“up-regulates activity”	PPARG	ubiquitination
NEDD4	“up-regulates quantity by stabilization”	BECN1	ubiquitination
NEDD4	“down-regulates quantity”	GRIA1	ubiquitination
NEDD4	“down-regulates quantity”	SAG	ubiquitination
NEDD4	“down-regulates quantity by destabilization”	SNCA	ubiquitination
NEDD4	“up-regulates activity”	APOBEC3G	ubiquitination
NEDD4	“down-regulates activity”	GRIN2D	ubiquitination
NEDD4	“down-regulates quantity by destabilization”	SQSTM1	ubiquitination
NEDD4	“down-regulates quantity by destabilization”	TUSC2	ubiquitination
NEDD4	“up-regulates activity”	IRS2	ubiquitination
NEDD4	“down-regulates quantity”	RAPGEF2	ubiquitination

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 145 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
Macroautophagy	7	10.3×	3e-03

GO biological processes:

GO term	Partners	Fold	FDR
autophagosome maturation	7	19.5×	3e-05
mitophagy	6	15.1×	9e-04
autophagosome assembly	6	10.7×	5e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	166
Likely benign	27
Benign	14

Top pathogenic / likely-pathogenic (0)

SpliceAI

4560 predictions. Top by Δscore:

Variant	Effect	Δscore
15:55830000:C:CC	acceptor_gain	1.0000
15:55833002:CCTTA:C	donor_loss	1.0000
15:55833003:CTTAC:C	donor_loss	1.0000
15:55833004:TTAC:T	donor_loss	1.0000
15:55833005:TACC:T	donor_loss	1.0000
15:55833006:A:AC	donor_gain	1.0000
15:55833007:C:CC	donor_gain	1.0000
15:55833100:ACAGC:A	acceptor_gain	1.0000
15:55833101:CAGC:C	acceptor_gain	1.0000
15:55833101:CAGCC:C	acceptor_gain	1.0000
15:55833102:AGC:A	acceptor_gain	1.0000
15:55833103:GC:G	acceptor_gain	1.0000
15:55833104:CC:C	acceptor_gain	1.0000
15:55833104:CCTGA:C	acceptor_loss	1.0000
15:55833105:C:CC	acceptor_gain	1.0000
15:55833105:C:T	acceptor_gain	1.0000
15:55833105:CTG:C	acceptor_loss	1.0000
15:55833106:T:G	acceptor_loss	1.0000
15:55834146:C:CC	acceptor_gain	1.0000
15:55834221:TCTTA:T	donor_loss	1.0000
15:55834222:CTTA:C	donor_loss	1.0000
15:55834223:TTA:T	donor_loss	1.0000
15:55834224:TACCT:T	donor_loss	1.0000
15:55834226:C:CG	donor_loss	1.0000
15:55837845:CAAGA:C	acceptor_gain	1.0000
15:55837850:C:CC	acceptor_gain	1.0000
15:55838099:ATACT:A	donor_loss	1.0000
15:55838100:TACTT:T	donor_loss	1.0000
15:55838101:ACT:A	donor_loss	1.0000
15:55838103:TTA:T	donor_loss	1.0000

AlphaMissense

5927 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:55829943:A:G	L1305P	1.000
15:55829988:A:G	L1290P	0.999
15:55829991:C:G	R1289P	0.999
15:55829996:A:C	F1287L	0.999
15:55829996:A:T	F1287L	0.999
15:55829998:A:G	F1287L	0.999
15:55830551:A:G	W1274R	0.999
15:55830551:A:T	W1274R	0.999
15:55830565:A:G	F1269S	0.999
15:55833049:C:T	G1248D	0.999
15:55833055:A:T	V1246D	0.999
15:55833064:A:G	L1243P	0.999
15:55834106:A:G	W1207R	0.999
15:55834106:A:T	W1207R	0.999
15:55838537:A:G	F1119S	0.999
15:55838582:A:G	L1104P	0.999
15:55840650:C:T	G1058D	0.999
15:55841998:A:G	W1011R	0.999
15:55841998:A:T	W1011R	0.999
15:55848413:A:G	W920R	0.999
15:55848413:A:T	W920R	0.999
15:55848569:A:G	W898R	0.999
15:55848569:A:T	W898R	0.999
15:55869649:A:G	L565P	0.999
15:55869655:A:G	L563P	0.999
15:55829912:A:C	F1315L	0.998
15:55829912:A:T	F1315L	0.998
15:55829914:A:G	F1315L	0.998
15:55829982:A:G	L1292S	0.998
15:55829992:G:T	R1289S	0.998

dbSNP variants (sampled 300 via entrez): RS1000021830 (15:55989313 T>A,C,G), RS1000058235 (15:55912627 A>G), RS1000063453 (15:55951048 A>C,G), RS1000082590 (15:55905832 A>G), RS1000085173 (15:55905636 T>C,G), RS1000089927 (15:55944870 G>A,C,T), RS1000106937 (15:55861339 T>C), RS1000122811 (15:55855257 T>C), RS1000151721 (15:55904501 C>T), RS1000162739 (15:55983235 A>G), RS1000195173 (15:55945343 T>C), RS1000210158 (15:55899677 G>A), RS1000278781 (15:55849266 C>T), RS1000297427 (15:55994462 G>A,C), RS1000304291 (15:55978386 A>C,T)

Disease associations

OMIM: gene MIM:602278 | disease phenotypes: MIM:209850

GenCC curated gene-disease

Mondo (1): autism (MONDO:0005260)

Orphanet (0):

HPO phenotypes

1 total (1 of 1 shown, HPO-id order):

HPO	Term
HP:0000717	Autism

GWAS associations

11 associations (top):

Study	Trait	p-value
GCST000773_1	Keloid	6.000000e-13
GCST001889_3	Brain connectivity	1.000000e-10
GCST002299_17	Chronic lymphocytic leukemia	4.000000e-07
GCST003998_13	Joint mobility (Beighton score)	1.000000e-08
GCST004146_37	Chronic lymphocytic leukemia	2.000000e-18
GCST004858_19	Dupuytren’s disease	3.000000e-10
GCST005580_303	Intraocular pressure	3.000000e-09
GCST005580_89	Intraocular pressure	4.000000e-11
GCST008156_125	Hip circumference adjusted for BMI	7.000000e-06
GCST010002_170	Refractive error	2.000000e-09
GCST90000025_215	Appendicular lean mass	1.000000e-12

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0007905	joint hypermobility measurement
EFO:0004229	Dupuytren Contracture
EFO:0004695	intraocular pressure measurement
EFO:0008039	BMI-adjusted hip circumference
EFO:0004980	appendicular lean mass

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D001321	Autistic Disorder	F03.625.164.113.500

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3621023 (SINGLE PROTEIN)

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

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs2288344	Dosage	3	warfarin

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs2288344	NEDD4	3	0.00	1	warfarin

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
6.30	IC50	500	nM	CHEMBL3621955
6.30	IC50	500	nM	CHEMBL3621954

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	5
arsenite	affects binding, decreases reaction, decreases methylation	2
potassium chromate(VI)	affects cotreatment, decreases expression	2
cadmium sulfate	increases expression	2
Air Pollutants	affects cotreatment, decreases expression, increases abundance	2
Arsenic	increases expression, affects methylation, affects cotreatment, increases abundance	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Valproic Acid	increases expression, decreases methylation	2
aristolochic acid I	decreases expression	1
FR900359	increases phosphorylation	1
dicrotophos	decreases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, decreases expression, increases abundance	1
bisphenol A	decreases expression	1
glycidyl methacrylate	increases expression	1
manganese chloride	increases expression, affects cotreatment, increases abundance	1
coumarin	increases phosphorylation	1
methacrylaldehyde	affects cotreatment, decreases expression, increases abundance	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
avobenzone	decreases expression	1
chromium hexavalent ion	decreases expression	1
perfluorooctane sulfonic acid	decreases expression	1
SB 203580	decreases reaction, increases reaction, increases ubiquitination, affects binding	1
2-palmitoylglycerol	increases expression	1
monomethylarsonous acid	increases expression	1
K 7174	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
abrine	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3626194	Binding	Binding affinity to Nedd4 (unknown origin) assessed as reduction in PPcY-Nedd4 protein interaction	Rational design of proteinprotein interaction inhibitors — Medchemcomm

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D7VM	Ubigene A-549 NEDD4 KO	Cancer cell line	Male
CVCL_TA22	HAP1 NEDD4 (-) 1	Cancer cell line	Male
CVCL_TA23	HAP1 NEDD4 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00211796	PHASE4	COMPLETED	Divalproex Sodium ER in Adult Autism
NCT00391261	PHASE4	COMPLETED	An Open-label Trial of Metformin for Weight Control of Pediatric Patients on Antipsychotic Medications.
NCT00409747	PHASE4	COMPLETED	Minocycline to Treat Childhood Regressive Autism
NCT00576732	PHASE4	COMPLETED	A Study of the Effectiveness and Safety of Two Doses of Risperidone in the Treatment of Children and Adolescents With Autistic Disorder
NCT00844753	PHASE4	COMPLETED	Atomoxetine, Placebo and Parent Management Training in Autism
NCT01028820	PHASE4	COMPLETED	FMRI Brain Activation of Aripiprazole Treatment in Autism Spectrum Disorders
NCT01098383	PHASE4	UNKNOWN	Treatment With Acetyl-Choline Esterase Inhibitors in Children With Autism Spectrum Disorders
NCT01333865	PHASE4	COMPLETED	A Study of Memantine Hydrochloride (Namenda®) for Cognitive and Behavioral Impairment in Adults With Autism Spectrum Disorders
NCT01337700	PHASE4	COMPLETED	Milnacipran in Autism and the Functional Locus Coeruleus and Noradrenergic Model of Autism
NCT01695200	PHASE4	COMPLETED	Omega-3 Fatty Acids in Autism Spectrum Disorders
NCT02069977	PHASE4	UNKNOWN	Study to Evaluate the Efficacy and Safety of Aripiprazole
NCT02096952	PHASE4	COMPLETED	Methylphenidate ER Liquid Formulation in Adults With ASD and ADHD
NCT02199925	PHASE4	UNKNOWN	An Open-Label Study to Evaluate the Efficacy of High-Dose Gammaplex in Children on the Autism Spectrum
NCT02235467	PHASE4	COMPLETED	Multisite Study: Parental Training Using Video Modelling to Develop Social Skills in Children With Autism
NCT02255565	PHASE4	COMPLETED	Dose Response Effects of Quillivant XR in Children With ADHD and Autism: A Pilot Study
NCT02940574	PHASE4	COMPLETED	Neural and Behavioral Effects of Oxytocin in Autism Spectrum Disorders
NCT03333629	PHASE4	COMPLETED	Promoting Positive Outcomes for Individuals With ASD: Linking Early Detection, Treatment, and Long-term Outcomes
NCT03337646	PHASE4	COMPLETED	Evaluation of the Effect and Safety of Lisdexamfetamine in Children Aged 6-12 With ADHD and Autism
NCT03538431	PHASE4	COMPLETED	Improving Driving in Young People With Autism Spectrum Disorders
NCT03757585	PHASE4	COMPLETED	Natural Treatments for the Management of Emotional Dysregulation in Youth With Non-verbal Learning Disability (NVLD) and/or Autism Spectrum Disorders (ASD)
NCT04903353	PHASE4	COMPLETED	Pragmatic Trial Comparing Weight Gain in Children With Autism Taking Risperidone Versus Aripiprazole
NCT05063656	PHASE4	COMPLETED	Biomarker-Driven Pharmacological Treatment of Adolescents With Autism Spectrum Disorder With Gabapentin
NCT05146245	PHASE4	UNKNOWN	Safety and Pharmacokinetics of Antipsychotics in Children 2: Studying TDM in an RCT
NCT05916339	PHASE4	RECRUITING	AWARE: Management of ADHD in Autism Spectrum Disorder
NCT05954052	PHASE4	TERMINATED	A Study of Glutathione in Children With Autism Spectrum Disorder
NCT06853665	PHASE4	RECRUITING	The TEAM Study - Treatment Efficacy for Autism/Attention Using Mixed Amphetamine
NCT07054697	PHASE4	COMPLETED	Pilot-RCT With Individualized Homeopathic Treatment in the Children With Autism Spectrum Disorder
NCT07161804	PHASE4	COMPLETED	Pilot RCT Using Homeopathic Medicines in ASD
NCT07439042	PHASE4	NOT_YET_RECRUITING	Buspirone for Anxiety in Autistic Youth
NCT00036231	PHASE3	TERMINATED	Synthetic Human Secretin in Children With Autism and Gastrointestinal Dysfunction
NCT00036244	PHASE3	COMPLETED	Synthetic Human Secretin in Children With Autism
NCT00065884	PHASE3	UNKNOWN	Valproate Response in Aggressive Autistic Adolescents
NCT00065962	PHASE3	COMPLETED	Secretin for the Treatment of Autism
NCT00252603	PHASE3	COMPLETED	Galantamine Versus Placebo in Childhood Autism
NCT00346736	PHASE3	COMPLETED	Use of Acupuncture In Children With Autistic Spectrum Disorder
NCT00352248	PHASE3	COMPLETED	Randomized Controlled Trial of Acupuncture Versus Sham Acupuncture in Autistic Spectrum Disorder
NCT00352352	PHASE3	COMPLETED	Use of Acupuncture In Children With Autistic Spectrum Disorder
NCT00355329	PHASE3	COMPLETED	Randomized Control Trial of Using Tongue Acupuncture in Autistic Spectrum Disorder Using PET Scan for Clinical Correlation
NCT00498173	PHASE3	COMPLETED	Effectiveness of Atomoxetine in Treating ADHD Symptoms in Children and Adolescents With Autism
NCT00541346	PHASE3	COMPLETED	A Pilot Study of Daytrana TM in Children With Autism Co-Morbid for Attention Deficit Hyperactivity Disorder (ADHD) Symptoms