ATG7

Summary

ATG7 (autophagy related 7, HGNC:16935) is a protein-coding gene on chromosome 3p25.3, encoding Ubiquitin-like modifier-activating enzyme ATG7 (O95352). E1-like activating enzyme involved in the 2 ubiquitin-like systems required for cytoplasm to vacuole transport (Cvt) and autophagy.

This gene encodes an E1-like activating enzyme that is essential for autophagy and cytoplasmic to vacuole transport. The encoded protein is also thought to modulate p53-dependent cell cycle pathways during prolonged metabolic stress. It has been associated with multiple functions, including axon membrane trafficking, axonal homeostasis, mitophagy, adipose differentiation, and hematopoietic stem cell maintenance. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 10533 — RefSeq curated summary.

At a glance

• Gene–disease (curated): spinocerebellar ataxia, autosomal recessive 31 (Strong, ClinGen)
• GWAS associations: 33
• Clinical variants (ClinVar): 196 total — 12 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 42
• Druggable target: yes
• Cancer driver (intOGen): loss-of-function (tumor-suppressor-like) across 1 cancer types
• MANE Select transcript: NM_001349232

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16935
Approved symbol	ATG7
Name	autophagy related 7
Location	3p25.3
Locus type	gene with protein product
Status	Approved
Aliases	GSA7, DKFZp434N0735
Ensembl gene	ENSG00000197548
Ensembl biotype	protein_coding
OMIM	608760
Entrez	10533

Gene structure

Transcript identifiers

Ensembl transcripts: 41 — 28 protein_coding, 5 protein_coding_CDS_not_defined, 4 nonsense_mediated_decay, 4 retained_intron

ENST00000354449, ENST00000354956, ENST00000414717, ENST00000418682, ENST00000419112, ENST00000423116, ENST00000424071, ENST00000427759, ENST00000434066, ENST00000435760, ENST00000444619, ENST00000446110, ENST00000446450, ENST00000451513, ENST00000451830, ENST00000460291, ENST00000460444, ENST00000461278, ENST00000464282, ENST00000467121, ENST00000469654, ENST00000470474, ENST00000478638, ENST00000488924, ENST00000685771, ENST00000693202, ENST00000891229, ENST00000891230, ENST00000891231, ENST00000891232, ENST00000891233, ENST00000891234, ENST00000891235, ENST00000891236, ENST00000911854, ENST00000911855, ENST00000911856, ENST00000968354, ENST00000968355, ENST00000968356, ENST00000968357

RefSeq mRNA: 10 — MANE Select: NM_001349232 NM_001136031, NM_001144912, NM_001349232, NM_001349233, NM_001349234, NM_001349235, NM_001349236, NM_001349237, NM_001349238, NM_006395

CCDS: CCDS2605, CCDS46752, CCDS46753

Canonical transcript exons

ENST00000693202 — 21 exons

Exon	Start	End
ENSE00000902859	11306943	11307060
ENSE00000902863	11331340	11331428
ENSE00000902868	11358418	11358612
ENSE00001030391	11362813	11362928
ENSE00001030397	11379972	11380052
ENSE00001030403	11364659	11364734
ENSE00001594914	11280994	11281102
ENSE00001635751	11282193	11282438
ENSE00001913950	11554811	11557665
ENSE00003274212	11426804	11426926
ENSE00003490994	11342135	11342279
ENSE00003530161	11347877	11348035
ENSE00003560324	11308984	11309061
ENSE00003561868	11315344	11315493
ENSE00003588186	11299362	11299416
ENSE00003604530	11360581	11360784
ENSE00003638636	11298686	11298855
ENSE00003653968	11332972	11333093
ENSE00003662435	11340645	11340735
ENSE00003787534	11313304	11313420
ENSE00003934791	11272397	11272430

Expression profiles

Bgee: expression breadth ubiquitous, 232 present calls, max score 96.62.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 25.4546 / max 1320.2105, expressed in 1818 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
35328	20.7201	1815
35329	2.4573	475
35327	2.2319	1145
35340	0.0453	27

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
monocyte	CL:0000576	96.62	gold quality
mononuclear cell	CL:0000842	95.79	gold quality
leukocyte	CL:0000738	95.39	gold quality
calcaneal tendon	UBERON:0003701	90.71	gold quality
adrenal tissue	UBERON:0018303	90.45	gold quality
oocyte	CL:0000023	89.37	gold quality
islet of Langerhans	UBERON:0000006	89.34	gold quality
colonic epithelium	UBERON:0000397	88.90	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	88.47	gold quality
granulocyte	CL:0000094	88.43	gold quality
blood	UBERON:0000178	88.40	gold quality
buccal mucosa cell	CL:0002336	88.30	gold quality
rectum	UBERON:0001052	88.30	gold quality
skin of leg	UBERON:0001511	87.95	gold quality
gall bladder	UBERON:0002110	87.82	gold quality
stromal cell of endometrium	CL:0002255	87.51	gold quality
prefrontal cortex	UBERON:0000451	87.26	gold quality
sural nerve	UBERON:0015488	87.06	gold quality
descending thoracic aorta	UBERON:0002345	86.97	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	86.96	gold quality
skin of abdomen	UBERON:0001416	86.89	gold quality
bone marrow cell	CL:0002092	86.59	gold quality
right testis	UBERON:0004534	86.24	gold quality
left testis	UBERON:0004533	86.17	gold quality
left coronary artery	UBERON:0001626	85.91	gold quality
popliteal artery	UBERON:0002250	85.82	gold quality
tibial artery	UBERON:0007610	85.81	gold quality
ascending aorta	UBERON:0001496	85.67	gold quality
thoracic aorta	UBERON:0001515	85.67	gold quality
tendon	UBERON:0000043	85.66	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.52
E-MTAB-9543	yes	6.63

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): E2F1, HSF1, KDM4A

miRNA regulators (miRDB)

95 targeting ATG7, 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-223-3P	99.99	70.14	1140
HSA-MIR-4650-5P	99.98	64.69	999
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-6508-5P	99.92	70.67	2465
HSA-MIR-106A-5P	99.90	73.94	2683
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-6783-3P	99.89	67.92	2059
HSA-MIR-1343-3P	99.89	66.78	1815
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-17-5P	99.89	73.83	2665
HSA-MIR-106B-5P	99.88	74.72	2795
HSA-MIR-20A-5P	99.88	74.76	2769
HSA-MIR-20B-5P	99.88	74.01	2621
HSA-MIR-519D-3P	99.88	73.97	2607
HSA-MIR-526B-3P	99.88	74.06	2587
HSA-MIR-93-5P	99.88	73.98	2606
HSA-MIR-129-5P	99.88	70.26	3273
HSA-MIR-3919	99.87	69.45	2489
HSA-MIR-30E-3P	99.87	69.68	2942
HSA-MIR-8067	99.86	69.59	2260
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-548AZ-5P	99.83	69.94	3230
HSA-MIR-548T-5P	99.83	69.91	3220
HSA-MIR-320A-3P	99.77	69.73	2107
HSA-MIR-320B	99.77	69.73	2107

Literature-anchored findings (GeneRIF, showing 40)

• Murine Atg8L/Apg8L modification is mediated by human Atg7. (PMID:16704426)
• The suppression of unfolded protein response or the suppression of expression of LC3 or Atg7, a protein that mediates LC3 lipidation, suppressed HCV replication. (PMID:18688877)
• Knockdown of p300 reduces acetylation of Atg5, Atg7, Atg8, and Atg12, although overexpressed p300 increases the acetylation of these same proteins. (PMID:19124466)
• The UBQLN protective effect requires the autophagy-related genes ATG5 and ATG7, two essential components of autophagy. (PMID:19148225)
• Data show that proteasome inhibition promoted autophagosome formation, stimulated autophagic flux, and upregulated expression of the autophagy-specific genes ATG5 and ATG7. (PMID:19881538)
• Data suggest that apoptosis-deficient cells rely on autophagy for cell death after Pc 4-PDT and that the strong activation of LC3 maturation in response to PDT could occur even in cells with limited or no Atg7 expression. (PMID:20083906)
• In response to stress, FoxO1 was acetylated by dissociation from sirtuin-2 (SIRT2), a NAD(+)-dependent histone deacetylase, and the acetylated FoxO1 bound to Atg7. (PMID:20543840)
• Data show that polymorphism in the Atg7 gene that substitutes alanine for valine (V471A) was associated with an earlier disease onset of 4 years. (PMID:20697744)
• Knockdown of autophagy-related protein beclin 1 (BCN1) or autophagy-related protein 7 (ATG7) in immortalized human hepatocytes (IHHs) inhibits hepatitis C virus growth. (PMID:21274862)
• Data show that both EGFR-TKIs increased ATG5 and ATG7 at the mRNA or protein levels (Figure 3), confirming the induction of autophagy by EGFR-TKIs. (PMID:21655094)
• The FAP motif of ATG7 is indispensable for formation of the ATG3-LC3 E2-substrate intermediate through the interaction of ATG7 with ATG3. (PMID:22170151)
• when nutrients are limited, Atg7 regulates p53-dependent cell cycle and cell death pathways (PMID:22499945)
• tetrandrine transcriptionally regulated the expression of autophagy related gene 7 (ATG7), which promoted tetrandrine-induced autophagy. (PMID:22927446)
• the sequence variants within the ATG7 gene promoter identified in PD patients may change ATG7 protein levels, which in turn would influence autophagic activity, contributing to Parkinson disease onset as a risk factor. (PMID:23295909)
• Heat shock factor 1 (HSF1) controls chemoresistance and autophagy through transcriptional regulation of autophagy-related protein 7 (ATG7) (PMID:23386620)
• 2-methoxyestradiol-dependent autophagosome formation in osteosarcoma cells requires ATG7 expression. (PMID:23527187)
• Data indicate mitogen lacritin stimulates FOXO3-ATG101 and FOXO1-ATG7 autophagic coupling and restores metabolic homeostasis. (PMID:23640897)
• the polymorphism is associated with a 6-years earlier disease onset (PMID:23894380)
• a protective mechanism for Atg4B, Atg3 and LC3-Atg3 conjugate from being inappropriately sequestered into p62 aggregates (PMID:24023838)
• the Atg7.caspase-9 complex performs a dual function of linking caspase-9 to the autophagic process while keeping in check its apoptotic activity. (PMID:24362031)
• PSMD10/gankyrin has a role in inducing autophagy to promote tumor progression through cytoplasmic interaction with ATG7 and nuclear transactivation of ATG7 expression (PMID:25905985)
• The region of human ATG3 that interacts with ATG7 is precisely identified using nuclear magnetic resonance. (PMID:26043688)
• Inhibition of Atg7-mediated autophagy within the epithelium may prevent the development and progression of colorectal cancer in genetically predisposed patients. (PMID:26214133)
• SNP rs11706903 in ATG7 was not associated with systemic lupus erythematosus I Chinese Han population. (PMID:26420661)
• These observations indicate that Atg7-mediated autophagy is dispensable for retinoid recycling and A2E deposition; however, autophagy plays a role in coping with stress caused by A2E accumulation. (PMID:26468292)
• Genetic polymorphisms of ATG5 and ATG7 could contribute to neutrophilic airway inflammation in the pathogenesis of adult asthma. (PMID:26701229)
• We have identified ATG7 as a potential tissue biomarker distinguishing active EoE from normal, EoE remission, and GERD. (PMID:26785669)
• knockdown of autophagy genes ATG5 or ATG7 resulted in reduced hematopoietic stem/progenitor cell frequencies in vitro as well as in vivo. (PMID:26930546)
• knockdown of ATG7 results in decreased glycolysis and increased flux of labeled carbons through the mitochondrial tricarboxylic acid cycle. (PMID:27168493)
• The U2AF35(S34F) mutation alters interaction with CFIm59, leading to increased use of a distal cleavage and polyadenylation site in the ATG7 pre-mRNA, decreasing levels of ATG7 protein and defective autophagy, ultimately leading to transformation. (PMID:27184077)
• the ATG5-ATG7-NCOA4 autophagic pathway has a role in ferroptosis (PMID:27245739)
• the inhibition of Atg7 appears to be a valid strategy to enhance chemosensitivity, and it could indeed improve outcomes in acute myeloid leukemia therapy. (PMID:27268264)
• Our data demonstrate that HOTAIR promotes the activation of autophagy in HCC cells by upregulating the expression of the autophagy-related genes ATG3 and ATG7. (PMID:27301338)
• Autophagy-related gene ATG7 was validated as a target of miR-17 seed family. (PMID:27501757)
• Aldo was revealed to induce autophagy, as indicated by the increased conversion from microtubuleassociated protein 1A/1Blight chain 3 (LC3)I to LC3II, the increased expression levels of autophagyrelated gene 7 (Atg7) and the increased degradation of p62, which was accompanied by MC proliferation (PMID:27748808)
• low serum ATG7 is associated with ulcerative colitis (PMID:27881025)
• miR-106a suppresses tumor cells death in colorectal cancer through targeting ATG7. (PMID:27981410)
• PVT1 overexpression increased the expression of Atg7 and Beclin1 by targeting miR-186, which induced protective autophagy, thus promoting glioma vascular endothelial cell proliferation, migration, and angiogenesis. Therefore, PVT1 and miR-186 can provide new therapeutic targets for future anti-angiogenic treatment of glioma (PMID:28351322)
• miR-210 inhibits autophagy via silencing of ATG7. (PMID:28667916)
• The G allele of rs8154 was correlated with breast cancer patients poorer survival. (PMID:28669927)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	atg7	ENSDARG00000102893
mus_musculus	Atg7	ENSMUSG00000030314
rattus_norvegicus	Atg7	ENSRNOG00000007486
drosophila_melanogaster	Atg7	FBGN0034366
caenorhabditis_elegans		WBGENE00010882

Paralogs (9): UBA6 (ENSG00000033178), UBA5 (ENSG00000081307), MOCS3 (ENSG00000124217), UBA2 (ENSG00000126261), UBA1 (ENSG00000130985), SAE1 (ENSG00000142230), UBA3 (ENSG00000144744), NAE1 (ENSG00000159593), UBA7 (ENSG00000182179)

Protein

Protein identifiers

Ubiquitin-like modifier-activating enzyme ATG7 — O95352 (reviewed: O95352)

Alternative names: ATG12-activating enzyme E1 ATG7, Autophagy-related protein 7, Ubiquitin-activating enzyme E1-like protein

All UniProt accessions (12): C9J415, C9JE55, C9JFF4, C9JGL2, C9JKA3, C9JNU2, O95352, H7BZ92, H7C059, H7C2J8, H7C2R3, H7C369

UniProt curated annotations — full annotation on UniProt →

Function. E1-like activating enzyme involved in the 2 ubiquitin-like systems required for cytoplasm to vacuole transport (Cvt) and autophagy. Activates ATG12 for its conjugation with ATG5 as well as the ATG8 family proteins for their conjugation with phosphatidylethanolamine. Both systems are needed for the ATG8 association to Cvt vesicles and autophagosomes membranes. Required for autophagic death induced by caspase-8 inhibition. Facilitates LC3-I lipidation with phosphatidylethanolamine to form LC3-II which is found on autophagosomal membranes. Required for mitophagy which contributes to regulate mitochondrial quantity and quality by eliminating the mitochondria to a basal level to fulfill cellular energy requirements and preventing excess ROS production. Modulates p53/TP53 activity to regulate cell cycle and survival during metabolic stress. Also plays a key role in the maintenance of axonal homeostasis, the prevention of axonal degeneration, the maintenance of hematopoietic stem cells, the formation of Paneth cell granules, as well as in adipose differentiation. Plays a role in regulating the liver clock and glucose metabolism by mediating the autophagic degradation of CRY1 (clock repressor) in a time-dependent manner.

Subunit / interactions. Homodimer. Interacts with ATG3; this interaction is essential for the transfer of ATG8-like proteins’s thioester from ATG7 to ATG3 and plays a role in the conjugation of ATG12 to ATG5. Interacts with ATG12. Forms intermediate conjugates with GABARAPL1. Forms intermediate conjugates with ATG8-like proteins such as GABARAP, GABARAPL2 or MAP1LC3A. Interacts with EP300 acetyltransferase. Interacts with FOXO1.

Subcellular location. Cytoplasm. Preautophagosomal structure.

Tissue specificity. Widely expressed, especially in kidney, liver, lymph nodes and bone marrow.

Post-translational modifications. Acetylated by EP300. Polyubiquitinated on Lys-45 via ‘Lys-63’-linked ubiquitin by TRIM32; this modification positiely regulates ATG8 and ATG12 activating enzyme activity leading to initiation of autophagy under metabolic stress.

Disease relevance. Spinocerebellar ataxia, autosomal recessive, 31 (SCAR31) [MIM:619422] A form of spinocerebellar ataxia, a clinically and genetically heterogeneous group of cerebellar disorders due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCAR30 is characterized by global developmental delay, hypotonia, variably impaired intellectual and language development, ataxic gait, tremor, and dysarthria. Most affected individuals have optic atrophy. Additional features may include retinitis pigmentosa, sensorineural deafness, dysmorphic facial features, and possibly endocrine dysfunction. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The C-terminal part of the protein is essential for the dimerization and interaction with ATG3 and ATG12. The N-terminal FAP motif (residues 15 to 17) is essential for the formation of the ATG89-PE and ATG5-ATG12 conjugates.

Induction. Expression is up-regulated by the transcription factor HSF1.

Similarity. Belongs to the ATG7 family.

Isoforms (3)

UniProt ID	Names	Canonical?
O95352-1	1	yes
O95352-2	2
O95352-3	3

RefSeq proteins (10): NP_001129503, NP_001138384, NP_001336161, NP_001336162, NP_001336163, NP_001336164, NP_001336165, NP_001336166, NP_001336167, NP_006386 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000594	ThiF_NAD_FAD-bd	Domain
IPR006285	Atg7	Family
IPR032197	Atg7_N	Domain
IPR035985	Ubiquitin-activating_enz	Homologous_superfamily
IPR042522	Atg7_N_1	Homologous_superfamily
IPR042523	Atg7_N_2	Homologous_superfamily
IPR045886	ThiF/MoeB/HesA	Family

Pfam: PF00899, PF16420

UniProt features (28 total): sequence variant 9, mutagenesis site 7, splice variant 3, sequence conflict 2, modified residue 2, initiator methionine 1, chain 1, short sequence motif 1, active site 1, cross-link 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O95352-F1	88.06	0.67

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): 572 (glycyl thioester intermediate)

Post-translational modifications (3): 2, 698, 45

Mutagenesis-validated functional residues (7):

Position	Phenotype
15	impairs conjugation activity; when associated with d-16 and d-17.
16	impairs conjugation activity; when associated with d-15 and d-17.
17	impairs conjugation activity; when associated with d-15 and d-16.
45	impairs interaction with atg12. impairs inrteraction with map1lc3b.
243	moderately impairs atg3 binding. moderately reduces gabarap-atg3 thioester bond formation. moderately reduces gabarap li
246	almost completely impairs atg3 binding. severely reduces gabarap-atg3 thioester bond formation. severely reduces gabarap
572	loss of lc3-i lipidation to form lc3-ii.

Function

Pathways and Gene Ontology

Reactome pathways

13 pathways

ID	Pathway
R-HSA-1632852	Macroautophagy
R-HSA-6798695	Neutrophil degranulation
R-HSA-6802952	Signaling by BRAF and RAF1 fusions
R-HSA-983168	Antigen processing: Ubiquitination & Proteasome degradation
R-HSA-9918485	Dengue Virus Attachment and Entry
R-HSA-1280218	Adaptive Immune System
R-HSA-1643685	Disease
R-HSA-168249	Innate Immune System
R-HSA-168256	Immune System
R-HSA-5663202	Diseases of signal transduction by growth factor receptors and second messengers
R-HSA-6802957	Oncogenic MAPK signaling
R-HSA-9612973	Autophagy
R-HSA-983169	Class I MHC mediated antigen processing & presentation

MSigDB gene sets: 291 (showing top): GSE45365_NK_CELL_VS_CD11B_DC_UP, GOBP_CIRCADIAN_RHYTHM, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_VACUOLE_ORGANIZATION, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, GOBP_LIPOPROTEIN_METABOLIC_PROCESS, REACTOME_CLASS_I_MHC_MEDIATED_ANTIGEN_PROCESSING_PRESENTATION, REACTOME_ANTIGEN_PROCESSING_UBIQUITINATION_PROTEASOME_DEGRADATION, GOCC_SECRETORY_GRANULE, STEARMAN_LUNG_CANCER_EARLY_VS_LATE_DN, GOBP_POSITIVE_REGULATION_OF_PROTEIN_CATABOLIC_PROCESS, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_MACROAUTOPHAGY, GOBP_REGULATION_OF_CIRCADIAN_RHYTHM, GOBP_RESPONSE_TO_INCREASED_OXYGEN_LEVELS

GO Biological Process (23): autophagosome assembly (GO:0000045), mitophagy (GO:0000423), protein lipidation (GO:0006497), autophagy (GO:0006914), cellular response to nitrogen starvation (GO:0006995), cellular response to starvation (GO:0009267), protein transport (GO:0015031), macroautophagy (GO:0016236), positive regulation of protein modification process (GO:0031401), protein modification by small protein conjugation (GO:0032446), cellular response to stress (GO:0033554), piecemeal microautophagy of the nucleus (GO:0034727), regulation of circadian rhythm (GO:0042752), positive regulation of apoptotic process (GO:0043065), positive regulation of protein catabolic process (GO:0045732), rhythmic process (GO:0048511), defense response to virus (GO:0051607), cellular response to hyperoxia (GO:0071455), positive regulation of catabolic process (GO:0009896), response to nutrient levels (GO:0031667), regulation of apoptotic process (GO:0042981), regulation of macromolecule metabolic process (GO:0060255), regulation of primary metabolic process (GO:0080090)

GO Molecular Function (5): Atg12 activating enzyme activity (GO:0019778), Atg8 activating enzyme activity (GO:0019779), protein homodimerization activity (GO:0042803), protein binding (GO:0005515), ubiquitin-like modifier activating enzyme activity (GO:0008641)

GO Cellular Component (7): phagophore assembly site (GO:0000407), extracellular region (GO:0005576), cytoplasm (GO:0005737), cytosol (GO:0005829), axoneme (GO:0005930), secretory granule lumen (GO:0034774), ficolin-1-rich granule lumen (GO:1904813)

Reactome top-level categories

Rollup of top-9 pathways:

Category	Pathways
Immune System	2
Autophagy	1
Innate Immune System	1
Oncogenic MAPK signaling	1
Class I MHC mediated antigen processing & presentation	1
Dengue Virus Infection	1
Disease	1
Diseases of signal transduction by growth factor receptors and second messengers	1
Adaptive Immune System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
protein modification process	2
catabolic process	2
positive regulation of protein metabolic process	2
ubiquitin-like modifier activating enzyme activity	2
cytoplasm	2
Atg12 activating enzyme activity	1
protein-phosphatidylethanolamide deconjugating activity	1
Atg12 conjugating enzyme activity	1
Atg12 ligase activity	1
organelle assembly	1
Atg1/ULK1 kinase complex assembly	1
autophagosome organization	1
autophagy of mitochondrion	1
macroautophagy	1
lipoprotein biosynthetic process	1
transmembrane transport	1
process utilizing autophagic mechanism	1
cellular response to starvation	1
cellular response to nitrogen levels	1
cellular response to nutrient levels	1
cellular response to stress	1
response to starvation	1
transport	1
intracellular protein localization	1
establishment of protein localization	1
autophagosome assembly	1
autophagy	1
regulation of protein modification process	1
protein modification by small protein conjugation or removal	1
response to stress	1
cellular response to stimulus	1
microautophagy	1
nucleophagy	1
nucleus disassembly	1
circadian rhythm	1
regulation of biological process	1
apoptotic process	1
regulation of apoptotic process	1
positive regulation of programmed cell death	1

Protein interactions and networks

STRING

4584 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ATG7	GABARAPL2	P60520	999
ATG7	ATG10	Q9H0Y0	999
ATG7	ATG3	Q9NT62	999
ATG7	F5GZY7	F5GZY7	999
ATG7	ATG12	O94817	999
ATG7	ATG5	Q9H1Y0	999
ATG7	FOXO1	Q12778	993
ATG7	ATG16L1	Q676U5	992
ATG7	SIRT1	Q96EB6	987
ATG7	BECN1	Q14457	980
ATG7	ATG4B	Q9Y4P1	972
ATG7	MAP1LC3A	Q9H492	968
ATG7	GABARAP	O95166	964
ATG7	ULK1	O75385	955
ATG7	MAP1LC3B	Q9GZQ8	954

IntAct

101 interactions, top by confidence:

A	B	Type	Score
ACBD6	NMT2	psi-mi:“MI:0914”(association)	0.870
KHDRBS2	KHDRBS3	psi-mi:“MI:0914”(association)	0.800
MAP1LC3B	ATG7	psi-mi:“MI:0914”(association)	0.740
GABARAPL2	ATG7	psi-mi:“MI:0407”(direct interaction)	0.740
MAP1LC3B	ATG7	psi-mi:“MI:0407”(direct interaction)	0.740
GABARAPL2	IPO5	psi-mi:“MI:0914”(association)	0.690
ATG10	ATG12	psi-mi:“MI:0914”(association)	0.670
GABARAP	ATG7	psi-mi:“MI:0407”(direct interaction)	0.670
ATG7	GABARAP	psi-mi:“MI:0914”(association)	0.670
RWDD2A	ATG7	psi-mi:“MI:0915”(physical association)	0.640
CCDC120	AIP	psi-mi:“MI:0914”(association)	0.640
RWDD2A	ATG7	psi-mi:“MI:0914”(association)	0.640
ATG7	SIRT1	psi-mi:“MI:0915”(physical association)	0.600
SIRT1	ATG7	psi-mi:“MI:0915”(physical association)	0.600
SIRT1	ATG7	psi-mi:“MI:0407”(direct interaction)	0.600
GABARAP	IPO5	psi-mi:“MI:0914”(association)	0.590
GABARAPL1	IPO5	psi-mi:“MI:0914”(association)	0.590
LGMN	ATG7	psi-mi:“MI:0914”(association)	0.530
ATG7	GFER	psi-mi:“MI:0914”(association)	0.530
ATG3	MAP1LC3B2	psi-mi:“MI:0914”(association)	0.530
KIAA0930	ATG7	psi-mi:“MI:0914”(association)	0.530

BioGRID (484): MAP1LC3A (Reconstituted Complex), GABARAPL2 (Biochemical Activity), GABARAP (Biochemical Activity), MAP1LC3A (Biochemical Activity), GABARAPL2 (Reconstituted Complex), GABARAP (Reconstituted Complex), ATG7 (Affinity Capture-Western), ATG7 (Affinity Capture-MS), ATG7 (Affinity Capture-MS), ATG7 (Affinity Capture-MS), ATG7 (Affinity Capture-MS), ATG7 (Affinity Capture-MS), ATG7 (Affinity Capture-MS), ATG7 (Affinity Capture-MS), ATG7 (Co-fractionation)

ESM2 similar proteins: A2VE39, A2X0Q3, A3KMV5, A4IG62, A7YW45, A8BQB4, D2HRF1, F4JVN6, O14744, O23617, O80585, O80738, O95352, P22314, P35573, P42898, P45437, Q02053, Q0WUI9, Q29504, Q295E6, Q29G21, Q2PQH8, Q4R5M3, Q5I598, Q5R698, Q5R981, Q5RGJ5, Q5U300, Q5ZJT0, Q60HE5, Q641Y5, Q6ESI7, Q6NUA1, Q6YXZ7, Q75HE6, Q8AVL0, Q8CIG8, Q8GWT4, Q8IYB8

Diamond homologs: A3LPA1, A5DLC6, A5E0T7, A6QXC6, A6ZT79, A7EI75, A7KAI6, A7KAL8, A7TEY0, F7W4M2, G2XR75, I1S0J7, M7U9B9, O31619, O43069, O93922, O95352, P0CM38, P0CM39, P38862, Q52CS0, Q59PZ3, Q5AWA2, Q5ZKY2, Q641Y5, Q6BGV9, Q6CBC3, Q6CXW3, Q6FQY7, Q756G8, Q86CR9, Q871U2, Q94CD5, Q9D906, W0TA05, O31702, O65041, P12282, P45211, Q56067

SIGNOR signaling

6 interactions.

A	Effect	B	Mechanism
ATG7	up-regulates	ATG12	binding
ATG7	up-regulates	MAP1LC3A	binding
ATG7	up-regulates	MAP1LC3B	binding
hsa-miR-199a-5p	“down-regulates quantity by repression”	ATG7	“post transcriptional regulation”
ATG7	“up-regulates activity”	MAP1LC3C	binding
ATG7	“up-regulates activity”	GABARAPL2	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 79 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Macroautophagy	9	19.6×	2e-07
Autophagy	6	16.8×	2e-04

GO biological processes:

GO term	Partners	Fold	FDR
mitophagy	11	51.4×	8e-14
autophagosome maturation	9	46.5×	4e-11
autophagosome assembly	11	36.4×	2e-12
macroautophagy	5	17.7×	1e-03

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: loss-of-function (tumor-suppressor-like) across 1 cancer types — CCRCC.

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	12
Likely pathogenic	1
Uncertain significance	127
Likely benign	16
Benign	4

Top pathogenic / likely-pathogenic (13)

Variant ID	HGVS	Classification
1177578	NM_001349232.2(ATG7):c.1727G>A (p.Arg576His)	Pathogenic
1177579	NM_001349232.2(ATG7):c.1870C>T (p.His624Tyr)	Pathogenic
1177580	NM_001349232.2(ATG7):c.782A>G (p.Gln261Arg)	Pathogenic
1177581	NM_001349232.2(ATG7):c.1532G>A (p.Gly511Asp)	Pathogenic
1177584	NM_001349232.2(ATG7):c.2080-2A>G	Pathogenic
1340006	GRCh37/hg19 3p25.3-25.2(chr3:10922740-12456978)x1	Pathogenic
1807689	GRCh37/hg19 3p25.3-25.2(chr3:10024917-11917048)x1	Pathogenic
2580292	GRCh37/hg19 3p25.3-25.2(chr3:10167260-12533766)x1	Pathogenic
3375357	NM_001349232.2(ATG7):c.339G>A (p.Trp113Ter)	Pathogenic
3900604	GRCh37/hg19 3p25.3(chr3:10239102-11732086)x1	Pathogenic
4071990	NM_001349232.2(ATG7):c.528+3A>G	Pathogenic
57766	GRCh38/hg38 3p25.3-25.2(chr3:10019780-12251358)x1	Pathogenic
4292912	NM_001349232.2(ATG7):c.1480-2A>T	Likely pathogenic

SpliceAI

4100 predictions. Top by Δscore:

Variant	Effect	Δscore
3:11298681:AATAG:A	acceptor_gain	1.0000
3:11298685:GGCAA:G	acceptor_gain	1.0000
3:11298831:GACAT:G	donor_gain	1.0000
3:11298853:ATG:A	donor_gain	1.0000
3:11298853:ATGG:A	donor_loss	1.0000
3:11298856:G:GG	donor_gain	1.0000
3:11298857:T:A	donor_loss	1.0000
3:11306938:TCTAG:T	acceptor_loss	1.0000
3:11306939:CTA:C	acceptor_loss	1.0000
3:11306940:TA:T	acceptor_loss	1.0000
3:11306941:A:AG	acceptor_gain	1.0000
3:11306941:A:T	acceptor_loss	1.0000
3:11306942:G:GG	acceptor_gain	1.0000
3:11306942:GGA:G	acceptor_gain	1.0000
3:11306942:GGAGT:G	acceptor_gain	1.0000
3:11307026:A:G	donor_gain	1.0000
3:11307060:GG:G	donor_loss	1.0000
3:11307061:GTTAG:G	donor_loss	1.0000
3:11309059:GCA:G	donor_gain	1.0000
3:11309062:G:GG	donor_gain	1.0000
3:11315338:TTTCA:T	acceptor_loss	1.0000
3:11315340:TCA:T	acceptor_loss	1.0000
3:11315341:CA:C	acceptor_loss	1.0000
3:11315343:GATT:G	acceptor_gain	1.0000
3:11315481:TCA:T	donor_gain	1.0000
3:11315506:T:TG	donor_gain	1.0000
3:11358416:A:AG	acceptor_gain	1.0000
3:11358416:A:AT	acceptor_loss	1.0000
3:11358416:AGAAT:A	acceptor_gain	1.0000
3:11358417:G:GA	acceptor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000010 (3:11562645 A>G), RS1000015342 (3:11494257 G>C), RS1000024293 (3:11536002 C>T), RS1000033241 (3:11277903 C>A,G), RS1000058840 (3:11453867 T>C), RS1000061613 (3:11563022 G>A,T), RS1000065620 (3:11354652 A>C), RS1000087766 (3:11493539 C>T), RS1000092869 (3:11573174 AAGAC>A,AAGACAGAC), RS1000099164 (3:11375357 A>G), RS1000102977 (3:11386941 A>G), RS1000108380 (3:11332809 A>G), RS1000112944 (3:11326599 A>G), RS1000127033 (3:11383080 T>C), RS1000129909 (3:11531031 C>A)

Disease associations

OMIM: gene MIM:608760 | disease phenotypes: MIM:619422, MIM:613282, MIM:613792

GenCC curated gene-disease

Disease	Classification	Inheritance
spinocerebellar ataxia, autosomal recessive 31	Strong	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
spinocerebellar ataxia, autosomal recessive 31	Strong	AR

Mondo (4): spinocerebellar ataxia, autosomal recessive 31 (MONDO:0030323), NAFLD1 (MONDO:0021105), 3p- syndrome (MONDO:0013424), primary ovarian failure (MONDO:0005387)

Orphanet (2): Distal deletion 3p syndrome (Orphanet:1620), NON RARE IN EUROPE: Primary ovarian failure (Orphanet:619)

HPO phenotypes

42 total (30 of 42 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000212	Gingival overgrowth
HP:0000218	High palate
HP:0000276	Long face
HP:0000278	Retrognathia
HP:0000319	Smooth philtrum
HP:0000486	Strabismus
HP:0000488	Retinopathy
HP:0000508	Ptosis
HP:0000544	External ophthalmoplegia
HP:0000648	Optic atrophy
HP:0000729	Autistic behavior
HP:0000742	Self-mutilation
HP:0000750	Delayed speech and language development
HP:0000767	Pectus excavatum
HP:0001250	Seizure
HP:0001251	Ataxia
HP:0001260	Dysarthria
HP:0001266	Choreoathetosis
HP:0001298	Encephalopathy
HP:0001321	Cerebellar hypoplasia
HP:0001324	Muscle weakness
HP:0001332	Dystonia
HP:0001337	Tremor
HP:0001344	Absent speech
HP:0001510	Growth delay
HP:0001611	Hypernasal speech
HP:0001761	Pes cavus
HP:0002015	Dysphagia
HP:0002059	Cerebral atrophy

GWAS associations

33 associations (top):

Study	Trait	p-value
GCST002183_5	Relative hand skill in reading disability	9.000000e-06
GCST002223_19	HDL cholesterol	5.000000e-08
GCST002899_36	HDL cholesterol	2.000000e-09
GCST004232_79	HDL cholesterol levels	4.000000e-08
GCST004389_1	Circulating chemerin levels	9.000000e-07
GCST005057_1	Small vessel stroke	3.000000e-06
GCST005057_2	Small vessel stroke	4.000000e-06
GCST006021_19	Systolic blood pressure	1.000000e-08
GCST006259_31	Systolic blood pressure	2.000000e-08
GCST006288_226	Heel bone mineral density	2.000000e-07
GCST006288_245	Heel bone mineral density	2.000000e-06
GCST006288_509	Heel bone mineral density	3.000000e-12
GCST006661_65	Male-pattern baldness	2.000000e-09
GCST007267_28	Systolic blood pressure	9.000000e-25
GCST007269_47	Pulse pressure	2.000000e-12
GCST008157_62	Body fat mass	5.000000e-06
GCST010989_212	Body size at age 10	3.000000e-17
GCST012227_983	Hip circumference adjusted for BMI	2.000000e-09
GCST012227_984	Hip circumference adjusted for BMI	2.000000e-10
GCST012229_42	Hip index	3.000000e-09
GCST012229_43	Hip index	4.000000e-11
GCST012489_118	Heel bone mineral density x serum urate levels interaction	3.000000e-10
GCST90011899_65	Aspartate aminotransferase levels	2.000000e-08
GCST90020025_1756	Waist-to-hip ratio adjusted for BMI	3.000000e-08
GCST90020026_155	Hip index	5.000000e-12
GCST90020026_156	Hip index	5.000000e-12
GCST90020026_158	Hip index	4.000000e-09
GCST90020028_725	Hip circumference adjusted for BMI	2.000000e-15
GCST90020028_726	Hip circumference adjusted for BMI	8.000000e-09
GCST90020028_727	Hip circumference adjusted for BMI	2.000000e-14

EFO canonical traits (12, from GWAS)

EFO ID	Trait name
EFO:0009902	handedness
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004573	chemerin measurement
EFO:1001504	small vessel stroke
EFO:0006335	systolic blood pressure
EFO:0009270	heel bone mineral density
EFO:0005763	pulse pressure measurement
EFO:0009819	comparative body size at age 10, self-reported
EFO:0008039	BMI-adjusted hip circumference
EFO:0004531	urate measurement
EFO:0004736	aspartate aminotransferase measurement
EFO:0007788	BMI-adjusted waist-hip ratio

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D016649	Primary Ovarian Insufficiency	C12.050.351.500.056.630.750; C12.100.250.056.630.750; C19.391.630.750
C536804	Chromosome 3, monosomy 3p (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2321621 (SINGLE PROTEIN)

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

Binding affinities (BindingDB)

1 measured of 3 human assays (3 total across all organisms); most potent 1 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
{(2R,3S,5R)-5-[4-amino-3-(1H-indol-3-ylsulfanyl)-1H-pyrazolo[3,4-d]pyrimidin- 1-yl]-3-hydroxytetrahydrofuran-2-yl}methyl sulfamate	IC50	300 nM	US-10865208: ATG7 inhibitors and the uses thereof

ChEMBL bioactivities

459 potent at pChembl≥5 of 460 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.85	IC50	14	nM	CHEMBL4577235
7.80	IC50	16	nM	CHEMBL4464238
7.77	IC50	17	nM	CHEMBL4554226
7.75	IC50	18	nM	CHEMBL4543856
7.70	IC50	20	nM	CHEMBL4466430
7.70	IC50	20	nM	CHEMBL4454053
7.70	IC50	20	nM	CHEMBL4457043
7.70	IC50	20	nM	CHEMBL4464322
7.70	IC50	20	nM	CHEMBL4558671
7.70	IC50	20	nM	CHEMBL4447381
7.70	IC50	20	nM	CHEMBL4543610
7.70	IC50	20	nM	CHEMBL4456716
7.70	IC50	20	nM	CHEMBL4526319
7.70	IC50	20	nM	CHEMBL4473356
7.70	IC50	20	nM	CHEMBL4537063
7.70	IC50	20	nM	CHEMBL4518410
7.70	IC50	20	nM	CHEMBL4518269
7.70	IC50	20	nM	CHEMBL4452757
7.70	IC50	20	nM	CHEMBL4557469
7.70	IC50	20	nM	CHEMBL4467807
7.70	IC50	20	nM	CHEMBL4483085
7.70	IC50	20	nM	CHEMBL4449596
7.70	IC50	20	nM	CHEMBL4471077
7.70	IC50	20	nM	CHEMBL4576658
7.70	IC50	20	nM	CHEMBL4557103
7.70	IC50	20	nM	CHEMBL4550475
7.70	IC50	20	nM	CHEMBL4546984
7.70	IC50	20	nM	CHEMBL4527646
7.70	IC50	20	nM	CHEMBL4449861
7.70	IC50	20	nM	CHEMBL4434940
7.70	IC50	20	nM	CHEMBL4521754
7.70	IC50	20	nM	CHEMBL4535927
7.70	IC50	20	nM	CHEMBL4579107
7.70	IC50	20	nM	CHEMBL4577562
7.70	IC50	20	nM	CHEMBL4476015
7.70	IC50	20	nM	CHEMBL4451885
7.70	IC50	20	nM	CHEMBL4439106
7.70	IC50	20	nM	CHEMBL4531796
7.70	IC50	20	nM	CHEMBL4471670
7.70	IC50	20	nM	CHEMBL4473245
7.70	IC50	20	nM	CHEMBL4453903
7.70	IC50	20	nM	CHEMBL4548069
7.70	IC50	20	nM	CHEMBL4465490
7.70	IC50	20	nM	CHEMBL4539952
7.70	IC50	20	nM	CHEMBL4476094
7.70	IC50	20	nM	CHEMBL4586427
7.70	IC50	20	nM	CHEMBL4455332
7.70	IC50	20	nM	CHEMBL4589701
7.70	IC50	20	nM	CHEMBL4551253
7.70	IC50	20	nM	CHEMBL4529186

PubChem BioAssay actives

74 with measured affinity, of 102 total; 38 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-(4-amino-3-methylsulfanylpyrazolo[3,4-d]pyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl sulfamate	1724437: Inhibition of recombinant His-tagged human ATG7 incubated for 105 mins in presence of GST-tagged ATG3 and Flag-tagged Gabarap and measured after 2 hrs by FRET assay relative to control	ic50	0.0140	uM
[(2R,3S,4R,5R)-5-[4-amino-3-(1H-pyrazol-4-ylsulfanyl)pyrazolo[3,4-d]pyrimidin-1-yl]-3,4-dihydroxyoxolan-2-yl]methyl sulfamate	1724437: Inhibition of recombinant His-tagged human ATG7 incubated for 105 mins in presence of GST-tagged ATG3 and Flag-tagged Gabarap and measured after 2 hrs by FRET assay relative to control	ic50	0.0160	uM
[(2R,3S,4R,5R)-5-(4-amino-3-propan-2-ylsulfanylpyrazolo[3,4-d]pyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl sulfamate	1724437: Inhibition of recombinant His-tagged human ATG7 incubated for 105 mins in presence of GST-tagged ATG3 and Flag-tagged Gabarap and measured after 2 hrs by FRET assay relative to control	ic50	0.0170	uM
[(2R,3S,4R,5R)-5-[4-amino-3-(3-methylphenyl)sulfanylpyrazolo[3,4-d]pyrimidin-1-yl]-3,4-dihydroxyoxolan-2-yl]methyl sulfamate	1724437: Inhibition of recombinant His-tagged human ATG7 incubated for 105 mins in presence of GST-tagged ATG3 and Flag-tagged Gabarap and measured after 2 hrs by FRET assay relative to control	ic50	0.0180	uM
[(2R,3R,4S,5R)-5-(4-amino-3-propan-2-ylsulfanylpyrazolo[3,4-d]pyrimidin-1-yl)-4-fluoro-3-hydroxyoxolan-2-yl]methyl sulfamate	1724437: Inhibition of recombinant His-tagged human ATG7 incubated for 105 mins in presence of GST-tagged ATG3 and Flag-tagged Gabarap and measured after 2 hrs by FRET assay relative to control	ic50	0.0200	uM
[(2R,3S,4R,5R)-5-(4-amino-3-ethylsulfanylpyrazolo[3,4-d]pyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl sulfamate	1724437: Inhibition of recombinant His-tagged human ATG7 incubated for 105 mins in presence of GST-tagged ATG3 and Flag-tagged Gabarap and measured after 2 hrs by FRET assay relative to control	ic50	0.0220	uM
[(2R,3S,4R,5R)-5-(4-amino-3-benzylsulfanylpyrazolo[3,4-d]pyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl sulfamate	1724437: Inhibition of recombinant His-tagged human ATG7 incubated for 105 mins in presence of GST-tagged ATG3 and Flag-tagged Gabarap and measured after 2 hrs by FRET assay relative to control	ic50	0.0230	uM
[(2R,3S,5R)-5-(4-amino-3-propan-2-ylsulfanylpyrazolo[3,4-d]pyrimidin-1-yl)-3-hydroxyoxolan-2-yl]methyl sulfamate	1724437: Inhibition of recombinant His-tagged human ATG7 incubated for 105 mins in presence of GST-tagged ATG3 and Flag-tagged Gabarap and measured after 2 hrs by FRET assay relative to control	ic50	0.0270	uM
[(2R,3S,4R,5R)-5-[4-amino-3-(difluoromethoxy)pyrazolo[3,4-d]pyrimidin-1-yl]-3,4-dihydroxyoxolan-2-yl]methyl sulfamate	1724437: Inhibition of recombinant His-tagged human ATG7 incubated for 105 mins in presence of GST-tagged ATG3 and Flag-tagged Gabarap and measured after 2 hrs by FRET assay relative to control	ic50	0.0290	uM
[(2R,3S,4R,5R)-5-(4-amino-3-phenylsulfanylpyrazolo[3,4-d]pyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl sulfamate	1724437: Inhibition of recombinant His-tagged human ATG7 incubated for 105 mins in presence of GST-tagged ATG3 and Flag-tagged Gabarap and measured after 2 hrs by FRET assay relative to control	ic50	0.0290	uM
[(2R,3R,4S,5R)-5-[4-amino-3-(3-chlorophenyl)sulfanylpyrazolo[3,4-d]pyrimidin-1-yl]-4-fluoro-3-hydroxyoxolan-2-yl]methyl sulfamate	1724437: Inhibition of recombinant His-tagged human ATG7 incubated for 105 mins in presence of GST-tagged ATG3 and Flag-tagged Gabarap and measured after 2 hrs by FRET assay relative to control	ic50	0.0310	uM
[(2R,3R,4S,5R)-5-[4-amino-3-(3-methylphenyl)sulfanylpyrazolo[3,4-d]pyrimidin-1-yl]-4-fluoro-3-hydroxyoxolan-2-yl]methyl sulfamate	1724437: Inhibition of recombinant His-tagged human ATG7 incubated for 105 mins in presence of GST-tagged ATG3 and Flag-tagged Gabarap and measured after 2 hrs by FRET assay relative to control	ic50	0.0350	uM
[(2R,3R,4S,5R)-5-(4-amino-3-methylsulfanylpyrazolo[3,4-d]pyrimidin-1-yl)-4-fluoro-3-hydroxyoxolan-2-yl]methyl sulfamate	1724437: Inhibition of recombinant His-tagged human ATG7 incubated for 105 mins in presence of GST-tagged ATG3 and Flag-tagged Gabarap and measured after 2 hrs by FRET assay relative to control	ic50	0.0410	uM
[(2R,3R,4S,5R)-5-[4-amino-3-(difluoromethoxy)pyrazolo[3,4-d]pyrimidin-1-yl]-4-fluoro-3-hydroxyoxolan-2-yl]methyl sulfamate	1724437: Inhibition of recombinant His-tagged human ATG7 incubated for 105 mins in presence of GST-tagged ATG3 and Flag-tagged Gabarap and measured after 2 hrs by FRET assay relative to control	ic50	0.0430	uM
[(2R,3S,5R)-5-(4-amino-3-methylsulfanylpyrazolo[3,4-d]pyrimidin-1-yl)-3-hydroxyoxolan-2-yl]methyl sulfamate	1724437: Inhibition of recombinant His-tagged human ATG7 incubated for 105 mins in presence of GST-tagged ATG3 and Flag-tagged Gabarap and measured after 2 hrs by FRET assay relative to control	ic50	0.0480	uM
[(2R,3S,5R)-5-(4-amino-3-ethylsulfanylpyrazolo[3,4-d]pyrimidin-1-yl)-3-hydroxyoxolan-2-yl]methyl sulfamate	1724437: Inhibition of recombinant His-tagged human ATG7 incubated for 105 mins in presence of GST-tagged ATG3 and Flag-tagged Gabarap and measured after 2 hrs by FRET assay relative to control	ic50	0.0520	uM
[(2S,3S,5R)-5-(4-amino-3-propan-2-ylsulfanylpyrazolo[3,4-d]pyrimidin-1-yl)-3-hydroxyoxolan-2-yl]methyl sulfamate	1724437: Inhibition of recombinant His-tagged human ATG7 incubated for 105 mins in presence of GST-tagged ATG3 and Flag-tagged Gabarap and measured after 2 hrs by FRET assay relative to control	ic50	0.0570	uM
[(2S,3S,5R)-5-[4-amino-3-(2-fluoro-4-methylphenyl)sulfanylpyrazolo[3,4-d]pyrimidin-1-yl]-3-hydroxyoxolan-2-yl]methyl sulfamate	1724437: Inhibition of recombinant His-tagged human ATG7 incubated for 105 mins in presence of GST-tagged ATG3 and Flag-tagged Gabarap and measured after 2 hrs by FRET assay relative to control	ic50	0.0620	uM
[(2R,3S,5R)-5-[4-amino-3-(2,3-dihydro-1H-inden-5-ylsulfanyl)pyrazolo[3,4-d]pyrimidin-1-yl]-3-hydroxyoxolan-2-yl]methyl sulfamate	1724437: Inhibition of recombinant His-tagged human ATG7 incubated for 105 mins in presence of GST-tagged ATG3 and Flag-tagged Gabarap and measured after 2 hrs by FRET assay relative to control	ic50	0.0660	uM
[(2R,3S,5R)-5-[4-amino-3-(2-fluoro-4-methylphenyl)sulfanylpyrazolo[3,4-d]pyrimidin-1-yl]-3-hydroxyoxolan-2-yl]methyl sulfamate	1724437: Inhibition of recombinant His-tagged human ATG7 incubated for 105 mins in presence of GST-tagged ATG3 and Flag-tagged Gabarap and measured after 2 hrs by FRET assay relative to control	ic50	0.0800	uM
[(2R,3S,4R,5R)-5-(4-amino-3-oxo-2H-pyrazolo[3,4-d]pyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl sulfamate	1724437: Inhibition of recombinant His-tagged human ATG7 incubated for 105 mins in presence of GST-tagged ATG3 and Flag-tagged Gabarap and measured after 2 hrs by FRET assay relative to control	ic50	0.0840	uM
[(2R,3S,4R,5R)-5-(4-amino-3-methoxypyrazolo[3,4-d]pyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl sulfamate	1724437: Inhibition of recombinant His-tagged human ATG7 incubated for 105 mins in presence of GST-tagged ATG3 and Flag-tagged Gabarap and measured after 2 hrs by FRET assay relative to control	ic50	0.0890	uM
[(2R,3S,5R)-5-[4-amino-3-(3-methylphenyl)sulfanylpyrazolo[3,4-d]pyrimidin-1-yl]-3-hydroxyoxolan-2-yl]methyl sulfamate	1724437: Inhibition of recombinant His-tagged human ATG7 incubated for 105 mins in presence of GST-tagged ATG3 and Flag-tagged Gabarap and measured after 2 hrs by FRET assay relative to control	ic50	0.0950	uM
[(2R,3S,5R)-5-[4-amino-3-(difluoromethoxy)pyrazolo[3,4-d]pyrimidin-1-yl]-3-hydroxyoxolan-2-yl]methyl sulfamate	1724437: Inhibition of recombinant His-tagged human ATG7 incubated for 105 mins in presence of GST-tagged ATG3 and Flag-tagged Gabarap and measured after 2 hrs by FRET assay relative to control	ic50	0.1000	uM
[(2R,3S,5R)-5-[4-amino-3-(3-chlorophenyl)sulfanylpyrazolo[3,4-d]pyrimidin-1-yl]-3-hydroxyoxolan-2-yl]methyl sulfamate	1724437: Inhibition of recombinant His-tagged human ATG7 incubated for 105 mins in presence of GST-tagged ATG3 and Flag-tagged Gabarap and measured after 2 hrs by FRET assay relative to control	ic50	0.1040	uM
[(2S,3S,5R)-5-(4-amino-3-methylsulfanylpyrazolo[3,4-d]pyrimidin-1-yl)-3-hydroxyoxolan-2-yl]methyl sulfamate	1724437: Inhibition of recombinant His-tagged human ATG7 incubated for 105 mins in presence of GST-tagged ATG3 and Flag-tagged Gabarap and measured after 2 hrs by FRET assay relative to control	ic50	0.1240	uM
[(2S,3S,4R,5R)-5-(4-amino-3-propan-2-ylsulfanylpyrazolo[3,4-d]pyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl sulfamate	1724437: Inhibition of recombinant His-tagged human ATG7 incubated for 105 mins in presence of GST-tagged ATG3 and Flag-tagged Gabarap and measured after 2 hrs by FRET assay relative to control	ic50	0.1290	uM
[(2S,3R,4S,5R)-5-(4-amino-3-methylsulfanylpyrazolo[3,4-d]pyrimidin-1-yl)-4-fluoro-3-hydroxyoxolan-2-yl]methyl sulfamate	1724437: Inhibition of recombinant His-tagged human ATG7 incubated for 105 mins in presence of GST-tagged ATG3 and Flag-tagged Gabarap and measured after 2 hrs by FRET assay relative to control	ic50	0.1450	uM
[(2S,3S,5R)-5-[4-amino-3-(2,3-dihydro-1H-inden-5-ylsulfanyl)pyrazolo[3,4-d]pyrimidin-1-yl]-3-hydroxyoxolan-2-yl]methyl sulfamate	1724437: Inhibition of recombinant His-tagged human ATG7 incubated for 105 mins in presence of GST-tagged ATG3 and Flag-tagged Gabarap and measured after 2 hrs by FRET assay relative to control	ic50	0.1560	uM
[(2R,3R,4S,5R)-5-(4-amino-3-methoxypyrazolo[3,4-d]pyrimidin-1-yl)-4-fluoro-3-hydroxyoxolan-2-yl]methyl sulfamate	1724437: Inhibition of recombinant His-tagged human ATG7 incubated for 105 mins in presence of GST-tagged ATG3 and Flag-tagged Gabarap and measured after 2 hrs by FRET assay relative to control	ic50	0.1770	uM
[(2S,3S,5R)-5-[4-amino-3-(3-chlorophenyl)sulfanylpyrazolo[3,4-d]pyrimidin-1-yl]-3-hydroxyoxolan-2-yl]methyl sulfamate	1724437: Inhibition of recombinant His-tagged human ATG7 incubated for 105 mins in presence of GST-tagged ATG3 and Flag-tagged Gabarap and measured after 2 hrs by FRET assay relative to control	ic50	0.1900	uM
[(2R,3S,5R)-5-(4-amino-3-methoxypyrazolo[3,4-d]pyrimidin-1-yl)-3-hydroxyoxolan-2-yl]methyl sulfamate	1724437: Inhibition of recombinant His-tagged human ATG7 incubated for 105 mins in presence of GST-tagged ATG3 and Flag-tagged Gabarap and measured after 2 hrs by FRET assay relative to control	ic50	0.2490	uM
[(2R,3S,4R,5R)-5-(4-amino-3-ethoxypyrazolo[3,4-d]pyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl sulfamate	1724437: Inhibition of recombinant His-tagged human ATG7 incubated for 105 mins in presence of GST-tagged ATG3 and Flag-tagged Gabarap and measured after 2 hrs by FRET assay relative to control	ic50	0.2550	uM
[(2R,3S,4R,5R)-5-(4-amino-3-phenylmethoxypyrazolo[3,4-d]pyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl sulfamate	1724437: Inhibition of recombinant His-tagged human ATG7 incubated for 105 mins in presence of GST-tagged ATG3 and Flag-tagged Gabarap and measured after 2 hrs by FRET assay relative to control	ic50	0.2640	uM
[(2S,3S,4R,5R)-5-(4-amino-3-methylsulfanylpyrazolo[3,4-d]pyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl sulfamate	1724437: Inhibition of recombinant His-tagged human ATG7 incubated for 105 mins in presence of GST-tagged ATG3 and Flag-tagged Gabarap and measured after 2 hrs by FRET assay relative to control	ic50	0.3250	uM
[(2R,3S,4R,5R)-5-[4-amino-3-(2-phenylethyl)pyrazolo[3,4-d]pyrimidin-1-yl]-3,4-dihydroxyoxolan-2-yl]methyl sulfamate	1724437: Inhibition of recombinant His-tagged human ATG7 incubated for 105 mins in presence of GST-tagged ATG3 and Flag-tagged Gabarap and measured after 2 hrs by FRET assay relative to control	ic50	0.3510	uM
[(2R,3S,4R,5R)-5-(4-aminopyrazolo[3,4-d]pyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl sulfamate	1724437: Inhibition of recombinant His-tagged human ATG7 incubated for 105 mins in presence of GST-tagged ATG3 and Flag-tagged Gabarap and measured after 2 hrs by FRET assay relative to control	ic50	0.4570	uM
[(2R,3S,4R,5R)-5-(4-amino-3-propan-2-yloxypyrazolo[3,4-d]pyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl sulfamate	1724437: Inhibition of recombinant His-tagged human ATG7 incubated for 105 mins in presence of GST-tagged ATG3 and Flag-tagged Gabarap and measured after 2 hrs by FRET assay relative to control	ic50	2.6000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
3-methyladenine	decreases reaction, increases expression, decreases expression, affects cotreatment	5
sodium arsenite	decreases reaction, affects cotreatment, decreases expression, increases abundance, increases methylation (+2 more)	4
Acetylcysteine	decreases reaction, increases expression, increases abundance	4
Benzo(a)pyrene	decreases expression	4
Arsenic Trioxide	increases reaction, affects reaction, decreases reaction, increases expression, increases degradation	3
Vorinostat	increases reaction, increases expression, affects response to substance, increases cleavage	3
Arsenic	decreases expression, affects methylation, affects reaction, increases abundance, increases expression (+1 more)	3
Doxorubicin	increases expression, decreases reaction, increases degradation, decreases expression	3
sodium arsenate	increases expression, decreases reaction, affects reaction, increases abundance	2
beta-lapachone	decreases reaction, increases expression, affects response to substance	2
Acrolein	increases expression, affects reaction, increases lipidation, decreases reaction	2
Ethanol	increases reaction, decreases reaction, increases expression	2
Amiodarone	increases cleavage, affects response to substance, increases expression, affects reaction	2
Cisplatin	decreases expression	2
Nickel	affects cotreatment, increases expression, decreases expression	2
Ozone	affects expression, increases abundance, increases expression	2
Paraquat	decreases reaction, increases expression, decreases expression	2
Rotenone	decreases expression, decreases reaction, increases expression	2
Tretinoin	affects reaction, decreases reaction, increases expression	2
Cyclosporine	affects cotreatment, increases expression	2
Aflatoxin B1	decreases expression, increases methylation	2
Cadmium Chloride	decreases reaction, increases abundance, increases expression, affects reaction	2
Palmitic Acid	affects cotreatment, decreases expression, affects reaction, decreases reaction, increases expression	2
Nanotubes, Carbon	decreases expression	2
BO-1012	increases reaction, decreases reaction, increases phosphorylation, increases cleavage	1
28-O-acetylbetulin-3-ylglucopyranoside	decreases reaction, increases activity	1
7-hydroxydehydronuciferine	increases expression	1
bisphenol F	increases expression	1
perfluorotetradecanoic acid	affects cotreatment, decreases expression	1
thymoquinone	decreases expression	1

ChEMBL screening assays

12 unique, capped per target: 12 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2328918	Binding	Inhibition of ATG7 (unknown origin)	Exploring a new frontier in cancer treatment: targeting the ubiquitin and ubiquitin-like activating enzymes. — J Med Chem

Cellosaurus cell lines

10 cell lines: 9 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_1636	Panc 04.03	Cancer cell line	Male
CVCL_B1A6	Abcam THP-1 ATG7 KO	Cancer cell line	Male
CVCL_B9VE	Abcam HeLa ATG7 KO	Cancer cell line	Female
CVCL_D8ZN	Ubigene HEK293 ATG7 KO	Transformed cell line	Female
CVCL_D9Y5	Ubigene HeLa ATG7 KO	Cancer cell line	Female
CVCL_HD54	DLD-1 ATG7(+/-)	Cancer cell line	Male
CVCL_HE14	Panc 04.03 MAP2K4(-/-)	Cancer cell line	Male
CVCL_SE02	HAP1 ATG7 (-) 1	Cancer cell line	Male
CVCL_SE03	HAP1 ATG7 (-) 2	Cancer cell line	Male
CVCL_SE04	HAP1 ATG7 (-) 3	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00417066	PHASE4	COMPLETED	Flexible GnRH Antagonist vs Flare up GnRH Agonist Protocol in Poor Responders
NCT00732693	PHASE4	COMPLETED	Evaluation of Physiologic and Standard Sex Steroid Replacement Regimens in Women With Premature Ovarian Failure
NCT00837616	PHASE4	COMPLETED	Estrogen Dosing in Turner Syndrome: Pharmacology and Metabolism
NCT01853501	PHASE4	UNKNOWN	Effects of ADSC Therapy in Women With POF
NCT02783937	PHASE4	COMPLETED	Filgrastim for Premature Ovarian Insufficiency
NCT03535480	PHASE4	UNKNOWN	Autologous Bone Marrow Stem Cell Ovarian Transplantation to Restore Ovarian Function in Premature Ovarian Failure
NCT00140998	PHASE3	COMPLETED	Estrogen Treatment (Oral vs. Patches) in Turner Syndrome
NCT00001951	PHASE2	COMPLETED	Hormone Replacement in Young Women With Premature Ovarian Failure
NCT00370019	PHASE2	WITHDRAWN	Effects of an Estrogen Replacement Therapy Skin Patch on Ovulation in Women With Premature Ovarian Failure
NCT00429494	PHASE2	COMPLETED	GnRH Analogue for Ovarian Function Preservation in Hematopoietic Stem Cell Transplantation Patients
NCT03816852	PHASE2	SUSPENDED	The Safety and Efficiency Study of Mesenchymal Stem Cell (19#iSCLife®-POI) in Premature Ovarian Insufficiency
NCT04536467	PHASE2	UNKNOWN	Prevention of Chemotherapy-Induced Ovarian Failure With Goserelin in Premenopausal Lymphoma Patients
NCT06117982	PHASE2	COMPLETED	The Impact of Granulocyte Colony Stimulating Factor on Premature Ovarian Insufficiency
NCT02912104	PHASE1	COMPLETED	A Therapeutic Trial of Human Amniotic Epithelial Cells Transplantation for Primary Ovarian Failure
NCT03178695	PHASE1	COMPLETED	Inovium Ovarian Rejuvenation Trials
NCT04815213	PHASE1	ACTIVE_NOT_RECRUITING	The Use of Expandeded Mesenchymal Stromal Cells (MSC) in Premature Ovarian Failure (POF) in Adult Humans
NCT05138367	PHASE1	COMPLETED	Effects of UCA-PSCs in Women With POF
NCT06132542	PHASE1	UNKNOWN	Autologous ADMSC Transplantation in Patients With POI
NCT00948857	PHASE2/PHASE3	TERMINATED	Dehydroepiandrosterone (DHEA) Treatment and Premature Ovarian Failure (POF)
NCT04031456	PHASE2/PHASE3	RECRUITING	Autologous PRP Infusion May Restore Ovarian Function and May Promote Folliculogenesis in POI Patients
NCT02043743	PHASE1/PHASE2	UNKNOWN	Autologous Stem Cells Transplantation in Patients With Idiopathic and Drug Induced Premature Ovarian Failure
NCT02062931	PHASE1/PHASE2	UNKNOWN	Autologous Mesenchymal Stem Cells Transplantation In Women With Premature Ovarian Failure
NCT02151890	PHASE1/PHASE2	COMPLETED	Pregnancy After Stem Cell Transplantation in Premature Ovarian Failure
NCT02372474	PHASE1/PHASE2	COMPLETED	It is a Real The First Baby Of Autologous Stem Cell Therapy in Premature Ovarian Failure
NCT02603744	PHASE1/PHASE2	UNKNOWN	Autologous Adipose Derived Mesenchymal Stromal Cells Transplantation in Women With Premature Ovarian Failure (POF)
NCT02644447	PHASE1/PHASE2	COMPLETED	Transplantation of HUC-MSCs With Injectable Collagen Scaffold for POF
NCT03069209	PHASE1/PHASE2	UNKNOWN	Autologous Bone Marrow-Derived Stem Cell Transplantation in Patients With Premature Ovarian Failure (POF)
NCT03985462	PHASE1/PHASE2	WITHDRAWN	Very Small Embryonic-like Stem Cells for Ovary
NCT04009473	PHASE1/PHASE2	UNKNOWN	Stem Cell Therapy and Growth Factor Ovarian in Vitro Activation
NCT04071574	PHASE1/PHASE2	COMPLETED	Comparative Study on the Efficacy of Ovarian Stimulation Protocols on the Success Rate of ICSI in Female Infertility
NCT04922398	PHASE1/PHASE2	UNKNOWN	Ovarian Injection of PRP (Platelet -Rich Plasma) Vs Normal Saline in Premature Ovarian Insufficiency
NCT05462379	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Autologous Heterotopic Fresh Ovarian Graft in Woman With LACC Eligible for Pelvic Radiotherapy Treatment.
NCT06202547	PHASE1/PHASE2	UNKNOWN	Intra-ovarian Injection of MSC-EVs in Idiopathic Premature Ovarian Failure
NCT01129947	EARLY_PHASE1	WITHDRAWN	The Use of DHEA in Women With Premature Ovarian Failure
NCT05522634	EARLY_PHASE1	UNKNOWN	A Clinical Study of Chinese Herbal Compound TJAOA101 in the Treatment of Premature Ovarian Insufficiency
NCT07308327	EARLY_PHASE1	ACTIVE_NOT_RECRUITING	The Influence of Gut Microbiota on Ovarian Function: A Single-center, Randomized,Double Blind, Parallel-controlled, Exploratory Clinical Trial
NCT00001275	Not specified	COMPLETED	Ovarian Follicle Function in Patients With Primary Ovarian Failure
NCT00001306	Not specified	COMPLETED	Steroid Therapy in Autoimmune Premature Ovarian Failure
NCT00006156	Not specified	COMPLETED	Feasibility Study for Development of an Early Test for Ovarian Failure
NCT00119925	Not specified	UNKNOWN	‘SPRING’-Study: Subfertility Guidelines: Patient Related Implementation in the Netherlands Among Gynaecologists