UBR5

Summary

UBR5 (ubiquitin protein ligase E3 component n-recognin 5, HGNC:16806) is a protein-coding gene on chromosome 8q22.3, encoding E3 ubiquitin-protein ligase UBR5 (O95071). E3 ubiquitin-protein ligase involved in different protein quality control pathways in the cytoplasm and nucleus. It is a selective cancer dependency (DepMap: 55.0% of cell lines).

This gene encodes a progestin-induced protein, which belongs to the HECT (homology to E6-AP carboxyl terminus) family. The HECT family proteins function as E3 ubiquitin-protein ligases, targeting specific proteins for ubiquitin-mediated proteolysis. This gene is localized to chromosome 8q22 which is disrupted in a variety of cancers. This gene potentially has a role in regulation of cell proliferation or differentiation.

Source: NCBI Gene 51366 — RefSeq curated summary.

At a glance

• Gene–disease (curated): neurodevelopmental disorder (Definitive, GenCC)
• GWAS associations: 6
• Clinical variants (ClinVar): 421 total — 7 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 62
• Cancer driver (intOGen): loss-of-function (tumor-suppressor-like) across 6 cancer types
• Cancer dependency (DepMap): dependent in 55.0% of screened cell lines
• MANE Select transcript: NM_015902

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16806
Approved symbol	UBR5
Name	ubiquitin protein ligase E3 component n-recognin 5
Location	8q22.3
Locus type	gene with protein product
Status	Approved
Aliases	DD5, HYD, EDD, KIAA0896
Ensembl gene	ENSG00000104517
Ensembl biotype	protein_coding
OMIM	608413
Entrez	51366

Gene structure

Transcript identifiers

Ensembl transcripts: 19 — 13 protein_coding, 5 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000220959, ENST00000517465, ENST00000518145, ENST00000518205, ENST00000519365, ENST00000519528, ENST00000520539, ENST00000520898, ENST00000521312, ENST00000521566, ENST00000521767, ENST00000521922, ENST00000522327, ENST00000926952, ENST00000926953, ENST00000926954, ENST00000926955, ENST00000926956, ENST00000956066

RefSeq mRNA: 2 — MANE Select: NM_015902 NM_001282873, NM_015902

CCDS: CCDS34933, CCDS64946

Canonical transcript exons

ENST00000520539 — 59 exons

Exon	Start	End
ENSE00000981200	102361582	102361626
ENSE00000981202	102361125	102361206
ENSE00000981205	102360071	102360190
ENSE00000981207	102346903	102347092
ENSE00000981209	102346236	102346395
ENSE00000981211	102345396	102345545
ENSE00000981213	102342473	102342684
ENSE00001165952	102268978	102269108
ENSE00001165958	102270039	102270183
ENSE00001165966	102271134	102271245
ENSE00001165974	102272529	102272772
ENSE00001166231	102275521	102275619
ENSE00001166243	102276972	102277192
ENSE00001166252	102278826	102278939
ENSE00001166257	102279036	102279208
ENSE00001166262	102280394	102280467
ENSE00001166266	102281289	102281519
ENSE00001166270	102285127	102285338
ENSE00001166293	102287433	102287564
ENSE00001166305	102289453	102289576
ENSE00001166308	102293605	102293844
ENSE00001166314	102293955	102294115
ENSE00001166319	102294982	102295111
ENSE00001166320	102295204	102295330
ENSE00001166336	102296893	102296984
ENSE00001166340	102297458	102297606
ENSE00001166347	102298392	102298489
ENSE00001166350	102298848	102298971
ENSE00001166355	102299452	102299547
ENSE00001166360	102300000	102300151
ENSE00001166365	102304043	102304169
ENSE00001166369	102305085	102305295
ENSE00001166374	102311299	102311496
ENSE00001166379	102311735	102311889
ENSE00001166383	102312134	102312245
ENSE00001166389	102312342	102312485
ENSE00001166396	102313804	102313916
ENSE00001166401	102314744	102314853
ENSE00001166407	102323311	102323495
ENSE00001166412	102326546	102326663
ENSE00001166417	102327742	102327896
ENSE00001166425	102329090	102329200
ENSE00001166431	102329283	102329399
ENSE00001216106	102252273	102254514
ENSE00001216174	102265100	102265278
ENSE00001505163	102285513	102285781
ENSE00001505164	102286360	102286617
ENSE00001505165	102295414	102295532
ENSE00001505166	102295636	102295782
ENSE00002109064	102412173	102412700
ENSE00003259418	102264474	102264558
ENSE00003352533	102261915	102262070
ENSE00003473910	102258985	102259129
ENSE00003494527	102257632	102257717
ENSE00003538593	102275708	102275828
ENSE00003652784	102288155	102288266
ENSE00003660785	102360589	102360665
ENSE00003676937	102266947	102267007
ENSE00003687184	102261146	102261259

Expression profiles

Bgee: expression breadth ubiquitous, 300 present calls, max score 98.28.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 34.6801 / max 297.9287, expressed in 1819 samples.

FANTOM5 promoters (13 alternative TSS)

Promoter ID	TPM avg	Samples expressed
94272	28.3325	1817
94273	1.9719	1203
94268	0.6516	255
94274	0.5802	336
94275	0.5495	303
94278	0.5339	306
94279	0.5216	283
94269	0.4420	206
94270	0.3523	144
94277	0.3427	178

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ventricular zone	UBERON:0003053	98.28	gold quality
sural nerve	UBERON:0015488	98.25	gold quality
ganglionic eminence	UBERON:0004023	97.22	gold quality
colonic epithelium	UBERON:0000397	97.18	gold quality
calcaneal tendon	UBERON:0003701	97.14	gold quality
left testis	UBERON:0004533	97.10	gold quality
mucosa of stomach	UBERON:0001199	97.04	gold quality
right testis	UBERON:0004534	97.01	gold quality
skin of abdomen	UBERON:0001416	96.56	gold quality
skin of leg	UBERON:0001511	96.55	gold quality
testis	UBERON:0000473	96.43	gold quality
left ovary	UBERON:0002119	96.41	gold quality
nerve	UBERON:0001021	96.33	gold quality
tibial nerve	UBERON:0001323	96.33	gold quality
muscle layer of sigmoid colon	UBERON:0035805	96.33	gold quality
tendon	UBERON:0000043	96.24	gold quality
body of uterus	UBERON:0009853	96.16	gold quality
right ovary	UBERON:0002118	96.15	gold quality
cortical plate	UBERON:0005343	96.14	gold quality
secondary oocyte	CL:0000655	96.12	gold quality
right uterine tube	UBERON:0001302	96.10	gold quality
endocervix	UBERON:0000458	95.95	gold quality
ectocervix	UBERON:0012249	95.93	gold quality
descending thoracic aorta	UBERON:0002345	95.91	gold quality
right lung	UBERON:0002167	95.90	gold quality
adenohypophysis	UBERON:0002196	95.90	gold quality
tibial artery	UBERON:0007610	95.86	gold quality
popliteal artery	UBERON:0002250	95.85	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	95.81	gold quality
lower esophagus muscularis layer	UBERON:0035833	95.72	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.94

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): TP53

miRNA regulators (miRDB)

204 targeting UBR5, 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-1252-5P	100.00	69.80	2774
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-223-3P	99.99	70.14	1140
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 55.0% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

• ubiquitin-protein ligase EDD interacts with importin alpha 5 through consensus basic nuclear localization signals and is localized in cell nuclei. EDD also binds progesterone receptor (PR) and potentiates progestin-mediated gene transactivation. (PMID:12011095)
• EDD is a novel mediator in DNA damage signal transduction via CHK2 and emphasize the potential importance of EDD in cancer. (PMID:17074762)
• EDD plays the role in the maintenance of genomic stability, emphasising the potential importance of dysregulated EDD expression and/or function in the evolution of cancer. (PMID:18073532)
• These results identify EDD as a new independent prognostic marker for outcome in serous ovarian cancer (PMID:18349819)
• study confirmed the presence of UBR5 mutation in exon 45 in high microsatellite instability cacarcinomas; could not identify exon 42 mutations in colorectal cancers and exon 51 mutations in breast cancers (PMID:20025491)
• Data show that in addition to PP2Ac, alpha4 interacts with EDD and PABP, suggesting its involvement in multiple steps in the mTOR pathway that leads to translation initiation and cell-cycle progression. (PMID:20544796)
• EDD ubiquitinates beta-catenin through Lys29- or Lys11-linked ubiquitin chains, leading to enhanced stability of beta-catenin. (PMID:21118991)
• identify UBR5 as a novel E3 ligase that regulates transcription and define an additional function of TFIIS in the regulation of CDK9. (PMID:21127351)
• The authors show that human EDD can interact independently with both human papillomavirus type 18 E6 and human E6AP. (PMID:21228227)
• through binding to p53, EDD actively inhibits p53 phosphorylation by ATM and plays a role in ensuring smooth G(1)/S progression. (PMID:21383020)
• EDD1 suppresses death-receptor expression, and its expression is elevated in breast, pancreas, and lung cancer cell lines resistant to death receptor-mediated apoptosis. (PMID:21949371)
• Increased p53 levels upon EDD depletion cause a G(1) arrest, as co-depletion of EDD and p53 completely rescues this effect on cell cycle progression. (PMID:22374670)
• Study shows that TRIP12 and UBR5, two HECT domain ubiquitin E3 ligases, control accumulation of RNF168, a rate-limiting component of a pathway that ubiquitylates histones after DNA breakage. (PMID:22884692)
• Ubiquitination assays showed that the C-lobe of UBR5 is able to form a thioester-linked E3-ubiquitin complex, although it does not physically interact with UBCH4 in NMR experiments (PMID:23027739)
• Interaction between microspherule protein Msp58 and ubiquitin E3 ligase EDD regulates cell cycle progression. (PMID:23069210)
• Data indicate that Dyrk2 phosphorylates TERT protein, which is then associated with the EDD-DDB1-VprBP E3 ligase complex for subsequent ubiquitin-mediated TERT protein degradation. (PMID:23362280)
• The recurrence and clustering of deleterious mutations implicate UBR5 mutations as a critical pathogenic event in a subgroup of mantle cell lymphoma. (PMID:23407552)
• As a molecular adaptor, Vpr enhanced the interaction between TERT and the VPRBP substrate receptor of the DYRK2-associated EDD-DDB1-VPRBP E3 ligase complex, resulting in increased ubiquitination of TERT. (PMID:23612978)
• These findings suggest that expression of UBR5-ZNF423 protein might contribute to the transformation of a subset of Nasopharyngeal carcinoma (PMID:23878065)
• Determined is the three-dimensional solution structure of the catalytic RING2 domain from HHARI. It shows glimpses of a HECT E3 ligase. (PMID:24058416)
• the alpha4 N-terminus binding to endogenous PP2Ac and PABP, and the C-terminus to EDD, is reported. (PMID:24145130)
• These results identify EDD as a dual regulator of cell survival and cisplatin resistance and suggest that EDD is a therapeutic target for ovarian cancer. (PMID:24379240)
• UBR5 knockdown results in accumulation of cellular pregnane X receptor and an increase in its activity. (PMID:24438055)
• Utilizing a high throughput RNAi screening approach author identified UBR5, a protein commonly amplified in breast cancer, as a novel regulator of ERalpha protein levels and transcriptional activity. (PMID:24441042)
• these observations highlight the potential role of EDD in regulating mitotic progression and the cellular response to perturbed mitosis. (PMID:25833949)
• results confirm the role of the MLLE domain of UBR5 in substrate recruitment and suggest a potential role in regulating UBR5 ligase activity. (PMID:26224628)
• Colony-formation assays and soft agar assays show that gain of function of TIP60 or depletion of EDD1 in HPV-positive cervical cancer cells significantly inhibits cell growth in vitro (PMID:26234678)
• Human herpesvirus-6 U14 induces cell cycle arrest in G2/M phase by associating with a cellular protein, EDD. (PMID:26340541)
• Elevated metaphase RanGTP levels use Ubr5 to couple overall chromosome congression to SAC silencing. (PMID:26438829)
• Study highlights many functional biological role of UBR5 especially in cancer where it seems to be a key regulator of cell signaling. [review] (PMID:26464214)
• Data show that ubiquitin protein ligase E3 component n-recognin 5 protein (UBR5) bound the tumor suppressor gastrokine 1 (GKN1) and increased its ubiquitination to reduce the protein stability of GKN1. (PMID:27590582)
• BMI1 and UBR5 repress the polymerase II (Pol II)-mediated transcription at damaged sites (PMID:27647897)
• UBR5 downregulates proapoptotic MOAP-1 and suggest that UBR5 can confer cisplatin resistance in ovarian cancer. (PMID:27721409)
• Findings unveil UBR5 as a novel and critical regulator of tumor growth, metastasis, and immune response in triple negative breast cancer. (PMID:28330927)
• Results found that EDD was consistent with GOLPH3 expression and also promoted the EMT process and activated Wnt/beta-catenin signaling in epithelial ovarian cancer. (PMID:28332316)
• Data suggest that UBR5 down-regulates levels of TRAF3, a key component of Toll-like receptor signaling, via the miRNA pathway; p90RSK is an upstream regulator of UBR5; p90RSK phosphorylates UBR5 as required for translational repression of TRAF3 mRNA. (UBR5 = ubiquitin protein ligase E3 component n-recognin 5 protein; TRAF3 = TNF receptor-associated factor 3; p90RSK = 90 kDa ribosomal protein S6 kinase) (PMID:28559278)
• Wnt-dependent inactivation of the Groucho/TLE co-repressor by the HECT E3 ubiquitin ligase Hyd/UBR5 is a key prerequisite that enables Armadillo/beta-catenin to activate transcription. (PMID:28689657)
• UBR5 directly binds to the tumor suppressor esophageal cancer-related gene 4, increasing its ubiquitination to reducing the protein stability of ECRG4 to promote colorectal cancer progression. (PMID:28856538)
• UBR5 was highly expressed in colon cancer not only at mRNA level but also at protein level; UBR5 promoted the growth of colon cancer cells, and inhibited apoptosis. (PMID:29441938)
• UBR5 ubiquitylates CSPP1, and that UBR5 is required for cytoplasmic organization of CSPP1-comprising centriolar satellites in centrosomal periphery. (PMID:29742019)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	ubr5	ENSDARG00000018192
mus_musculus	Ubr5	ENSMUSG00000037487
rattus_norvegicus	Ubr5	ENSRNOG00000006816
drosophila_melanogaster	hyd	FBGN0002431

Paralogs (24): HECW1 (ENSG00000002746), UBE3C (ENSG00000009335), NEDD4L (ENSG00000049759), NEDD4 (ENSG00000069869), ITCH (ENSG00000078747), HACE1 (ENSG00000085382), HUWE1 (ENSG00000086758), HECTD1 (ENSG00000092148), 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 UBR5 — O95071 (reviewed: O95071)

Alternative names: E3 ubiquitin-protein ligase, HECT domain-containing 1, Hyperplastic discs protein homolog, Progestin-induced protein

All UniProt accessions (6): O95071, E5RFK7, E7EMW7, E7ET84, H0YAV7, H0YBB4

UniProt curated annotations — full annotation on UniProt →

Function. E3 ubiquitin-protein ligase involved in different protein quality control pathways in the cytoplasm and nucleus. Mainly acts as a ubiquitin chain elongator that extends pre-ubiquitinated substrates. Component of the N-end rule pathway: ubiquitinates proteins bearing specific N-terminal residues that are destabilizing according to the N-end rule, leading to their degradation. Recognizes type-1 N-degrons, containing positively charged amino acids (Arg, Lys and His). Together with UBR4, part of a cytoplasm protein quality control pathway that prevents protein aggregation by catalyzing assembly of heterotypic ‘Lys-11’-/‘Lys-48’-linked branched ubiquitin chains on aggregated proteins, leading to substrate recognition by the segregase p97/VCP and degradation by the proteasome: UBR5 is probably branching multiple ‘Lys-48’-linked chains of substrates initially modified with mixed conjugates by UBR4. Together with ITCH, catalyzes ‘Lys-48’-/‘Lys-63’-branched ubiquitination of TXNIP, leading to its degradation: UBR5 mediates branching of ‘Lys-48’-linked chains of substrates initially modified with ‘Lys-63’-linked conjugates by ITCH. Catalytic component of a nuclear protein quality control pathway that mediates ubiquitination and degradation of unpaired transcription factors (i.e. transcription factors that are not assembled into functional multiprotein complexes): specifically recognizes and binds degrons that are not accessible when transcription regulators are associated with their coactivators. Ubiquitinates various unpaired transcription regulator (MYC, SUPT4H1, SUPT5H, CDC20 and MCRS1), as well as ligand-bound nuclear receptors (ESR1, NR1H3, NR3C1, PGR, RARA, RXRA AND VDR) that are not associated with their nuclear receptor coactivators (NCOAs). Involved in maturation and/or transcriptional regulation of mRNA by mediating polyubiquitination and activation of CDK9. Also acts as a regulator of DNA damage response by acting as a suppressor of RNF168, an E3 ubiquitin-protein ligase that promotes accumulation of ‘Lys-63’-linked histone H2A and H2AX at DNA damage sites, thereby acting as a guard against excessive spreading of ubiquitinated chromatin at damaged chromosomes. Regulates DNA topoisomerase II binding protein (TopBP1) in the DNA damage response. Ubiquitinates acetylated PCK1. Acts as a positive regulator of the canonical Wnt signaling pathway by mediating (1) ubiquitination and stabilization of CTNNB1, and (2) ‘Lys-48’-linked ubiquitination and degradation of TLE3. Promotes disassembly of the mitotic checkpoint complex (MCC) from the APC/C complex by catalyzing ubiquitination of BUB1B, BUB3 and CDC20. Plays an essential role in extraembryonic development. Required for the maintenance of skeletal tissue homeostasis by acting as an inhibitor of hedgehog (HH) signaling.

Subunit / interactions. Homotetramer; composed of a dimer of dimers. Associates with CDK9 and TFIIS/TCEA1 and forms a transcription regulatory complex made of CDK9, RNAP II, UBR5 and TFIIS/TCEA1 that can stimulate target gene transcription (e.g. gamma fibrinogen/FGG) by recruiting their promoters. Associates with the E3 ligase complex containing DYRK2, EDD/UBR5, DDB1 and DCAF1 proteins (EDVP complex). Binds TOPBP1. Interacts with PIH1D1. Interacts with CIB1. (Microbial infection) Interacts with human T-cell leukemia virus 1/HTLV-1 protein HBZ; this interaction modulates HBZ stability.

Subcellular location. Nucleus. Cytoplasm.

Tissue specificity. Widely expressed. Most abundant in testis and expressed at high levels in brain, pituitary and kidney.

Domain organisation. The UBR-type zinc finger forms a pocket that mediates recognition of type 1 N-degrons. The UBA domain recognizes and binds ubiquitin. It acts as an ubiquitin acceptor required to place ‘Lys-48’ of ubiquitin into the HECT domain activie site, thereby potentiating the E3 ubiquitin-protein ligase activity.

Pathway. Protein modification; protein ubiquitination.

Similarity. Belongs to the UBR5 family.

Isoforms (2)

UniProt ID	Names	Canonical?
O95071-1	1	yes
O95071-2	2

RefSeq proteins (2): NP_001269802, NP_056986* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000569	HECT_dom	Domain
IPR002004	PABP_HYD_C	Domain
IPR003126	Znf_UBR	Domain
IPR009091	RCC1/BLIP-II	Homologous_superfamily
IPR024725	UBR5_UBA	Domain
IPR035983	Hect_E3_ubiquitin_ligase	Homologous_superfamily
IPR036053	PABP-dom	Homologous_superfamily
IPR047503	UBR-box_UBR5	Domain

Pfam: PF00632, PF00658, PF11547

UniProt features (307 total): helix 95, strand 81, modified residue 34, turn 22, compositionally biased region 20, region of interest 12, binding site 12, sequence conflict 11, mutagenesis site 11, domain 3, initiator methionine 1, chain 1, active site 1, zinc finger region 1, splice variant 1, sequence variant 1

Structure

Experimental structures (PDB)

11 structures.

PDB	Method	Resolution (Å)
1I2T	X-RAY DIFFRACTION	1.04
2QHO	X-RAY DIFFRACTION	1.85
3PT3	X-RAY DIFFRACTION	1.97
8E0Q	ELECTRON MICROSCOPY	2.66
8C06	ELECTRON MICROSCOPY	2.7
8D4X	ELECTRON MICROSCOPY	2.8
8BJA	ELECTRON MICROSCOPY	3
8C07	ELECTRON MICROSCOPY	3.3
8P82	ELECTRON MICROSCOPY	3.36
8EWI	ELECTRON MICROSCOPY	3.5
8P83	ELECTRON MICROSCOPY	3.87

Predicted structure (AlphaFold)

No AlphaFold model available for O95071 — AlphaFold DB does not currently provide models for proteins above ~3000 aa.

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): 2768 (glycyl thioester intermediate)

Ligand- & substrate-binding residues (12): 1179; 1196; 1199; 1208; 1211; 1211; 1215; 1216; 1219; 1232; 1234; 1240

Post-translational modifications (34): 2, 110, 327, 352, 578, 612, 637, 808, 928, 1018, 1115, 1135, 1227, 1308, 1355, 1375, 1481, 1549, 1736, 1741 …

Mutagenesis-validated functional residues (11):

Position	Phenotype
196	abolished binding to ubiquitin, leading to strongly reduced e3 ubiquitin-protein ligase activity.
214	does not affect binding to ubiquitin.
218	does not affect binding to ubiquitin.
224	abolished binding to ubiquitin.
1914	impaired tetramerization.
1926	impaired tetramerization.
1931	impaired tetramerization.
2576	reduced but not abolished e3 ubiquitin-protein ligase activity.
2732	strongly reduced e3 ubiquitin-protein ligase activity.
2768	loss of e3 ubiquitin-protein ligase activity.
2790	strongly reduced e3 ubiquitin-protein ligase activity.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 356 (showing top): GSE18804_BRAIN_VS_COLON_TUMORAL_MACROPHAGE_DN, MORF_MBD4, MORF_RAB5A, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, GOBP_CELLULAR_RESPONSE_TO_LIPID, TGCACTT_MIR519C_MIR519B_MIR519A, TTTGTAG_MIR520D, GOBP_POSITIVE_REGULATION_OF_INTRACELLULAR_PROTEIN_TRANSPORT, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOBP_POSITIVE_REGULATION_OF_PROTEIN_LOCALIZATION, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, MORF_RAD21, GOBP_REGULATION_OF_WNT_SIGNALING_PATHWAY, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_ORGANELLE, MORF_PSMC2

GO Biological Process (24): protein polyubiquitination (GO:0000209), DNA repair (GO:0006281), DNA damage response (GO:0006974), positive regulation of gene expression (GO:0010628), heterochromatin boundary formation (GO:0033696), protein K29-linked ubiquitination (GO:0035519), positive regulation of protein import into nucleus (GO:0042307), proteasome-mediated ubiquitin-dependent protein catabolic process (GO:0043161), negative regulation of smoothened signaling pathway (GO:0045879), progesterone receptor signaling pathway (GO:0050847), protein K48-linked ubiquitination (GO:0070936), protein K11-linked ubiquitination (GO:0070979), cytoplasm protein quality control by the ubiquitin-proteasome system (GO:0071629), nuclear protein quality control by the ubiquitin-proteasome system (GO:0071630), positive regulation of canonical Wnt signaling pathway (GO:0090263), cytoplasm protein quality control (GO:0140455), DNA repair-dependent chromatin remodeling (GO:0140861), protein branched polyubiquitination (GO:0141198), response to oxidative stress (GO:0006979), proteasomal protein catabolic process (GO:0010498), protein ubiquitination (GO:0016567), estrogen receptor signaling pathway (GO:0030520), retinoic acid receptor signaling pathway (GO:0048384), vitamin D receptor signaling pathway (GO:0070561)

GO Molecular Function (9): RNA binding (GO:0003723), zinc ion binding (GO:0008270), ubiquitin-ubiquitin ligase activity (GO:0034450), ubiquitin binding (GO:0043130), ubiquitin protein ligase activity (GO:0061630), ubiquitin-protein transferase activity (GO:0004842), protein binding (GO:0005515), transferase activity (GO:0016740), metal ion binding (GO:0046872)

GO Cellular Component (8): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), membrane (GO:0016020), protein-containing complex (GO:0032991), perinuclear region of cytoplasm (GO:0048471)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	6
protein polyubiquitination	4
DNA damage response	2
proteasome-mediated ubiquitin-dependent protein catabolic process	2
cellular response to misfolded protein	2
protein quality control for misfolded or incompletely synthesized proteins	2
cytoplasm	2
protein ubiquitination	1
DNA metabolic process	1
cellular response to stress	1
gene expression	1
regulation of gene expression	1
positive regulation of macromolecule biosynthetic process	1
heterochromatin formation	1
heterochromatin organization	1
protein import into nucleus	1
regulation of protein import into nucleus	1
positive regulation of nucleocytoplasmic transport	1
positive regulation of intracellular protein transport	1
positive regulation of protein localization to nucleus	1
ubiquitin-dependent protein catabolic process	1
proteasomal protein catabolic process	1
smoothened signaling pathway	1
regulation of smoothened signaling pathway	1
negative regulation of signal transduction	1
nuclear receptor-mediated steroid hormone signaling pathway	1
cytoplasm protein quality control	1
positive regulation of Wnt signaling pathway	1
canonical Wnt signaling pathway	1
regulation of canonical Wnt signaling pathway	1
chromatin remodeling	1
response to stress	1
protein catabolic process	1
nucleic acid binding	1
transition metal ion binding	1
ubiquitin protein ligase activity	1
ubiquitin-like protein binding	1
ubiquitin-protein transferase activity	1
ubiquitin-like protein ligase activity	1
ubiquitin-like protein transferase activity	1

Protein interactions and networks

STRING

3044 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
UBR5	UBR1	Q8IWV7	913
UBR5	QKI	Q96PU8	847
UBR5	NOVA1	P51513	785
UBR5	OTUD5	Q96G74	782
UBR5	PCK1	P35558	774
UBR5	DCAF1	Q9Y4B6	718
UBR5	DDB1	Q16531	714
UBR5	ATMIN	O43313	707
UBR5	DYRK2	Q92630	706
UBR5	UBR2	Q8IWV8	673
UBR5	UBR7	Q8N806	644
UBR5	UBR3	Q6ZT12	622
UBR5	ZUP1	Q96AP4	621
UBR5	TP53	P04637	618
UBR5	UBR4	Q5T4S7	595

IntAct

291 interactions, top by confidence:

A	B	Type	Score
MED19	MED19	psi-mi:“MI:0914”(association)	0.730
MED26	MED19	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
PKN3	ARHGAP10	psi-mi:“MI:0914”(association)	0.680
BUB1	NDC80	psi-mi:“MI:0915”(physical association)	0.670
P4HA3	FAM171A2	psi-mi:“MI:0914”(association)	0.640
Cep78	UBR5	psi-mi:“MI:0915”(physical association)	0.560
PLK1	C1orf226	psi-mi:“MI:0914”(association)	0.560
TTC7A	UBR5	psi-mi:“MI:0915”(physical association)	0.560
EBNA-LP	HAX1	psi-mi:“MI:0914”(association)	0.530
FAF2	PJA2	psi-mi:“MI:0914”(association)	0.530
PRSS37	MANBA	psi-mi:“MI:0914”(association)	0.530
POGLUT1	ZZEF1	psi-mi:“MI:0914”(association)	0.530
DDX28	PTCD1	psi-mi:“MI:0914”(association)	0.530
ILK	ILVBL	psi-mi:“MI:0914”(association)	0.530
MINK1	CNOT1	psi-mi:“MI:0914”(association)	0.530
ZNF223	PPM1G	psi-mi:“MI:0914”(association)	0.530
HTRA2	HAX1	psi-mi:“MI:2364”(proximity)	0.420
Bub1	NDC80	psi-mi:“MI:0915”(physical association)	0.400
Ubr5	UBR5	psi-mi:“MI:0915”(physical association)	0.400
Bub1b	NDC80	psi-mi:“MI:0915”(physical association)	0.400
UBR5	UBE2E1	psi-mi:“MI:0915”(physical association)	0.370
UBE2E2	UBR5	psi-mi:“MI:0915”(physical association)	0.370
UBR5	UBE2E3	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (857): UBR5 (Affinity Capture-MS), UBR5 (Biochemical Activity), UBR5 (Affinity Capture-MS), UBR5 (Affinity Capture-MS), UBR5 (Affinity Capture-MS), MRS2 (Affinity Capture-MS), C1QBP (Affinity Capture-MS), BUB3 (Affinity Capture-MS), XPNPEP3 (Affinity Capture-MS), UBR5 (Affinity Capture-Western), UBR5 (Affinity Capture-Western), UBR5 (Affinity Capture-Western), UBR5 (Affinity Capture-Western), ACTR1A (Co-fractionation), EIF3I (Co-fractionation)

ESM2 similar proteins: A0A1L8GLK3, A0A974CYQ5, A2AHJ4, A5WW08, D2HNY3, D2HWM5, E7F6T8, F1ND48, O15040, O70260, O95071, P59328, Q3TLR7, Q4V837, Q58DC2, Q58WW2, Q5E9J6, Q5F479, Q5FWP4, Q5NVC7, Q5R9B8, Q5RF77, Q5RGA4, Q5RHI5, Q5ZLG9, Q62671, Q66JG1, Q6DDH2, Q6P1W0, Q6P256, Q6PCD5, Q6PJI9, Q6RI45, Q80TP3, Q80U93, Q810L3, Q8C0M0, Q8CBW4, Q8CIK8, Q8CIN9

Diamond homologs: A0A0D1DWZ5, A1CRM1, A1D4K4, A2A5N3, A2Q848, A3LXL0, A4QUF0, A5DM21, A5DW14, F1QB54, F4HT49, O04319, O09032, O14102, O22173, O64380, O88569, O95071, P04147, P0CB38, P0CP46, P0CP47, P11940, P19684, P20965, P21187, P22626, P26378, P29341, P31209, P32588, P39684, P42731, P49313, P51989, P51990, P60047, P60048, P60049, P60050

SIGNOR signaling

11 interactions.

A	Effect	B	Mechanism
TCEA1	up-regulates	UBR5	binding
UBR5	“down-regulates quantity”	RNF168	ubiquitination
UBR5	“down-regulates quantity by destabilization”	PCK1	ubiquitination
Ub:E2	“up-regulates activity”	UBR5	ubiquitination
UBR5	“form complex”	EDVP	binding
UBR5	“down-regulates quantity by destabilization”	PAIP2	polyubiquitination
UBR5	“down-regulates quantity by destabilization”	SOX2	polyubiquitination
UBR5	“down-regulates quantity by destabilization”	MOAP1	ubiquitination
UBR5	“down-regulates quantity by destabilization”	TOPBP1	polyubiquitination
UBE2D2	“up-regulates activity”	UBR5	ubiquitination
UBE2D3	“up-regulates activity”	UBR5	ubiquitination

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 211 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
Amplification of signal from the kinetochores	6	8.8×	6e-03
Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal	10	8.6×	4e-05
EML4 and NUDC in mitotic spindle formation	11	7.6×	4e-05
Resolution of Sister Chromatid Cohesion	11	7.0×	6e-05
RHO GTPases Activate Formins	12	6.9×	4e-05
Separation of Sister Chromatids	14	6.3×	3e-05
Mitotic Prometaphase	11	5.6×	5e-04

GO biological processes:

GO term	Partners	Fold	FDR
mitotic spindle assembly checkpoint signaling	5	16.1×	4e-03
mitotic spindle organization	7	10.9×	2e-03
protein phosphorylation	21	8.2×	2e-10
intracellular signal transduction	16	3.5×	4e-03

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: loss-of-function (tumor-suppressor-like) across 6 cancer types — AML, BRCA, CHRCC, CSCC, MEL, STAD.

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	7
Likely pathogenic	1
Uncertain significance	254
Likely benign	49
Benign	10

Top pathogenic / likely-pathogenic (8)

Variant ID	HGVS	Classification
4279507	NM_015902.6(UBR5):c.455G>C (p.Arg152Pro)	Pathogenic
4279508	NM_015902.6(UBR5):c.6557_6562del (p.Leu2186_Gly2187del)	Pathogenic
4279509	NM_015902.6(UBR5):c.3616TGT[2] (p.Cys1208del)	Pathogenic
4279510	NM_015902.6(UBR5):c.3682C>T (p.Pro1228Ser)	Pathogenic
4279512	NM_015902.6(UBR5):c.734G>C (p.Gly245Ala)	Pathogenic
4829735	NM_015902.6(UBR5):c.8125C>T (p.Gln2709Ter)	Pathogenic
4833014	NM_015902.6(UBR5):c.4771dup (p.His1591fs)	Pathogenic
563524	GRCh37/hg19 8q22.3(chr8:102584167-104236192)x1	Likely pathogenic

SpliceAI

9234 predictions. Top by Δscore:

Variant	Effect	Δscore
8:102254512:AACC:A	acceptor_loss	1.0000
8:102254513:ACCT:A	acceptor_loss	1.0000
8:102254514:CCT:C	acceptor_loss	1.0000
8:102257626:A:C	donor_gain	1.0000
8:102257626:ACTT:A	donor_loss	1.0000
8:102257627:CTT:C	donor_loss	1.0000
8:102257628:TTA:T	donor_loss	1.0000
8:102257629:TACAA:T	donor_loss	1.0000
8:102257630:A:AC	donor_gain	1.0000
8:102257630:AC:A	donor_loss	1.0000
8:102257631:C:CT	donor_gain	1.0000
8:102257631:CA:C	donor_gain	1.0000
8:102257631:CAA:C	donor_gain	1.0000
8:102257631:CAAG:C	donor_gain	1.0000
8:102257631:CAAGA:C	donor_gain	1.0000
8:102257713:TTCTC:T	acceptor_gain	1.0000
8:102257715:CTC:C	acceptor_gain	1.0000
8:102257716:TCCT:T	acceptor_loss	1.0000
8:102257718:C:CC	acceptor_gain	1.0000
8:102257719:T:G	acceptor_loss	1.0000
8:102257724:A:AC	acceptor_gain	1.0000
8:102257724:A:C	acceptor_gain	1.0000
8:102258981:CTAC:C	donor_loss	1.0000
8:102258982:TACC:T	donor_loss	1.0000
8:102258983:A:C	donor_loss	1.0000
8:102258984:C:T	donor_loss	1.0000
8:102259126:TTGC:T	acceptor_gain	1.0000
8:102261144:A:AC	donor_gain	1.0000
8:102261145:C:CC	donor_gain	1.0000
8:102261166:C:CT	donor_gain	1.0000

AlphaMissense

18355 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:102254308:A:C	F2798L	1.000
8:102254308:A:T	F2798L	1.000
8:102254309:A:C	F2798C	1.000
8:102254309:A:G	F2798S	1.000
8:102254310:A:G	F2798L	1.000
8:102254312:C:T	G2797D	1.000
8:102254313:C:G	G2797R	1.000
8:102254314:A:C	F2796L	1.000
8:102254314:A:T	F2796L	1.000
8:102254316:A:G	F2796L	1.000
8:102254330:A:T	I2791N	1.000
8:102254333:G:T	A2790D	1.000
8:102254336:A:G	L2789P	1.000
8:102254342:A:G	L2787S	1.000
8:102254354:A:G	L2783P	1.000
8:102254354:A:T	L2783H	1.000
8:102254373:A:C	Y2777D	1.000
8:102254378:G:C	P2775R	1.000
8:102254378:G:T	P2775Q	1.000
8:102254379:G:T	P2775T	1.000
8:102254381:A:T	V2774D	1.000
8:102254387:A:C	L2772R	1.000
8:102254387:A:G	L2772P	1.000
8:102254387:A:T	L2772H	1.000
8:102254390:C:G	R2771P	1.000
8:102254393:G:A	S2770F	1.000
8:102254393:G:T	S2770Y	1.000
8:102254394:A:G	S2770P	1.000
8:102254396:A:C	I2769S	1.000
8:102254396:A:T	I2769N	1.000

dbSNP variants (sampled 300 via entrez): RS1000017045 (8:102388318 T>C), RS1000027247 (8:102297360 A>C,T), RS1000037676 (8:102345976 G>T), RS1000045483 (8:102336419 G>C), RS1000058292 (8:102297768 C>G), RS1000121829 (8:102288519 G>A,C), RS1000125535 (8:102384411 C>G), RS1000138356 (8:102394338 G>A), RS1000166760 (8:102304858 C>A), RS1000237060 (8:102356805 G>C), RS1000246333 (8:102370463 G>T), RS1000260743 (8:102412336 C>A,G), RS1000272255 (8:102375165 A>G), RS1000293314 (8:102311083 T>C), RS1000324177 (8:102311538 A>G)

Disease associations

OMIM: gene MIM:608413 | disease phenotypes: MIM:621372

GenCC curated gene-disease

Disease	Classification	Inheritance
neurodevelopmental disorder	Definitive	Autosomal dominant

Mondo (3): long QT syndrome (MONDO:0002442), neurodevelopmental disorder (MONDO:0700092), neurodevelopmental disorder with speech delay and behavioral abnormalities (MONDO:0980700)

Orphanet (0):

HPO phenotypes

62 total (30 of 62 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000028	Cryptorchidism
HP:0000054	Micropenis
HP:0000189	Narrow palate
HP:0000201	Pierre-Robin sequence
HP:0000248	Brachycephaly
HP:0000252	Microcephaly
HP:0000256	Macrocephaly
HP:0000278	Retrognathia
HP:0000286	Epicanthus
HP:0000311	Round face
HP:0000316	Hypertelorism
HP:0000445	Wide nose
HP:0000463	Anteverted nares
HP:0000577	Exotropia
HP:0000601	Hypotelorism
HP:0000637	Long palpebral fissure
HP:0000664	Synophrys
HP:0000713	Agitation
HP:0000717	Autism
HP:0000729	Autistic behavior
HP:0000732	Inflexible adherence to routines
HP:0000733	Motor stereotypy
HP:0000739	Anxiety
HP:0000750	Delayed speech and language development
HP:0000957	Cafe-au-lait spot
HP:0001159	Syndactyly
HP:0001249	Intellectual disability
HP:0001252	Hypotonia
HP:0001256	Mild intellectual disability

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST004125_7	Type 2 diabetes (age of onset)	2.000000e-06
GCST004371_2	Rate of cognitive decline in mild cognitive impairment (time interaction)	4.000000e-14
GCST008940_2	Chromosomal aberration frequency (total)	1.000000e-06
GCST90002389_184	Lymphocyte percentage of white cells	9.000000e-10
GCST90002390_610	Mean corpuscular hemoglobin	4.000000e-09
GCST90002392_591	Mean corpuscular volume	2.000000e-11

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0007710	cognitive decline measurement
EFO:0008336	disease progression measurement
EFO:0009860	chromosomal aberration frequency
EFO:0007993	lymphocyte percentage of leukocytes
EFO:0004527	mean corpuscular hemoglobin

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D008133	Long QT Syndrome	C14.280.067.565; C14.280.123.625; C16.131.240.400.715; C23.550.073.547
D065886	Neurodevelopmental Disorders	F03.625

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
trichostatin A	affects cotreatment, decreases expression, affects expression, increases expression	3
sodium arsenite	decreases expression, increases abundance	2
Hydrogen Peroxide	affects expression, increases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Tetrachlorodibenzodioxin	decreases expression	2
Valproic Acid	affects expression, increases expression	2
TAK-243	increases sumoylation	1
2,4,6-tribromophenol	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases expression	1
decabromobiphenyl ether	decreases expression	1
beta-lapachone	decreases expression	1
arsenite	decreases reaction, affects binding	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
tetrabromobisphenol A	decreases expression	1
cupric chloride	increases expression	1
coumarin	decreases phosphorylation	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
ICG 001	increases expression	1
abrine	increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
2-(1H-indazol-4-yl)-6-(4-methanesulfonylpiperazin-1-ylmethyl)-4-morpholin-4-ylthieno(3,2-d)pyrimidine	increases expression, increases response to substance	1
jinfukang	affects cotreatment, decreases expression	1
Arsenic Trioxide	decreases expression	1
Acetaminophen	decreases expression	1
Arsenic	decreases expression, increases abundance	1
Benzene	increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT02513940	PHASE4	COMPLETED	Influence of Testosterone Administration on Drug-Induced QT Interval Prolongation and Torsades de Pointes
NCT03834883	PHASE4	COMPLETED	Reducing the Risk of Drug-Induced QT Interval Lengthening in Women
NCT04169100	PHASE4	UNKNOWN	Novel Form of Acquired Long QT Syndrome
NCT04675788	PHASE4	COMPLETED	Novel Approaches for Minimizing Drug-Induced QT Interval Lengthening
NCT02559102	PHASE3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	PHASE3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	PHASE3	RECRUITING	Reducing Missed Appointments
NCT07377032	PHASE3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT02909959	PHASE2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	PHASE2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	PHASE2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT01648205	PHASE2	COMPLETED	Long-term Efficacy Study of Sodium Channel Blocker in LQT3 Patients
NCT02412709	PHASE2	UNKNOWN	Long QT Syndrome Screening in Newborns
NCT04581408	PHASE2	COMPLETED	Mutation-specific Therapy for the Long QT Syndrome
NCT00503191	PHASE1	COMPLETED	NeuroModulation Technique Treatment of Autism
NCT04475848	PHASE1	COMPLETED	A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants
NCT06300398	PHASE1	COMPLETED	IAMA-6 Oral Dose Study in Healthy Adults
NCT00316459	PHASE1	COMPLETED	Study Evaluating the Effects of Multiple Oral Doses of ERB-041 on Cardiac Repolarization in Healthy Subjects
NCT01849003	PHASE1	COMPLETED	Study of the Effect of GS-6615 in Subjects With LQT-3
NCT02365532	PHASE1	COMPLETED	Effect of Oral GS-6615 on Dofetilide-Induced QT Prolongation, Safety, and Tolerability in Healthy Adults
NCT02412098	PHASE1	COMPLETED	Pharmacokinetics of Eleclazine in Adults With Normal and Impaired Hepatic Function
NCT02441829	PHASE1	COMPLETED	Pharmacokinetics of Eleclazine in Adults With Normal and Impaired Renal Function
NCT05759962	PHASE1	COMPLETED	Phase 1 Study of LQT-1213 in Healthy Adults
NCT01783041	PHASE2/PHASE3	COMPLETED	Effect of Early L-Carnitine Supplementation on Neurodevelopmental Outcomes in Very Preterm Infants
NCT05767385	PHASE2/PHASE3	RECRUITING	Fetal Cerebrovascular Autoregulation in Congenital Heart Disease and Association With Neonatal Neurobehavior
NCT05675098	EARLY_PHASE1	NOT_YET_RECRUITING	Central Nervous System Stimulants and Physical Function in Children With Cerebral Palsy
NCT00783783	Not specified	COMPLETED	CYP2D6 Pharmacogenetics in Risperidone-Treated Children
NCT01778504	Not specified	RECRUITING	Studying Childhood-onset Behavioral, Psychiatric, and Developmental Disorders
NCT01850784	Not specified	UNKNOWN	High Energy Formula Feeding in Infants With Congenital Heart Disease
NCT01922791	Not specified	COMPLETED	Nutrition and Pregnancy Intervention Study
NCT01942525	Not specified	UNKNOWN	Influence of Intrauterine Growth Restriction on Amplitude-integrated EEG in Preterm Infants
NCT02003170	Not specified	COMPLETED	Etiology and Early Diagnosis of Neurodevelopmental Disorders
NCT02118649	Not specified	ACTIVE_NOT_RECRUITING	Enhancing Behavior and Brain Response to Visual Targets Using a Computer Game
NCT02557191	Not specified	TERMINATED	Biomarkers, Neurodevelopment and Preterm Infants
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