UBA7

Summary

UBA7 (ubiquitin like modifier activating enzyme 7, HGNC:12471) is a protein-coding gene on chromosome 3p21.31, encoding Ubiquitin-like modifier-activating enzyme 7 (P41226). E1-activating enzyme that catalyzes the covalent conjugation of the ubiquitin-like protein product of ISG15 to additional interferon stimulated proteins (ISGs) as well as other cellular proteins such as P53 in a process termed protein ISGylation.

The modification of proteins with ubiquitin is an important cellular mechanism for targeting abnormal or short-lived proteins for degradation. Ubiquitination involves at least three classes of enzymes: ubiquitin-activating enzymes, or E1s, ubiquitin-conjugating enzymes, or E2s, and ubiquitin-protein ligases, or E3s. This gene encodes a member of the E1 ubiquitin-activating enzyme family. The encoded enzyme is a retinoid target that triggers promyelocytic leukemia (PML)/retinoic acid receptor alpha (RARalpha) degradation and apoptosis in acute promyelocytic leukemia, where it is involved in the conjugation of the ubiquitin-like interferon-stimulated gene 15 protein.

Source: NCBI Gene 7318 — RefSeq curated summary.

At a glance

• GWAS associations: 15
• Clinical variants (ClinVar): 197 total
• Druggable target: yes
• MANE Select transcript: NM_003335

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12471
Approved symbol	UBA7
Name	ubiquitin like modifier activating enzyme 7
Location	3p21.31
Locus type	gene with protein product
Status	Approved
Aliases	D8, UBE2, UBA1B
Ensembl gene	ENSG00000182179
Ensembl biotype	protein_coding
OMIM	191325
Entrez	7318

Gene structure

Transcript identifiers

Ensembl transcripts: 43 — 33 protein_coding, 9 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000333486, ENST00000460516, ENST00000460703, ENST00000473992, ENST00000478688, ENST00000478875, ENST00000483751, ENST00000488536, ENST00000489826, ENST00000494212, ENST00000497908, ENST00000905598, ENST00000905599, ENST00000905600, ENST00000905601, ENST00000905602, ENST00000905603, ENST00000905604, ENST00000905605, ENST00000905606, ENST00000905607, ENST00000905608, ENST00000905609, ENST00000905610, ENST00000905611, ENST00000905612, ENST00000905613, ENST00000905614, ENST00000905615, ENST00000905616, ENST00000905617, ENST00000905618, ENST00000905619, ENST00000905620, ENST00000942947, ENST00000942948, ENST00000942949, ENST00000942950, ENST00000942951, ENST00000942952, ENST00000942953, ENST00000942954, ENST00000942955

RefSeq mRNA: 1 — MANE Select: NM_003335 NM_003335

CCDS: CCDS2805

Canonical transcript exons

ENST00000333486 — 24 exons

Exon	Start	End
ENSE00001290993	49805897	49805997
ENSE00001296922	49812648	49812738
ENSE00001302228	49810517	49810672
ENSE00001305417	49809978	49810183
ENSE00001306981	49806073	49806165
ENSE00001308226	49808020	49808112
ENSE00001309957	49809542	49809725
ENSE00001310351	49805209	49805437
ENSE00001315668	49809390	49809464
ENSE00001317890	49812408	49812543
ENSE00001319543	49811870	49812016
ENSE00001327136	49810263	49810428
ENSE00001329222	49807736	49807927
ENSE00001390269	49813732	49813953
ENSE00003460711	49810752	49810832
ENSE00003472931	49813479	49813647
ENSE00003477747	49811273	49811455
ENSE00003501998	49813062	49813168
ENSE00003524556	49810984	49811091
ENSE00003526651	49809815	49809879
ENSE00003576146	49813249	49813383
ENSE00003583075	49808976	49809159
ENSE00003623921	49808386	49808468
ENSE00003677778	49812109	49812206

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 99.13.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 9.9943 / max 177.5294, expressed in 1334 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
42280	9.9464	1329
42279	0.0479	19

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	99.13	gold quality
spleen	UBERON:0002106	98.60	gold quality
right uterine tube	UBERON:0001302	98.59	gold quality
lymph node	UBERON:0000029	98.45	gold quality
small intestine Peyer’s patch	UBERON:0003454	97.99	gold quality
vermiform appendix	UBERON:0001154	97.96	gold quality
duodenum	UBERON:0002114	97.86	gold quality
small intestine	UBERON:0002108	97.73	gold quality
gall bladder	UBERON:0002110	97.62	gold quality
right ovary	UBERON:0002118	97.37	gold quality
left ovary	UBERON:0002119	97.23	gold quality
right lobe of thyroid gland	UBERON:0001119	97.17	gold quality
fallopian tube	UBERON:0003889	96.82	gold quality
right coronary artery	UBERON:0001625	96.80	gold quality
left lobe of thyroid gland	UBERON:0001120	96.76	gold quality
rectum	UBERON:0001052	96.73	gold quality
prostate gland	UBERON:0002367	96.73	gold quality
body of uterus	UBERON:0009853	96.67	gold quality
ovary	UBERON:0000992	96.64	gold quality
thyroid gland	UBERON:0002046	96.62	gold quality
transverse colon	UBERON:0001157	96.53	gold quality
upper lobe of left lung	UBERON:0008952	96.52	gold quality
left uterine tube	UBERON:0001303	96.49	gold quality
right lung	UBERON:0002167	96.47	gold quality
fundus of stomach	UBERON:0001160	96.43	gold quality
apex of heart	UBERON:0002098	96.33	gold quality
blood	UBERON:0000178	96.31	gold quality
monocyte	CL:0000576	96.29	gold quality
descending thoracic aorta	UBERON:0002345	96.28	gold quality
metanephros cortex	UBERON:0010533	96.20	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.78

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): PML

miRNA regulators (miRDB)

9 targeting UBA7, 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-3667-3P	99.99	67.17	1636
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-6132	99.60	65.83	1554
HSA-MIR-6836-5P	99.60	65.62	1538
HSA-MIR-4318	99.38	66.94	1505
HSA-MIR-1909-5P	98.94	64.01	484
HSA-MIR-4296	96.35	63.55	1233
HSA-MIR-24-1-5P	95.57	65.85	492
HSA-MIR-24-2-5P	95.57	66.16	484

Literature-anchored findings (GeneRIF, showing 8)

• UBE1L is a retinoid target that triggers PML/RARalpha degradation and apoptosis in acute promyelocytic leukemia (PMID:11891284)
• RA treatment of APL and other RA-responsive leukemic cells induced expression of UBE1L and ISG15 as well as intracellular ISG15 conjugates. A physical association was found between UBE1L and ISG15 in vivo. (PMID:14976209)
• Ube1L was required for transfer of ISG15 to UbcH8 and for binding of Ube1L to UbcH8 (PMID:18583345)
• UBE1L-ISG15 preferentially inhibits cyclin D1 in lung cancer (PMID:19074853)
• the cellular effects of progerin expression in Hutchinson-Gilford progeria syndrome are transduced, at least in part, through reduced function of the Ran GTPase and E2 SUMOylation pathways. (PMID:21670151)
• RNF170, an endoplasmic reticulum (ER)-associated ubiquitin E3 ligase, interacted with pUL50 and promoted pUL50-mediated UBE1L degradation via ubiquitination. (PMID:29743376)
• TNF-alpha, similar to the response by IFN-beta, could directly induce expression of ISG15 and its conjugation machinery, UbE1L and UbcH8, in human lung carcinoma. (PMID:31428903)
• Type I Interferon Regulates a Coordinated Gene Network to Enhance Cytotoxic T Cell-Mediated Tumor Killing. (PMID:31974171)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	uba1	ENSDARG00000037559
danio_rerio	uba7	ENSDARG00000061222
mus_musculus	Uba7	ENSMUSG00000032596
rattus_norvegicus	Uba7	ENSRNOG00000029195

Paralogs (9): UBA6 (ENSG00000033178), UBA5 (ENSG00000081307), MOCS3 (ENSG00000124217), UBA2 (ENSG00000126261), UBA1 (ENSG00000130985), SAE1 (ENSG00000142230), UBA3 (ENSG00000144744), NAE1 (ENSG00000159593), ATG7 (ENSG00000197548)

Protein

Protein identifiers

Ubiquitin-like modifier-activating enzyme 7 — P41226 (reviewed: P41226)

Alternative names: D8, Ubiquitin-activating enzyme E1 homolog

All UniProt accessions (1): P41226

UniProt curated annotations — full annotation on UniProt →

Function. E1-activating enzyme that catalyzes the covalent conjugation of the ubiquitin-like protein product of ISG15 to additional interferon stimulated proteins (ISGs) as well as other cellular proteins such as P53 in a process termed protein ISGylation. Plays an essential role in antiviral immunity together with ISG15 by restricting the replication of many viruses including rabies virus, influenza virus, sindbis virus, rotavirus or human cytomegalovirus. For example, ISG15 modification of influenza A protein NS1 disrupts the association of the NS1 with importin-alpha leading to NS1 nuclear import inhibition. ISGylation of human cytomegalovirs protein UL26 regulates its stability and inhibits its activities to suppress NF-kappa-B signaling.

Subunit / interactions. (Microbial infection) Interacts with human cytomegalovirus proteins NEC2/UL50 and UL26; these interactions inhibit ISGylation and cause proteasomal degradation of UBA7. (Microbial infection) Interacts with rotavirus non-structural protein 5 (NSP5); this interaction promotes UBA7 proteasomal degradation. Monomer. Binds and is involved in the conjugation of G1P2/ISG15.

Subcellular location. Cytoplasm. Nucleus.

Tissue specificity. Expressed in a variety of normal and tumor cell types, but is reduced in lung cancer cell lines.

Post-translational modifications. ISGylated. Ubiquitinated by RNF170.

Induction. By DNA damage. Upon interferon-alpha exposure.

Pathway. Protein modification; protein ubiquitination.

Miscellaneous. There are two active sites within the E1 molecule, allowing it to accommodate two ubiquitin moieties at a time, with a new ubiquitin forming an adenylate intermediate as the previous one is transferred to the thiol site.

Similarity. Belongs to the ubiquitin-activating E1 family.

RefSeq proteins (1): NP_003326* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000011	UBQ/SUMO-activ_enz_E1-like	Family
IPR000594	ThiF_NAD_FAD-bd	Domain
IPR018075	UBQ-activ_enz_E1	Family
IPR018965	Ub-activating_enz_E1_C	Domain
IPR019572	UBA_E1_SCCH	Domain
IPR033127	UBQ-activ_enz_E1_Cys_AS	Active_site
IPR035985	Ubiquitin-activating_enz	Homologous_superfamily
IPR038252	UBA_E1_C_sf	Homologous_superfamily
IPR042063	Ubi_acti_E1_SCCH	Homologous_superfamily
IPR042302	E1_FCCH_sf	Homologous_superfamily
IPR042449	Ub-E1_IAD_1	Homologous_superfamily
IPR045886	ThiF/MoeB/HesA	Family

Pfam: PF00899, PF09358, PF10585

UniProt features (119 total): strand 48, helix 45, turn 15, sequence variant 3, repeat 2, chain 1, sequence conflict 1, region of interest 1, active site 1, binding site 1, modified residue 1

Structure

Experimental structures (PDB)

6 structures.

PDB	Method	Resolution (Å)
8SE9	ELECTRON MICROSCOPY	3.2
8SEB	ELECTRON MICROSCOPY	3.24
8SV8	ELECTRON MICROSCOPY	3.38
8SEA	ELECTRON MICROSCOPY	3.4
8OIF	ELECTRON MICROSCOPY	3.5
8WWX	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P41226-F1	89.36	0.69

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): 599 (glycyl thioester intermediate)

Ligand- & substrate-binding residues (1): 442–471

Post-translational modifications (1): 266

Function

Pathways and Gene Ontology

Reactome pathways

7 pathways

ID	Pathway
R-HSA-1169408	ISG15 antiviral mechanism
R-HSA-168928	DDX58/IFIH1-mediated induction of interferon-alpha/beta
R-HSA-5656169	Termination of translesion DNA synthesis
R-HSA-936440	Negative regulators of DDX58/IFIH1 signaling
R-HSA-983168	Antigen processing: Ubiquitination & Proteasome degradation
R-HSA-9909505	Modulation of host responses by IFN-stimulated genes
R-HSA-9918485	Dengue Virus Attachment and Entry

MSigDB gene sets: 265 (showing top): REACTOME_DDX58_IFIH1_MEDIATED_INDUCTION_OF_INTERFERON_ALPHA_BETA, REACTOME_INNATE_IMMUNE_SYSTEM, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, REACTOME_CLASS_I_MHC_MEDIATED_ANTIGEN_PROCESSING_PRESENTATION, REACTOME_ANTIGEN_PROCESSING_UBIQUITINATION_PROTEASOME_DEGRADATION, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GRAESSMANN_RESPONSE_TO_MC_AND_SERUM_DEPRIVATION_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, RIZKI_TUMOR_INVASIVENESS_3D_DN, BROWNE_HCMV_INFECTION_48HR_DN, CAIRO_HEPATOBLASTOMA_CLASSES_DN, IRF7_01

GO Biological Process (6): DNA damage response (GO:0006974), protein ubiquitination (GO:0016567), modification-dependent protein catabolic process (GO:0019941), ISG15-protein conjugation (GO:0032020), innate immune response (GO:0045087), protein modification process (GO:0036211)

GO Molecular Function (7): ubiquitin-protein transferase activity (GO:0004842), ATP binding (GO:0005524), ISG15 activating enzyme activity (GO:0019782), nucleotide binding (GO:0000166), protein binding (GO:0005515), ubiquitin-like modifier activating enzyme activity (GO:0008641), ligase activity (GO:0016874)

GO Cellular Component (4): nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), nucleus (GO:0005634)

Reactome top-level categories

Rollup of top-7 pathways:

Category	Pathways
Antimicrobial mechanism of IFN-stimulated genes	1
Innate Immune System	1
Translesion synthesis by Y family DNA polymerases bypasses lesions on DNA template	1
DDX58/IFIH1-mediated induction of interferon-alpha/beta	1
Class I MHC mediated antigen processing & presentation	1
Interferon Signaling	1
Dengue Virus Infection	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
protein modification by small protein conjugation	2
cellular response to stress	1
protein catabolic process	1
protein modification process	1
modification-dependent macromolecule catabolic process	1
immune response	1
defense response to symbiont	1
protein metabolic process	1
macromolecule modification	1
ubiquitin-like protein transferase activity	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
ubiquitin-like modifier activating enzyme activity	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
ligase activity, forming carbon-sulfur bonds	1
catalytic activity, acting on a protein	1
ATP-dependent activity	1
catalytic activity	1
nuclear lumen	1
intracellular anatomical structure	1
cytoplasm	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

2522 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
UBA7	UBE2L6	O14933	951
UBA7	HERC5	Q9UII4	943
UBA7	ISG15	P05161	903
UBA7	USP18	Q9UMW8	882
UBA7	UBE2E2	Q96LR5	878
UBA7	UBE2B	P23567	745
UBA7	UBE2A	P49459	727
UBA7	UBE2N	P61088	712
UBA7	TRIM25	Q14258	698
UBA7	NEDD8	Q15843	639
UBA7	HERC6	Q8IVU3	636
UBA7	NEDD4	P46934	633
UBA7	IFNB1	P01574	604
UBA7	TSG101	Q99816	583
UBA7	UBE2S	Q16763	575

IntAct

24 interactions, top by confidence:

A	B	Type	Score
ISG15	UBA7	psi-mi:“MI:0915”(physical association)	0.890
UBA7	ISG15	psi-mi:“MI:0915”(physical association)	0.890
UBA7	ISG15	psi-mi:“MI:0407”(direct interaction)	0.890
UBA7	ISG15	psi-mi:“MI:0914”(association)	0.890
UBA7	TARDBP	psi-mi:“MI:0915”(physical association)	0.560
FOXA1	NFIC	psi-mi:“MI:0914”(association)	0.350
FOXK1	AP5Z1	psi-mi:“MI:0914”(association)	0.350
FOXP4	DDX39A	psi-mi:“MI:0914”(association)	0.350
GRIP1	UBA7	psi-mi:“MI:0914”(association)	0.350
	ESYT2	psi-mi:“MI:0914”(association)	0.350
SEM1	PSMD9	psi-mi:“MI:0914”(association)	0.350
UBA7	ISG15	psi-mi:“MI:0915”(physical association)	0.000
LCOR	UBA7	psi-mi:“MI:0915”(physical association)	0.000
RSPH1	UBA7	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (29): ISG15 (Two-hybrid), UBE2L6 (Biochemical Activity), UBE2L3 (Biochemical Activity), UBE2E1 (Biochemical Activity), ISG15 (Two-hybrid), UBA7 (Affinity Capture-MS), UBA7 (Affinity Capture-MS), UBA7 (Affinity Capture-MS), ISG15 (Two-hybrid), STMN3 (Affinity Capture-MS), ISG15 (Affinity Capture-MS), UBA7 (Affinity Capture-MS), UBE2L3 (Biochemical Activity), UBE2L6 (Biochemical Activity), UBA7 (Reconstituted Complex)

ESM2 similar proteins: A0A7N9VSG0, A0JNU3, D3ZBP4, D3ZX08, F1MH07, O43542, O55137, O55171, O88202, O88267, P15575, P16444, P22412, P31429, P41226, P43477, Q08DH8, Q0P5I5, Q14CH7, Q2KHY1, Q2V057, Q32Q92, Q3SZM7, Q3UQ84, Q5E9L5, Q5JTZ9, Q5M876, Q5RCH4, Q66KF6, Q68FW7, Q6P3H4, Q6PAY6, Q86U10, Q8K4F6, Q8K4V2, Q8R123, Q8TDZ2, Q8VCZ9, Q8VDG5, Q8VDP3

Diamond homologs: A0AVT1, A2VE14, A3KMV5, O31619, O42939, O65041, O94609, P20973, P22314, P22515, P31251, P31252, P31254, P31255, P41226, P52495, P92974, P93028, Q02053, Q06624, Q09765, Q18217, Q19360, Q29504, Q54QG9, Q54WI4, Q55C16, Q5R4A0, Q5U300, Q7ZVX6, Q8C7R4, Q8C878, Q8TBC4, Q99344, Q99MI7, Q9DBK7, Q9V6U8, Q9VTE9, A1A4L8, A1CAZ7

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	144
Likely benign	20
Benign	4

Top pathogenic / likely-pathogenic (0)

SpliceAI

4043 predictions. Top by Δscore:

Variant	Effect	Δscore
3:49806166:C:CC	acceptor_gain	1.0000
3:49807923:TTGCT:T	acceptor_gain	1.0000
3:49807924:TGCT:T	acceptor_gain	1.0000
3:49807926:CT:C	acceptor_gain	1.0000
3:49807926:CTCTG:C	acceptor_loss	1.0000
3:49807927:TCTGC:T	acceptor_loss	1.0000
3:49807928:C:CC	acceptor_gain	1.0000
3:49807928:CT:C	acceptor_loss	1.0000
3:49807929:T:A	acceptor_loss	1.0000
3:49808015:GTTAC:G	donor_loss	1.0000
3:49808016:TTA:T	donor_loss	1.0000
3:49808017:TA:T	donor_loss	1.0000
3:49808018:A:AT	donor_loss	1.0000
3:49808019:C:CT	donor_loss	1.0000
3:49808019:CCTGG:C	donor_gain	1.0000
3:49808108:TCATC:T	acceptor_gain	1.0000
3:49808109:CATC:C	acceptor_gain	1.0000
3:49808109:CATCC:C	acceptor_gain	1.0000
3:49808110:ATC:A	acceptor_gain	1.0000
3:49808111:TC:T	acceptor_gain	1.0000
3:49808111:TCC:T	acceptor_loss	1.0000
3:49808112:CC:C	acceptor_gain	1.0000
3:49808113:C:CC	acceptor_gain	1.0000
3:49808114:T:G	acceptor_loss	1.0000
3:49808115:G:GC	acceptor_gain	1.0000
3:49808123:C:T	acceptor_gain	1.0000
3:49808381:CCCA:C	donor_loss	1.0000
3:49808382:CCAC:C	donor_loss	1.0000
3:49808383:CA:C	donor_loss	1.0000
3:49808384:ACCT:A	donor_loss	1.0000

AlphaMissense

6543 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:49809587:A:C	F681L	0.969
3:49809587:A:T	F681L	0.969
3:49809589:A:G	F681L	0.969
3:49810535:G:C	F483L	0.962
3:49810535:G:T	F483L	0.962
3:49810537:A:G	F483L	0.962
3:49812729:G:C	F159L	0.958
3:49812729:G:T	F159L	0.958
3:49812731:A:G	F159L	0.958
3:49811074:G:C	F380L	0.953
3:49811074:G:T	F380L	0.953
3:49811076:A:G	F380L	0.953
3:49809862:A:C	F619L	0.949
3:49809862:A:T	F619L	0.949
3:49809864:A:G	F619L	0.949
3:49810638:T:A	K449I	0.948
3:49811273:C:A	K374N	0.946
3:49811273:C:G	K374N	0.946
3:49813557:C:A	K49N	0.942
3:49813557:C:G	K49N	0.942
3:49810536:A:G	F483S	0.938
3:49810420:C:A	K492N	0.936
3:49810420:C:G	K492N	0.936
3:49809850:G:C	F623L	0.934
3:49809850:G:T	F623L	0.934
3:49809852:A:G	F623L	0.934
3:49810161:G:C	C552W	0.932
3:49813561:G:T	A48D	0.930
3:49809129:C:G	A732P	0.929
3:49813562:C:G	A48P	0.929

dbSNP variants (sampled 300 via entrez): RS1000797550 (3:49808736 T>C), RS1000827279 (3:49808231 C>T), RS1000837316 (3:49810454 G>A), RS1001288377 (3:49811173 G>A), RS1001459573 (3:49811718 T>C), RS1001670157 (3:49805049 C>T), RS1001827609 (3:49810113 C>G), RS1003079643 (3:49806381 A>G), RS1003473325 (3:49808870 G>A), RS1003590668 (3:49815937 C>T), RS1004902079 (3:49814739 C>A,G), RS1005032107 (3:49808209 G>A,T), RS1005279404 (3:49815021 G>A,T), RS1006697672 (3:49812821 C>T), RS1006844772 (3:49812203 T>A,C)

Disease associations

OMIM: gene MIM:191325 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): intellectual disability (MONDO:0001071)

Orphanet (1): NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

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

GWAS associations

15 associations (top):

Study	Trait	p-value
GCST000964_6	Ulcerative colitis	2.000000e-17
GCST002541_47	Menarche (age at onset)	1.000000e-16
GCST002541_48	Menarche (age at onset)	8.000000e-12
GCST005951_49	Body mass index	1.000000e-08
GCST006920_7	Regular attendance at a gym or sports club	6.000000e-10
GCST006922_9	Regular attendance at a religious group	3.000000e-08
GCST007044_11	Extremely high intelligence	4.000000e-08
GCST007559_24	Sleep duration (short sleep)	3.000000e-08
GCST010002_422	Refractive error	4.000000e-14
GCST010698_80	Subcortical volume (min-P)	3.000000e-24
GCST010699_110	Brain morphology (min-P)	4.000000e-08
GCST010701_52	Cortical surface area (MOSTest)	1.000000e-16
GCST010702_36	Subcortical volume (MOSTest)	1.000000e-10
GCST010703_262	Brain morphology (MOSTest)	2.000000e-13
GCST012226_609	Waist circumference adjusted for body mass index	2.000000e-08

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0004703	age at menarche
EFO:0004340	body mass index
EFO:0009592	social interaction measurement
EFO:0004337	intelligence
EFO:0004346	neuroimaging measurement
EFO:0007789	BMI-adjusted waist circumference

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2321623 (SINGLE PROTEIN)

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

ChEMBL bioactivities

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

pChembl	Type	Value	Unit	Molecule
5.40	IC50	4000	nM	CHEMBL2017005

PubChem BioAssay actives

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

Compound	Assay	Type	Value	Unit
[(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	727136: Inhibition of UBA7 (unknown origin) in presence of ATP	ic50	4.0000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Tretinoin	increases expression	3
Valproic Acid	affects expression, decreases expression, increases methylation	3
potassium chromate(VI)	affects cotreatment, decreases expression	2
epigallocatechin gallate	affects expression, affects reaction, increases expression, affects cotreatment, decreases expression	2
Doxorubicin	decreases expression	2
Estradiol	affects cotreatment, decreases expression, increases expression	2
Tobacco Smoke Pollution	decreases expression	2
tert-Butylhydroperoxide	decreases expression, decreases reaction	2
sotorasib	affects cotreatment, increases expression	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
glycidyl methacrylate	decreases expression	1
ethyl-p-hydroxybenzoate	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	increases expression	1
sulindac sulfide	decreases expression	1
ferrous chloride	increases expression	1
arsenic disulfide	decreases expression	1
tamibarotene	increases expression	1
chromium hexavalent ion	decreases expression	1
monomethylarsonous acid	increases expression	1
pyrazolanthrone	decreases expression	1
abrine	decreases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
licochalcone B	increases expression	1
bisphenol S	increases expression	1
trametinib	affects cotreatment, increases expression	1
(+)-JQ1 compound	decreases expression	1
NVP-BKM120	affects cotreatment, increases expression	1
Resveratrol	affects expression, affects reaction, increases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2328927	Binding	Inhibition of UBA7 (unknown origin) in presence of ATP	Exploring a new frontier in cancer treatment: targeting the ubiquitin and ubiquitin-like activating enzymes. — J Med Chem

Cellosaurus cell lines

4 cell lines: 4 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_E1DL	Ubigene THP-1 UBA7 KO	Cancer cell line	Male
CVCL_TV38	HAP1 UBA7 (-) 1	Cancer cell line	Male
CVCL_TV39	HAP1 UBA7 (-) 2	Cancer cell line	Male
CVCL_TV40	HAP1 UBA7 (-) 3	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT05657860	PHASE4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	PHASE4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	PHASE4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	PHASE4	NOT_YET_RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
NCT02270736	PHASE3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
NCT02304302	PHASE2	COMPLETED	Down Syndrome Memantine Follow-up Study
NCT03862950	PHASE2	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome (Met)
NCT04529226	PHASE2	UNKNOWN	Study to Compare Clozapine vs Treatment as Usual in People With Intellectual Disability & Treatment-resistant Psychosis
NCT04821856	PHASE2	COMPLETED	Evaluation of the Effectiveness of Cannabidiol in Treating Severe Behavioural Problems in Children and Adolescents With Intellectual Disability
NCT05273320	PHASE1	COMPLETED	Clinical Trial of Nabilone for Aggression in Adults With Intellectual and Developmental Disabilities
NCT05301361	PHASE1	ENROLLING_BY_INVITATION	Sensitivity of the NIH Toolbox to Stimulant Treatment in Intellectual Disabilities
NCT06016764	PHASE1	COMPLETED	Use of MRI and cTBS for Catatonia in Autism
NCT06586827	PHASE1	COMPLETED	Impact of Competency-Based Training and Technical Assistance Employment Outcomes of Individuals With ID/DD
NCT07531940	PHASE1	NOT_YET_RECRUITING	Escalating Doses of Memantine in Down Syndrome (MEDS-123)
NCT03479476	PHASE2/PHASE3	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome
NCT02616796	PHASE1/PHASE2	COMPLETED	Effects of Social Gaze Training on Brain and Behavior in Fragile X Syndrome
NCT06860672	EARLY_PHASE1	RECRUITING	Clinical Trial of the Dual Vector Base Editor for the Treatment of the CHD3-R1025W Mutation
NCT00597948	Not specified	COMPLETED	Healthy Lifestyles for People With Intellectual Disabilities
NCT01087320	Not specified	RECRUITING	Genome Medical Sequencing for Gene Discovery
NCT01652963	Not specified	UNKNOWN	Picture-based Computerised Assessment and Training of Cognitive Behaviour Therapy Skills
NCT01695395	Not specified	COMPLETED	Mental Health Care Provision for Adults With Intellectual Disability and a Mental Disorder
NCT01867554	Not specified	COMPLETED	Research and Characterization of New Genes Involved in Intellectual Disability
NCT01915381	Not specified	COMPLETED	Improving Adherence Healthy Lifestyle With a Smartphone Application Based on Adults With Intellectual Disabilities
NCT01988623	Not specified	COMPLETED	Pivotal Response Treatment for Individuals With Intellectual Disabilities
NCT02099773	Not specified	COMPLETED	Support Staff-client Interactions With Augmentative and Alternative Communication
NCT02136849	Not specified	COMPLETED	Inter-regional Project of the Great Western Exploration Approach for Exome Molecular Causes Severe Intellectual Disability Isolated or Syndromic
NCT02225041	Not specified	COMPLETED	Sedation Strategy and Cognitive Outcome After Critical Illness in Early Childhood
NCT02414438	Not specified	COMPLETED	Establishing the Clinical Utility of First StepDx PLUS and NextStepDx PLUS Study
NCT02451761	Not specified	COMPLETED	Apparently Balanced Chromosomal Translocation/ Next-generation Sequencing/ Intellectual Disability
NCT02461420	Not specified	ACTIVE_NOT_RECRUITING	Mapping the Genotype, Phenotype, and Natural History of Phelan-McDermid Syndrome
NCT02461459	Not specified	ACTIVE_NOT_RECRUITING	Autism Spectrum Disorder (ASD) and Intellectual Disability (ID) Determinants in Tuberous Sclerosis Complex (TSC)
NCT02486081	Not specified	COMPLETED	Development and Application-Smart Football for Movement Evaluation and Training in the Special Education Population
NCT02504502	Not specified	COMPLETED	Enhancing Genomic Laboratory Reports to Enhance Communication and Empower Patients
NCT02513277	Not specified	COMPLETED	Diabetes Screening & Prevention for People With Learning (Intellectual) Disabilities:STOP Diabetes Study
NCT02561754	Not specified	COMPLETED	Weight Management for Adolescents With IDD
NCT02591446	Not specified	COMPLETED	Transcranial Magnetic Stimulation Studies in Autism Spectrum Disorders
NCT02714868	Not specified	COMPLETED	Evaluation of Project TEAM (Teens Making Environmental and Activity Modifications)
NCT02721394	Not specified	UNKNOWN	FCT With Young Children With ID in the UK: A Feasibility Project V.1
NCT02746614	Not specified	COMPLETED	Psychomotor Therapy Effects in Adaptive Behavior and Motor Proficiency in Intellectual Disability
NCT02836405	Not specified	COMPLETED	TMS for the Investigation of Brain Plasticity in Autism Spectrum Disorders