NAE1

Summary

NAE1 (NEDD8 activating enzyme E1 subunit 1, HGNC:621) is a protein-coding gene on chromosome 16q22.1, encoding NEDD8-activating enzyme E1 regulatory subunit (Q13564). Regulatory subunit of the dimeric UBA3-NAE1 E1 enzyme. It is a selective cancer dependency (DepMap: 83.2% of cell lines).

The protein encoded by this gene binds to the beta-amyloid precursor protein. Beta-amyloid precursor protein is a cell surface protein with signal-transducing properties, and it is thought to play a role in the pathogenesis of Alzheimer’s disease. In addition, the encoded protein can form a heterodimer with UBE1C and bind and activate NEDD8, a ubiquitin-like protein. This protein is required for cell cycle progression through the S/M checkpoint. Three transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 8883 — RefSeq curated summary.

At a glance

• Gene–disease (curated): neurodevelopmental disorder with dysmorphic facies and ischiopubic hypoplasia (Strong, GenCC)
• GWAS associations: 2
• Clinical variants (ClinVar): 102 total — 3 pathogenic
• Phenotypes (HPO): 26
• Druggable target: yes — 3 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 83.2% of screened cell lines
• MANE Select transcript: NM_003905

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:621
Approved symbol	NAE1
Name	NEDD8 activating enzyme E1 subunit 1
Location	16q22.1
Locus type	gene with protein product
Status	Approved
Aliases	ula-1, APP-BP1
Ensembl gene	ENSG00000159593
Ensembl biotype	protein_coding
OMIM	603385
Entrez	8883

Gene structure

Transcript identifiers

Ensembl transcripts: 33 — 21 protein_coding, 7 retained_intron, 4 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000290810, ENST00000359087, ENST00000379463, ENST00000394074, ENST00000561579, ENST00000562074, ENST00000562428, ENST00000562757, ENST00000563185, ENST00000563221, ENST00000563253, ENST00000563419, ENST00000564040, ENST00000565535, ENST00000566336, ENST00000566663, ENST00000567521, ENST00000567743, ENST00000568672, ENST00000569348, ENST00000569388, ENST00000569963, ENST00000859016, ENST00000859017, ENST00000859018, ENST00000859019, ENST00000934203, ENST00000934204, ENST00000934205, ENST00000934206, ENST00000952148, ENST00000952149, ENST00000952150

RefSeq mRNA: 4 — MANE Select: NM_003905 NM_001018159, NM_001018160, NM_001286500, NM_003905

CCDS: CCDS10820, CCDS42171, CCDS42172, CCDS67050

Canonical transcript exons

ENST00000290810 — 20 exons

Exon	Start	End
ENSE00001046603	66808989	66809075
ENSE00001046614	66810374	66810413
ENSE00001046627	66808521	66808613
ENSE00001104186	66816581	66816672
ENSE00001104192	66805912	66806026
ENSE00001139952	66810697	66810772
ENSE00001139961	66813564	66813697
ENSE00003465740	66816965	66817028
ENSE00003519507	66823529	66823600
ENSE00003523215	66826523	66826583
ENSE00003554100	66824855	66824885
ENSE00003566559	66818528	66818637
ENSE00003572445	66823227	66823306
ENSE00003604154	66817425	66817487
ENSE00003620149	66805777	66805826
ENSE00003648181	66813787	66813846
ENSE00003669652	66821450	66821559
ENSE00003672944	66830847	66830976
ENSE00003682567	66826677	66826780
ENSE00003844767	66802878	66803118

Expression profiles

Bgee: expression breadth ubiquitous, 299 present calls, max score 99.26.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 42.9221 / max 588.8369, expressed in 1817 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
157719	42.5173	1816
157721	0.3826	179
157720	0.0221	9

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	99.26	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	98.21	gold quality
calcaneal tendon	UBERON:0003701	97.51	gold quality
oocyte	CL:0000023	97.46	gold quality
ventricular zone	UBERON:0003053	97.30	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	97.19	gold quality
cerebellar hemisphere	UBERON:0002245	96.99	gold quality
right hemisphere of cerebellum	UBERON:0014890	96.98	gold quality
cerebellar cortex	UBERON:0002129	96.97	gold quality
ganglionic eminence	UBERON:0004023	96.78	gold quality
cerebellum	UBERON:0002037	96.49	gold quality
tibia	UBERON:0000979	96.48	gold quality
skin of hip	UBERON:0001554	96.36	gold quality
embryo	UBERON:0000922	95.96	gold quality
esophagus squamous epithelium	UBERON:0006920	95.70	gold quality
left ovary	UBERON:0002119	95.66	gold quality
upper leg skin	UBERON:0004262	95.59	gold quality
adenohypophysis	UBERON:0002196	95.39	gold quality
pons	UBERON:0000988	95.31	gold quality
ovary	UBERON:0000992	95.29	gold quality
parietal pleura	UBERON:0002400	95.27	gold quality
seminal vesicle	UBERON:0000998	95.19	gold quality
bronchial epithelial cell	CL:0002328	95.16	gold quality
body of uterus	UBERON:0009853	95.10	gold quality
parotid gland	UBERON:0001831	95.09	gold quality
pituitary gland	UBERON:0000007	95.04	gold quality
right ovary	UBERON:0002118	95.04	gold quality
oral cavity	UBERON:0000167	94.97	gold quality
corpus epididymis	UBERON:0004359	94.95	gold quality
adrenal tissue	UBERON:0018303	94.94	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-GEOD-134144	yes	29.30
E-HCAD-10	yes	17.65
E-ANND-3	yes	8.26
E-GEOD-125970	yes	6.42

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

12 targeting NAE1, 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-570-3P	99.96	72.41	4910
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-6845-3P	99.94	66.88	1439
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-33A-3P	99.70	70.27	3362
HSA-MIR-646	99.68	67.84	1645
HSA-MIR-1252-3P	99.55	67.71	2862
HSA-MIR-582-5P	99.47	70.79	2635
HSA-MIR-4477A	98.83	69.75	2952
HSA-MIR-374B-3P	98.63	68.24	1360
HSA-MIR-603	98.58	68.28	1603
HSA-MIR-4275	97.96	68.42	1549

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 83.2% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 11)

• structure and mutational analysis of human APPBP1-UBA3, the heterodimeric E1 enzyme for NEDD8 (PMID:12646924)
• Conservation in the mechanism of Nedd8 activation by the human AppBp1-Uba3 heterodimer. (PMID:12740388)
• Data report the structure of the quaternary complex between human APPBP1-UBA3, a heterodimeric E1, its ubl NEDD8, and ATP. (PMID:14690597)
• APP-BP1 is degraded by ubiquitin-dependent proteolysis. (PMID:18627766)
• APP-BP1 displayed decreased expression levels in HPV-positive head and neck squamous cell carcinoma (PMID:19795456)
• APP-BP1 plays an important role in the cell cycle progression of fetal neural stem cells (PMID:21151996)
• our results suggest that APP-BP1 modulates neuronal differentiation by altering gene expression profiles in fetal neural stem cells (PMID:22182960)
• analysis of a metal-based inhibitor of NEDD8-activating enzyme (PMID:23185368)
• E1 (NAE1 and UBA3) and E2 (UBC12) enzymes, as well as global NEDD8 conjugation, were upregulated in over 2/3 of human intrahepatic cholangiocarcinoma (PMID:25229838)
• Here we report that high expression of neddylation components, NEDD8 and NAE1, are associated with poor survival of Pancreatic ductal adenocarcinoma patients. Blockage of neddylation by MLN4924 significantly sensitizes pancreatic cancer cells to gemcitabine, reduced clonogenic survival, decreased invasion capacity, increased apoptosis and senescence (PMID:28535453)
• NAE1 expression was readily detectable in Uveal Melanoma. Inhibition of the neddylation pathway by MLN4924 repressed the cancer stem-like cells properties in Uveal Melanoma (PMID:29233905)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	nae1	ENSDARG00000011301
mus_musculus	Nae1	ENSMUSG00000031878
rattus_norvegicus	Nae1	ENSRNOG00000033133
drosophila_melanogaster	APP-BP1	FBGN0261112
caenorhabditis_elegans		WBGENE00006735

Paralogs (9): UBA6 (ENSG00000033178), UBA5 (ENSG00000081307), MOCS3 (ENSG00000124217), UBA2 (ENSG00000126261), UBA1 (ENSG00000130985), SAE1 (ENSG00000142230), UBA3 (ENSG00000144744), UBA7 (ENSG00000182179), ATG7 (ENSG00000197548)

Protein

Protein identifiers

NEDD8-activating enzyme E1 regulatory subunit — Q13564 (reviewed: Q13564)

Alternative names: Amyloid beta precursor protein-binding protein 1, 59 kDa, Amyloid protein-binding protein 1, Proto-oncogene protein 1

All UniProt accessions (11): Q13564, H3BMN8, H3BMR3, H3BQ16, H3BQW6, H3BS69, H3BSS8, J3KRK3, J3KTE3, J3QLH4, J3QRA5

UniProt curated annotations — full annotation on UniProt →

Function. Regulatory subunit of the dimeric UBA3-NAE1 E1 enzyme. E1 activates NEDD8 by first adenylating its C-terminal glycine residue with ATP, thereafter linking this residue to the side chain of the catalytic cysteine, yielding a NEDD8-UBA3 thioester and free AMP. E1 finally transfers NEDD8 to the catalytic cysteine of UBE2M. Necessary for cell cycle progression through the S-M checkpoint. Overexpression of NAE1 causes apoptosis through deregulation of NEDD8 conjugation. The covalent attachment of NEDD8 to target proteins is known as ’neddylation’ and the process is involved in the regulation of cell growth, viability and development.

Subunit / interactions. Heterodimer of UBA3 and NAE1. The complex binds NEDD8 and UBE2M. Binds APP and TP53BP2.

Subcellular location. Cell membrane.

Tissue specificity. Ubiquitous in fetal tissues. Expressed throughout the adult brain.

Post-translational modifications. Ubiquitinated by TRIP12, leading to its degradation by the proteasome.

Disease relevance. Neurodevelopmental disorder with dysmorphic facies and ischiopubic hypoplasia (NEDFIH) [MIM:620210] An autosomal recessive disorder characterized by moderate to severe global developmental delay, facial dysmorphism, and ischiopubic synchondrosis hypoplasia. Affected individuals show infection-triggered lymphopenia, and loss of developmental milestones associated with epileptic spasms. Diminished white matter volume, enlarged ventricles, and thin corpus callosum are visible on brain imaging. The disease may be caused by variants affecting the gene represented in this entry.

Activity regulation. Binding of TP53BP2 to the regulatory subunit NAE1 decreases neddylation activity.

Pathway. Protein modification; protein neddylation.

Miscellaneous. NAE1 and UBA3 correspond to the N-terminal and the C-terminal part of yeast UBA3. In yeast the two subunits form a single polypeptide chain.

Similarity. Belongs to the ubiquitin-activating E1 family. ULA1 subfamily.

Isoforms (4)

UniProt ID	Names	Canonical?
Q13564-1	1	yes
Q13564-2	2
Q13564-3	3
Q13564-4	4

RefSeq proteins (4): NP_001018169, NP_001018170, NP_001273429, NP_003896* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000594	ThiF_NAD_FAD-bd	Domain
IPR030667	APP-BP1	Family
IPR035985	Ubiquitin-activating_enz	Homologous_superfamily
IPR045886	ThiF/MoeB/HesA	Family

Pfam: PF00899

Enzyme classification (BRENDA):

• EC 6.2.1.64 — E1 NEDD8-activating enzyme (BRENDA: 5 organisms, 13 substrates, 51 inhibitors, 16 Km, 7 kcat entries)

Substrate kinetics (BRENDA)

3 substrates with measured Km, best-characterized 3. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ATP	0.0045–0.175	9
DIPHOSPHATE	0.005–0.0511	4
UBIQUITIN	0.0006–0.0012	3

UniProt features (67 total): helix 26, strand 15, turn 8, sequence variant 5, modified residue 3, splice variant 3, sequence conflict 2, initiator methionine 1, chain 1, mutagenesis site 1, region of interest 1, site 1

Structure

Experimental structures (PDB)

9 structures.

PDB	Method	Resolution (Å)
1TT5	X-RAY DIFFRACTION	2.6
1YOV	X-RAY DIFFRACTION	2.6
2NVU	X-RAY DIFFRACTION	2.8
3DBH	X-RAY DIFFRACTION	2.85
3DBL	X-RAY DIFFRACTION	2.9
1R4M	X-RAY DIFFRACTION	3
3GZN	X-RAY DIFFRACTION	3
3DBR	X-RAY DIFFRACTION	3.05
1R4N	X-RAY DIFFRACTION	3.6

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q13564-F1	96.27	0.94

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): 211 (interaction with uba3)

Post-translational modifications (3): 2, 6, 341

Mutagenesis-validated functional residues (1):

Position	Phenotype
331	impairs the formation of the nedd8-uba3 thioester.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-8951664	Neddylation

MSigDB gene sets: 285 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_BRAIN_TUMORAL_MACROPHAGE_DN, GSE18804_SPLEEN_MACROPHAGE_VS_TUMORAL_MACROPHAGE_DN, MORF_DNMT1, chr16q22, PAX4_01, TGCGCANK_UNKNOWN, GOBP_SYNAPSE_ASSEMBLY, GOBP_CELL_CYCLE_PHASE_TRANSITION, MORF_RRM1, MORF_CDK2, GOBP_PROTEIN_NEDDYLATION, GOBP_REGULATION_OF_CELL_JUNCTION_ASSEMBLY, TGACCTY_ERR1_Q2, MORF_HDAC2, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS

GO Biological Process (8): signal transduction (GO:0007165), mitotic DNA replication checkpoint signaling (GO:0033314), regulation of apoptotic process (GO:0042981), regulation of neuron apoptotic process (GO:0043523), protein neddylation (GO:0045116), neuron apoptotic process (GO:0051402), regulation of postsynapse assembly (GO:0150052), apoptotic process (GO:0006915)

GO Molecular Function (5): NEDD8 activating enzyme activity (GO:0019781), ubiquitin protein ligase binding (GO:0031625), protein heterodimerization activity (GO:0046982), protein binding (GO:0005515), ubiquitin-like modifier activating enzyme activity (GO:0008641)

GO Cellular Component (6): cytoplasm (GO:0005737), cytosol (GO:0005829), plasma membrane (GO:0005886), protein-containing complex (GO:0032991), glutamatergic synapse (GO:0098978), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Post-translational protein modification	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
apoptotic process	2
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
DNA replication checkpoint signaling	1
mitotic cell cycle	1
mitotic DNA integrity checkpoint signaling	1
mitotic G2/M transition checkpoint	1
regulation of programmed cell death	1
regulation of apoptotic process	1
neuron apoptotic process	1
protein modification by small protein conjugation	1
regulation of synapse assembly	1
postsynapse assembly	1
regulation of postsynapse organization	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
ubiquitin-like modifier activating enzyme activity	1
ubiquitin-like protein ligase binding	1
protein dimerization activity	1
binding	1
ligase activity, forming carbon-sulfur bonds	1
catalytic activity, acting on a protein	1
ATP-dependent activity	1
intracellular anatomical structure	1
cytoplasm	1
membrane	1
cell periphery	1
cellular_component	1
synapse	1

Protein interactions and networks

STRING

2944 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NAE1	UBE2M	P61081	999
NAE1	UBA3	Q8TBC4	999
NAE1	NEDD8	Q15843	998
NAE1	APP	P05067	986
NAE1	UBE2F	Q969M7	917
NAE1	CUL1	Q13616	813
NAE1	UBA1	P22314	788
NAE1	COPS5	Q92905	752
NAE1	RBX1	P62877	742
NAE1	SENP8	Q96LD8	742
NAE1	CUL4A	Q13619	735
NAE1	DCUN1D1	Q96GG9	721
NAE1	RNF7	Q9UBF6	704
NAE1	MEI1	Q5TIA1	677
NAE1	PSMD14	O00487	625

IntAct

60 interactions, top by confidence:

A	B	Type	Score
NEDD8	UBE2M	psi-mi:“MI:0914”(association)	0.940
NEDD8	NAE1	psi-mi:“MI:0915”(physical association)	0.670
NEDD8	NAE1	psi-mi:“MI:0914”(association)	0.670
FBXO11	TP53	psi-mi:“MI:0567”(neddylation reaction)	0.650
NAE1	UBA3	psi-mi:“MI:0915”(physical association)	0.560
NAE1	HEXB	psi-mi:“MI:0915”(physical association)	0.560
APP	NAE1	psi-mi:“MI:0915”(physical association)	0.560
UBE2M	RHOBTB1	psi-mi:“MI:0914”(association)	0.530
DDX21	MED19	psi-mi:“MI:2364”(proximity)	0.480
TGS1	NAE1	psi-mi:“MI:0915”(physical association)	0.400
	DENR	psi-mi:“MI:0915”(physical association)	0.400
NAE1	rep	psi-mi:“MI:0915”(physical association)	0.370
NAE1	SREBF2	psi-mi:“MI:0915”(physical association)	0.370
NAE1	ALG8	psi-mi:“MI:0915”(physical association)	0.370
PRNP	CARNS1	psi-mi:“MI:0914”(association)	0.350
NEDD8	DDX3X	psi-mi:“MI:0914”(association)	0.350
NEDD8	FBXO21	psi-mi:“MI:0914”(association)	0.350
LRRK2		psi-mi:“MI:0914”(association)	0.350
ZBTB44	NAE1	psi-mi:“MI:0914”(association)	0.350
UIMC1	PYCR3	psi-mi:“MI:0914”(association)	0.350
SAR1B	UBA6	psi-mi:“MI:0914”(association)	0.350
UBE2M	SRPRA	psi-mi:“MI:0914”(association)	0.350
ANKRD39	UBA6	psi-mi:“MI:0914”(association)	0.350

BioGRID (146): NAE1 (Affinity Capture-MS), UBA3 (Reconstituted Complex), UBE2M (Biochemical Activity), UBE2F (Biochemical Activity), NAE1 (Reconstituted Complex), NAE1 (Affinity Capture-MS), NAE1 (Co-fractionation), NAE1 (Co-fractionation), PLOD1 (Co-fractionation), UBA3 (Co-fractionation), UBA5 (Co-fractionation), XRCC6 (Co-fractionation), NAE1 (Affinity Capture-MS), NAE1 (Synthetic Lethality), NAE1 (Affinity Capture-MS)

ESM2 similar proteins: A0AVT1, A3KMX8, A5DLC6, A6H630, A6QXC6, A6ZT79, A7KAI6, G2XR75, I1S0J7, O43069, O94609, P0DI12, P0DI13, P20973, P22178, P22515, P31251, P31252, P38862, P42744, P52495, P79064, P92974, P93028, Q09765, Q13564, Q19360, Q4R3L6, Q54QG9, Q55C16, Q5AWA2, Q5ZIE6, Q6AXB1, Q6CBC3, Q6CXW3, Q6DJA3, Q6NTW6, Q756G8, Q7SXP2, Q8C7R4

Diamond homologs: A0AVT1, A1A4L8, A1CAZ7, A1DED8, A2BDX3, A2R3H4, A2VE14, A5DSR2, A5GFZ6, A6ZT19, A7TEY0, A7THV5, B0Y0P7, B3LSM6, B4GKQ3, B4HYP0, B4JBC4, B4KI53, B4LRB9, B4N7R4, B4NXF7, B5DS72, B5VK45, D4GSF3, O59954, O94609, P0DI12, P0DI13, P12282, P18500, P30138, P38820, P41226, P42744, P46048, P46049, P52495, Q06624, Q12059, Q13564

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
NAE1	“form complex”	NAE	binding
APP	“up-regulates activity”	NAE1	binding
NAE1	up-regulates	Apoptosis
NAE1	up-regulates	Cell_death
TRIP12	“down-regulates quantity by destabilization”	NAE1	ubiquitination

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	0
Uncertain significance	65
Likely benign	5
Benign	0

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
1526415	NM_003905.4(NAE1):c.1289G>A (p.Arg430Gln)	Pathogenic
1526416	NM_003905.4(NAE1):c.882C>G (p.Cys294Trp)	Pathogenic
1676942	NM_003905.4(NAE1):c.147G>C (p.Leu49Phe)	Pathogenic

SpliceAI

3582 predictions. Top by Δscore:

Variant	Effect	Δscore
16:66805827:C:CC	acceptor_gain	1.0000
16:66805910:A:AC	donor_gain	1.0000
16:66805911:C:CA	donor_gain	1.0000
16:66805911:CA:C	donor_gain	1.0000
16:66805911:CAATT:C	donor_gain	1.0000
16:66805955:ATT:A	donor_gain	1.0000
16:66806024:CTC:C	acceptor_gain	1.0000
16:66806026:CCTAA:C	acceptor_loss	1.0000
16:66806027:C:CC	acceptor_gain	1.0000
16:66806027:C:CG	acceptor_loss	1.0000
16:66808614:C:CC	acceptor_gain	1.0000
16:66808980:TATAC:T	donor_loss	1.0000
16:66808981:ATACT:A	donor_loss	1.0000
16:66808982:TACTT:T	donor_loss	1.0000
16:66808983:ACT:A	donor_loss	1.0000
16:66808984:CTTAC:C	donor_loss	1.0000
16:66808985:TT:T	donor_loss	1.0000
16:66808987:A:AC	donor_gain	1.0000
16:66808987:A:T	donor_loss	1.0000
16:66808988:C:A	donor_loss	1.0000
16:66808988:C:CA	donor_gain	1.0000
16:66808988:CT:C	donor_gain	1.0000
16:66808988:CTA:C	donor_gain	1.0000
16:66808988:CTAA:C	donor_gain	1.0000
16:66808988:CTAAT:C	donor_gain	1.0000
16:66809072:CTGC:C	acceptor_gain	1.0000
16:66809076:C:CA	acceptor_loss	1.0000
16:66809076:C:CC	acceptor_gain	1.0000
16:66810372:A:AC	donor_gain	1.0000
16:66810373:C:CC	donor_gain	1.0000

AlphaMissense

3528 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:66826776:A:G	W20R	1.000
16:66826776:A:T	W20R	1.000
16:66803094:T:A	K507I	0.999
16:66826694:T:A	K47I	0.999
16:66826774:C:A	W20C	0.999
16:66826774:C:G	W20C	0.999
16:66830847:C:A	R18M	0.999
16:66830847:C:G	R18T	0.999
16:66803075:A:C	F513L	0.998
16:66803075:A:T	F513L	0.998
16:66803077:A:G	F513L	0.998
16:66805780:C:A	G498W	0.998
16:66805821:C:G	R484P	0.998
16:66810759:C:G	A350P	0.998
16:66813573:A:G	L342P	0.998
16:66813598:C:G	A334P	0.998
16:66816619:C:G	A268P	0.998
16:66826693:T:A	K47N	0.998
16:66826693:T:G	K47N	0.998
16:66826732:G:C	C34W	0.998
16:66826763:C:T	G24E	0.998
16:66826764:C:A	G24W	0.998
16:66826778:A:G	L19S	0.998
16:66826780:C:A	R18S	0.998
16:66826780:C:G	R18S	0.998
16:66830850:A:G	L17P	0.998
16:66830852:C:A	Q16H	0.998
16:66830852:C:G	Q16H	0.998
16:66830856:C:G	R15P	0.998
16:66803093:T:A	K507N	0.997

dbSNP variants (sampled 300 via entrez): RS1000088829 (16:66804828 G>A), RS1000162037 (16:66812323 T>C), RS1000181850 (16:66805127 C>T), RS1000403264 (16:66805648 AAAAG>A), RS1000448077 (16:66819002 A>G), RS1000520852 (16:66806786 G>A,T), RS1000681158 (16:66806769 TTATATC>T), RS1000911985 (16:66832550 C>G), RS1000983404 (16:66832866 G>A), RS1001165401 (16:66813059 G>A), RS1001285046 (16:66830590 T>A,C), RS1001390909 (16:66825118 A>C), RS1001424026 (16:66826359 A>G), RS1002035954 (16:66812949 G>A,C), RS1002047742 (16:66813168 G>C)

Disease associations

OMIM: gene MIM:603385 | disease phenotypes: MIM:620210

GenCC curated gene-disease

Disease	Classification	Inheritance
neurodevelopmental disorder with dysmorphic facies and ischiopubic hypoplasia	Strong	Autosomal recessive

Mondo (1): neurodevelopmental disorder with dysmorphic facies and ischiopubic hypoplasia (MONDO:0859361)

Orphanet (0):

HPO phenotypes

26 total (26 of 26 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000010	Recurrent urinary tract infections
HP:0000175	Cleft palate
HP:0001250	Seizure
HP:0001252	Hypotonia
HP:0001263	Global developmental delay
HP:0001373	Joint dislocation
HP:0001382	Joint hypermobility
HP:0001387	Joint stiffness
HP:0001581	Recurrent skin infections
HP:0001629	Ventricular septal defect
HP:0001680	Coarctation of aorta
HP:0001744	Splenomegaly
HP:0001882	Decreased total leukocyte count
HP:0001888	Decreased total lymphocyte count
HP:0002079	Hypoplasia of the corpus callosum
HP:0002119	Ventriculomegaly
HP:0002180	Neurodegeneration
HP:0002188	Delayed CNS myelination
HP:0002205	Recurrent respiratory infections
HP:0002240	Hepatomegaly
HP:0002850	Decreased circulating total IgM
HP:0004315	Decreased circulating IgG concentration
HP:0004322	Short stature
HP:0004349	Reduced bone mineral density
HP:0008897	Postnatal growth retardation

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST010241_8	Apolipoprotein A1 levels	3.000000e-19
GCST010242_2	HDL cholesterol levels	2.000000e-18

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004614	apolipoprotein A 1 measurement
EFO:0004612	high density lipoprotein cholesterol measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL2016431 (SINGLE PROTEIN), CHEMBL3831283 (PROTEIN COMPLEX)

Molecules with ChEMBL bioactivity

3 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 179,552 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1014	CANDESARTAN CILEXETIL	4	11,194
CHEMBL58	MITOXANTRONE	4	166,878
CHEMBL1231160	PEVONEDISTAT	3	1,480

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

Binding affinities (BindingDB)

5 measured of 22 human assays (22 total across all organisms); most potent 5 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
[4-[4-(2,3-dihydro-1H-inden-1-ylamino)pyrrolo[2,3-d]pyrimidin-7-yl]-2-hydroxycyclopentyl]methyl sulfamate	IC50	12 nM	US-9963456: Pyrrolopyrimidine compound or salt thereof and compositions containing the pyrrolopyrimidine compound or salt thereof
[2-hydroxy-4-[7-(2-thiophen-2-ylethylamino)triazolo[4,5-d]pyrimidin-3-yl]cyclopentyl]methyl sulfamate	IC50	550 nM	US-12378251: Triazolopyrimidine compound and salt, composition and use thereof
[2-hydroxy-4-[7-(3-phenylpropylamino)triazolo[4,5-d]pyrimidin-3-yl]cyclopentyl]methyl sulfamate	IC50	550 nM	US-12378251: Triazolopyrimidine compound and salt, composition and use thereof
[2-hydroxy-4-[7-[[(1R,2S)-2-[(2-methoxyacetyl)amino]-2,3-dihydro-1H-inden-1-yl]amino]triazolo[4,5-d]pyrimidin-3-yl]cyclopentyl]methyl sulfamate	IC50	550 nM	US-12378251: Triazolopyrimidine compound and salt, composition and use thereof
[2-hydroxy-4-[7-[[(1S)-1’-methylspiro[1,2-dihydroindene-3,4’-piperidine]-1-yl]amino]triazolo[4,5-d]pyrimidin-3-yl]cyclopentyl]methyl sulfamate	IC50	550 nM	US-12378251: Triazolopyrimidine compound and salt, composition and use thereof

ChEMBL bioactivities

185 potent at pChembl≥5 of 189 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.70	IC50	0.02	nM	CHEMBL5170838
9.68	IC50	0.21	nM	CHEMBL5182746
9.59	IC50	0.26	nM	PEVONEDISTAT
9.30	IC50	0.5	nM	CHEMBL5177755
9.26	IC50	0.55	nM	CHEMBL5177755
9.24	IC50	0.57	nM	CHEMBL5206652
9.22	IC50	0.6	nM	CHEMBL4569826
9.05	IC50	0.9	nM	CHEMBL4582044
9.02	IC50	0.955	nM	CHEMBL5175806
9.00	IC50	1	nM	CHEMBL5181979
8.65	IC50	2.23	nM	CHEMBL5173723
8.64	IC50	2.28	nM	CHEMBL5192493
8.45	IC50	3.56	nM	CHEMBL5197178
8.40	IC50	4	nM	PEVONEDISTAT
8.40	IC50	4	nM	CHEMBL5633567
8.38	IC50	4.2	nM	CHEMBL5209054
8.33	IC50	4.7	nM	CHEMBL2322194
8.30	IC50	5	nM	CHEMBL4577730
8.24	IC50	5.77	nM	CHEMBL5188530
8.22	IC50	6	nM	CHEMBL5193236
8.21	IC50	6.11	nM	CHEMBL5177700
8.10	IC50	8	nM	CHEMBL4585101
8.10	IC50	8	nM	CHEMBL5181979
8.01	IC50	9.76	nM	CHEMBL5178136
8.00	IC50	10	nM	CHEMBL2017005
8.00	IC50	10	nM	CHEMBL4573232
8.00	IC50	10	nM	CHEMBL4847817
8.00	IC50	9.98	nM	CHEMBL5192527
7.92	IC50	12	nM	CHEMBL4514025
7.89	IC50	13	nM	CHEMBL4580824
7.82	IC50	15	nM	CHEMBL4558498
7.80	IC50	15.9	nM	CHEMBL5169743
7.72	IC50	19	nM	CHEMBL4566409
7.70	IC50	20	nM	CHEMBL4570552
7.68	IC50	21.1	nM	CHEMBL5170141
7.68	IC50	21.1	nM	CHEMBL5179467
7.66	IC50	22	nM	CHEMBL4521457
7.64	IC50	23	nM	CHEMBL4860740
7.54	IC50	29	nM	CHEMBL4878088
7.52	EC50	30	nM	PEVONEDISTAT
7.51	IC50	31	nM	CHEMBL4878832
7.51	IC50	30.6	nM	CHEMBL5207989
7.50	IC50	32	nM	CHEMBL4852015
7.50	IC50	32	nM	CHEMBL4860960
7.43	IC50	37	nM	CHEMBL4561991
7.19	IC50	64	nM	CHEMBL4853360
7.19	IC50	64	nM	CHEMBL4848442
7.17	IC50	66.9	nM	CHEMBL5201960
7.09	IC50	81.8	nM	CHEMBL5206633
7.09	IC50	80.9	nM	CHEMBL5206263

PubChem BioAssay actives

104 with measured affinity, of 289 total; 50 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
[(1S,2S,4R)-4-[7-[[(1S)-1’-(tert-butylcarbamoyl)spiro[1,2-dihydroindene-3,4’-piperidine]-1-yl]amino]triazolo[4,5-d]pyrimidin-3-yl]-2-hydroxycyclopentyl]methyl sulfamate	1894757: Inhibition of NAE (unknown origin) mediated neddylation assessed as decrease in NEDD8-Ubcl2 adduct formation incubated for 2 hrs in presence of L-glutathione and ATP by HTRF assay	ic50	<0.0001	uM
[(1S,2S,4R)-4-[7-[[(1S)-2,3-dihydro-1H-inden-1-yl]amino]triazolo[4,5-d]pyrimidin-3-yl]-2-hydroxycyclopentyl]methyl sulfamate	1894757: Inhibition of NAE (unknown origin) mediated neddylation assessed as decrease in NEDD8-Ubcl2 adduct formation incubated for 2 hrs in presence of L-glutathione and ATP by HTRF assay	ic50	0.0002	uM
[(1S,2S,4R)-4-[4-[[(1S)-2,3-dihydro-1H-inden-1-yl]amino]pyrrolo[2,3-d]pyrimidin-7-yl]-2-hydroxycyclopentyl]methyl sulfamate	1894757: Inhibition of NAE (unknown origin) mediated neddylation assessed as decrease in NEDD8-Ubcl2 adduct formation incubated for 2 hrs in presence of L-glutathione and ATP by HTRF assay	ic50	0.0003	uM
methyl (1S)-1-[[3-[(1R,3S,4S)-3-hydroxy-4-(sulfamoyloxymethyl)cyclopentyl]triazolo[4,5-d]pyrimidin-7-yl]amino]spiro[1,2-dihydroindene-3,4’-piperidine]-1’-carboxylate	1872487: Inhibition of NAE (unknown origin)	ic50	0.0005	uM
[(3R)-oxolan-3-yl] (1S)-1-[[3-[(1R,3S,4S)-3-hydroxy-4-(sulfamoyloxymethyl)cyclopentyl]triazolo[4,5-d]pyrimidin-7-yl]amino]spiro[1,2-dihydroindene-3,4’-piperidine]-1’-carboxylate	1894757: Inhibition of NAE (unknown origin) mediated neddylation assessed as decrease in NEDD8-Ubcl2 adduct formation incubated for 2 hrs in presence of L-glutathione and ATP by HTRF assay	ic50	0.0006	uM
4-amino-7-[(2R,3R,4S,5R)-3,4-dihydroxy-5-[(sulfamoylamino)methyl]oxolan-2-yl]-5-[2-(2-ethoxy-6-fluorophenyl)ethynyl]pyrrolo[2,3-d]pyrimidine	1872481: Inhibition of recombinant human APPBP1/UBA3 expressed in Escherichia coli assessed as Ub/Ubl thioester transfer	ic50	0.0010	uM
[(2R,3S,4R,5R)-5-[4-amino-5-[2-(2-ethoxy-6-fluorophenyl)ethynyl]pyrrolo[2,3-d]pyrimidin-7-yl]-3,4-dihydroxyoxolan-2-yl]methyl sulfamate	1894758: Inhibition of NAE (unknown origin)	ic50	0.0010	uM
ethyl (1S)-1-[[3-[(1R,3S,4S)-3-hydroxy-4-(sulfamoyloxymethyl)cyclopentyl]triazolo[4,5-d]pyrimidin-7-yl]amino]spiro[1,2-dihydroindene-3,4’-piperidine]-1’-carboxylate	1894757: Inhibition of NAE (unknown origin) mediated neddylation assessed as decrease in NEDD8-Ubcl2 adduct formation incubated for 2 hrs in presence of L-glutathione and ATP by HTRF assay	ic50	0.0022	uM
[(1S,2S,4R)-2-hydroxy-4-[7-[[(1R,2S)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]amino]triazolo[4,5-d]pyrimidin-3-yl]cyclopentyl]methyl sulfamate	1894757: Inhibition of NAE (unknown origin) mediated neddylation assessed as decrease in NEDD8-Ubcl2 adduct formation incubated for 2 hrs in presence of L-glutathione and ATP by HTRF assay	ic50	0.0023	uM
[(1S,2S,4R)-2-hydroxy-4-[7-[[(1R,2S)-2-(2-methoxyethoxy)-2,3-dihydro-1H-inden-1-yl]amino]triazolo[4,5-d]pyrimidin-3-yl]cyclopentyl]methyl sulfamate	1894757: Inhibition of NAE (unknown origin) mediated neddylation assessed as decrease in NEDD8-Ubcl2 adduct formation incubated for 2 hrs in presence of L-glutathione and ATP by HTRF assay	ic50	0.0036	uM
4-amino-7-[(2S,3S,4R,5S)-3,4-dihydroxy-5-[(sulfamoylamino)methyl]oxolan-2-yl]-5-[2-(2-ethoxy-6-fluorophenyl)ethynyl]pyrrolo[2,3-d]pyrimidine	2139635: Inhibition of NAE (unknown origin)	ic50	0.0040	uM
propan-2-yl (1S)-1-[[3-[(1R,3S,4S)-3-hydroxy-4-(sulfamoyloxymethyl)cyclopentyl]triazolo[4,5-d]pyrimidin-7-yl]amino]spiro[1,2-dihydroindene-3,4’-piperidine]-1’-carboxylate	1894757: Inhibition of NAE (unknown origin) mediated neddylation assessed as decrease in NEDD8-Ubcl2 adduct formation incubated for 2 hrs in presence of L-glutathione and ATP by HTRF assay	ic50	0.0042	uM
[(1S,2S,4R)-4-[4-[[(1S)-2,3-dihydro-1H-inden-1-yl]amino]-5,6-dihydropyrrolo[2,3-d]pyrimidin-7-yl]-2-hydroxycyclopentyl]methyl sulfamate	727128: Inhibition of NAE (unknown origin)	ic50	0.0047	uM
[(1S,2S,4R)-2-hydroxy-4-[7-[[(1S)-1’-(2-methoxyacetyl)spiro[1,2-dihydroindene-3,4’-piperidine]-1-yl]amino]triazolo[4,5-d]pyrimidin-3-yl]cyclopentyl]methyl sulfamate	1894757: Inhibition of NAE (unknown origin) mediated neddylation assessed as decrease in NEDD8-Ubcl2 adduct formation incubated for 2 hrs in presence of L-glutathione and ATP by HTRF assay	ic50	0.0058	uM
2-fluoroethyl (1S)-1-[[3-[(1R,3S,4S)-3-hydroxy-4-(sulfamoyloxymethyl)cyclopentyl]triazolo[4,5-d]pyrimidin-7-yl]amino]spiro[1,2-dihydroindene-3,4’-piperidine]-1’-carboxylate	1894757: Inhibition of NAE (unknown origin) mediated neddylation assessed as decrease in NEDD8-Ubcl2 adduct formation incubated for 2 hrs in presence of L-glutathione and ATP by HTRF assay	ic50	0.0060	uM
[(1S,2S,4R)-4-[7-[(2-fluorophenyl)methylamino]triazolo[4,5-d]pyrimidin-3-yl]-2-hydroxycyclopentyl]methyl sulfamate	1894757: Inhibition of NAE (unknown origin) mediated neddylation assessed as decrease in NEDD8-Ubcl2 adduct formation incubated for 2 hrs in presence of L-glutathione and ATP by HTRF assay	ic50	0.0061	uM
tert-butyl (1S)-1-[[3-[(1R,3S,4S)-3-hydroxy-4-(sulfamoyloxymethyl)cyclopentyl]triazolo[4,5-d]pyrimidin-7-yl]amino]spiro[1,2-dihydroindene-3,4’-piperidine]-1’-carboxylate	1894757: Inhibition of NAE (unknown origin) mediated neddylation assessed as decrease in NEDD8-Ubcl2 adduct formation incubated for 2 hrs in presence of L-glutathione and ATP by HTRF assay	ic50	0.0098	uM
[(2R,3S,4R,5R)-5-[6-[[(1S)-2,3-dihydro-1H-inden-1-yl]amino]purin-9-yl]-3,4-dihydroxyoxolan-2-yl]methyl sulfamate	1894758: Inhibition of NAE (unknown origin)	ic50	0.0100	uM
[(1R,2S,4R)-4-[[5-[1-[(3-bromophenyl)methyl]pyrrole-3-carbonyl]pyrimidin-4-yl]amino]-2-hydroxycyclopentyl]methyl sulfamate	1775497: Inhibition of recombinant NAE (unknown origin) in presence of ATP at Km concentration by HTRF assay	ic50	0.0100	uM
2-morpholin-4-ylethyl (1S)-1-[[3-[(1R,3S,4S)-3-hydroxy-4-(sulfamoyloxymethyl)cyclopentyl]triazolo[4,5-d]pyrimidin-7-yl]amino]spiro[1,2-dihydroindene-3,4’-piperidine]-1’-carboxylate	1894757: Inhibition of NAE (unknown origin) mediated neddylation assessed as decrease in NEDD8-Ubcl2 adduct formation incubated for 2 hrs in presence of L-glutathione and ATP by HTRF assay	ic50	0.0100	uM
[(1S,2S,4R)-2-hydroxy-4-[7-(thiophen-2-ylmethylamino)triazolo[4,5-d]pyrimidin-3-yl]cyclopentyl]methyl sulfamate	1894757: Inhibition of NAE (unknown origin) mediated neddylation assessed as decrease in NEDD8-Ubcl2 adduct formation incubated for 2 hrs in presence of L-glutathione and ATP by HTRF assay	ic50	0.0159	uM
[(1S,2S,4R)-4-[7-(hexylamino)triazolo[4,5-d]pyrimidin-3-yl]-2-hydroxycyclopentyl]methyl sulfamate	1894757: Inhibition of NAE (unknown origin) mediated neddylation assessed as decrease in NEDD8-Ubcl2 adduct formation incubated for 2 hrs in presence of L-glutathione and ATP by HTRF assay	ic50	0.0211	uM
1,1,1,3,3,3-hexafluoropropan-2-yl (1S)-1-[[3-[(1R,3S,4S)-3-hydroxy-4-(sulfamoyloxymethyl)cyclopentyl]triazolo[4,5-d]pyrimidin-7-yl]amino]spiro[1,2-dihydroindene-3,4’-piperidine]-1’-carboxylate	1894757: Inhibition of NAE (unknown origin) mediated neddylation assessed as decrease in NEDD8-Ubcl2 adduct formation incubated for 2 hrs in presence of L-glutathione and ATP by HTRF assay	ic50	0.0211	uM
[(1R,2S,4R)-4-[[5-(1-benzylpyrrole-3-carbonyl)pyrimidin-4-yl]amino]-2-hydroxycyclopentyl]methyl sulfamate	1775497: Inhibition of recombinant NAE (unknown origin) in presence of ATP at Km concentration by HTRF assay	ic50	0.0230	uM
[(1R,2R,3S,4R)-4-[[5-(1-benzylpyrazole-3-carbonyl)pyrimidin-4-yl]amino]-2,3-dihydroxycyclopentyl]methyl sulfamate	1775497: Inhibition of recombinant NAE (unknown origin) in presence of ATP at Km concentration by HTRF assay	ic50	0.0290	uM
[(1S,2S,4R)-4-[7-(furan-2-ylmethylamino)triazolo[4,5-d]pyrimidin-3-yl]-2-hydroxycyclopentyl]methyl sulfamate	1894757: Inhibition of NAE (unknown origin) mediated neddylation assessed as decrease in NEDD8-Ubcl2 adduct formation incubated for 2 hrs in presence of L-glutathione and ATP by HTRF assay	ic50	0.0306	uM
[(1R,2R,3S,4R)-4-[[5-[4-[1-(6-bromo-2-pyridinyl)-1-hydroxyethyl]thiophene-2-carbonyl]pyrimidin-4-yl]amino]-2,3-dihydroxycyclopentyl]methyl sulfamate	1775497: Inhibition of recombinant NAE (unknown origin) in presence of ATP at Km concentration by HTRF assay	ic50	0.0310	uM
[(1R,2S,4R)-2-hydroxy-4-[[5-(1-phenylpyrazole-3-carbonyl)pyrimidin-4-yl]amino]cyclopentyl]methyl sulfamate	1775497: Inhibition of recombinant NAE (unknown origin) in presence of ATP at Km concentration by HTRF assay	ic50	0.0320	uM
[(1R,2S,4R)-4-[[5-[4-[(3-chlorophenyl)methyl]-5-methylthiophene-2-carbonyl]pyrimidin-4-yl]amino]-2-hydroxycyclopentyl]methyl sulfamate	1775497: Inhibition of recombinant NAE (unknown origin) in presence of ATP at Km concentration by HTRF assay	ic50	0.0320	uM
[(1R,2S,4R)-4-[[5-[4-[(3-chlorophenyl)-hydroxymethyl]-5-methylthiophene-2-carbonyl]pyrimidin-4-yl]amino]-2-hydroxycyclopentyl]methyl sulfamate	1775497: Inhibition of recombinant NAE (unknown origin) in presence of ATP at Km concentration by HTRF assay	ic50	0.0640	uM
[(1R,2S,4R)-4-[[5-[4-[(3-chlorophenyl)methyl]thiophene-2-carbonyl]pyrimidin-4-yl]amino]-2-hydroxycyclopentyl]methyl sulfamate	1775497: Inhibition of recombinant NAE (unknown origin) in presence of ATP at Km concentration by HTRF assay	ic50	0.0640	uM
[(1S,2S,4R)-2-hydroxy-4-[7-[[(1S)-spiro[1,2-dihydroindene-3,4’-piperidine]-1-yl]amino]triazolo[4,5-d]pyrimidin-3-yl]cyclopentyl]methyl sulfamate	1894757: Inhibition of NAE (unknown origin) mediated neddylation assessed as decrease in NEDD8-Ubcl2 adduct formation incubated for 2 hrs in presence of L-glutathione and ATP by HTRF assay	ic50	0.0669	uM
methyl (1R,4S)-4-[[3-[(1R,3S,4S)-3-hydroxy-4-(sulfamoyloxymethyl)cyclopentyl]triazolo[4,5-d]pyrimidin-7-yl]amino]cyclopent-2-ene-1-carboxylate	1894757: Inhibition of NAE (unknown origin) mediated neddylation assessed as decrease in NEDD8-Ubcl2 adduct formation incubated for 2 hrs in presence of L-glutathione and ATP by HTRF assay	ic50	0.0809	uM
[(1S,2S,4R)-2-hydroxy-4-[7-(2-phenylethylamino)triazolo[4,5-d]pyrimidin-3-yl]cyclopentyl]methyl sulfamate	1894757: Inhibition of NAE (unknown origin) mediated neddylation assessed as decrease in NEDD8-Ubcl2 adduct formation incubated for 2 hrs in presence of L-glutathione and ATP by HTRF assay	ic50	0.0818	uM
[(1R,2S,4R)-4-[[5-[4-(7-chloro-3,4-dihydro-1H-isochromen-1-yl)-5-methylthiophene-2-carbonyl]pyrimidin-4-yl]amino]-2-hydroxycyclopentyl]methyl sulfamate	1775497: Inhibition of recombinant NAE (unknown origin) in presence of ATP at Km concentration by HTRF assay	ic50	0.0870	uM
[(1R,2S,4R)-4-[[5-[4-[(3-bromophenyl)methyl]thiophene-2-carbonyl]pyrimidin-4-yl]amino]-2-hydroxycyclopentyl]methyl sulfamate	1775497: Inhibition of recombinant NAE (unknown origin) in presence of ATP at Km concentration by HTRF assay	ic50	0.0910	uM
[(1R,2S,4R)-4-[[5-[4-(3,4-dihydro-1H-isochromen-1-yl)-5-methylthiophene-2-carbonyl]pyrimidin-4-yl]amino]-2-hydroxycyclopentyl]methyl sulfamate	1775497: Inhibition of recombinant NAE (unknown origin) in presence of ATP at Km concentration by HTRF assay	ic50	0.1020	uM
[(1S,2S,4R)-2-hydroxy-4-[7-(2-thiophen-2-ylethylamino)triazolo[4,5-d]pyrimidin-3-yl]cyclopentyl]methyl sulfamate	1894757: Inhibition of NAE (unknown origin) mediated neddylation assessed as decrease in NEDD8-Ubcl2 adduct formation incubated for 2 hrs in presence of L-glutathione and ATP by HTRF assay	ic50	0.1070	uM
[(1R,2S,4R)-4-[[5-[4-[(3-chlorophenyl)-hydroxymethyl]thiophene-2-carbonyl]pyrimidin-4-yl]amino]-2-hydroxycyclopentyl]methyl sulfamate	1775497: Inhibition of recombinant NAE (unknown origin) in presence of ATP at Km concentration by HTRF assay	ic50	0.1140	uM
1,3-dihydroxypropan-2-yl (1S)-1-[[3-[(1R,3S,4S)-3-hydroxy-4-(sulfamoyloxymethyl)cyclopentyl]triazolo[4,5-d]pyrimidin-7-yl]amino]spiro[1,2-dihydroindene-3,4’-piperidine]-1’-carboxylate	1894757: Inhibition of NAE (unknown origin) mediated neddylation assessed as decrease in NEDD8-Ubcl2 adduct formation incubated for 2 hrs in presence of L-glutathione and ATP by HTRF assay	ic50	0.1200	uM
[(1R,2S,4R)-4-[[5-(1-benzylpyrazole-4-carbonyl)pyrimidin-4-yl]amino]-2-hydroxycyclopentyl]methyl sulfamate	1775497: Inhibition of recombinant NAE (unknown origin) in presence of ATP at Km concentration by HTRF assay	ic50	0.1220	uM
[(1S,2S,4R)-2-hydroxy-4-[7-(3-phenylpropylamino)triazolo[4,5-d]pyrimidin-3-yl]cyclopentyl]methyl sulfamate	1894757: Inhibition of NAE (unknown origin) mediated neddylation assessed as decrease in NEDD8-Ubcl2 adduct formation incubated for 2 hrs in presence of L-glutathione and ATP by HTRF assay	ic50	0.1490	uM
[(1S,2S,4R)-2-hydroxy-4-[7-[[(1R,2S)-2-[(2-methoxyacetyl)amino]-2,3-dihydro-1H-inden-1-yl]amino]triazolo[4,5-d]pyrimidin-3-yl]cyclopentyl]methyl sulfamate	1894757: Inhibition of NAE (unknown origin) mediated neddylation assessed as decrease in NEDD8-Ubcl2 adduct formation incubated for 2 hrs in presence of L-glutathione and ATP by HTRF assay	ic50	0.1700	uM
[(1S,2S,4R)-2-hydroxy-4-[7-[[(1S)-1’-methylspiro[1,2-dihydroindene-3,4’-piperidine]-1-yl]amino]triazolo[4,5-d]pyrimidin-3-yl]cyclopentyl]methyl sulfamate	1894757: Inhibition of NAE (unknown origin) mediated neddylation assessed as decrease in NEDD8-Ubcl2 adduct formation incubated for 2 hrs in presence of L-glutathione and ATP by HTRF assay	ic50	0.1870	uM
[(1R,2S,4R)-4-[[5-(1-benzylpyrazole-3-carbonyl)pyrimidin-4-yl]amino]-2-hydroxycyclopentyl]methyl sulfamate	1775497: Inhibition of recombinant NAE (unknown origin) in presence of ATP at Km concentration by HTRF assay	ic50	0.1900	uM
[(1R,2S,4R)-4-[[5-[4-[(1R)-3,4-dihydro-1H-isochromen-1-yl]thiophene-2-carbonyl]pyrimidin-4-yl]amino]-2-hydroxycyclopentyl]methyl sulfamate	1775497: Inhibition of recombinant NAE (unknown origin) in presence of ATP at Km concentration by HTRF assay	ic50	0.1980	uM
[(1R,2S,4R)-4-[[5-[4-(2-chloro-6,8-dihydro-5H-pyrano[3,4-b]pyridin-8-yl)-5-methylthiophene-2-carbonyl]pyrimidin-4-yl]amino]-2-hydroxycyclopentyl]methyl sulfamate	1775497: Inhibition of recombinant NAE (unknown origin) in presence of ATP at Km concentration by HTRF assay	ic50	0.2030	uM
[(1S,2S,4R)-4-[7-[[(1R,2S)-2-(dimethylamino)-2,3-dihydro-1H-inden-1-yl]amino]triazolo[4,5-d]pyrimidin-3-yl]-2-hydroxycyclopentyl]methyl sulfamate	1894757: Inhibition of NAE (unknown origin) mediated neddylation assessed as decrease in NEDD8-Ubcl2 adduct formation incubated for 2 hrs in presence of L-glutathione and ATP by HTRF assay	ic50	0.2070	uM
[(1R,2S,4R)-4-[[5-[1-[(2-chlorophenyl)methyl]pyrazole-3-carbonyl]pyrimidin-4-yl]amino]-2-hydroxycyclopentyl]methyl sulfamate	1775497: Inhibition of recombinant NAE (unknown origin) in presence of ATP at Km concentration by HTRF assay	ic50	0.2150	uM
[(1S,2S,4R)-4-[[6-[[(1S)-2,3-dihydro-1H-inden-1-yl]amino]-5-fluoropyrimidin-4-yl]amino]-2-hydroxycyclopentyl]methyl sulfamate	1894757: Inhibition of NAE (unknown origin) mediated neddylation assessed as decrease in NEDD8-Ubcl2 adduct formation incubated for 2 hrs in presence of L-glutathione and ATP by HTRF assay	ic50	0.2190	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, increases expression	3
Valproic Acid	affects expression, decreases expression, increases methylation	3
sodium arsenite	decreases expression	2
Air Pollutants	affects expression, increases abundance, decreases expression	2
Tretinoin	increases reaction, decreases expression	2
aristolochic acid I	decreases expression, increases expression	1
dicrotophos	decreases expression	1
2,4,6-tribromophenol	increases expression	1
triphenyl phosphate	affects expression	1
uranyl acetate	affects expression	1
decabromobiphenyl ether	increases expression	1
afimoxifene	affects response to substance	1
cobaltous chloride	decreases expression	1
tetrabromobisphenol A	increases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
CGP 52608	affects binding, increases reaction	1
erucylphospho-N,N,N-trimethylpropylammonium	decreases expression	1
nutlin 3	affects cotreatment, increases secretion	1
abrine	decreases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
hexabrominated diphenyl ether 153	increases expression	1
bisphenol S	increases expression	1
7-(benzylamino)-1,3,4,8-tetrahydropyrrolo(4,3,2-de)quinolin-8(1H)-one	decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Dactinomycin	affects cotreatment, increases secretion	1
Dinitrochlorobenzene	affects binding	1
Hydrogen Peroxide	affects expression	1
Ivermectin	decreases expression	1
Ozone	affects expression, increases abundance	1

ChEMBL screening assays

134 unique, capped per target: 134 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2019641	Binding	Inhibition of APPBP1-mediated NEDD8 activation at 10 mM after 1.5 hrs by Western blot analysis	Identification of NAE Inhibitors Exhibiting Potent Activity in Leukemia Cells: Exploring the Structural Determinants of NAE Specificity. — ACS Med Chem Lett

Clinical trials (associated diseases)

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