ATG13

Summary

ATG13 (autophagy related 13, HGNC:29091) is a protein-coding gene on chromosome 11p11.2, encoding Autophagy-related protein 13 (O75143). Autophagy factor required for autophagosome formation and mitophagy.

The protein encoded by this gene is an autophagy factor and a target of the TOR kinase signaling pathway. The encoded protein is essential for autophagosome formation and mitophagy.

Source: NCBI Gene 9776 — RefSeq curated summary.

At a glance

• GWAS associations: 10
• Clinical variants (ClinVar): 88 total
• Druggable target: yes
• MANE Select transcript: NM_001346311

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29091
Approved symbol	ATG13
Name	autophagy related 13
Location	11p11.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000175224
Ensembl biotype	protein_coding
OMIM	615088
Entrez	9776

Gene structure

Transcript identifiers

Ensembl transcripts: 102 — 89 protein_coding, 6 retained_intron, 5 protein_coding_CDS_not_defined, 2 nonsense_mediated_decay

ENST00000359513, ENST00000395549, ENST00000524625, ENST00000525009, ENST00000525850, ENST00000526485, ENST00000526508, ENST00000526715, ENST00000527907, ENST00000528145, ENST00000528494, ENST00000528704, ENST00000528984, ENST00000529395, ENST00000529655, ENST00000530500, ENST00000530942, ENST00000531933, ENST00000532067, ENST00000533316, ENST00000533325, ENST00000534610, ENST00000577256, ENST00000578626, ENST00000579280, ENST00000580238, ENST00000581416, ENST00000581438, ENST00000582547, ENST00000583249, ENST00000683050, ENST00000890924, ENST00000890925, ENST00000890926, ENST00000890927, ENST00000890928, ENST00000890929, ENST00000890930, ENST00000890931, ENST00000890932, ENST00000890933, ENST00000890934, ENST00000890935, ENST00000890936, ENST00000890937, ENST00000890938, ENST00000890939, ENST00000890940, ENST00000890941, ENST00000890942, ENST00000890943, ENST00000890944, ENST00000890945, ENST00000890946, ENST00000890947, ENST00000890948, ENST00000890949, ENST00000890950, ENST00000890951, ENST00000890952, ENST00000890953, ENST00000890954, ENST00000890955, ENST00000890956, ENST00000890957, ENST00000890958, ENST00000890959, ENST00000890960, ENST00000890961, ENST00000890962, ENST00000890963, ENST00000934000, ENST00000934001, ENST00000934002, ENST00000934003, ENST00000934004, ENST00000934005, ENST00000934006, ENST00000934007, ENST00000934008, ENST00000934009, ENST00000934010, ENST00000934011, ENST00000934012, ENST00000934013, ENST00000934014, ENST00000934015, ENST00000934016, ENST00000959950, ENST00000959951, ENST00000959952, ENST00000959953, ENST00000959954, ENST00000959955, ENST00000959956, ENST00000959957, ENST00000959958, ENST00000959959, ENST00000959960, ENST00000959961, ENST00000959962, ENST00000959963

RefSeq mRNA: 51 — MANE Select: NM_001346311 NM_001142673, NM_001205119, NM_001205120, NM_001205121, NM_001205122, NM_001346311, NM_001346312, NM_001346313, NM_001346314, NM_001346315, NM_001346316, NM_001346317, NM_001346318, NM_001346319, NM_001346320, NM_001346321, NM_001346322, NM_001346323, NM_001346324, NM_001346325, NM_001346326, NM_001346327, NM_001346328, NM_001346329, NM_001346330, NM_001346331, NM_001346332, NM_001346333, NM_001346334, NM_001346335, NM_001346336, NM_001346337, NM_001346338, NM_001346340, NM_001346342, NM_001346344, NM_001346346, NM_001346348, NM_001346349, NM_001346350, NM_001346351, NM_001346352, NM_001346353, NM_001346354, NM_001346355, NM_001346356, NM_001346357, NM_001346358, NM_001346359, NM_001346360, NM_014741

CCDS: CCDS44582, CCDS55760, CCDS55761, CCDS7921

Canonical transcript exons

ENST00000683050 — 19 exons

Exon	Start	End
ENSE00001181630	46668794	46668910
ENSE00001181647	46664849	46664959
ENSE00001263895	46630045	46630100
ENSE00001478380	46663997	46664095
ENSE00003500836	46650177	46650317
ENSE00003535424	46659392	46659485
ENSE00003565203	46656233	46656273
ENSE00003592715	46667773	46667887
ENSE00003604635	46657524	46657622
ENSE00003605235	46665383	46665519
ENSE00003611132	46669404	46669532
ENSE00003669479	46644279	46644360
ENSE00003670978	46645870	46645989
ENSE00003682203	46668499	46668576
ENSE00003692251	46649137	46649183
ENSE00003784118	46645339	46645419
ENSE00003785763	46657095	46657191
ENSE00003916390	46617553	46617890
ENSE00003920556	46672255	46674518

Expression profiles

Bgee: expression breadth ubiquitous, 286 present calls, max score 97.64.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 30.5124 / max 215.3042, expressed in 1821 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
114148	26.8773	1818
114147	3.6352	1487

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left testis	UBERON:0004533	97.64	gold quality
right testis	UBERON:0004534	97.53	gold quality
testis	UBERON:0000473	96.04	gold quality
adenohypophysis	UBERON:0002196	96.03	gold quality
pituitary gland	UBERON:0000007	95.95	gold quality
colonic epithelium	UBERON:0000397	95.74	gold quality
prefrontal cortex	UBERON:0000451	95.69	gold quality
right frontal lobe	UBERON:0002810	95.67	gold quality
skin of leg	UBERON:0001511	95.06	gold quality
tibial nerve	UBERON:0001323	94.84	gold quality
right hemisphere of cerebellum	UBERON:0014890	94.81	gold quality
body of pancreas	UBERON:0001150	94.77	gold quality
stromal cell of endometrium	CL:0002255	94.60	gold quality
gall bladder	UBERON:0002110	94.58	gold quality
Brodmann (1909) area 9	UBERON:0013540	94.53	gold quality
cerebellar hemisphere	UBERON:0002245	94.39	gold quality
mucosa of stomach	UBERON:0001199	94.35	gold quality
cerebellar cortex	UBERON:0002129	94.35	gold quality
cortical plate	UBERON:0005343	94.19	gold quality
cingulate cortex	UBERON:0003027	94.12	gold quality
anterior cingulate cortex	UBERON:0009835	94.06	gold quality
frontal cortex	UBERON:0001870	93.95	gold quality
right adrenal gland cortex	UBERON:0035827	93.91	gold quality
skin of abdomen	UBERON:0001416	93.90	gold quality
putamen	UBERON:0001874	93.85	gold quality
right adrenal gland	UBERON:0001233	93.82	gold quality
minor salivary gland	UBERON:0001830	93.79	gold quality
lower esophagus mucosa	UBERON:0035834	93.78	gold quality
right lobe of thyroid gland	UBERON:0001119	93.77	gold quality
caudate nucleus	UBERON:0001873	93.74	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	10.92

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ULK1

miRNA regulators (miRDB)

141 targeting ATG13, 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-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-6772-5P	99.94	67.01	577
HSA-MIR-1-3P	99.93	72.35	1914
HSA-MIR-206	99.93	72.50	1893
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-613	99.91	71.50	1710
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-424-5P	99.89	71.90	2641
HSA-MIR-6838-5P	99.89	71.94	2690
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-6875-3P	99.82	70.26	2983

Literature-anchored findings (GeneRIF, showing 26)

• The functions of ULK1 and ULK2 are controlled by autophosphorylation and conformational changes involving exposure of the C-terminal domain and interaction with the putative human homologue of Atg13. (PMID:18936157)
• The gene product is the functional homologue of yeast Atg13, and required for autophagy in mammalian cells. (PMID:18936157)
• mTORC1 suppresses autophagy through direct regulation of the approximately 3-MDa ULK1-Atg13-FIP200 complex. (PMID:19211835)
• The ULK-Atg13-FIP200 complexes are direct targets of mTOR and important regulators of autophagy in response to mTOR signaling. (PMID:19225151)
• ATG13 and ULK1 are phosphorylated by the mTOR pathway in a nutrient starvation-regulated manner, indicating that the ULK1.ATG13.FIP200 complex acts as a node for integrating incoming autophagy signals into autophagosome biogenesis. (PMID:19258318)
• The identification of the novel protein, Atg101, and the validation of Atg13 and Atg101 as ULK1-interacting proteins, suggests an Atg1 complex is involved in the induction of macroautophagy in mammalian cells. (PMID:19287211)
• These data suggest that Atg101 is a novel Atg protein that functions together with ULK, Atg13 and FIP200. (PMID:19597335)
• Studies elucidated the inhibitory mechanism in which mTORC1 phosphorylates the autophagy regulatory complex containing unc-51-like kinase 1 (ULK1), the mammalian Atg13 protein, and focal adhesion kinase interacting protein of 200 kD (FIP200). (PMID:19690328)
• In response to DNA damage, ULK1 and ULK2 are upregulated by p53. The upregulation of ULK1 (ULK2)/ATG13 complex by p53 is necessary for the sustained autophagy activity induced by DNA damage. (PMID:21475306)
• Specific affinity of the LC3 isoforms to the Atg13 LC3-interacting region is required for proper autophagosome formation. (PMID:24290141)
• Structure of the human Atg13-Atg101 HORMA heterodimer in the ULK1 complex that controls autophagy has been described. (PMID:26299944)
• These results show that the SiMoA technology can detect quantitatively low levels of endogenous biomarkers with the ability to detect the loss of pSer(318)-Atg13 upon ULK1 inhibition. (PMID:27387056)
• these results demonstrate the effective anti-autophagic of NRAGE in non-small-cell lung cancer cells through AMPK/Ulk1/Atg13 autophagy signaling pathways. Therefore, NRAGE could be used as a potential therapeutic target for lung cancer. (PMID:28639909)
• ATG13 restricts viral replication by induction of type I interferon. (PMID:31270922)
• Klotho-mediated changes in the expression of Atg13 alter formation of ULK1 complex and thus initiation of ER- and Golgi-stress response mediated autophagy. (PMID:31732843)
• The unc-51 like autophagy activating kinase 1-autophagy related 13 complex has distinct functions in tunicamycin-treated cells. (PMID:32035621)
• CircMUC16 promotes autophagy of epithelial ovarian cancer via interaction with ATG13 and miR-199a. (PMID:32111227)
• ATG13 dynamics in nonselective autophagy and mitophagy: insights from live imaging studies and mathematical modeling. (PMID:32320309)
• the positive function of ULK1-ATG13 and their phosphorylation by CDK1 in mitotic autophagy regulation, is reported. (PMID:32516310)
• LUBAC and OTULIN regulate autophagy initiation and maturation by mediating the linear ubiquitination and the stabilization of ATG13. (PMID:32543267)
• The ERK1/2-ATG13-FIP200 signaling cascade is required for autophagy induction to protect renal cells from hypoglycemia-induced cell death. (PMID:33682133)
• Circ-PKD2 promotes Atg13-mediated autophagy by inhibiting miR-646 to increase the sensitivity of cisplatin in oral squamous cell carcinomas. (PMID:35220397)
• Elevated ATG13 in serum of patients with ME/CFS stimulates oxidative stress response in microglial cells via activation of receptor for advanced glycation end products (RAGE). (PMID:35487443)
• The effect of lactoferrin on ULK1 and ATG13 genes expression in breast cancer cell line MCF7 and bioinformatics studies of protein interaction between lactoferrin and the autophagy initiation complex. (PMID:36169801)
• Metamorphosis by ATG13 and ATG101 in human autophagy initiation. (PMID:37394799)
• The role of the HORMA domain proteins ATG13 and ATG101 in initiating autophagosome biogenesis. (PMID:37567770)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	atg13	ENSDARG00000036040
mus_musculus	Atg13	ENSMUSG00000027244
rattus_norvegicus	Atg13	ENSRNOG00000016984
drosophila_melanogaster	Atg13	FBGN0261108
caenorhabditis_elegans		WBGENE00017045

Protein

Protein identifiers

Autophagy-related protein 13 — O75143 (reviewed: O75143)

All UniProt accessions (14): A0A1B0GXJ3, E9PPR2, O75143, H0YCL5, H0YDR0, H0YEM7, H0YF43, J3KRU6, J3KST9, J3QLH7, J3QR16, J3QR83, J3QRL1, J9JIF6

UniProt curated annotations — full annotation on UniProt →

Function. Autophagy factor required for autophagosome formation and mitophagy. Target of the TOR kinase signaling pathway that regulates autophagy through the control of the phosphorylation status of ATG13 and ULK1, and the regulation of the ATG13-ULK1-RB1CC1 complex. Through its regulation of ULK1 activity, plays a role in the regulation of the kinase activity of mTORC1 and cell proliferation.

Subunit / interactions. Part of a complex consisting of ATG13, ULK1 and RB1CC1. Interacts with ATG101. Interacts with ULK1 (via C-terminus); this interaction is increased in the absence of TMEM39A. Interacts with ULK2 (via C-terminus). Interacts (via the LIR motif) with GABARAP, GABARAPL, GABARAPL2. Interacts (via the LIR motif) with MAP1LC3A, MAP1LC3B and MAP1LC3C. Interacts with TAB2 and TAB3. Interacts with C9orf72. Interacts with RB1CC1; this interaction is increased in the absence of TMEM39A.

Subcellular location. Cytoplasm. Cytosol. Preautophagosomal structure.

Post-translational modifications. Phosphorylated by ULK1, ULK2 and mTOR. Phosphorylation status depends on nutrient-rich conditions; dephosphorylated during starvation or following treatment with rapamycin. ULK1-mediated phosphorylation of ATG13 at Ser-355 is required for efficient clearance of depolarized mitochondria.

Domain organisation. The LIR motif (LC3-interacting region) is required for the interaction with the ATG8 family proteins GABARAP, GABARAPL, GABARAPL2, and MAP1LC3A.

Similarity. Belongs to the ATG13 family. Metazoan subfamily.

Isoforms (5)

UniProt ID	Names	Canonical?
O75143-1	1	yes
O75143-2	2
O75143-3	3
O75143-4	4
O75143-5	5

RefSeq proteins (51): NP_001136145, NP_001192048, NP_001192049, NP_001192050, NP_001192051, NP_001333240, NP_001333241, NP_001333242, NP_001333243, NP_001333244, NP_001333245, NP_001333246, NP_001333247, NP_001333248, NP_001333249, NP_001333250, NP_001333251, NP_001333252, NP_001333253, NP_001333254, NP_001333255, NP_001333256, NP_001333257, NP_001333258, NP_001333259, NP_001333260, NP_001333261, NP_001333262, NP_001333263, NP_001333264, NP_001333265, NP_001333266, NP_001333267, NP_001333269, NP_001333271, NP_001333273, NP_001333275, NP_001333277, NP_001333278, NP_001333279, NP_001333280, NP_001333281, NP_001333282, NP_001333283, NP_001333284, NP_001333285, NP_001333286, NP_001333287, NP_001333288, NP_001333289, NP_055556 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR018731	Atg13_N	Domain
IPR036570	HORMA_dom_sf	Homologous_superfamily
IPR040182	ATG13	Family

Pfam: PF10033

UniProt features (39 total): strand 8, splice variant 6, mutagenesis site 6, helix 6, region of interest 4, modified residue 4, turn 2, chain 1, short sequence motif 1, compositionally biased region 1

Structure

Experimental structures (PDB)

15 structures.

PDB	Method	Resolution (Å)
6HYN	X-RAY DIFFRACTION	1.14
5C50	X-RAY DIFFRACTION	1.63
3WAN	X-RAY DIFFRACTION	1.77
5XUY	X-RAY DIFFRACTION	2.2
8DO8	X-RAY DIFFRACTION	2.41
5XV6	X-RAY DIFFRACTION	2.46
5XV1	X-RAY DIFFRACTION	2.51
5XV3	X-RAY DIFFRACTION	2.57
3WAO	X-RAY DIFFRACTION	2.6
5XV4	X-RAY DIFFRACTION	2.95
3WAP	X-RAY DIFFRACTION	3.1
8SOI	ELECTRON MICROSCOPY	4.2
8SRM	ELECTRON MICROSCOPY	4.46
8SQZ	ELECTRON MICROSCOPY	5.85
9C82	ELECTRON MICROSCOPY	6.84

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O75143-F1	64.64	0.33

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): 361, 1, 355, 356

Mutagenesis-validated functional residues (6):

Position	Phenotype
127	abolishes interaction with atg101; when associated with d-133.
131	decreases interaction with atg101; when associated with d-134.
133	abolishes interaction with atg101; when associated with h-127.
134	decreases interaction with atg101; when associated with d-131.
444	decreases interaction with map1lc3a.
447	decreases interaction with map1lc3a.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-1632852	Macroautophagy
R-HSA-9612973	Autophagy

MSigDB gene sets: 192 (showing top): GOBP_REGULATION_OF_AUTOPHAGY, WANG_CLIM2_TARGETS_UP, GOBP_VACUOLE_ORGANIZATION, GOBP_LIPOPROTEIN_METABOLIC_PROCESS, GOBP_PROTEIN_TARGETING, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_ORGANELLE, GGGTGGRR_PAX4_03, GOBP_MACROAUTOPHAGY, GOMF_KINASE_ACTIVATOR_ACTIVITY, PID_MTOR_4PATHWAY, BROWNE_HCMV_INFECTION_48HR_DN, GOBP_REGULATION_OF_CATABOLIC_PROCESS, KOYAMA_SEMA3B_TARGETS_UP, GOBP_POSITIVE_REGULATION_OF_CATABOLIC_PROCESS, GOBP_LIPOPROTEIN_BIOSYNTHETIC_PROCESS

GO Biological Process (10): autophagosome assembly (GO:0000045), mitophagy (GO:0000423), negative regulation of cell population proliferation (GO:0008285), positive regulation of autophagy (GO:0010508), protein localization to phagophore assembly site (GO:0034497), piecemeal microautophagy of the nucleus (GO:0034727), response to mitochondrial depolarisation (GO:0098780), obsolete positive regulation of protein targeting to mitochondrion (GO:1903955), autophagy (GO:0006914), regulation of cell population proliferation (GO:0042127)

GO Molecular Function (5): kinase activator activity (GO:0019209), protein kinase regulator activity (GO:0019887), protein kinase binding (GO:0019901), protein binding (GO:0005515), protein serine/threonine kinase activator activity (GO:0043539)

GO Cellular Component (8): phagophore assembly site (GO:0000407), cytoplasm (GO:0005737), mitochondrion (GO:0005739), autophagosome (GO:0005776), endoplasmic reticulum membrane (GO:0005789), cytosol (GO:0005829), phagophore assembly site membrane (GO:0034045), Atg1/ULK1 kinase complex (GO:1990316)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Autophagy	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cytoplasm	4
cellular anatomical structure	3
cell population proliferation	2
kinase regulator activity	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
regulation of cell population proliferation	1
negative regulation of cellular process	1
autophagy	1
positive regulation of catabolic process	1
regulation of autophagy	1
autophagosome assembly	1
intracellular protein localization	1
microautophagy	1
nucleophagy	1
nucleus disassembly	1
cellular response to stress	1
catabolic process	1
transmembrane transport	1
process utilizing autophagic mechanism	1
regulation of cellular process	1
enzyme activator activity	1
kinase activity	1
protein kinase activity	1
protein kinase binding	1
kinase binding	1
binding	1
protein serine/threonine kinase activity	1
protein kinase activator activity	1
intracellular anatomical structure	1
intracellular membrane-bounded organelle	1
vacuole	1
organelle membrane	1

Protein interactions and networks

STRING

2150 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ATG13	ULK1	O75385	999
ATG13	RB1CC1	Q8TDY2	998
ATG13	ATG101	Q9BSB4	998
ATG13	ULK2	Q8IYT8	997
ATG13	ATG10	Q9H0Y0	978
ATG13	ATG14	Q6ZNE5	970
ATG13	F5GZY7	F5GZY7	965
ATG13	GABARAPL2	P60520	964
ATG13	PIK3C3	Q8NEB9	961
ATG13	BECN1	Q14457	948
ATG13	CIB1	Q99828	939
ATG13	ATG5	Q9H1Y0	918
ATG13	PIK3R4	Q99570	916
ATG13	ATG12	O94817	877
ATG13	WIPI1	Q5MNZ9	876

IntAct

103 interactions, top by confidence:

A	B	Type	Score
ATG101	ATG13	psi-mi:“MI:0914”(association)	0.950
ATG13	ATG101	psi-mi:“MI:0915”(physical association)	0.950
ATG101	ATG13	psi-mi:“MI:0915”(physical association)	0.950
ATG13	ATG101	psi-mi:“MI:0407”(direct interaction)	0.950
ATG13	ULK1	psi-mi:“MI:0914”(association)	0.940
ULK1	ATG13	psi-mi:“MI:0914”(association)	0.940
ULK1	ATG13	psi-mi:“MI:0915”(physical association)	0.940
ATG13	ULK1	psi-mi:“MI:2364”(proximity)	0.940
HUS1	RAD1	psi-mi:“MI:0914”(association)	0.840
ATG13	RB1CC1	psi-mi:“MI:0915”(physical association)	0.820
RB1CC1	ATG13	psi-mi:“MI:0914”(association)	0.820

BioGRID (458): ATG101 (Affinity Capture-MS), ATG13 (Affinity Capture-Western), RB1CC1 (Affinity Capture-Western), ULK1 (Affinity Capture-Western), ATG101 (Affinity Capture-Western), ULK1 (Affinity Capture-Western), MUL1 (Affinity Capture-Western), ATG13 (Biochemical Activity), ATG13 (Affinity Capture-Western), ATG13 (Affinity Capture-MS), ATG13 (Affinity Capture-MS), ATG13 (Affinity Capture-MS), ATG13 (Affinity Capture-MS), ATG13 (Affinity Capture-RNA), ATG13 (Affinity Capture-Western)

ESM2 similar proteins: A2BDA5, A4IIM9, A5A6N3, A9ZLX4, D2HNW6, F4HRV8, O35589, O54828, O70240, O75143, O75916, O88566, P49140, P49805, Q00IB7, Q08DY8, Q0IIJ3, Q13506, Q1LV22, Q3B7M3, Q4V7B1, Q5BJU7, Q5NVG8, Q5RE28, Q61122, Q62722, Q68EF0, Q69ZK7, Q6A098, Q6P1H6, Q6PFH3, Q6ZPF3, Q6ZPJ0, Q76CY8, Q7SYE0, Q7TP65, Q80TD3, Q80U16, Q86XL3, Q8AVJ1

Diamond homologs: A4IIM9, A5A6N3, O75143, P34379, Q08DY8, Q5RE28, Q7SYE0, Q91YI1, Q9VHR6

SIGNOR signaling

8 interactions.

A	Effect	B	Mechanism
ULK1	up-regulates	ATG13	phosphorylation
MTOR	down-regulates	ATG13	phosphorylation
ATG13	up-regulates	RB1CC1	binding
ATG13	up-regulates	ULK2	binding
ULK2	up-regulates	ATG13	phosphorylation
ATG101	up-regulates	ATG13	binding
ATG13	“form complex”	ULK1/Atg13/Fip200	binding
OFD1	“down-regulates quantity by destabilization”	ATG13	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 45 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
TBC/RABGAPs	5	43.3×	3e-06
Macroautophagy	10	38.5×	1e-11
TP53 Regulates Metabolic Genes	6	25.9×	3e-06
Translocation of SLC2A4 (GLUT4) to the plasma membrane	5	25.7×	3e-05
Autophagy	5	24.7×	4e-05
G2/M DNA damage checkpoint	6	24.0×	4e-06
SARS-CoV-1 Infection	5	23.8×	4e-05
G2/M Checkpoints	5	22.4×	5e-05

GO biological processes:

GO term	Partners	Fold	FDR
mitophagy	8	65.2×	4e-11
autophagosome assembly	10	57.6×	3e-13
autophagosome maturation	6	54.0×	1e-07
macroautophagy	5	30.9×	3e-05
autophagy	8	22.6×	1e-07
intracellular protein localization	6	16.1×	7e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	64
Likely benign	0
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

2887 predictions. Top by Δscore:

Variant	Effect	Δscore
11:46644277:A:AG	acceptor_gain	1.0000
11:46644278:G:GC	acceptor_gain	1.0000
11:46644278:GA:G	acceptor_gain	1.0000
11:46644278:GAT:G	acceptor_gain	1.0000
11:46644278:GATT:G	acceptor_gain	1.0000
11:46644278:GATTC:G	acceptor_gain	1.0000
11:46644356:TCAAG:T	donor_loss	1.0000
11:46644357:CAAG:C	donor_loss	1.0000
11:46644358:AAG:A	donor_loss	1.0000
11:46644360:GGT:G	donor_loss	1.0000
11:46644361:GT:G	donor_loss	1.0000
11:46644362:T:A	donor_loss	1.0000
11:46645868:A:AG	acceptor_gain	1.0000
11:46645869:G:GA	acceptor_gain	1.0000
11:46645869:GT:G	acceptor_gain	1.0000
11:46645869:GTT:G	acceptor_gain	1.0000
11:46645869:GTTC:G	acceptor_gain	1.0000
11:46645869:GTTCA:G	acceptor_gain	1.0000
11:46645989:GG:G	donor_loss	1.0000
11:46645991:T:G	donor_loss	1.0000
11:46649131:CTACA:C	acceptor_loss	1.0000
11:46649132:TACA:T	acceptor_loss	1.0000
11:46649133:ACAG:A	acceptor_gain	1.0000
11:46649134:CA:C	acceptor_loss	1.0000
11:46649135:A:AC	acceptor_loss	1.0000
11:46649135:A:AG	acceptor_gain	1.0000
11:46649135:AG:A	acceptor_gain	1.0000
11:46649136:G:GG	acceptor_gain	1.0000
11:46649136:G:GT	acceptor_loss	1.0000
11:46649136:GG:G	acceptor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000017961 (11:46655561 A>G), RS1000029630 (11:46636892 C>G,T), RS1000037324 (11:46652941 A>G), RS1000073983 (11:46649677 G>C,T), RS1000092180 (11:46630575 T>TTTTG), RS1000194244 (11:46617167 C>T), RS1000335390 (11:46625826 C>G,T), RS1000366501 (11:46626148 G>A,C,T), RS1000427784 (11:46668512 G>A), RS1000468669 (11:46649482 T>C), RS1000482277 (11:46641684 G>C), RS1000490937 (11:46672395 T>C), RS1000524254 (11:46660333 G>A), RS1000584440 (11:46660897 A>G,T), RS1000631653 (11:46654307 A>G)

Disease associations

OMIM: gene MIM:615088 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): prostate cancer (MONDO:0008315)

Orphanet (1): Familial prostate cancer (Orphanet:1331)

HPO phenotypes

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

GWAS associations

10 associations (top):

Study	Trait	p-value
GCST000763_2	Immunoglobulin A	2.000000e-06
GCST003814_31	Selective IgA deficiency	7.000000e-10
GCST004521_122	Autism spectrum disorder or schizophrenia	3.000000e-13
GCST004521_165	Autism spectrum disorder or schizophrenia	3.000000e-08
GCST005337_27	Headache	4.000000e-08
GCST006268_525	Reaction time	7.000000e-09
GCST006803_20	Schizophrenia	3.000000e-13
GCST007335_21	Age at first sexual intercourse	5.000000e-09
GCST007825_4	Alzheimer’s disease or fasting glucose levels (pleiotropy)	3.000000e-16
GCST90000025_154	Appendicular lean mass	2.000000e-11

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004747	protein measurement
EFO:0008393	reaction time measurement
EFO:0009749	age at first sexual intercourse measurement
EFO:0004980	appendicular lean mass

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D011471	Prostatic Neoplasms	C04.588.945.440.770; C12.100.500.260.750; C12.100.500.565.625; C12.200.294.260.750; C12.200.294.565.625; C12.200.758.409.750; C12.900.619.750

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067019 (SINGLE PROTEIN)

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

Binding affinities (BindingDB)

39 measured of 39 human assays (39 total across all organisms); most potent 39 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
4-(1-aminoethyl)-N-(2-thiophen-3-yl-1H-pyrrolo[2,3-b]pyridin-4-yl)cyclohexane-1-carboxamide	IC50	5 nM	US-12473284: Small molecule inhibitors of ULK1
US12473284, Compound MSK-A185	IC50	12.1 nM	US-12473284: Small molecule inhibitors of ULK1
US12473284, Compound MSK-A184-1	IC50	15.5 nM	US-12473284: Small molecule inhibitors of ULK1
US12473284, Compound MSK-A195	IC50	15.6 nM	US-12473284: Small molecule inhibitors of ULK1
4-(1-aminoethyl)-N-(2-phenyl-1H-pyrrolo[2,3-b]pyridin-4-yl)cyclohexane-1-carboxamide	IC50	18 nM	US-12473284: Small molecule inhibitors of ULK1
US12473284, Compound MSK-A189	IC50	18.3 nM	US-12473284: Small molecule inhibitors of ULK1
US12473284, Compound MSK-A184	IC50	18.9 nM	US-12473284: Small molecule inhibitors of ULK1
US12473284, Compound MSK-A188	IC50	19.4 nM	US-12473284: Small molecule inhibitors of ULK1
US12473284, Compound MSK-A192	IC50	20.2 nM	US-12473284: Small molecule inhibitors of ULK1
US12473284, Compound MSK-A191	IC50	20.6 nM	US-12473284: Small molecule inhibitors of ULK1
US12473284, Compound MSK-A196	IC50	20.8 nM	US-12473284: Small molecule inhibitors of ULK1
US12473284, Compound MSK-A182	IC50	22.9 nM	US-12473284: Small molecule inhibitors of ULK1
US12473284, Compound MSK-A176-2	IC50	23.6 nM	US-12473284: Small molecule inhibitors of ULK1
US12473284, Compound MSK-A190	IC50	23.8 nM	US-12473284: Small molecule inhibitors of ULK1
US12473284, Compound MSK-A197	IC50	25.7 nM	US-12473284: Small molecule inhibitors of ULK1
US12473284, Compound MSK-A193	IC50	26.3 nM	US-12473284: Small molecule inhibitors of ULK1
US12473284, Compound MSK-A194	IC50	29.2 nM	US-12473284: Small molecule inhibitors of ULK1
US12473284, Compound MSK-A186	IC50	29.8 nM	US-12473284: Small molecule inhibitors of ULK1
US12473284, Compound MSK-A184-2	IC50	38.9 nM	US-12473284: Small molecule inhibitors of ULK1
US12473284, Compound MSK-A200	IC50	39.2 nM	US-12473284: Small molecule inhibitors of ULK1
US12473284, Compound MSK-A187	IC50	40.5 nM	US-12473284: Small molecule inhibitors of ULK1
US12473284, Compound MSK-A191-1	IC50	40.8 nM	US-12473284: Small molecule inhibitors of ULK1
US12473284, Compound MSK-A198	IC50	43.3 nM	US-12473284: Small molecule inhibitors of ULK1
US12473284, Compound MSK-A178	IC50	47 nM	US-12473284: Small molecule inhibitors of ULK1
US12473284, Compound MSK-A177	IC50	54 nM	US-12473284: Small molecule inhibitors of ULK1
US12473284, Compound MSK-A176-1	IC50	56.2 nM	US-12473284: Small molecule inhibitors of ULK1
US12473284, Compound MSK-A191-2	IC50	59.1 nM	US-12473284: Small molecule inhibitors of ULK1
US12473284, Compound MSK-A157	IC50	73 nM	US-12473284: Small molecule inhibitors of ULK1
US12473284, Compound MSK-A178-2	IC50	89.1 nM	US-12473284: Small molecule inhibitors of ULK1
US12473284, Compound MSK-A199	IC50	109 nM	US-12473284: Small molecule inhibitors of ULK1
US12473284, Compound MSK-A172	IC50	110 nM	US-12473284: Small molecule inhibitors of ULK1
US12473284, Compound MSK-A202	IC50	156 nM	US-12473284: Small molecule inhibitors of ULK1
US12473284, Compound MSK-A183	IC50	185 nM	US-12473284: Small molecule inhibitors of ULK1
US12473284, Compound MSK-A178-1	IC50	352 nM	US-12473284: Small molecule inhibitors of ULK1
US12473284, Compound MSK-A181	IC50	515 nM	US-12473284: Small molecule inhibitors of ULK1
4-(1-aminoethyl)-N-(2-pyrazol-1-yl-1H-pyrrolo[2,3-b]pyridin-4-yl)cyclohexane-1-carboxamide	IC50	630 nM	US-12473284: Small molecule inhibitors of ULK1
US12473284, Compound MSK-A171	IC50	1450 nM	US-12473284: Small molecule inhibitors of ULK1
US12473284, Compound MSK-A091	IC50	2200 nM	US-12473284: Small molecule inhibitors of ULK1
US12473284, Compound MSK-A180	IC50	2380 nM	US-12473284: Small molecule inhibitors of ULK1

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.05	Kd	893.7	nM	CHEMBL5653589
5.74	ED50	1828	nM	CHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 2 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
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2147902: Binding affinity to human ATG13 incubated for 45 mins by Kinobead based pull down assay	kd	0.8937	uM

CTD chemical–gene interactions

29 total (human), top 29 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects methylation, increases expression	2
Cyclosporine	increases expression	2
metarrestin	affects binding, decreases reaction, increases reaction	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases methylation	1
arsenite	increases expression	1
coumarin	increases phosphorylation	1
cadmium sulfide	increases expression	1
bafilomycin A	decreases expression, decreases reaction, increases reaction	1
benzyloxycarbonylleucyl-leucyl-leucine aldehyde	increases reaction, decreases expression	1
amyloid beta-protein (1-42)	decreases expression, decreases reaction	1
perfluorooctane sulfonic acid	increases expression	1
jinfukang	affects cotreatment, increases expression	1
Imatinib Mesylate	increases phosphorylation	1
Anisomycin	decreases expression	1
Antimycin A	increases expression, increases reaction	1
Benzo(a)pyrene	increases expression	1
Chlorogenic Acid	decreases expression, decreases reaction	1
Cisplatin	affects cotreatment, increases expression	1
Cycloheximide	decreases expression	1
Drugs, Chinese Herbal	increases expression	1
Gallic Acid	increases expression	1
Nitrogen	decreases expression, decreases reaction, increases reaction, increases expression	1
Selenium	increases expression	1
Silicon Dioxide	increases expression	1
Thimerosal	decreases expression	1
Thiram	increases expression	1
Tobacco Smoke Pollution	increases expression	1
Tunicamycin	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
CHEMBL5650944	Binding	Binding affinity to human ATG13 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Cellosaurus cell lines

9 cell lines: 9 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_C2VP	HeLa S3 penta KO-ATG13 KO	Cancer cell line	Female
CVCL_D9Y3	Ubigene HeLa ATG13 KO	Cancer cell line	Female
CVCL_E1HE	HeLa S3 ATG13 KO clone #1	Cancer cell line	Female
CVCL_E6FA	HeLa S3 BNIP3 KO clone #1	Cancer cell line	Female
CVCL_F1YY	HeLa S3 ATG13 KO	Cancer cell line	Female
CVCL_F1YZ	HeLa S3 ATG13 KO+HaloTag-LC3	Cancer cell line	Female
CVCL_F1Z0	HeLa S3 ATG13 KO+Halo-LC3+HA-ATG13-WT	Cancer cell line	Female
CVCL_F1Z1	HeLa S3 ATG13 KO+Halo-LC3+HA-ATG13-HF:DD	Cancer cell line	Female
CVCL_SD92	HAP1 ATG13 (-)	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00029224	PHASE4	COMPLETED	Treatment With Zoledronic Acid in Patients With Breast Cancer, Multiple Myeloma, and Prostate Cancer With Cancer Related Bone Lesions
NCT00035997	PHASE4	COMPLETED	Open-label Trial on the Effect of I.V. Zoledronic Acid 4 mg on Bone Density in Hormone Sensitive Prostate Cancer Patients With Bone Metastasis
NCT00063609	PHASE4	COMPLETED	The Effect of Zoledronic Acid on Bone Loss in Prostate Cancer Patients Undergoing Androgen Deprivation Therapy
NCT00103623	PHASE4	SUSPENDED	The Plenaxis® Experience Study
NCT00106392	PHASE4	COMPLETED	A Safety and Efficacy Study of Prograf in the Prevention of Erectile Dysfunction After Radical Prostatectomy
NCT00185029	PHASE4	UNKNOWN	MR-Lymphography and Lymph Node Staging in Prostate Cancer
NCT00199485	PHASE4	COMPLETED	Angelica Sinensis for the Treatment of Hot Flashes in Men Undergoing LHRH Therapy for Prostate Cancer
NCT00219219	PHASE4	COMPLETED	Zoledronic Acid in the Prevention of Skeletal-related Events in Hormone Refractory and Hormone-sensitive Prostate Cancer Patients With Bone Metastases
NCT00219271	PHASE4	COMPLETED	Effect Of Zoledronic Acid On Circulating And Bone Marrow-Residing Prostate Cancer Cells In Patients With Clinically Localized Prostate Cancer
NCT00237146	PHASE4	COMPLETED	Study to Evaluate Zoledronic Acid on Quality of Life and Skeletal-related Events as Adjuvant Treatment in Patients With Hormone-naïve Prostate Cancer and Bone Metastasis Who Have Undergone Orchiectomy
NCT00242554	PHASE4	COMPLETED	Open-label Phase IV Clinical Trial to Evaluate the Safety and Tolerability of Zoledronic Acid in Patients With Prostate Cancer and Bone Metastases
NCT00280098	PHASE4	COMPLETED	Docetaxel in the Treatment of Hormone Refractory Prostate Cancer
NCT00293696	PHASE4	COMPLETED	Casodex/Zoladex Biomarkers in Localised Prostate Cancer
NCT00334139	PHASE4	COMPLETED	Effect of Zoledronic Acid on Bone Metabolism in Patients With Bone Metastasis and Prostate or Breast Cancer
NCT00375765	PHASE4	COMPLETED	Effects On Dihydrotestosterone Regulated Gene Expression In Benign Prostatic Hyperplasia Or Prostate Cancer
NCT00391690	PHASE4	COMPLETED	Evaluation of Bone Markers as Diagnostic Tools for Early Detection of Bone Metastases in Patients With High Risk Prostate Cancer
NCT00422708	PHASE4	COMPLETED	Local Anesthesia for Prostate Biopsy
NCT00526331	PHASE4	COMPLETED	Evaluation of Arterial Pressure Based Cardiac Output for Goal-Directed Perioperative Therapy
NCT00590213	PHASE4	COMPLETED	Compare the Value of Prophylactic Versus Therapeutic Breast Radiotherapy in CASODEX
NCT00629330	PHASE4	TERMINATED	Dissemination of Prostate Cancer Screening to PCP’s in African American Communities
NCT00771966	PHASE4	COMPLETED	Radical Prostatectomy and Perioperative Fluid Therapy
NCT00805701	PHASE4	COMPLETED	Study Assessing The Efficacy And Safety Of Avodart (Dutasteride) At Improving Urinary Symptoms In Men With Prostate Cancer Who Are Undergoing Seed Implantation
NCT00859027	PHASE4	COMPLETED	Effect Of Risedronate On Bone Mass In Older Men Receiving Neoadjuvant Therapy For Prostate Cancer
NCT00906269	PHASE4	UNKNOWN	Can Hyperbaric Oxygen Improve Erectile Function Following Surgery for Prostate Cancer
NCT00953277	PHASE4	COMPLETED	Study of Nerve Reconstruction Using AVANCE in Subjects Who Undergo Robotic Assisted Prostatectomy for Treatment of Prostate Cancer
NCT00982800	PHASE4	COMPLETED	Does Postoperative Gabapentin Reduce Pain, Opioid Consumption and Anxiety and Have a Positive Effect on Health Related Quality of Life After Radical Prostatectomy?
NCT01083199	PHASE4	COMPLETED	Global Performance Evaluation of the AMS CONTINUUM™ Device
NCT01136226	PHASE4	COMPLETED	Evaluate Recovery of Testosterone for Patients Using Eligard
NCT01161563	PHASE4	COMPLETED	Randomized Crossover Trial to Assess the Tolerability of Gonadotropin Releasing Hormone (GnRH) Analogue Administration
NCT01230905	PHASE4	COMPLETED	Study to Monitor the Effects of Androgen Suppression Treatment on the Heart
NCT01296672	PHASE4	COMPLETED	3 Month Finasteride Challenge Test Can Significantly Improve the Performance of Screening for Prostate Cancer
NCT01365143	PHASE4	TERMINATED	Prospective Randomized Trial Comparing Robotic Versus Open Radical Prostatectomy
NCT01379742	PHASE4	UNKNOWN	Comparison of Between ThinSeed™ and OncoSeed™ for Permanent Prostate Brachytherapy
NCT01486563	PHASE4	COMPLETED	Hydroxyethyl Starch and Renal Function After Radical Prostatectomy
NCT01511874	PHASE4	COMPLETED	Efficacy and Safety Study of ELIGARD 22.5mg With Prostate Cancer
NCT01512472	PHASE4	TERMINATED	Firmagon (Degarelix) Intermittent Therapy
NCT01547416	PHASE4	COMPLETED	The Effect of Combined General/Epidural Anesthesia Versus General Anesthesia on Diaphragmatic Function
NCT01571544	PHASE4	COMPLETED	The Use of Thermal Suits as Preventing Hypothermia During Surgery
NCT01581749	PHASE4	UNKNOWN	Evaluation of Truebeam for Low-Intermediate Risk Prostate Cancer
NCT01649635	PHASE4	COMPLETED	Study of Cabazitaxel Combined With Prednisone and Prophylaxis of Neutropenia Complications in the Treatment of Patients With Metastatic Castration-resistant Prostate Cancer