SAE1

Summary

SAE1 (SUMO1 activating enzyme subunit 1, HGNC:30660) is a protein-coding gene on chromosome 19q13.32, encoding SUMO-activating enzyme subunit 1 (Q9UBE0). The heterodimer acts as an E1 ligase for SUMO1, SUMO2, SUMO3, and probably SUMO4. It is a common-essential gene (DepMap: required in 98.7% of cancer cell lines).

Posttranslational modification of proteins by the addition of the small protein SUMO (see SUMO1; MIM 601912), or sumoylation, regulates protein structure and intracellular localization. SAE1 and UBA2 (MIM 613295) form a heterodimer that functions as a SUMO-activating enzyme for the sumoylation of proteins (Okuma et al., 1999 [PubMed 9920803]).

Source: NCBI Gene 10055 — RefSeq curated summary.

At a glance

• GWAS associations: 13
• Clinical variants (ClinVar): 62 total
• Druggable target: yes — 3 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 98.7% of screened cell lines (common-essential)
• MANE Select transcript: NM_005500

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30660
Approved symbol	SAE1
Name	SUMO1 activating enzyme subunit 1
Location	19q13.32
Locus type	gene with protein product
Status	Approved
Aliases	AOS1, FLJ3091, Sua1
Ensembl gene	ENSG00000142230
Ensembl biotype	protein_coding
OMIM	613294
Entrez	10055

Gene structure

Transcript identifiers

Ensembl transcripts: 30 — 25 protein_coding, 5 nonsense_mediated_decay

ENST00000270225, ENST00000392776, ENST00000413379, ENST00000414294, ENST00000594144, ENST00000594526, ENST00000596995, ENST00000597808, ENST00000598840, ENST00000600706, ENST00000600753, ENST00000659110, ENST00000660039, ENST00000664120, ENST00000906414, ENST00000906415, ENST00000906416, ENST00000906417, ENST00000906418, ENST00000906419, ENST00000924096, ENST00000924097, ENST00000924098, ENST00000924099, ENST00000924100, ENST00000924101, ENST00000924102, ENST00000924103, ENST00000924104, ENST00000965680

RefSeq mRNA: 3 — MANE Select: NM_005500 NM_001145713, NM_001145714, NM_005500

CCDS: CCDS12696, CCDS54284, CCDS54285

Canonical transcript exons

ENST00000270225 — 9 exons

Exon	Start	End
ENSE00003031595	47130835	47131028
ENSE00003470630	47169818	47169923
ENSE00003475863	47152898	47153040
ENSE00003484649	47150202	47150375
ENSE00003537997	47197233	47197377
ENSE00003578598	47203671	47203740
ENSE00003589118	47143494	47143605
ENSE00003686620	47155114	47155213
ENSE00003893781	47209159	47210636

Expression profiles

Bgee: expression breadth ubiquitous, 284 present calls, max score 98.18.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 55.6000 / max 598.3145, expressed in 1825 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
176629	46.3346	1824
176630	8.7232	1725
176628	0.5423	240

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ventricular zone	UBERON:0003053	98.18	gold quality
ganglionic eminence	UBERON:0004023	97.57	gold quality
muscle layer of sigmoid colon	UBERON:0035805	97.27	gold quality
embryo	UBERON:0000922	97.26	gold quality
lower esophagus muscularis layer	UBERON:0035833	96.76	gold quality
lower esophagus	UBERON:0013473	96.74	gold quality
stromal cell of endometrium	CL:0002255	96.59	gold quality
left testis	UBERON:0004533	96.47	gold quality
right testis	UBERON:0004534	96.47	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	96.43	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	96.43	gold quality
cortical plate	UBERON:0005343	96.12	gold quality
oocyte	CL:0000023	95.97	gold quality
prefrontal cortex	UBERON:0000451	95.92	gold quality
smooth muscle tissue	UBERON:0001135	95.89	gold quality
testis	UBERON:0000473	95.56	gold quality
popliteal artery	UBERON:0002250	95.46	gold quality
tibial artery	UBERON:0007610	95.46	gold quality
right frontal lobe	UBERON:0002810	95.30	gold quality
mucosa of stomach	UBERON:0001199	95.14	gold quality
rectum	UBERON:0001052	95.11	gold quality
calcaneal tendon	UBERON:0003701	95.09	gold quality
esophagus	UBERON:0001043	94.93	gold quality
aorta	UBERON:0000947	94.88	gold quality
anterior cingulate cortex	UBERON:0009835	94.75	gold quality
cingulate cortex	UBERON:0003027	94.73	gold quality
right lobe of thyroid gland	UBERON:0001119	94.68	gold quality
left uterine tube	UBERON:0001303	94.63	gold quality
adult organism	UBERON:0007023	94.58	gold quality
left lobe of thyroid gland	UBERON:0001120	94.51	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-HCAD-10	yes	36.57
E-ANND-3	yes	8.95

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MYC, ZBTB17

miRNA regulators (miRDB)

54 targeting SAE1, 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-4795-3P	100.00	74.62	4024
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-629-3P	99.85	67.99	1875
HSA-MIR-204-5P	99.79	71.62	2439
HSA-MIR-211-5P	99.79	71.65	2440
HSA-MIR-4713-5P	99.78	67.80	1794
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-6892-3P	99.68	66.40	1178
HSA-MIR-7150	99.62	66.80	1322
HSA-MIR-4499	99.62	67.29	1470
HSA-MIR-5003-5P	99.61	69.13	1624
HSA-MIR-548B-3P	99.38	67.26	1000
HSA-MIR-377-3P	99.37	70.18	1905
HSA-MIR-499A-3P	99.18	69.20	1392
HSA-MIR-499B-3P	99.18	69.27	1391
HSA-MIR-4795-5P	99.11	66.90	876
HSA-MIR-29A-5P	99.08	68.59	1813
HSA-MIR-4801	98.96	69.42	2096
HSA-MIR-382-3P	98.83	67.10	1074
HSA-MIR-4539	98.78	67.18	888
HSA-MIR-4260	98.78	65.37	848
HSA-MIR-502-5P	98.77	66.51	906
HSA-MIR-1227-5P	98.65	65.32	1549
HSA-MIR-4710	98.61	65.96	1048

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 98.7% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 16)

• structures of heterodimeric Sae1/Sae2-Mg.ATP and Sae1/Sae2-SUMO-1-Mg.ATP complexes (PMID:15660128)
• SUMO-1 controls the protein stability and the biological function of phosducin. (PMID:16421094)
• The mammalian E1 subunits can be imported separately, identify nuclear localization signals (NLSs) in Aos1 and in Uba2, and demonstrate that their import is mediated by importin alpha/beta in vitro and in intact cells. (PMID:21209321)
• loss of SAE1/2 activity drives synthetic lethality with Myc; inactivation of SAE2 leads to mitotic catastrophe and cell death upon Myc hyperactivation; findings in Myc-high breast cancers suggest low tumor SAE1 and SAE2 correlates metastasis-free survival (PMID:22157079)
• Data show that the SAE2 subunit of the small ubiquitin-like modifier (SUMO) E1 is autoSUMOylated at residue Lys-236, and SUMOylation was catalyzed by Ubc9 at several additional Lys residues surrounding the catalytic Cys-173 of SAE2. (PMID:22403398)
• Data indicate the role of anti-SUMO activating enzyme SAE1 and SAE2 antibody as marker of dermatomyositis. (PMID:22884621)
• as it has been shown by flow cytometry analysis, specific knockdown of SAE1 slowed down the cell population at G0/G1 phase and induced apoptosis of RKO cells. (PMID:25842831)
• the expression of SENP8, SAE1, PIAS1, PIAS2 and ZMIZ1 is deregulated in the majority of PTC tissues, likely contributing to the PTC phenotype. (PMID:26403403)
• SAE1 promotes human glioma progression through activating AKT SUMOylation-mediated signaling (PMID:31345225)
• SUMOylation of the transcription factor ZFHX3 at Lys-2806 requires SAE1, UBC9, and PIAS2 and enhances its stability and function in cell proliferation. (PMID:32249212)
• Increased SUMO-activating enzyme SAE1/UBA2 promotes glycolysis and pathogenic behavior of rheumatoid fibroblast-like synoviocytes. (PMID:32938830)
• SUMO-Activating Enzyme Subunit 1 (SAE1) Is a Promising Diagnostic Cancer Metabolism Biomarker of Hepatocellular Carcinoma. (PMID:33477333)
• An engineered transcriptional reporter of protein localization identifies regulators of mitochondrial and ER membrane protein trafficking in high-throughput CRISPRi screens. (PMID:34414886)
• Increased Small Ubiquitin-like Modifier-Activating Enzyme SAE1 Promotes Hepatocellular Carcinoma by Enhancing mTOR SUMOylation. (PMID:36748193)
• Circ-RAPGEF5 promotes intrahepatic cholangiocarcinoma progression by stabilizing SAE1 to facilitate SUMOylation. (PMID:37705041)
• ROS-mediated up-regulation of SAE1 by Helicobacter pylori promotes human gastric tumor genesis and progression. (PMID:38351014)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	sae1	ENSDARG00000010487
mus_musculus	Sae1	ENSMUSG00000052833
rattus_norvegicus	Sae1	ENSRNOG00000015128
drosophila_melanogaster	Aos1	FBGN0029512
caenorhabditis_elegans		WBGENE00000142

Paralogs (9): UBA6 (ENSG00000033178), UBA5 (ENSG00000081307), MOCS3 (ENSG00000124217), UBA2 (ENSG00000126261), UBA1 (ENSG00000130985), UBA3 (ENSG00000144744), NAE1 (ENSG00000159593), UBA7 (ENSG00000182179), ATG7 (ENSG00000197548)

Protein

Protein identifiers

SUMO-activating enzyme subunit 1 — Q9UBE0 (reviewed: Q9UBE0)

Alternative names: Ubiquitin-like 1-activating enzyme E1A

All UniProt accessions (12): Q9UBE0, A0A590UK93, A0A590UKA0, A0A590UKC5, B3KNJ4, M0QX65, M0QYM8, M0QYP2, M0QZS6, M0R054, M0R286, M0R375

UniProt curated annotations — full annotation on UniProt →

Function. The heterodimer acts as an E1 ligase for SUMO1, SUMO2, SUMO3, and probably SUMO4. It mediates ATP-dependent activation of SUMO proteins followed by formation of a thioester bond between a SUMO protein and a conserved active site cysteine residue on UBA2/SAE2.

Subunit / interactions. Heterodimer of SAE1 and UBA2/SAE2. The heterodimer corresponds to the two domains that are encoded on a single polypeptide chain in ubiquitin-activating enzyme E1. Interacts with UBE2I.

Subcellular location. Nucleus.

Tissue specificity. Expression level increases during S phase and drops in G2 phase (at protein level).

Pathway. Protein modification; protein sumoylation.

Similarity. Belongs to the ubiquitin-activating E1 family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9UBE0-1	1	yes
Q9UBE0-2	2
Q9UBE0-3	3

RefSeq proteins (3): NP_001139185, NP_001139186, NP_005491* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000011	UBQ/SUMO-activ_enz_E1-like	Family
IPR000594	ThiF_NAD_FAD-bd	Domain
IPR035985	Ubiquitin-activating_enz	Homologous_superfamily
IPR045886	ThiF/MoeB/HesA	Family

Pfam: PF00899

UniProt features (50 total): helix 17, strand 13, sequence conflict 5, splice variant 4, modified residue 4, chain 2, mutagenesis site 2, turn 2, initiator methionine 1

Structure

Experimental structures (PDB)

14 structures.

PDB	Method	Resolution (Å)
9QN5	X-RAY DIFFRACTION	1.97
6XOG	X-RAY DIFFRACTION	1.98
6XOI	X-RAY DIFFRACTION	2
8VY5	X-RAY DIFFRACTION	2.01
6XOH	X-RAY DIFFRACTION	2.23
1Y8Q	X-RAY DIFFRACTION	2.25
3KYC	X-RAY DIFFRACTION	2.45
6CWY	X-RAY DIFFRACTION	2.46
9IF6	X-RAY DIFFRACTION	2.51
3KYD	X-RAY DIFFRACTION	2.61
9DRJ	ELECTRON MICROSCOPY	2.7
1Y8R	X-RAY DIFFRACTION	2.75
6CWZ	X-RAY DIFFRACTION	3.1
9DQB	ELECTRON MICROSCOPY	3.6

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UBE0-F1	91.78	0.85

Functional residue map

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

Post-translational modifications (4): 1, 2, 12, 198

Mutagenesis-validated functional residues (2):

Position	Phenotype
21	abolishes atp-dependent activation of sumo proteins.
24–26	abolishes atp-dependent activation of sumo proteins.

Function

Pathways and Gene Ontology

Reactome pathways

6 pathways

ID	Pathway
R-HSA-3065676	SUMO is conjugated to E1 (UBA2:SAE1)
R-HSA-3065678	SUMO is transferred from E1 to E2 (UBE2I, UBC9)
R-HSA-2990846	SUMOylation
R-HSA-3215018	Processing and activation of SUMO
R-HSA-392499	Metabolism of proteins
R-HSA-597592	Post-translational protein modification

MSigDB gene sets: 230 (showing top): TGCGCANK_UNKNOWN, CMYB_01, GOBP_REGULATION_OF_PROTEIN_SUMOYLATION, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOBP_PROTEIN_TARGETING, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_ORGANELLE, GOBP_PEPTIDYL_LYSINE_MODIFICATION, BLALOCK_ALZHEIMERS_DISEASE_UP, USF_01, GOBP_PROTEIN_SUMOYLATION, GOBP_REGULATION_OF_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_MITOCHONDRION, GOBP_POST_TRANSLATIONAL_PROTEIN_MODIFICATION, FISCHER_DREAM_TARGETS, BASAKI_YBX1_TARGETS_UP, KEGG_UBIQUITIN_MEDIATED_PROTEOLYSIS

GO Biological Process (5): protein sumoylation (GO:0016925), positive regulation of protein sumoylation (GO:0033235), obsolete positive regulation of protein targeting to mitochondrion (GO:1903955), protein ubiquitination (GO:0016567), protein modification process (GO:0036211)

GO Molecular Function (9): ubiquitin activating enzyme activity (GO:0004839), enzyme activator activity (GO:0008047), ATP-dependent protein binding (GO:0043008), small protein activating enzyme binding (GO:0044388), protein heterodimerization activity (GO:0046982), protein binding (GO:0005515), ubiquitin-like modifier activating enzyme activity (GO:0008641), ligase activity (GO:0016874), SUMO activating enzyme activity (GO:0019948)

GO Cellular Component (4): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), SUMO activating enzyme complex (GO:0031510)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Processing and activation of SUMO	2
Post-translational protein modification	1
SUMOylation	1
Metabolism of proteins	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein modification by small protein conjugation	2
ubiquitin-like modifier activating enzyme activity	2
catalytic activity	2
cellular anatomical structure	2
peptidyl-lysine modification	1
protein sumoylation	1
regulation of protein sumoylation	1
positive regulation of protein modification by small protein conjugation or removal	1
protein metabolic process	1
macromolecule modification	1
protein ubiquitination	1
enzyme regulator activity	1
molecular function activator activity	1
protein binding	1
enzyme 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 membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1
nuclear protein-containing complex	1
catalytic complex	1

Protein interactions and networks

STRING

3230 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SAE1	UBA2	Q9UBT2	993
SAE1	UBE2I	P50550	987
SAE1	SUMO2	P55855	953
SAE1	SUMO1	P55856	945
SAE1	RANGAP1	P46060	911
SAE1	SENP1	Q9P0U3	889
SAE1	MORC3	Q14149	852
SAE1	PIAS1	O75925	850
SAE1	RANBP2	P49792	815
SAE1	TRIM33	Q9UPN9	806
SAE1	NEDD8	Q15843	781
SAE1	SUMO4	Q6EEV6	759
SAE1	SENP5	Q96HI0	739
SAE1	PIAS4	Q8N2W9	715
SAE1	PIAS2	O75928	715

IntAct

120 interactions, top by confidence:

A	B	Type	Score
UBA2	SAE1	psi-mi:“MI:0407”(direct interaction)	0.950
SAE1	UBA2	psi-mi:“MI:0407”(direct interaction)	0.950
UBA2	SAE1	psi-mi:“MI:0915”(physical association)	0.950
SAE1	UBA2	psi-mi:“MI:0915”(physical association)	0.950
EIF3D	EIF3A	psi-mi:“MI:0914”(association)	0.860
SAE1	SUMO1	psi-mi:“MI:0915”(physical association)	0.730
DCTN2	DCTN3	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
RBM4	RBM4B	psi-mi:“MI:0914”(association)	0.640
NFYC	SAE1	psi-mi:“MI:0915”(physical association)	0.560
PAX5	SAE1	psi-mi:“MI:0915”(physical association)	0.560
PAX6	SAE1	psi-mi:“MI:0915”(physical association)	0.560
MEOX2	SAE1	psi-mi:“MI:0915”(physical association)	0.560
CRX	SAE1	psi-mi:“MI:0915”(physical association)	0.560
PAX8	SAE1	psi-mi:“MI:0915”(physical association)	0.560
CPNE5	RAD21	psi-mi:“MI:0914”(association)	0.530
TRIM35	MTA2	psi-mi:“MI:0914”(association)	0.530
UBE2I	RCC1	psi-mi:“MI:0914”(association)	0.530

BioGRID (277): SAE1 (Affinity Capture-MS), UBE2I (Biochemical Activity), SAE1 (Affinity Capture-MS), SAE1 (Affinity Capture-MS), SAE1 (Two-hybrid), FRG1B (Co-fractionation), SAE1 (Co-fractionation), SAE1 (Co-fractionation), SAE1 (Co-fractionation), SAE1 (Co-fractionation), SUMO3 (Co-fractionation), TYMS (Co-fractionation), SAE1 (Affinity Capture-MS), SAE1 (Synthetic Lethality), SAE1 (Synthetic Lethality)

ESM2 similar proteins: A2VE14, A5PLN9, B1WC68, D3Z7P3, O54865, O89050, O94925, P13264, P16068, P20595, P38024, P51583, P97834, Q02153, Q0VCB2, Q0VCJ8, Q13042, Q13098, Q3TIR1, Q4R4U1, Q4ZHR9, Q5F450, Q5M887, Q5NVN7, Q5R5F8, Q5RB35, Q5RB59, Q5RBN9, Q5RKN4, Q5ZJB7, Q5ZMH6, Q67FW5, Q6AXQ0, Q6NRT5, Q86TJ2, Q8R349, Q8VH37, Q91YQ7, Q99LD4, Q99PV3

Diamond homologs: A1A4L8, A1CAZ7, A1DED8, A2BDX3, A2R3H4, A3ACF3, A3LQF9, A4RPM5, A5DMB6, A5DSR2, A5GFZ6, A6ZT19, A7F582, A7THV5, A8WRE3, B0W377, B0Y0P7, B3LSM6, B3MLX7, B4FAT0, B4GKQ3, B4HYP0, B4JBC4, B4KI53, B4LRB9, B4N7R4, B4NXF7, B5DS72, B5VK45, B6TNK6, D4GSF3, O23034, O31619, O31702, O32037, O44510, O59954, O65041, O94609, O95396

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
SAE1	“form complex”	“SAE1/SAE2 complex”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 104 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
SUMOylation of transcription factors	5	38.1×	2e-05
SUMOylation of SUMOylation proteins	5	21.8×	2e-04
SUMOylation of DNA replication proteins	6	19.9×	5e-05
SUMOylation of RNA binding proteins	5	15.9×	6e-04
SUMOylation of DNA damage response and repair proteins	7	13.7×	6e-05
SUMOylation of chromatin organization proteins	6	12.7×	3e-04

GO biological processes:

GO term	Partners	Fold	FDR
protein sumoylation	5	17.2×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	44
Likely benign	7
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

2597 predictions. Top by Δscore:

Variant	Effect	Δscore
19:47130970:G:GT	donor_gain	1.0000
19:47130973:G:GT	donor_gain	1.0000
19:47130984:G:GG	donor_gain	1.0000
19:47143491:CA:C	acceptor_loss	1.0000
19:47143492:A:AG	acceptor_gain	1.0000
19:47143492:A:AT	acceptor_loss	1.0000
19:47143492:AG:A	acceptor_gain	1.0000
19:47143492:AGGCT:A	acceptor_gain	1.0000
19:47143493:G:GT	acceptor_gain	1.0000
19:47143493:GG:G	acceptor_gain	1.0000
19:47143493:GGC:G	acceptor_gain	1.0000
19:47143493:GGCT:G	acceptor_gain	1.0000
19:47143493:GGCTG:G	acceptor_gain	1.0000
19:47150197:CCTA:C	acceptor_loss	1.0000
19:47150198:CTA:C	acceptor_loss	1.0000
19:47150199:TAGGT:T	acceptor_loss	1.0000
19:47150200:A:C	acceptor_loss	1.0000
19:47150201:GGT:G	acceptor_gain	1.0000
19:47150201:GGTA:G	acceptor_gain	1.0000
19:47150371:ATGCT:A	donor_gain	1.0000
19:47150372:TGCT:T	donor_gain	1.0000
19:47150373:GCT:G	donor_gain	1.0000
19:47150373:GCTG:G	donor_gain	1.0000
19:47150374:CT:C	donor_gain	1.0000
19:47150375:TG:T	donor_loss	1.0000
19:47150376:G:GG	donor_gain	1.0000
19:47150377:TAAG:T	donor_loss	1.0000
19:47153023:A:T	donor_gain	1.0000
19:47153036:GTAGA:G	donor_gain	1.0000
19:47153037:TAGA:T	donor_gain	1.0000

AlphaMissense

2275 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:47130985:T:C	Y19H	1.000
19:47130996:G:C	Q22H	1.000
19:47130996:G:T	Q22H	1.000
19:47130998:T:C	I23T	1.000
19:47130998:T:G	I23S	1.000
19:47131004:T:C	L25P	1.000
19:47131006:T:A	W26R	1.000
19:47131006:T:C	W26R	1.000
19:47131008:G:C	W26C	1.000
19:47131008:G:T	W26C	1.000
19:47131009:G:A	G27R	1.000
19:47131009:G:C	G27R	1.000
19:47131010:G:A	G27E	1.000
19:47131023:G:C	Q31H	1.000
19:47131023:G:T	Q31H	1.000
19:47143554:G:C	K53N	1.000
19:47143554:G:T	K53N	1.000
19:47143565:T:C	L57S	1.000
19:47143571:G:A	G59E	1.000
19:47130976:G:C	A16P	0.999
19:47130986:A:G	Y19C	0.999
19:47130988:G:C	D20H	0.999
19:47130989:A:C	D20A	0.999
19:47130989:A:G	D20G	0.999
19:47130989:A:T	D20V	0.999
19:47130990:C:A	D20E	0.999
19:47130990:C:G	D20E	0.999
19:47130991:C:G	R21G	0.999
19:47130992:G:C	R21P	0.999
19:47130998:T:A	I23N	0.999

dbSNP variants (sampled 300 via entrez): RS1000001417 (19:47211122 G>A), RS1000024363 (19:47192017 G>A,T), RS1000088314 (19:47194845 T>A), RS1000110305 (19:47174005 C>T), RS1000122699 (19:47206863 A>G), RS1000152058 (19:47149691 C>G), RS1000194948 (19:47128847 C>G), RS1000295149 (19:47163834 G>A), RS1000339981 (19:47179234 G>A), RS1000346821 (19:47163457 G>A,C), RS1000349262 (19:47178294 C>G,T), RS1000362955 (19:47200566 G>A), RS1000410668 (19:47164021 G>A), RS1000412755 (19:47184280 G>A), RS1000458211 (19:47158681 A>G,T)

Disease associations

OMIM: gene MIM:613294 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

13 associations (top):

Study	Trait	p-value
GCST001198_56	Multiple sclerosis	5.000000e-07
GCST004610_95	White blood cell count	4.000000e-09
GCST004627_103	Lymphocyte count	2.000000e-16
GCST007122_5	Multiple sclerosis and triglyceride levels (pleiotropy)	1.000000e-06
GCST009597_109	Multiple sclerosis	2.000000e-09
GCST90002383_290	Hematocrit	1.000000e-27
GCST90002384_459	Hemoglobin	2.000000e-25
GCST90002388_375	Lymphocyte count	2.000000e-37
GCST90002389_408	Lymphocyte percentage of white cells	3.000000e-13
GCST90002393_666	Monocyte count	1.000000e-12
GCST90002399_440	Neutrophil percentage of white cells	4.000000e-12
GCST90002403_306	Red blood cell count	3.000000e-14
GCST90002407_631	White blood cell count	2.000000e-17

EFO canonical traits (8, from GWAS)

EFO ID	Trait name
EFO:0004587	lymphocyte count
EFO:0004530	triglyceride measurement
EFO:0004348	hematocrit
EFO:0004509	hemoglobin measurement
EFO:0007993	lymphocyte percentage of leukocytes
EFO:0005091	monocyte count
EFO:0007990	neutrophil percentage of leukocytes
EFO:0004305	erythrocyte count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (3): CHEMBL1615388 (SINGLE PROTEIN), CHEMBL2095174 (PROTEIN COMPLEX), CHEMBL3137290 (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: 41,249 (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
CHEMBL1231160	PEVONEDISTAT	3	1,480
CHEMBL33864	LIPOIC ACID, ALPHA	3	19,339
CHEMBL269277	BETULINIC ACID	1	20,430

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

Binding affinities (BindingDB)

186 measured of 204 human assays (254 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
MLS000079917	EC50	0.0133 nM
MLS000527128	IC50	540 nM
MLS000591719	EC50	950 nM
1-benzyl-N-butyl-2-[(2-chlorobenzoyl)amino]pyrrolo[3,2-b]quinoxaline-3-carboxamide	IC50	1100 nM	US-9045483: Inhibition of small ubiquitin-like modifier enzymes with substituted pyrrolo[2,3-b]quinoxalines
(E)-2-cyano-3-[5-(4-nitrophenyl)-2-furanyl]-N-(4-thiophen-2-yl-2-thiazolyl)-2-propenamide	IC50	1180 nM
2-[2,6-bis(chloranyl)-4-[(Z)-[3-[2-[(4-methylphenyl)amino]-2-oxidanylidene-ethyl]-2,4-bis(oxidanylidene)-1,3-thiazolidin-5-ylidene]methyl]phenoxy]ethanoic acid	IC50	1200 nM
2-{3-[(2-Hydroxy-benzoyl)-hydrazono]-2-oxo-2,3-dihydro-indol-1-yl}-N-o-tolyl-acetamide	IC50	1230 nM
3-[4-[(Z)-(4-keto-2-thioxo-thiazolidin-5-ylidene)methyl]-1-phenyl-pyrazol-3-yl]-N,N-dimethyl-benzenesulfonamide	IC50	1440 nM
(5Z)-3-[[(E)-(6-keto-3-nitro-cyclohexa-2,4-dien-1-ylidene)methyl]amino]-5-[(5-methyl-2-furyl)methylene]-2-thioxo-thiazolidin-4-one	IC50	1530 nM
(5Z)-2-azanylidene-3-(4-fluorophenyl)-5-[(4-hydroxyphenyl)methylidene]-1,3-thiazolidin-4-one	IC50	1550 nM
4-[5-(5-Cyano-2-hydroxy-4-methyl-6-oxo-6H-pyridin-3-ylidenemethyl)-furan-2-yl]-b	IC50	1590 nM
MLS000588669	IC50	1610 nM
MLS000686315	IC50	1610 nM
3-hydroxy-N-[[5-[4-(2-pyrimidinylsulfamoyl)phenyl]-2-furanyl]methylideneamino]-2-naphthalenecarboxamide	IC50	1630 nM
3,6,7-trimethoxyphenanthrene-2,5-diol	IC50	1950 nM
4-[(5E)-4-keto-5-p-anisylidene-2-thioxo-thiazolidin-3-yl]-N-thiazol-2-yl-benzenesulfonamide	IC50	1980 nM
cid_5754238	IC50	2000 nM
cid_367783	IC50	2080 nM
MLS001213411	IC50	2170 nM
cid_344131	IC50	2230 nM
(E)-4-(1,3-benzothiazol-2-yl)-5-[4-(N-methylanilino)-3-nitro-phenyl]pent-4-enoic acid	IC50	2270 nM
6-(4-fluorobenzyl)-2-(2-furfurylidene)thiazolo[3,2-b][1,2,4]triazine-3,7-quinone	IC50	2350 nM
2-(2-carbomethoxy-4-hydroxy-6-methoxy-phenoxy)-6-hydroxy-4-methyl-benzoic acid	IC50	2420 nM
(3S,4S)-5-[(3S,4S)-4,10-dihydroxy-7,9-dimethoxy-3-methyl-3,4-dihydro-1H-benz[g]isochromen-5-yl]-7,9-dimethoxy-3-methyl-3,4-dihydro-1H-benz[g]isochromene-4,10-diol	IC50	2510 nM
2-{3-[(3-Hydroxy-naphthalene-2-carbonyl)-hydrazono]-2-oxo-2,3-dihydro-indol-1-yl}-N-p-tolyl-acetamide	IC50	2570 nM
4-({[4-(2-fluorophenyl)-3a,4,5,9b-tetrahydro-3H-cyclopenta[c]quinolin-8-yl]sulfonyl}amino)benzoic acid	IC50	2580 nM
3-[[(E)-3-[4-[(4-chlorophenyl)methoxy]-3-methoxyphenyl]-2-cyanoprop-2-enoyl]amino]benzoic acid	IC50	2600 nM
MLS000544577	IC50	2630 nM
cid_2851352	IC50	2630 nM
2-hydroxy-N-[(Z)-[1-[2-(2-methoxyanilino)-2-oxoethyl]-2-oxo-3-indolylidene]amino]benzamide	IC50	2740 nM
2-(4-bromoanilino)-6-nitro-1,3-benzothiazin-4-one	IC50	2740 nM
2-amino-3-hydroxy-N’-(2,3,4-trihydroxybenzyl)propionohydrazide;hydrochloride	IC50	3050 nM
4-ethyl-N-(4-keto-1-naphthylidene)benzenesulfonamide	IC50	3110 nM
MLS000716282	IC50	3680 nM
3-[[4-chloranyl-2-oxidanylidene-5-[[(3-oxidanylnaphthalen-2-yl)carbonylhydrazinylidene]methyl]-1,3-thiazol-3-yl]methyl]benzoic acid	IC50	3740 nM
2-[[5-[(4-chlorobenzyl)thio]-1,3,4-thiadiazol-2-yl]thio]-N’-[(Z)-indol-3-ylidenemethyl]acetohydrazide	IC50	3820 nM
SMR000123743	IC50	3840 nM
2-[4-[[6-ethoxycarbonyl-7-methyl-3-oxo-5-(4-propan-2-yloxyphenyl)-5H-[1,3]thiazolo[3,2-a]pyrimidin-2-ylidene]methyl]phenoxy]acetic acid	IC50	3850 nM
4-[8-[(3-methoxyphenyl)sulfamoyl]-3a,4,5,9b-tetrahydro-3H-cyclopenta[c]quinolin-4-yl]benzoic acid	EC50	3880 nM
MLS000591126	IC50	3910 nM
5-[[5-(2,5-dichlorophenyl)-1H-pyrrol-2-yl]methylidene]-1,3-diazinane-2,4,6-trione	EC50	4040 nM
(6E)-5-azanylidene-6-[[2,5-dimethyl-1-(phenylmethyl)pyrrol-3-yl]methylidene]-2-(furan-2-yl)-[1,3,4]thiadiazolo[3,2-a]pyrimidin-7-one	IC50	4060 nM
2-(1,3-benzoxazol-2-ylamino)-6-methyl-4-(4-methylphenyl)-N-phenyl-1,4-dihydropyrimidine-5-carboxamide	IC50	4070 nM
MLS000537135	IC50	4140 nM
2-azanylidene-3-(4-bromophenyl)sulfonyl-1-(furan-2-ylmethyl)dipyrido[1,2-d:3’,4’-f]pyrimidin-5-one	IC50	4160 nM
5-[[1-(4-hydroxyphenyl)-2-pyrrolyl]methylidene]-2-sulfanylidene-1,3-diazinane-4,6-dione	IC50	4450 nM
3-(4-chlorophenyl)sulfonyl-1-(2-furanylmethyl)-2-imino-5-dipyrido[1,2-d:3’,4’-f]pyrimidinone	IC50	4470 nM
N-(1-butyl-3-cyano-6,7-dimethylpyrrolo[3,2-b]quinoxalin-2-yl)-4-chlorobenzamide	IC50	4500 nM	US-9045483: Inhibition of small ubiquitin-like modifier enzymes with substituted pyrrolo[2,3-b]quinoxalines
cid_1334850	IC50	4640 nM
MLS000054169	IC50	4690 nM

ChEMBL bioactivities

494 potent at pChembl≥5 of 864 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.00	IC50	0.1	nM	CHEMBL4878832
10.00	IC50	0.1	nM	CHEMBL4858933
9.70	IC50	0.2	nM	CHEMBL4860263
9.70	IC50	0.2	nM	CHEMBL4854038
9.70	IC50	0.2	nM	CHEMBL4864361
9.70	IC50	0.2	nM	CHEMBL4850183
9.70	IC50	0.2	nM	CHEMBL4873487
9.52	IC50	0.3	nM	CHEMBL4848442
9.52	IC50	0.3	nM	CHEMBL4852516
9.52	IC50	0.3	nM	CHEMBL4860917
9.52	IC50	0.3	nM	CHEMBL4848140
9.40	IC50	0.4	nM	CHEMBL4870385
9.40	IC50	0.4	nM	CHEMBL4877684
9.40	IC50	0.4	nM	CHEMBL4856793
9.40	IC50	0.4	nM	CHEMBL4848114
9.40	IC50	0.4	nM	CHEMBL4873956
9.30	IC50	0.5	nM	CHEMBL4861509
9.22	IC50	0.6	nM	CHEMBL4847817
9.15	IC50	0.7	nM	CHEMBL4864280
9.15	IC50	0.7	nM	CHEMBL4874906
9.15	IC50	0.7	nM	CHEMBL4862248
9.10	IC50	0.8	nM	CHEMBL4856040
9.00	IC50	1	nM	CHEMBL4878088
9.00	IC50	1	nM	CHEMBL4870143
9.00	IC50	1	nM	CHEMBL4853360
9.00	IC50	1	nM	CHEMBL4860263
9.00	IC50	1	nM	CHEMBL4849766
9.00	IC50	1	nM	CHEMBL4862901
9.00	IC50	1	nM	CHEMBL4865157
8.96	IC50	1.1	nM	CHEMBL4865787
8.96	IC50	1.1	nM	CHEMBL4861240
8.96	IC50	1.1	nM	CHEMBL4862322
8.92	IC50	1.2	nM	CHEMBL4860960
8.89	IC50	1.3	nM	CHEMBL4855964
8.82	IC50	1.5	nM	CHEMBL4862248
8.80	IC50	1.6	nM	CHEMBL4851718
8.77	IC50	1.7	nM	CHEMBL4866755
8.77	IC50	1.7	nM	CHEMBL4860740
8.77	IC50	1.7	nM	CHEMBL4862587
8.70	IC50	2	nM	CHEMBL4865086
8.70	IC50	2	nM	CHEMBL4852740
8.70	IC50	2	nM	CHEMBL4866614
8.68	IC50	2.1	nM	CHEMBL4869144
8.64	IC50	2.3	nM	CHEMBL4860471
8.60	IC50	2.5	nM	CHEMBL4861656
8.54	IC50	2.9	nM	CHEMBL4859486
8.52	IC50	3	nM	CHEMBL4867650
8.52	IC50	3	nM	CHEMBL4856793
8.49	IC50	3.2	nM	CHEMBL4866833
8.44	IC50	3.6	nM	CHEMBL4872222

PubChem BioAssay actives

186 with measured affinity, of 355 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
[(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	1775495: Inhibition of recombinant SAE (unknown origin) assessed as reduction in transfer of SUMO1 to UBC9 using SUMO1 as a substrate in presence of ATP at Km concentration by HTRF assay	ic50	0.0001	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	1775495: Inhibition of recombinant SAE (unknown origin) assessed as reduction in transfer of SUMO1 to UBC9 using SUMO1 as a substrate in presence of ATP at Km concentration by HTRF assay	ic50	0.0001	uM
[(1R,2S,4R)-4-[[5-[5-chloro-4-[(6-chloro-2-pyridinyl)-hydroxymethyl]thiophene-2-carbonyl]pyrimidin-4-yl]amino]-2-hydroxycyclopentyl]methyl sulfamate	1775495: Inhibition of recombinant SAE (unknown origin) assessed as reduction in transfer of SUMO1 to UBC9 using SUMO1 as a substrate in presence of ATP at Km concentration by HTRF assay	ic50	0.0002	uM
[(1R,2S,4R)-4-[[5-[4-[1-(3-chlorophenyl)-1-hydroxyethyl]thiophene-2-carbonyl]pyrimidin-4-yl]amino]-2-hydroxycyclopentyl]methyl sulfamate	1775495: Inhibition of recombinant SAE (unknown origin) assessed as reduction in transfer of SUMO1 to UBC9 using SUMO1 as a substrate in presence of ATP at Km concentration by HTRF assay	ic50	0.0002	uM
[(1R,2S,4R)-4-[[5-[4-[(3-chlorophenyl)-hydroxymethyl]thiophene-2-carbonyl]pyrimidin-4-yl]amino]-2-hydroxycyclopentyl]methyl sulfamate	1775495: Inhibition of recombinant SAE (unknown origin) assessed as reduction in transfer of SUMO1 to UBC9 using SUMO1 as a substrate in presence of ATP at Km concentration by HTRF assay	ic50	0.0002	uM
[(1R,2S,4R)-4-[[5-[4-[amino-(3-chlorophenyl)methyl]-5-methylthiophene-2-carbonyl]pyrimidin-4-yl]amino]-2-hydroxycyclopentyl]methyl sulfamate	1775495: Inhibition of recombinant SAE (unknown origin) assessed as reduction in transfer of SUMO1 to UBC9 using SUMO1 as a substrate in presence of ATP at Km concentration by HTRF assay	ic50	0.0002	uM
[(1R,2S,4R)-4-[[5-[4-(6,8-dihydro-5H-pyrano[3,4-b]pyridin-8-yl)-5-methylthiophene-2-carbonyl]pyrimidin-4-yl]amino]-2-hydroxycyclopentyl]methyl sulfamate	1775495: Inhibition of recombinant SAE (unknown origin) assessed as reduction in transfer of SUMO1 to UBC9 using SUMO1 as a substrate in presence of ATP at Km concentration by HTRF assay	ic50	0.0002	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	1775495: Inhibition of recombinant SAE (unknown origin) assessed as reduction in transfer of SUMO1 to UBC9 using SUMO1 as a substrate in presence of ATP at Km concentration by HTRF assay	ic50	0.0003	uM
[(1R,2S,4R)-4-[[5-[5-chloro-4-[(3-chlorophenyl)-hydroxymethyl]thiophene-2-carbonyl]pyrimidin-4-yl]amino]-2-hydroxycyclopentyl]methyl sulfamate	1775495: Inhibition of recombinant SAE (unknown origin) assessed as reduction in transfer of SUMO1 to UBC9 using SUMO1 as a substrate in presence of ATP at Km concentration by HTRF assay	ic50	0.0003	uM
[(1R,2S,4R)-4-[[5-[4-[(3-chlorophenyl)-hydroxymethyl]-5-methylthiophene-2-carbonyl]pyrimidin-4-yl]amino]-2-hydroxycyclopentyl]methyl sulfamate	1775495: Inhibition of recombinant SAE (unknown origin) assessed as reduction in transfer of SUMO1 to UBC9 using SUMO1 as a substrate in presence of ATP at Km concentration by HTRF assay	ic50	0.0003	uM
[(1R,2S,4R)-4-[[5-[4-[1-amino-1-(3-chlorophenyl)ethyl]thiophene-2-carbonyl]pyrimidin-4-yl]amino]-2-hydroxycyclopentyl]methyl sulfamate	1775495: Inhibition of recombinant SAE (unknown origin) assessed as reduction in transfer of SUMO1 to UBC9 using SUMO1 as a substrate in presence of ATP at Km concentration by HTRF assay	ic50	0.0003	uM
[(1R,2S,4R)-4-[[5-[5-chloro-4-(7-chloro-1,2,3,4-tetrahydroisoquinolin-1-yl)thiophene-2-carbonyl]pyrimidin-4-yl]amino]-2-hydroxycyclopentyl]methyl sulfamate	1775495: Inhibition of recombinant SAE (unknown origin) assessed as reduction in transfer of SUMO1 to UBC9 using SUMO1 as a substrate in presence of ATP at Km concentration by HTRF assay	ic50	0.0004	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	1775495: Inhibition of recombinant SAE (unknown origin) assessed as reduction in transfer of SUMO1 to UBC9 using SUMO1 as a substrate in presence of ATP at Km concentration by HTRF assay	ic50	0.0004	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	1775495: Inhibition of recombinant SAE (unknown origin) assessed as reduction in transfer of SUMO1 to UBC9 using SUMO1 as a substrate in presence of ATP at Km concentration by HTRF assay	ic50	0.0004	uM
[(1R,2S,4R)-4-[[5-[4-[amino-(3-chlorophenyl)methyl]-5-chlorothiophene-2-carbonyl]pyrimidin-4-yl]amino]-2-hydroxycyclopentyl]methyl sulfamate	1775495: Inhibition of recombinant SAE (unknown origin) assessed as reduction in transfer of SUMO1 to UBC9 using SUMO1 as a substrate in presence of ATP at Km concentration by HTRF assay	ic50	0.0004	uM
[(1R,2S,4R)-4-[[5-[1-[(3-bromophenyl)methyl]pyrazole-3-carbonyl]pyrimidin-4-yl]amino]-2-hydroxycyclopentyl]methyl sulfamate	1775495: Inhibition of recombinant SAE (unknown origin) assessed as reduction in transfer of SUMO1 to UBC9 using SUMO1 as a substrate in presence of ATP at Km concentration by HTRF assay	ic50	0.0004	uM
[(1R,2S,4R)-4-[[5-[4-(7-chloro-3,4-dihydro-1H-isochromen-1-yl)thiophene-2-carbonyl]pyrimidin-4-yl]amino]-2-hydroxycyclopentyl]methyl sulfamate	1775495: Inhibition of recombinant SAE (unknown origin) assessed as reduction in transfer of SUMO1 to UBC9 using SUMO1 as a substrate in presence of ATP at Km concentration by HTRF assay	ic50	0.0005	uM
[(1R,2S,4R)-4-[[5-[1-[(3-bromophenyl)methyl]pyrrole-3-carbonyl]pyrimidin-4-yl]amino]-2-hydroxycyclopentyl]methyl sulfamate	1775495: Inhibition of recombinant SAE (unknown origin) assessed as reduction in transfer of SUMO1 to UBC9 using SUMO1 as a substrate in presence of ATP at Km concentration by HTRF assay	ic50	0.0006	uM
[(1R,2S,4R)-4-[[5-[1-[(6-bromo-2-pyridinyl)methyl]pyrazole-3-carbonyl]pyrimidin-4-yl]amino]-2-hydroxycyclopentyl]methyl sulfamate	1775495: Inhibition of recombinant SAE (unknown origin) assessed as reduction in transfer of SUMO1 to UBC9 using SUMO1 as a substrate in presence of ATP at Km concentration by HTRF assay	ic50	0.0007	uM
[(1R,2S,4R)-4-[[5-[1-[(3-chlorophenyl)methyl]pyrazole-3-carbonyl]pyrimidin-4-yl]amino]-2-hydroxycyclopentyl]methyl sulfamate	1775495: Inhibition of recombinant SAE (unknown origin) assessed as reduction in transfer of SUMO1 to UBC9 using SUMO1 as a substrate in presence of ATP at Km concentration by HTRF assay	ic50	0.0007	uM
[(1R,2S,4R)-4-[[5-[4-[amino-(3-chlorophenyl)methyl]thiophene-2-carbonyl]pyrimidin-4-yl]amino]-2-hydroxycyclopentyl]methyl sulfamate	1775495: Inhibition of recombinant SAE (unknown origin) assessed as reduction in transfer of SUMO1 to UBC9 using SUMO1 as a substrate in presence of ATP at Km concentration by HTRF assay	ic50	0.0007	uM
[(1R,2S,4R)-4-[[5-[4-(7-chloro-1,2,3,4-tetrahydroisoquinolin-1-yl)thiophene-2-carbonyl]pyrimidin-4-yl]amino]-2-hydroxycyclopentyl]methyl sulfamate	1775495: Inhibition of recombinant SAE (unknown origin) assessed as reduction in transfer of SUMO1 to UBC9 using SUMO1 as a substrate in presence of ATP at Km concentration by HTRF assay	ic50	0.0008	uM
[(1R,2R,3S,4R)-4-[[5-(1-benzylpyrazole-3-carbonyl)pyrimidin-4-yl]amino]-2,3-dihydroxycyclopentyl]methyl sulfamate	1775495: Inhibition of recombinant SAE (unknown origin) assessed as reduction in transfer of SUMO1 to UBC9 using SUMO1 as a substrate in presence of ATP at Km concentration by HTRF assay	ic50	0.0010	uM
[(1R,2S,4R)-4-[[5-[4-[(1R)-7-chloro-1,2,3,4-tetrahydroisoquinolin-1-yl]-5-methylthiophene-2-carbonyl]pyrimidin-4-yl]amino]-2-hydroxycyclopentyl]methyl sulfamate	1775495: Inhibition of recombinant SAE (unknown origin) assessed as reduction in transfer of SUMO1 to UBC9 using SUMO1 as a substrate in presence of ATP at Km concentration by HTRF assay	ic50	0.0010	uM
[(1R,2S,4R)-4-[[5-[5-chloro-4-(7-chloro-3,4-dihydro-1H-isochromen-1-yl)thiophene-2-carbonyl]pyrimidin-4-yl]amino]-2-hydroxycyclopentyl]methyl sulfamate	1775495: Inhibition of recombinant SAE (unknown origin) assessed as reduction in transfer of SUMO1 to UBC9 using SUMO1 as a substrate in presence of ATP at Km concentration by HTRF assay	ic50	0.0010	uM
[(1R,2S,4R)-4-[[5-[4-[(3-chlorophenyl)methyl]thiophene-2-carbonyl]pyrimidin-4-yl]amino]-2-hydroxycyclopentyl]methyl sulfamate	1775495: Inhibition of recombinant SAE (unknown origin) assessed as reduction in transfer of SUMO1 to UBC9 using SUMO1 as a substrate in presence of ATP at Km concentration by HTRF assay	ic50	0.0010	uM
[(1R,2S,4R)-2-hydroxy-4-[[5-[4-(1,2,3,4-tetrahydroisoquinolin-1-yl)thiophene-2-carbonyl]pyrimidin-4-yl]amino]cyclopentyl]methyl sulfamate	1775495: Inhibition of recombinant SAE (unknown origin) assessed as reduction in transfer of SUMO1 to UBC9 using SUMO1 as a substrate in presence of ATP at Km concentration by HTRF assay	ic50	0.0010	uM
[(1R,2S,4R)-4-[[5-[1-[(6-chloro-2-pyridinyl)methyl]pyrazole-3-carbonyl]pyrimidin-4-yl]amino]-2-hydroxycyclopentyl]methyl sulfamate	1775495: Inhibition of recombinant SAE (unknown origin) assessed as reduction in transfer of SUMO1 to UBC9 using SUMO1 as a substrate in presence of ATP at Km concentration by HTRF assay	ic50	0.0010	uM
[(1R,2S,4R)-4-[[5-[1-[(5-chlorofuran-2-yl)methyl]pyrazole-3-carbonyl]pyrimidin-4-yl]amino]-2-hydroxycyclopentyl]methyl sulfamate	1775495: Inhibition of recombinant SAE (unknown origin) assessed as reduction in transfer of SUMO1 to UBC9 using SUMO1 as a substrate in presence of ATP at Km concentration by HTRF assay	ic50	0.0011	uM
[(1R,2S,4R)-2-hydroxy-4-[[5-[1-[[3-(trifluoromethyl)phenyl]methyl]pyrazole-3-carbonyl]pyrimidin-4-yl]amino]cyclopentyl]methyl sulfamate	1775495: Inhibition of recombinant SAE (unknown origin) assessed as reduction in transfer of SUMO1 to UBC9 using SUMO1 as a substrate in presence of ATP at Km concentration by HTRF assay	ic50	0.0011	uM
[(1R,2S,4R)-4-[[5-[1-[(3-ethynylphenyl)methyl]pyrazole-3-carbonyl]pyrimidin-4-yl]amino]-2-hydroxycyclopentyl]methyl sulfamate	1775495: Inhibition of recombinant SAE (unknown origin) assessed as reduction in transfer of SUMO1 to UBC9 using SUMO1 as a substrate in presence of ATP at Km concentration by HTRF assay	ic50	0.0011	uM
[(1R,2S,4R)-4-[[5-[4-[(3-chlorophenyl)methyl]-5-methylthiophene-2-carbonyl]pyrimidin-4-yl]amino]-2-hydroxycyclopentyl]methyl sulfamate	1775495: Inhibition of recombinant SAE (unknown origin) assessed as reduction in transfer of SUMO1 to UBC9 using SUMO1 as a substrate in presence of ATP at Km concentration by HTRF assay	ic50	0.0012	uM
[(1R,2S,4R)-4-[[5-[4-[(3-bromophenyl)methyl]thiophene-2-carbonyl]pyrimidin-4-yl]amino]-2-hydroxycyclopentyl]methyl sulfamate	1775495: Inhibition of recombinant SAE (unknown origin) assessed as reduction in transfer of SUMO1 to UBC9 using SUMO1 as a substrate in presence of ATP at Km concentration by HTRF assay	ic50	0.0013	uM
[(1R,2S,4R)-4-[[5-[4-(6-chloro-2,3-dihydro-1H-isoindol-1-yl)thiophene-2-carbonyl]pyrimidin-4-yl]amino]-2-hydroxycyclopentyl]methyl sulfamate	1775495: Inhibition of recombinant SAE (unknown origin) assessed as reduction in transfer of SUMO1 to UBC9 using SUMO1 as a substrate in presence of ATP at Km concentration by HTRF assay	ic50	0.0016	uM
[(1R,2S,4R)-4-[[5-(1-benzylpyrrole-3-carbonyl)pyrimidin-4-yl]amino]-2-hydroxycyclopentyl]methyl sulfamate	1775495: Inhibition of recombinant SAE (unknown origin) assessed as reduction in transfer of SUMO1 to UBC9 using SUMO1 as a substrate in presence of ATP at Km concentration by HTRF assay	ic50	0.0017	uM
[(1R,2S,4R)-2-hydroxy-4-[[5-[1-[(3-methylphenyl)methyl]pyrazole-3-carbonyl]pyrimidin-4-yl]amino]cyclopentyl]methyl sulfamate	1775495: Inhibition of recombinant SAE (unknown origin) assessed as reduction in transfer of SUMO1 to UBC9 using SUMO1 as a substrate in presence of ATP at Km concentration by HTRF assay	ic50	0.0017	uM
[(1R,2S,4R)-4-[[5-[4-(5-chloro-3,4-dihydro-1H-isochromen-1-yl)thiophene-2-carbonyl]pyrimidin-4-yl]amino]-2-hydroxycyclopentyl]methyl sulfamate	1775495: Inhibition of recombinant SAE (unknown origin) assessed as reduction in transfer of SUMO1 to UBC9 using SUMO1 as a substrate in presence of ATP at Km concentration by HTRF assay	ic50	0.0017	uM
[(1R,2S,4R)-4-[[5-[1-[(5-chlorothiophen-2-yl)methyl]pyrazole-3-carbonyl]pyrimidin-4-yl]amino]-2-hydroxycyclopentyl]methyl sulfamate	1775495: Inhibition of recombinant SAE (unknown origin) assessed as reduction in transfer of SUMO1 to UBC9 using SUMO1 as a substrate in presence of ATP at Km concentration by HTRF assay	ic50	0.0020	uM
[(1R,2S,4R)-4-[[5-(1-benzylpyrazole-3-carbonyl)pyrimidin-4-yl]amino]-2-hydroxycyclopentyl]methyl sulfamate	1775495: Inhibition of recombinant SAE (unknown origin) assessed as reduction in transfer of SUMO1 to UBC9 using SUMO1 as a substrate in presence of ATP at Km concentration by HTRF assay	ic50	0.0020	uM
[(1R,2S,4R)-4-[[5-[5-[(3-bromophenyl)methyl]furan-2-carbonyl]pyrimidin-4-yl]amino]-2-hydroxycyclopentyl]methyl sulfamate	1775495: Inhibition of recombinant SAE (unknown origin) assessed as reduction in transfer of SUMO1 to UBC9 using SUMO1 as a substrate in presence of ATP at Km concentration by HTRF assay	ic50	0.0020	uM
[(1R,2S,4R)-2-hydroxy-4-[[5-[1-[[3-(trifluoromethoxy)phenyl]methyl]pyrazole-3-carbonyl]pyrimidin-4-yl]amino]cyclopentyl]methyl sulfamate	1775495: Inhibition of recombinant SAE (unknown origin) assessed as reduction in transfer of SUMO1 to UBC9 using SUMO1 as a substrate in presence of ATP at Km concentration by HTRF assay	ic50	0.0021	uM
[(1R,2R,3R,4R)-4-[[5-(1-benzylpyrazole-3-carbonyl)pyrimidin-4-yl]amino]-3-fluoro-2-hydroxycyclopentyl]methyl sulfamate	1775495: Inhibition of recombinant SAE (unknown origin) assessed as reduction in transfer of SUMO1 to UBC9 using SUMO1 as a substrate in presence of ATP at Km concentration by HTRF assay	ic50	0.0023	uM
[(1R,2S,4R)-4-[[5-[4-(7-chloro-2-methyl-3,4-dihydro-1H-isoquinolin-1-yl)thiophene-2-carbonyl]pyrimidin-4-yl]amino]-2-hydroxycyclopentyl]methyl sulfamate	1775495: Inhibition of recombinant SAE (unknown origin) assessed as reduction in transfer of SUMO1 to UBC9 using SUMO1 as a substrate in presence of ATP at Km concentration by HTRF assay	ic50	0.0025	uM
[(1R,2S,4R)-4-[[5-[1-[(3-fluorophenyl)methyl]pyrazole-3-carbonyl]pyrimidin-4-yl]amino]-2-hydroxycyclopentyl]methyl sulfamate	1775495: Inhibition of recombinant SAE (unknown origin) assessed as reduction in transfer of SUMO1 to UBC9 using SUMO1 as a substrate in presence of ATP at Km concentration by HTRF assay	ic50	0.0029	uM
[(1R,2S,4R)-4-[[5-[5-chloro-4-(6-chloro-1,3-dihydro-2-benzofuran-1-yl)thiophene-2-carbonyl]pyrimidin-4-yl]amino]-2-hydroxycyclopentyl]methyl sulfamate	1775495: Inhibition of recombinant SAE (unknown origin) assessed as reduction in transfer of SUMO1 to UBC9 using SUMO1 as a substrate in presence of ATP at Km concentration by HTRF assay	ic50	0.0030	uM
[(1R,2S,4R)-4-[[5-[1-[(2-chlorophenyl)methyl]pyrazole-3-carbonyl]pyrimidin-4-yl]amino]-2-hydroxycyclopentyl]methyl sulfamate	1775495: Inhibition of recombinant SAE (unknown origin) assessed as reduction in transfer of SUMO1 to UBC9 using SUMO1 as a substrate in presence of ATP at Km concentration by HTRF assay	ic50	0.0032	uM
[(1R,2S,4R)-4-[[5-[5-chloro-4-[(3-chlorophenyl)methyl]thiophene-2-carbonyl]pyrimidin-4-yl]amino]-2-hydroxycyclopentyl]methyl sulfamate	1775495: Inhibition of recombinant SAE (unknown origin) assessed as reduction in transfer of SUMO1 to UBC9 using SUMO1 as a substrate in presence of ATP at Km concentration by HTRF assay	ic50	0.0036	uM
[(1R,2S,4R)-4-[[5-[4-[(3-chlorophenyl)-(methylamino)methyl]thiophene-2-carbonyl]pyrimidin-4-yl]amino]-2-hydroxycyclopentyl]methyl sulfamate	1775495: Inhibition of recombinant SAE (unknown origin) assessed as reduction in transfer of SUMO1 to UBC9 using SUMO1 as a substrate in presence of ATP at Km concentration by HTRF assay	ic50	0.0037	uM
[(1R,2R,3S,4R)-4-[[5-(1-benzylpyrazole-3-carbonyl)pyrimidin-4-yl]amino]-3-fluoro-2-hydroxycyclopentyl]methyl sulfamate	1775495: Inhibition of recombinant SAE (unknown origin) assessed as reduction in transfer of SUMO1 to UBC9 using SUMO1 as a substrate in presence of ATP at Km concentration by HTRF assay	ic50	0.0038	uM
[(1R,2R,4R)-4-[[5-(1-benzylpyrazole-3-carbonyl)pyrimidin-4-yl]amino]-3,3-difluoro-2-hydroxycyclopentyl]methyl sulfamate	1775495: Inhibition of recombinant SAE (unknown origin) assessed as reduction in transfer of SUMO1 to UBC9 using SUMO1 as a substrate in presence of ATP at Km concentration by HTRF assay	ic50	0.0039	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, increases expression	2
TAK-243	increases sumoylation	1
pyrogallol 1,3-dimethyl ether	affects localization, increases expression, affects cotreatment	1
sodium arsenite	increases expression	1
cobaltous chloride	decreases expression	1
ochratoxin A	increases expression, affects cotreatment	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, increases expression	1
di-n-butylphosphoric acid	affects expression	1
chloropicrin	increases expression	1
ezogabine	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
ICG 001	increases expression	1
bisphenol B	increases expression	1
LDN 193189	affects cotreatment, increases expression	1
(+)-JQ1 compound	decreases expression	1
bisphenol AF	increases expression	1
Sunitinib	decreases expression	1
Arsenic Trioxide	increases expression	1
Benzo(a)pyrene	affects methylation	1
Benztropine	affects cotreatment, decreases expression	1
Cisplatin	increases expression	1
Citrinin	affects cotreatment, increases expression	1
Coumestrol	affects cotreatment, increases expression	1
Cuprizone	increases expression, affects cotreatment, decreases expression	1
Dichlorodiphenyl Dichloroethylene	increases expression	1
Dexamethasone	decreases expression	1
Doxorubicin	decreases expression	1
Emodin	decreases expression	1
Furaldehyde	affects cotreatment, affects localization, increases expression	1
Haloperidol	increases expression, affects cotreatment	1

ChEMBL screening assays

40 unique, capped per target: 38 binding, 2 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2328917	Binding	Inhibition of SAE (unknown origin)	Exploring a new frontier in cancer treatment: targeting the ubiquitin and ubiquitin-like activating enzymes. — J Med Chem
CHEMBL1614105	Functional	PUBCHEM_BIOASSAY: AlphaScreen confirmatory assay for validation of inhibitors of SUMOylation. (Class of assay: confirmatory) [Related pubchem assays (depositor defined):AID2006, AID2011, AID2069, AID2614, AID2658]	PubChem BioAssay data set

Clinical trials (associated diseases)

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