ATG101

Summary

ATG101 (autophagy related 101, HGNC:25679) is a protein-coding gene on chromosome 12q13.13, encoding Autophagy-related protein 101 (Q9BSB4). Autophagy factor required for autophagosome formation.

Enables identical protein binding activity. Involved in autophagosome assembly and negative regulation of cell population proliferation. Located in phagophore assembly site. Part of Atg1/ULK1 kinase complex. Biomarker of cholangiocarcinoma; colon cancer; and hepatocellular carcinoma.

Source: NCBI Gene 60673 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 40 total
• MANE Select transcript: NM_021934

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25679
Approved symbol	ATG101
Name	autophagy related 101
Location	12q13.13
Locus type	gene with protein product
Status	Approved
Aliases	FLJ11773
Ensembl gene	ENSG00000123395
Ensembl biotype	protein_coding
OMIM	615089
Entrez	60673

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 12 protein_coding, 2 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000336854, ENST00000547409, ENST00000548915, ENST00000550604, ENST00000552544, ENST00000552947, ENST00000553049, ENST00000908677, ENST00000908678, ENST00000938048, ENST00000938049, ENST00000938050, ENST00000938051, ENST00000938052, ENST00000938053

RefSeq mRNA: 2 — MANE Select: NM_021934 NM_001098673, NM_021934

CCDS: CCDS8820

Canonical transcript exons

ENST00000336854 — 4 exons

Exon	Start	End
ENSE00001060717	52070354	52070483
ENSE00001331249	52073575	52073902
ENSE00001348222	52076786	52077495
ENSE00001423435	52069978	52070242

Expression profiles

Bgee: expression breadth ubiquitous, 278 present calls, max score 96.25.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 22.2122 / max 129.2132, expressed in 1811 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
125570	22.0794	1811
125571	0.1328	12

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
stromal cell of endometrium	CL:0002255	96.25	gold quality
parotid gland	UBERON:0001831	93.14	gold quality
mucosa of transverse colon	UBERON:0004991	92.71	gold quality
body of stomach	UBERON:0001161	92.58	gold quality
skin of abdomen	UBERON:0001416	91.70	gold quality
skin of leg	UBERON:0001511	91.61	gold quality
gall bladder	UBERON:0002110	91.48	gold quality
islet of Langerhans	UBERON:0000006	91.06	gold quality
saliva-secreting gland	UBERON:0001044	90.98	gold quality
left testis	UBERON:0004533	90.94	gold quality
granulocyte	CL:0000094	90.85	gold quality
prefrontal cortex	UBERON:0000451	90.77	gold quality
right testis	UBERON:0004534	90.69	gold quality
minor salivary gland	UBERON:0001830	90.66	gold quality
gastrocnemius	UBERON:0001388	90.56	gold quality
zone of skin	UBERON:0000014	90.24	gold quality
muscle of leg	UBERON:0001383	90.24	gold quality
upper lobe of left lung	UBERON:0008952	90.23	gold quality
stomach	UBERON:0000945	90.15	gold quality
hindlimb stylopod muscle	UBERON:0004252	90.11	gold quality
monocyte	CL:0000576	89.96	gold quality
ascending aorta	UBERON:0001496	89.95	gold quality
testis	UBERON:0000473	89.93	gold quality
left uterine tube	UBERON:0001303	89.91	gold quality
adenohypophysis	UBERON:0002196	89.83	gold quality
thoracic aorta	UBERON:0001515	89.80	gold quality
apex of heart	UBERON:0002098	89.78	gold quality
mononuclear cell	CL:0000842	89.73	gold quality
mouth mucosa	UBERON:0003729	89.73	gold quality
upper lobe of lung	UBERON:0008948	89.69	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-GEOD-93593	yes	7.66
E-ANND-3	yes	6.81
E-CURD-11	no	99.26

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

20 targeting ATG101, 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-4531	99.99	69.70	3181
HSA-MIR-6744-5P	99.93	66.82	748
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-519A-3P	99.67	71.67	1868
HSA-MIR-519B-3P	99.67	71.67	1868
HSA-MIR-519C-3P	99.67	71.67	1870
HSA-MIR-7156-5P	99.64	68.81	1369
HSA-MIR-3136-3P	99.57	66.59	781
HSA-MIR-7155-3P	99.57	66.48	794
HSA-MIR-4273	99.45	67.93	1206
HSA-MIR-3182	99.40	68.15	2454
HSA-MIR-185-5P	99.35	68.60	2497
HSA-MIR-4644	99.35	69.12	2514
HSA-MIR-520A-5P	99.35	66.72	1632
HSA-MIR-525-5P	99.35	66.85	1615
HSA-MIR-4685-5P	99.25	65.99	1563
HSA-MIR-6827-5P	98.46	64.88	1256
HSA-MIR-6511A-3P	97.60	66.61	713
HSA-MIR-6511B-3P	97.60	66.61	713
HSA-MIR-12115	94.19	66.37	738

Literature-anchored findings (GeneRIF, showing 9)

• 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)
• Data indicate mitogen lacritin stimulates FOXO3-ATG101 and FOXO1-ATG7 autophagic coupling and restores metabolic homeostasis. (PMID:23640897)
• Structure of the human Atg13-Atg101 HORMA heterodimer in the ULK1 complex that controls autophagy has been described. (PMID:26299944)
• The C-terminal deletion of ATG101 shows a significant defect in the interaction with PtdIns3K components and subsequently impairs autophagosome formation. This result clearly presents an additional role of ATG101 for bridging the ULK1 and PtdIns3K complexes in the mammalian autophagy process. (PMID:30081750)
• ATG101 Degradation by HUWE1-Mediated Ubiquitination Impairs Autophagy and Reduces Survival in Cancer Cells. (PMID:34502089)
• ATG101-related signature predicts prognosis and therapeutic option in hepatocellular carcinoma. (PMID:36302799)
• 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	atg101	ENSDARG00000043287
mus_musculus	Atg101	ENSMUSG00000037204
rattus_norvegicus	Atg101	ENSRNOG00000007756
drosophila_melanogaster	Atg101	FBGN0030960
caenorhabditis_elegans		WBGENE00022078

Protein

Protein identifiers

Autophagy-related protein 101 — Q9BSB4 (reviewed: Q9BSB4)

All UniProt accessions (4): Q9BSB4, F8VQD9, F8VVA0, H3BMZ4

UniProt curated annotations — full annotation on UniProt →

Function. Autophagy factor required for autophagosome formation. Stabilizes ATG13, protecting it from proteasomal degradation.

Subunit / interactions. Interacts with ATG13. Associates with a complex composed of ATG13, ULK1 and RB1CC1; the association with this complex requires the presence of ATG13.

Subcellular location. Cytoplasm. Preautophagosomal structure.

Similarity. Belongs to the ATG101 family.

RefSeq proteins (2): NP_001092143, NP_068753* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR012445	ATG101	Family

Pfam: PF07855

UniProt features (28 total): strand 13, helix 7, mutagenesis site 5, chain 1, region of interest 1, sequence conflict 1

Structure

Experimental structures (PDB)

8 structures.

PDB	Method	Resolution (Å)
5C50	X-RAY DIFFRACTION	1.63
4WZG	X-RAY DIFFRACTION	1.9
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
5XV4	X-RAY DIFFRACTION	2.95

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BSB4-F1	90.30	0.81

Functional residue map

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

Mutagenesis-validated functional residues (5):

Position	Phenotype
31	impairs interaction with atg13; when associated with r-54.
54	impairs interaction with atg13; when associated with s-31.
152	abolishes interaction with atg13; when associated with d-153 and d-156.
153	abolishes interaction with atg13; when associated with d-152 and d-156.
156	abolishes interaction with atg13; when associated with d-152 and d-152.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

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

MSigDB gene sets: 163 (showing top): GOBP_REGULATION_OF_AUTOPHAGY, GOBP_VACUOLE_ORGANIZATION, GOBP_LIPOPROTEIN_METABOLIC_PROCESS, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, NAGASHIMA_NRG1_SIGNALING_UP, GOBP_MACROAUTOPHAGY, GOBP_REGULATION_OF_CATABOLIC_PROCESS, GOBP_POSITIVE_REGULATION_OF_CATABOLIC_PROCESS, WCTCNATGGY_UNKNOWN, GOBP_LIPOPROTEIN_BIOSYNTHETIC_PROCESS, GOBP_ORGANELLE_ASSEMBLY, GOBP_REGULATION_OF_LIPOPROTEIN_METABOLIC_PROCESS, GOBP_POSITIVE_REGULATION_OF_AUTOPHAGY, GOBP_AUTOPHAGOSOME_ORGANIZATION, GOCC_TRANSFERASE_COMPLEX_TRANSFERRING_PHOSPHORUS_CONTAINING_GROUPS

GO Biological Process (4): autophagosome assembly (GO:0000045), negative regulation of cell population proliferation (GO:0008285), positive regulation of autophagy (GO:0010508), autophagy (GO:0006914)

GO Molecular Function (4): protein kinase binding (GO:0019901), identical protein binding (GO:0042802), protein-containing complex binding (GO:0044877), protein binding (GO:0005515)

GO Cellular Component (5): phagophore assembly site (GO:0000407), endoplasmic reticulum membrane (GO:0005789), cytosol (GO:0005829), Atg1/ULK1 kinase complex (GO:1990316), cytoplasm (GO:0005737)

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	3
cellular anatomical structure	3
binding	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
cell population proliferation	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
catabolic process	1
transmembrane transport	1
process utilizing autophagic mechanism	1
kinase binding	1
protein binding	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
serine/threonine protein kinase complex	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1186 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ATG101	RB1CC1	Q8TDY2	998
ATG101	ULK1	O75385	998
ATG101	ATG13	O75143	998
ATG101	ULK2	Q8IYT8	997
ATG101	CIB1	Q99828	922
ATG101	ATG5	Q9H1Y0	897
ATG101	ATG14	Q6ZNE5	892
ATG101	WIPI1	Q5MNZ9	875
ATG101	PIK3C3	Q8NEB9	864
ATG101	PIK3R4	Q99570	863
ATG101	ATG12	O94817	857
ATG101	BECN1	Q14457	845
ATG101	ATG16L1	Q676U5	845
ATG101	ATG10	Q9H0Y0	840
ATG101	ATG3	Q9NT62	839

IntAct

68 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
ATG13	ULK1	psi-mi:“MI:2364”(proximity)	0.940
RB1CC1	ATG101	psi-mi:“MI:0915”(physical association)	0.860
HUS1	RAD1	psi-mi:“MI:0914”(association)	0.840
RB1CC1	ATG13	psi-mi:“MI:0914”(association)	0.820
MAP1LC3C	ATG13	psi-mi:“MI:0914”(association)	0.750
BRK1	HSBP1	psi-mi:“MI:0914”(association)	0.740
MAP1LC3B	ATG13	psi-mi:“MI:0914”(association)	0.730
ATG101	MAP1LC3C	psi-mi:“MI:0407”(direct interaction)	0.730
ATG101	MAP1LC3C	psi-mi:“MI:0915”(physical association)	0.730

BioGRID (236): ATG101 (Affinity Capture-MS), ATG101 (Affinity Capture-MS), ATG101 (Affinity Capture-MS), ATG101 (Affinity Capture-MS), RB1CC1 (Affinity Capture-Western), ATG13 (Affinity Capture-Western), ULK1 (Affinity Capture-Western), ATG101 (Affinity Capture-Western), ATG101 (Affinity Capture-Western), ATG101 (Affinity Capture-Western), ATG101 (Affinity Capture-MS), ATG101 (Affinity Capture-MS), ATG101 (Affinity Capture-MS), ATG101 (Affinity Capture-MS), ATG101 (Affinity Capture-MS)

ESM2 similar proteins: A4IH75, B0S6R1, F4K265, O14417, O75165, O94915, P28660, P60670, P97878, Q10LJ0, Q2HJE0, Q2TBN7, Q3B736, Q3B8G8, Q3TPX4, Q499N2, Q4R6Q7, Q4R708, Q556Y9, Q5E9X5, Q5R6U8, Q5R8B7, Q5RBT3, Q5VZE5, Q5XHA1, Q5ZHV2, Q642Q3, Q6AY69, Q6DE58, Q6DKG0, Q6GLR7, Q6NPF4, Q6P2C8, Q6PFL0, Q6PHQ8, Q6Q7J5, Q7T322, Q8BJ63, Q8TAT6, Q8VDP2

Diamond homologs: A4IH75, Q2HJE0, Q3B736, Q6AY69, Q6DE58, Q9BSB4, Q9D8Z6

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
ATG101	up-regulates	ATG13	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 41 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	11	47.0×	3e-14
Autophagy	5	27.5×	5e-05

GO biological processes:

GO term	Partners	Fold	FDR
mitophagy	9	79.5×	2e-13
autophagosome assembly	11	68.7×	1e-15
autophagosome maturation	6	58.5×	5e-08
positive regulation of autophagy	5	28.9×	3e-05
autophagy	6	18.4×	3e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	29
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

894 predictions. Top by Δscore:

Variant	Effect	Δscore
12:52076781:CCCA:C	acceptor_loss	1.0000
12:52076783:CAGGA:C	acceptor_loss	1.0000
12:52076784:A:AC	acceptor_loss	1.0000
12:52076784:A:AG	acceptor_gain	1.0000
12:52076784:AG:A	acceptor_gain	1.0000
12:52076784:AGGAT:A	acceptor_gain	1.0000
12:52076785:G:GT	acceptor_gain	1.0000
12:52076785:GG:G	acceptor_gain	1.0000
12:52076785:GGA:G	acceptor_gain	1.0000
12:52076785:GGAT:G	acceptor_gain	1.0000
12:52076785:GGATG:G	acceptor_gain	1.0000
12:52070025:A:T	donor_gain	0.9800
12:52070432:G:GT	donor_gain	0.9800
12:52073886:T:TA	donor_gain	0.9800
12:52073887:T:TA	donor_gain	0.9800
12:52073900:AAGG:A	donor_loss	0.9800
12:52073901:AG:A	donor_loss	0.9800
12:52073902:GGTAA:G	donor_loss	0.9800
12:52073903:GTAAG:G	donor_loss	0.9800
12:52073904:T:TC	donor_loss	0.9800
12:52070033:G:GA	donor_gain	0.9700
12:52070046:C:T	donor_gain	0.9700
12:52070061:G:GA	donor_gain	0.9700
12:52070069:G:T	donor_gain	0.9700
12:52070436:GGCA:G	donor_gain	0.9700
12:52072497:C:G	donor_gain	0.9700
12:52073902:GGT:G	donor_gain	0.9700
12:52070240:G:GT	donor_gain	0.9600
12:52070455:G:GT	donor_gain	0.9600
12:52070479:TCAAG:T	donor_loss	0.9600

AlphaMissense

1421 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:52073744:C:A	R32S	1.000
12:52076838:T:C	F102S	1.000
12:52076861:T:A	W110R	1.000
12:52076861:T:C	W110R	1.000
12:52076888:T:A	W119R	1.000
12:52076888:T:C	W119R	1.000
12:52076890:G:C	W119C	1.000
12:52076890:G:T	W119C	1.000
12:52076897:T:A	W122R	1.000
12:52076897:T:C	W122R	1.000
12:52077066:T:C	F178S	1.000
12:52077168:T:A	I212N	1.000
12:52073745:G:C	R32P	0.999
12:52073747:A:C	S33R	0.999
12:52073749:C:A	S33R	0.999
12:52073749:C:G	S33R	0.999
12:52073753:G:C	G35R	0.999
12:52073754:G:A	G35D	0.999
12:52073759:T:C	F37L	0.999
12:52073760:T:C	F37S	0.999
12:52073761:C:A	F37L	0.999
12:52073761:C:G	F37L	0.999
12:52073783:T:G	Y45D	0.999
12:52076837:T:C	F102L	0.999
12:52076839:C:A	F102L	0.999
12:52076839:C:G	F102L	0.999
12:52076863:G:C	W110C	0.999
12:52076863:G:T	W110C	0.999
12:52076889:G:C	W119S	0.999
12:52076943:G:C	R137P	0.999

dbSNP variants (sampled 300 via entrez): RS1001053778 (12:52071738 C>T), RS1001149777 (12:52072006 C>T), RS1001155595 (12:52070202 C>T), RS1001268854 (12:52076061 T>C), RS1001379833 (12:52066747 A>G), RS1001379922 (12:52063332 C>A,T), RS1001704666 (12:52068948 G>A), RS1001762535 (12:52075841 A>C,G), RS1001828856 (12:52074716 T>C,G), RS1001837236 (12:52067821 C>T), RS1002091441 (12:52074374 G>T), RS1002707833 (12:52070042 G>C), RS1002788265 (12:52069470 G>A,C), RS1002808292 (12:52063889 GAAAA>G,GAAA,GAAAAA), RS1003035710 (12:52074435 C>T)

Disease associations

OMIM: gene MIM:615089 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST004602_156	Mean corpuscular volume	4.000000e-11
GCST004630_182	Mean corpuscular hemoglobin	4.000000e-12
GCST009391_271	Metabolite levels	6.000000e-06
GCST90002392_382	Mean corpuscular volume	4.000000e-22

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004527	mean corpuscular hemoglobin
EFO:0010428	triacylglycerol 56:10 measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases expression, decreases reaction	3
Valproic Acid	affects expression, increases expression	3
Tobacco Smoke Pollution	increases expression	2
aristolochic acid I	increases expression	1
bisphenol A	affects expression	1
trichostatin A	affects expression	1
fisetin	decreases expression, decreases reaction	1
di-n-butylphosphoric acid	affects expression	1
amyloid beta-protein (1-42)	decreases expression, decreases reaction	1
perfluorooctane sulfonic acid	increases expression	1
trovafloxacin	increases expression	1
abrine	increases expression	1
PCI 5002	affects cotreatment, increases expression	1
Sunitinib	increases expression	1
Acetaminophen	increases expression	1
Air Pollutants	increases expression, increases abundance	1
Arsenic	affects methylation	1
Chlorogenic Acid	decreases expression, decreases reaction	1
Copper	affects binding, decreases expression	1
Diazinon	increases methylation	1
Dieldrin	increases response to substance	1
Disulfiram	affects binding, decreases expression	1
Drugs, Chinese Herbal	increases expression	1
Smoke	decreases expression	1
Dihydrotestosterone	increases expression	1
Dronabinol	decreases expression	1
Thiram	increases expression	1
Zinc	affects cotreatment, increases expression	1
Cyclosporine	increases expression	1
Aflatoxin B1	decreases methylation	1

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1KC	Abcam HeLa ATG101 KO	Cancer cell line	Female
CVCL_SG01	HAP1 ATG101 (-) 1	Cancer cell line	Male
CVCL_SG02	HAP1 ATG101 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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