ATG14

Summary

ATG14 (autophagy related 14, HGNC:19962) is a protein-coding gene on chromosome 14q22.3, encoding Beclin 1-associated autophagy-related key regulator (Q6ZNE5). Required for both basal and inducible autophagy.

Enables GTPase binding activity; phosphatidylinositol 3-kinase inhibitor activity; and protein-membrane adaptor activity. Involved in several processes, including early endosome to late endosome transport; macroautophagy; and phosphatidylinositol 3-kinase/protein kinase B signal transduction. Acts upstream of or within endosome to lysosome transport. Located in autophagosome and phagophore assembly site membrane. Is extrinsic component of omegasome membrane and extrinsic component of phagophore assembly site membrane. Part of phosphatidylinositol 3-kinase complex, class III. Is active in phagophore assembly site.

Source: NCBI Gene 22863 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 82 total — 2 pathogenic, 1 likely-pathogenic
• Druggable target: yes
• MANE Select transcript: NM_014924

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19962
Approved symbol	ATG14
Name	autophagy related 14
Location	14q22.3
Locus type	gene with protein product
Status	Approved
Aliases	ATG14L
Ensembl gene	ENSG00000126775
Ensembl biotype	protein_coding
OMIM	613515
Entrez	22863

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 1 protein_coding, 1 retained_intron

ENST00000247178, ENST00000558189

RefSeq mRNA: 1 — MANE Select: NM_014924 NM_014924

CCDS: CCDS32087

Canonical transcript exons

ENST00000247178 — 10 exons

Exon	Start	End
ENSE00001193872	55390911	55390992
ENSE00001490305	55395940	55395982
ENSE00001490307	55397372	55397434
ENSE00001490309	55411602	55411830
ENSE00003464951	55380573	55380690
ENSE00003490931	55381962	55382191
ENSE00003502442	55377819	55377904
ENSE00003557134	55377984	55378074
ENSE00003599053	55385859	55386096
ENSE00003657403	55366391	55369925

Expression profiles

Bgee: expression breadth ubiquitous, 292 present calls, max score 92.93.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 16.3177 / max 293.3452, expressed in 1791 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
143371	16.2389	1788
143372	0.0788	29

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	92.93	gold quality
oocyte	CL:0000023	92.07	gold quality
gluteal muscle	UBERON:0002000	91.62	gold quality
upper leg skin	UBERON:0004262	90.69	gold quality
triceps brachii	UBERON:0001509	90.57	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	90.29	gold quality
skin of hip	UBERON:0001554	89.47	gold quality
quadriceps femoris	UBERON:0001377	89.02	gold quality
vastus lateralis	UBERON:0001379	88.76	gold quality
deltoid	UBERON:0001476	88.63	silver quality
biceps brachii	UBERON:0001507	88.48	gold quality
tibialis anterior	UBERON:0001385	87.87	gold quality
blood vessel layer	UBERON:0004797	87.31	gold quality
calcaneal tendon	UBERON:0003701	87.16	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	87.14	gold quality
skeletal muscle tissue	UBERON:0001134	87.05	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	86.94	gold quality
muscle tissue	UBERON:0002385	86.65	gold quality
cardiac muscle of right atrium	UBERON:0003379	86.54	gold quality
left ventricle myocardium	UBERON:0006566	86.35	gold quality
muscle organ	UBERON:0001630	85.91	gold quality
skeletal muscle organ	UBERON:0014892	85.91	gold quality
myocardium	UBERON:0002349	85.82	gold quality
tendon	UBERON:0000043	85.24	gold quality
hindlimb stylopod muscle	UBERON:0004252	84.99	gold quality
muscle of leg	UBERON:0001383	84.97	gold quality
gastrocnemius	UBERON:0001388	84.63	gold quality
trabecular bone tissue	UBERON:0002483	84.51	gold quality
mucosa of stomach	UBERON:0001199	83.80	gold quality
bone element	UBERON:0001474	83.63	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.92

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): BMAL1, CLOCK, KDM4A

miRNA regulators (miRDB)

201 targeting ATG14, 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-9-5P	100.00	72.28	2361
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-188-3P	100.00	68.76	1240
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-6793-5P	99.97	65.95	758
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-495-3P	99.96	72.81	4197

Literature-anchored findings (GeneRIF, showing 38)

• These results suggest that mammalian cells have at least two distinct class III PI3-kinase complexes, and that beclin 1 interacts distinctly with mammalian Atg14 and UVRAG in two of these complexes. (PMID:18843052)
• Barkor/KIAA0831 functions as an autophagy targeting factor for Beclin 1 and the class III PI3 kinase. Barkor and UVRAG form two distinct protein complexes with the core class III PI3 kinase. Barkor is a functional ortholog of yeast Atg14. (PMID:19050071)
• study defines a regulatory signaling pathway mediated by Barkor (KIAA0831) that positively controls autophagy through Beclin 1 (PMID:19050071)
• Two Beclin 1 associated proteins, Atg14L and Rubicon, were identified. (PMID:19270696)
• Data suggest that the Atg14L-dependent appearance of phosphatidylinositol 3-phosphate in the endoplasmic reticulum makes this organelle the platform for autophagosome formation. (PMID:20713597)
• analysis of how the Beclin1 coiled-coil domain interface regulates homodimer and heterodimer formation with Atg14L and UVRAG (PMID:22314358)
• Our findings reveal that Atg14L, previously considered to be solely a Beclin 1-binding autophagy protein, plays a novel role in the late stage of endocytic trafficking in conjunction with Snapin (PMID:22797916)
• Atg14 is a new target gene of FoxOs and the core clock machinery, and this gene plays an important role in hepatic lipid metabolism (PMID:22992773)
• Anaplasma actively induces autophagy by secreting Ats-1 that hijacks the Beclin 1-Atg14L autophagy initiation pathway likely to acquire host nutrients for its growth (PMID:23197835)
• Atg14 is critical in controlling an autophagy-dependent phosphorylation of beclin-1. We map novel phosphorylation sites to serines 90 and 93 and demonstrate that phosphorylation at these sites is necessary for maximal autophagy. (PMID:23878393)
• Cisplatin upregulated Barkor protein levels of the Saos-2 cell line. (PMID:24337183)
• These data provide evidence for additional roles of Atg2A and Atg14L in the formation of early autophagosomal membranes and also in lipid metabolism. (PMID:24776541)
• data suggest an autophagy-specific membrane fusion mechanism in which oligomeric ATG14 directly binds to STX17-SNAP29 binary t-SNARE complex on autophagosomes and primes it for VAMP8 interaction to promote autophagosome-endolysosome fusion (PMID:25686604)
• These results define a key molecular event for the starvation-induced activation of the ATG14-containing PtdIns3K complex by ULK1. (PMID:27046250)
• use circular dichroism and small-angle X-ray scattering (SAXS) to show that the ATG14 coiled-coil domain (CCD) is significantly disordered but becomes more helical in the BECN1:ATG14 heterodimer, although it is less well-folded than the BECN1 CCD homodimer (PMID:27383850)
• This study identifies an unexpected role for PtdIns(4,5)P2 signaling in the regulation of ATG14 complex and autophagy. (PMID:27621469)
• we found that ATG14 interacted with Ulk1 and LC3, and knock down of Ulk1 prevented the lipidation of LC3 and autophagy in HeLa-ATG14 cells. We also identified a phosphatidylethanolamine (PE) binding region in ATG14, and the addition of Ulk1 to Hela-ATG14 cells decreased the ATG14-PE interaction. (PMID:28069524)
• polar BECN2 CCD interface residues result in a metastable homodimer, facilitating dissociation, but enable better interactions with polar ATG14 residues stabilizing the BECN2:ATG14 heterodimer. (PMID:28218432)
• that BECN1 Ser30 is a ULK1 target site whose phosphorylation activates the ATG14-containing PIK3C3 complex and stimulates autophagosome formation in response to amino acid starvation, hypoxia, and MTORC1 inhibition (PMID:29313410)
• Knockdown of ATG14 protein leds to decreased autophagy and chemoresistance of melphalan-resistant myeloma cells (PMID:30121664)
• miR-129-5p inhibited autophagy and apoptosis in H2O2-induced H9c2 cells partly by down-regulation of ATG14 through the activation of PI3K/AKT/mTOR pathway. (PMID:30348524)
• ULK1 O-GlcNAcylation is crucial for binding and phosphorylation of ATG14L, allowing the activation of lipid kinase VPS34. (PMID:30517873)
• USP36 as regulator for the Parkin-dependent mitophagy at least in part via the Beclin-1-ATG14L pathway. (PMID:31550441)
• Our research indicated that the novel axis of SNHG14/miR-186/ATG14 could play a vital role in regulating colorectal cancer (CRC) cell progression; this axis showed its clinical potential in regulating cisplatin resistance during CRC treatment. (PMID:31704614)
• miR-29c-3p inhibits autophagy and cisplatin resistance in ovarian cancer by regulating FOXP1/ATG14 pathway. (PMID:31885310)
• Streptococcus pneumoniae promotes its own survival via choline-binding protein CbpC-mediated degradation of ATG14. (PMID:32508214)
• LncRNA PVT1 promotes gemcitabine resistance of pancreatic cancer via activating Wnt/beta-catenin and autophagy pathway through modulating the miR-619-5p/Pygo2 and miR-619-5p/ATG14 axes. (PMID:32727463)
• ATG4 promotes cell proliferation, migration and invasion in HCC and predicts a poor prognosis. (PMID:33378015)
• HIF-1alpha-induced expression of m6A reader YTHDF1 drives hypoxia-induced autophagy and malignancy of hepatocellular carcinoma by promoting ATG2A and ATG14 translation. (PMID:33619246)
• ATG14 and RB1CC1 play essential roles in maintaining muscle homeostasis. (PMID:33794726)
• [MicroRNA-424 inhibits autophagy and proliferation of hepatocellular carcinoma cells by targeting ATG14]. (PMID:34308850)
• SNAP47 Interacts with ATG14 to Promote VP1 Conjugation and CVB3 Propagation. (PMID:34440910)
• [miR-148b-3p inhibits the proliferation and autophagy of acute myeloid leukemia cells by targeting ATG14]. (PMID:34670664)
• Down-regulation of circ_0058058 suppresses proliferation, angiogenesis and metastasis in multiple myeloma through miR-338-3p/ATG14 pathway. (PMID:34930344)
• CircCBFB is a mediator of hepatocellular carcinoma cell autophagy and proliferation through miR-424-5p/ATG14 axis. (PMID:35066780)
• KLF15 Transcriptionally Activates ATG14 to Promote Autophagy and Attenuate Damage of ox-LDL-Induced HAECs. (PMID:37043109)
• ATG14 plays a critical role in hepatic lipid droplet homeostasis. (PMID:37741434)
• Control of ATG14 solubility and autophagy by MARCHF7/MARCH7-mediated ubiquitination. (PMID:37915253)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	atg14	ENSDARG00000002670
mus_musculus	Atg14	ENSMUSG00000037526
rattus_norvegicus	Atg14	ENSRNOG00000011873
drosophila_melanogaster	Atg14	FBGN0039636

Protein

Protein identifiers

Beclin 1-associated autophagy-related key regulator — Q6ZNE5 (reviewed: Q6ZNE5)

Alternative names: Autophagy-related protein 14-like protein

All UniProt accessions (1): Q6ZNE5

UniProt curated annotations — full annotation on UniProt →

Function. Required for both basal and inducible autophagy. Determines the localization of the autophagy-specific PI3-kinase complex PI3KC3-C1. Plays a role in autophagosome formation and MAP1LC3/LC3 conjugation to phosphatidylethanolamine. Promotes BECN1 translocation from the trans-Golgi network to autophagosomes. Enhances PIK3C3 activity in a BECN1-dependent manner. Essential for the autophagy-dependent phosphorylation of BECN1. Stimulates the phosphorylation of BECN1, but suppresses the phosphorylation PIK3C3 by AMPK. Binds to STX17-SNAP29 binary t-SNARE complex on autophagosomes and primes it for VAMP8 interaction to promote autophagosome-endolysosome fusion. Modulates the hepatic lipid metabolism.

Subunit / interactions. Forms homooligomers; homo-oligomerization is essential for the roles in membrane tethering and enhancement of SNARE-mediated fusion. Component of the PI3K (PI3KC3/PI3K-III/class III phosphatidylinositol 3-kinase) complex I (PI3KC3-C1) in which the core composed of the catalytic subunit PIK3C3, the regulatory subunit PIK3R4 and BECN1 is associated with ATG14. PI3KC3-C1 displays a V-shaped architecture with PIK3R4 serving as a bridge between PIK3C3 and the ATG14:BECN1 subcomplex. PI3KC3-C1 can associate with further regulatory subunits. Interacts with PIK3CB. Interacts (via coiled-coil domain) with BECN2 (via coiled-coil domain); this interaction is tighter than BECN2 self-association. Interacts with the STX17-SNAP29 binary t-SNARE complex. Interacts with NRBF2. Interacts with PIK3C3 and BECN1; this interaction is increased in the absence of TMEM39A. Interacts with STEEP1; the interaction is required for trafficking of STING1 from the endoplasmic reticulum. Interacts with ARMC3 (via ARM domains).

Subcellular location. Cytoplasm. Endoplasmic reticulum membrane. Preautophagosomal structure membrane. Cytoplasmic vesicle. Autophagosome membrane.

Post-translational modifications. Ubiquitinated via ‘Lys-6’, ‘Lys-11’ and ‘Lys-63’-linked polyubiquitin chains on multiple lysines by MARCHF7, leading to ATG14 aggregation and loss of interaction with STX17.

Domain organisation. The coiled-coil domain is required for BECN1- and PIK3C3-binding and for autophagy. The final 80 residues in the C-terminus define a minimum required region for autophagosome binding called BATS. The N-terminal cysteine repeats are required for proper localization to the endoplasmic reticulum.

Similarity. Belongs to the ATG14 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q6ZNE5-1	1	yes
Q6ZNE5-2	2

RefSeq proteins (1): NP_055739* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR018791	UV_resistance/autophagy_Atg14	Family

Pfam: PF10186

Enzyme classification (BRENDA):

• EC 2.7.1.137 — phosphatidylinositol 3-kinase (BRENDA: 29 organisms, 131 substrates, 146 inhibitors, 16 Km, 0 kcat entries)

Substrate kinetics (BRENDA)

6 substrates with measured Km, best-characterized 6. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ATP	0.03–44	7
PHOSPHATIDYLINOSITOL	0.034–64	3
PHOSPHATIDYLINOSITOL 4,5-BISPHOSPHATE	0.004–15	2
PHOSPHATIDYLINOSITOL 4-PHOSPHATE	0.009–10	2
1,2-DIOCTANOYLPHOSPHATIDYLINOSITOL 4,5-DIPHOSPHA	0.05	1
PHOSPHATIDYLINOSITOL-4,5-BISPHOSPHATE	0.011	1

UniProt features (33 total): helix 9, strand 5, mutagenesis site 4, region of interest 3, modified residue 3, sequence variant 2, compositionally biased region 2, chain 1, splice variant 1, sequence conflict 1, turn 1, coiled-coil region 1

Structure

Experimental structures (PDB)

7 structures.

PDB	Method	Resolution (Å)
6HOL	X-RAY DIFFRACTION	1.4
9MHF	ELECTRON MICROSCOPY	2.73
9MHG	ELECTRON MICROSCOPY	3.2
13BV	ELECTRON MICROSCOPY	3.77
9MHH	ELECTRON MICROSCOPY	4.5
9C82	ELECTRON MICROSCOPY	6.84
8SOR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6ZNE5-F1	74.84	0.43

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 (3): 29, 416, 429

Mutagenesis-validated functional residues (4):

Position	Phenotype
43	in atg14l4c4a; fails to localize to the endoplasmic reticulum; when associated with a-46; a-55 and a-58.
46	in atg14l4c4a; fails to localize to the endoplasmic reticulum; when associated with a-43; a-55 and a-58.
55	in atg14l4c4a; fails to localize to the endoplasmic reticulum; when associated with a-43; a-46 and a-58.
58	in atg14l4c4a; fails to localize to the endoplasmic reticulum; when associated with a-43; a-46 and a-55.

Function

Pathways and Gene Ontology

Reactome pathways

14 pathways

ID	Pathway
R-HSA-1632852	Macroautophagy
R-HSA-9705671	SARS-CoV-2 activates/modulates innate and adaptive immune responses
R-HSA-983170	Antigen Presentation: Folding, assembly and peptide loading of class I MHC
R-HSA-9920951	Dengue virus modulates apoptosis
R-HSA-1280218	Adaptive Immune System
R-HSA-1643685	Disease
R-HSA-168256	Immune System
R-HSA-5663205	Infectious disease
R-HSA-9612973	Autophagy
R-HSA-9679506	SARS-CoV Infections
R-HSA-9694516	SARS-CoV-2 Infection
R-HSA-9705683	SARS-CoV-2-host interactions
R-HSA-9824446	Viral Infection Pathways
R-HSA-983169	Class I MHC mediated antigen processing & presentation

MSigDB gene sets: 317 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_TUMORAL_MACROPHAGE_UP, GOBP_REGULATION_OF_AUTOPHAGY, GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, GOBP_PHOSPHATIDYLINOSITOL_METABOLIC_PROCESS, GOBP_LYSOSOMAL_TRANSPORT, GOBP_REGULATION_OF_TRIGLYCERIDE_METABOLIC_PROCESS, GOBP_VACUOLE_ORGANIZATION, GOBP_REGULATION_OF_PHOSPHORYLATION, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, REACTOME_ANTIGEN_PRESENTATION_FOLDING_ASSEMBLY_AND_PEPTIDE_LOADING_OF_CLASS_I_MHC, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, REACTOME_CLASS_I_MHC_MEDIATED_ANTIGEN_PROCESSING_PRESENTATION, GOCC_VACUOLAR_MEMBRANE, AAGCCAT_MIR135A_MIR135B

GO Biological Process (22): autophagosome assembly (GO:0000045), mitophagy (GO:0000423), negative regulation of protein phosphorylation (GO:0001933), positive regulation of protein phosphorylation (GO:0001934), protein targeting to lysosome (GO:0006622), endosome to lysosome transport (GO:0008333), cellular response to starvation (GO:0009267), post-transcriptional regulation of gene expression (GO:0010608), macroautophagy (GO:0016236), autophagosome membrane docking (GO:0016240), regulation of macroautophagy (GO:0016241), phosphatidylinositol-3-phosphate biosynthetic process (GO:0036092), cellular response to glucose starvation (GO:0042149), phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0043491), early endosome to late endosome transport (GO:0045022), innate immune response (GO:0045087), defense response to virus (GO:0051607), regulation of protein complex stability (GO:0061635), regulation of triglyceride metabolic process (GO:0090207), autophagosome maturation (GO:0097352), response to mitochondrial depolarisation (GO:0098780), autophagy (GO:0006914)

GO Molecular Function (5): phosphatidylinositol 3-kinase regulator activity (GO:0035014), protein-membrane adaptor activity (GO:0043495), GTPase binding (GO:0051020), phosphatidylinositol 3-kinase inhibitor activity (GO:0141039), protein binding (GO:0005515)

GO Cellular Component (17): phagophore assembly site (GO:0000407), autophagosome membrane (GO:0000421), autophagosome (GO:0005776), endoplasmic reticulum membrane (GO:0005789), cytosol (GO:0005829), axoneme (GO:0005930), phagophore assembly site membrane (GO:0034045), phosphatidylinositol 3-kinase complex, class III (GO:0035032), mitochondria-associated endoplasmic reticulum membrane contact site (GO:0044233), phagocytic vesicle (GO:0045335), extrinsic component of omegasome membrane (GO:0097629), extrinsic component of phagophore assembly site membrane (GO:0097632), cytoplasm (GO:0005737), endoplasmic reticulum (GO:0005783), membrane (GO:0016020), cytoplasmic vesicle (GO:0031410), protein-containing complex (GO:0032991)

Reactome top-level categories

Rollup of top-11 pathways:

Category	Pathways
Autophagy	1
SARS-CoV-2-host interactions	1
Class I MHC mediated antigen processing & presentation	1
Dengue Virus-Host Interactions	1
Immune System	1
Disease	1
Viral Infection Pathways	1
SARS-CoV Infections	1
SARS-CoV-2 Infection	1
Infectious disease	1
Adaptive Immune System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cytoplasm	5
cellular anatomical structure	5
macroautophagy	3
regulation of protein phosphorylation	2
protein phosphorylation	2
lysosomal transport	2
extrinsic component of organelle membrane	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
negative regulation of protein modification process	1
negative regulation of phosphorylation	1
positive regulation of protein modification process	1
positive regulation of phosphorylation	1
protein targeting to vacuole	1
protein localization to lysosome	1
intercellular transport	1
vesicle-mediated transport	1
cellular response to nutrient levels	1
cellular response to stress	1
response to starvation	1
regulation of gene expression	1
autophagosome assembly	1
autophagy	1
autophagosome maturation	1
organelle localization by membrane tethering	1
regulation of autophagy	1
phosphatidylinositol phosphate biosynthetic process	1
cellular response to starvation	1
intracellular signaling cassette	1
vesicle-mediated transport between endosomal compartments	1
immune response	1
defense response to symbiont	1
defense response	1
response to virus	1

Protein interactions and networks

STRING

1432 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ATG14	BECN1	Q14457	999
ATG14	PIK3C3	Q8NEB9	999
ATG14	PIK3R4	Q99570	999
ATG14	UVRAG	Q9P2Y5	999
ATG14	AMBRA1	Q9C0C7	997
ATG14	STX17	P56962	996
ATG14	NRBF2	Q96F24	995
ATG14	SNAP29	O95721	993
ATG14	BECN2	A8MW95	982
ATG14	RUBCN	Q92622	979
ATG14	ATG13	O75143	970
ATG14	ATG7	O95352	950
ATG14	VAMP8	Q9BV40	947
ATG14	SH3GLB1	Q9Y371	947
ATG14	BCL2	P10415	929

IntAct

100 interactions, top by confidence:

A	B	Type	Score
ATG14	BECN1	psi-mi:“MI:0915”(physical association)	0.980
ATG14	BECN1	psi-mi:“MI:0407”(direct interaction)	0.980
BECN1	ATG14	psi-mi:“MI:0914”(association)	0.980
ATG14	BECN1	psi-mi:“MI:0914”(association)	0.980
BECN1	ATG14	psi-mi:“MI:0915”(physical association)	0.980
BECN1	ATG14	psi-mi:“MI:0407”(direct interaction)	0.980

BioGRID (554): ATG14 (Affinity Capture-Western), BECN1 (Affinity Capture-Western), PIK3C3 (Affinity Capture-Western), ATG14 (Affinity Capture-Western), ATG14 (Affinity Capture-Western), ATG14 (Affinity Capture-MS), ATG14 (Affinity Capture-Western), BECN1 (Affinity Capture-Western), ATG14 (Affinity Capture-Western), PIK3C3 (Affinity Capture-Western), ATG14 (Reconstituted Complex), ATG14 (Affinity Capture-Western), ATG14 (Affinity Capture-MS), USP18 (Affinity Capture-Western), ATG14 (Affinity Capture-MS)

ESM2 similar proteins: A3KN05, A4IG66, B5DFG1, D3Z8X7, D4A4K3, O35144, O75182, P0DKR2, P82649, P82650, Q15554, Q28C41, Q3SZV6, Q3V0L5, Q5F479, Q5PPN7, Q5R8S0, Q5REP2, Q5RFI6, Q5TC12, Q5U2X7, Q6AY04, Q6IRU7, Q6P1H6, Q6PCG6, Q6ZNE5, Q7L8L6, Q7TP65, Q811I0, Q86XL3, Q8BHE8, Q8BM55, Q8C008, Q8CDJ3, Q8K1S6, Q8N163, Q8N9B5, Q8TF30, Q8VDP4, Q8WWC4

Diamond homologs: D4A4K3, Q6ZNE5, Q8CDJ3

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
ULK1	“up-regulates activity”	ATG14	phosphorylation
ATG14	“up-regulates activity”	PIK3C3	binding
ATG14	“form complex”	“Vps34 Complex I”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 32 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.

GO biological processes:

GO term	Partners	Fold	FDR
phosphatidylinositol 3-kinase/protein kinase B signal transduction	5	36.3×	1e-04
negative regulation of apoptotic process	6	7.2×	7e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	1
Uncertain significance	68
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
3061843	GRCh38/hg38 14q22.2-22.3(chr14:53949639-56297420)x1	Pathogenic
815659	GRCh37/hg19 14q22.3(chr14:55615073-58043694)x1	Pathogenic
3338471	GRCh37/hg19 14q22.2-22.3(chr14:54866611-57272174)x1	Likely pathogenic

SpliceAI

1948 predictions. Top by Δscore:

Variant	Effect	Δscore
14:55377901:CATG:C	acceptor_gain	1.0000
14:55377903:TG:T	acceptor_gain	1.0000
14:55377903:TGC:T	acceptor_loss	1.0000
14:55377904:GCTAA:G	acceptor_loss	1.0000
14:55377905:C:A	acceptor_loss	1.0000
14:55377905:C:CC	acceptor_gain	1.0000
14:55377906:T:C	acceptor_loss	1.0000
14:55377978:TCATA:T	donor_loss	1.0000
14:55377979:CATA:C	donor_loss	1.0000
14:55377980:ATAC:A	donor_loss	1.0000
14:55377982:A:C	donor_loss	1.0000
14:55377983:CC:C	donor_loss	1.0000
14:55378070:ATTCA:A	acceptor_gain	1.0000
14:55378071:TTCA:T	acceptor_gain	1.0000
14:55378071:TTCAC:T	acceptor_loss	1.0000
14:55378072:TCA:T	acceptor_gain	1.0000
14:55378072:TCACT:T	acceptor_loss	1.0000
14:55378073:CA:C	acceptor_gain	1.0000
14:55378073:CAC:C	acceptor_gain	1.0000
14:55378073:CACTG:C	acceptor_loss	1.0000
14:55378074:ACTGT:A	acceptor_loss	1.0000
14:55378075:C:CC	acceptor_gain	1.0000
14:55378076:T:G	acceptor_loss	1.0000
14:55383105:T:TA	donor_gain	1.0000
14:55385877:T:TA	donor_gain	1.0000
14:55385878:C:A	donor_gain	1.0000
14:55385980:CCAGG:C	donor_gain	1.0000
14:55390909:A:AC	donor_gain	1.0000
14:55390910:C:CC	donor_gain	1.0000
14:55390910:CTTTT:C	donor_gain	1.0000

AlphaMissense

3248 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:55382089:C:A	W250C	1.000
14:55382089:C:G	W250C	1.000
14:55382091:A:G	W250R	1.000
14:55382091:A:T	W250R	1.000
14:55411696:A:G	C43R	1.000
14:55369793:C:A	W435C	0.999
14:55369793:C:G	W435C	0.999
14:55369795:A:G	W435R	0.999
14:55369795:A:T	W435R	0.999
14:55411651:A:G	C58R	0.999
14:55411660:A:G	C55R	0.999
14:55411687:A:G	C46R	0.999
14:55411695:C:G	C43S	0.999
14:55411696:A:T	C43S	0.999
14:55411707:G:T	A39D	0.999
14:55369665:G:T	A478E	0.998
14:55369668:G:T	A477E	0.998
14:55378018:A:G	L351P	0.998
14:55382090:C:G	W250S	0.998
14:55382106:A:C	Y245D	0.998
14:55382120:G:T	A240D	0.998
14:55382121:C:G	A240P	0.998
14:55382129:A:G	L237P	0.998
14:55382129:A:T	L237H	0.998
14:55411647:A:T	V59D	0.998
14:55411650:C:G	C58S	0.998
14:55411651:A:T	C58S	0.998
14:55411659:C:T	C55Y	0.998
14:55411686:C:G	C46S	0.998
14:55411686:C:T	C46Y	0.998

dbSNP variants (sampled 300 via entrez): RS1000043192 (14:55383617 TAAC>T), RS1000054702 (14:55405807 A>C), RS1000099990 (14:55383421 G>A), RS1000156089 (14:55370067 G>A,T), RS1000235421 (14:55398498 T>G), RS1000369373 (14:55389496 A>G,T), RS1000404609 (14:55394840 C>A,G,T), RS1000494435 (14:55368649 G>A,T), RS1000574437 (14:55399882 G>C), RS1000685043 (14:55411523 G>A), RS1000770176 (14:55374504 T>C), RS1000840660 (14:55412303 C>T), RS1000865011 (14:55387099 G>A,T), RS1000874490 (14:55380676 T>C,G), RS1000930624 (14:55366720 ATTAC>A)

Disease associations

OMIM: gene MIM:613515 | disease phenotypes: MIM:128230, MIM:610125

GenCC curated gene-disease

Mondo (2): dystonia 5 (MONDO:0007495), syndromic microphthalmia type 5 (MONDO:0012413)

Orphanet (2): Autosomal dominant dopa-responsive dystonia (Orphanet:98808), Syndromic microphthalmia type 5 (Orphanet:178364)

HPO phenotypes

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

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST004616_55	Platelet distribution width	9.000000e-10
GCST004635_27	Testicular germ cell tumor	3.000000e-08
GCST008552_2	Statin-induced myopathy	8.000000e-06
GCST90002382_224	Eosinophil percentage of white cells	2.000000e-17
GCST90002407_621	White blood cell count	1.000000e-09

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0007984	platelet component distribution width
EFO:0007991	eosinophil percentage of leukocytes

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C566441	Microphthalmia, Syndromic 5 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6196106 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases reaction, increases expression, decreases expression	2
sodium arsenite	increases abundance, increases expression	2
cobaltous chloride	increases expression	2
Air Pollutants	affects cotreatment, increases abundance, increases oxidation, affects expression	2
Ozone	affects cotreatment, increases oxidation, increases abundance, affects expression	2
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
astaxanthine	decreases reaction, increases expression	1
deoxynivalenol	increases expression	1
2,4,5,2’,4’,5’-hexachlorobiphenyl	decreases expression	1
butyraldehyde	decreases expression	1
perfluorooctanoic acid	decreases expression	1
cadmium sulfide	increases expression	1
methacrylaldehyde	increases abundance, affects cotreatment, increases oxidation	1
pentanal	decreases expression	1
trovafloxacin	decreases reaction, increases expression	1
2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one	increases expression, decreases reaction	1
K 7174	increases expression	1
3-(4-methylphenylsulfonyl)-2-propenenitrile	decreases reaction, increases expression	1
abrine	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
2-(1H-indazol-4-yl)-6-(4-methanesulfonylpiperazin-1-ylmethyl)-4-morpholin-4-ylthieno(3,2-d)pyrimidine	increases response to substance, increases expression	1
5-amino-7-(cyclohexylamino)-1-ethyl-6-fluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid	increases expression, decreases reaction	1
Sunitinib	increases expression	1
Acetylcysteine	decreases reaction, increases expression	1
Acrolein	increases abundance, affects cotreatment, increases oxidation	1
Arsenic	increases abundance, increases expression	1
Benzo(a)pyrene	affects methylation	1
Coumestrol	decreases expression	1
Dexamethasone	decreases reaction, increases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL6099658	Binding	Induction of stabilization of ATG14L in human A549 cells assessed as increase in melting temperature at 100 uM incubated for 24 hrs by CETSA method	Structure-Activity Relationship Studies of an Autophagy Inhibitor That Targets the ATG14L-Beclin1 Protein-Protein Interaction Reveal Modifications That Improve Potency and Solubility and Maintain Selectivity. — J Med Chem

Cellosaurus cell lines

7 cell lines: 7 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1A3	Abcam THP-1 ATG14 KO	Cancer cell line	Male
CVCL_B1KD	Abcam HeLa ATG14 KO	Cancer cell line	Female
CVCL_B8BM	Abcam HCT 116 ATG14 KO	Cancer cell line	Male
CVCL_C2VQ	HeLa S3 penta KO-ATG14 KO	Cancer cell line	Female
CVCL_SD93	HAP1 ATG14 (-) 1	Cancer cell line	Male
CVCL_SD94	HAP1 ATG14 (-) 2	Cancer cell line	Male
CVCL_SD95	HAP1 ATG14 (-) 3	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT03428009	Not specified	RECRUITING	Dystonia Genotype-Phenotype Correlation
NCT07018271	Not specified	NOT_YET_RECRUITING	A Study on the Use of Sulpegfilgrastim to Prevent the Incidence of Neutropenia With Infection in Newly Diagnosed Non-transplant Multiple Myeloma Patients