MAP1LC3A

Summary

MAP1LC3A (microtubule associated protein 1 light chain 3 alpha, HGNC:6838) is a protein-coding gene on chromosome 20q11.22, encoding Microtubule-associated protein 1 light chain 3 alpha (Q9H492). Ubiquitin-like modifier involved in formation of autophagosomal vacuoles (autophagosomes).

MAP1A and MAP1B are microtubule-associated proteins which mediate the physical interactions between microtubules and components of the cytoskeleton. MAP1A and MAP1B each consist of a heavy chain subunit and multiple light chain subunits. The protein encoded by this gene is one of the light chain subunits and can associate with either MAP1A or MAP1B. Two transcript variants encoding different isoforms have been found for this gene. The expression of variant 1 is suppressed in many tumor cell lines, suggesting that may be involved in carcinogenesis.

Source: NCBI Gene 84557 — RefSeq curated summary.

At a glance

• GWAS associations: 8
• Clinical variants (ClinVar): 15 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_032514

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6838
Approved symbol	MAP1LC3A
Name	microtubule associated protein 1 light chain 3 alpha
Location	20q11.22
Locus type	gene with protein product
Status	Approved
Aliases	MAP1BLC3, MAP1ALC3, LC3, LC3A, ATG8E
Ensembl gene	ENSG00000101460
Ensembl biotype	protein_coding
OMIM	601242
Entrez	84557

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 8 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000360668, ENST00000374837, ENST00000397709, ENST00000476428, ENST00000909925, ENST00000909926, ENST00000909927, ENST00000941363, ENST00000941364

RefSeq mRNA: 2 — MANE Select: NM_032514 NM_032514, NM_181509

CCDS: CCDS13237, CCDS13238

Canonical transcript exons

ENST00000360668 — 4 exons

Exon	Start	End
ENSE00000860117	34559208	34559263
ENSE00001529814	34558718	34558908
ENSE00003481730	34559347	34559453
ENSE00003688273	34559736	34560345

Expression profiles

Bgee: expression breadth ubiquitous, 244 present calls, max score 98.77.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 49.8586 / max 920.4542, expressed in 1528 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
184235	34.8448	1499
184236	9.4473	1297
184234	3.3844	1133
184232	0.8064	76
184239	0.5233	256
184237	0.5090	215
184238	0.3433	148

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right hemisphere of cerebellum	UBERON:0014890	98.77	gold quality
right frontal lobe	UBERON:0002810	98.59	gold quality
cerebellar hemisphere	UBERON:0002245	98.53	gold quality
cerebellar cortex	UBERON:0002129	98.51	gold quality
Brodmann (1909) area 9	UBERON:0013540	98.51	gold quality
anterior cingulate cortex	UBERON:0009835	98.50	gold quality
prefrontal cortex	UBERON:0000451	98.42	gold quality
hypothalamus	UBERON:0001898	98.17	gold quality
cerebellum	UBERON:0002037	98.04	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	97.95	gold quality
amygdala	UBERON:0001876	97.72	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	97.59	gold quality
adenohypophysis	UBERON:0002196	97.46	gold quality
frontal cortex	UBERON:0001870	97.22	gold quality
nucleus accumbens	UBERON:0001882	97.10	gold quality
spinal cord	UBERON:0002240	96.97	gold quality
mucosa of stomach	UBERON:0001199	96.92	gold quality
neocortex	UBERON:0001950	96.86	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	96.84	gold quality
putamen	UBERON:0001874	96.79	gold quality
caudate nucleus	UBERON:0001873	96.78	gold quality
pituitary gland	UBERON:0000007	96.68	gold quality
substantia nigra	UBERON:0002038	96.61	gold quality
apex of heart	UBERON:0002098	96.57	gold quality
tibial nerve	UBERON:0001323	96.49	gold quality
mucosa of transverse colon	UBERON:0004991	96.44	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	96.43	gold quality
lower esophagus muscularis layer	UBERON:0035833	96.29	gold quality
lower esophagus	UBERON:0013473	96.26	gold quality
brain	UBERON:0000955	96.16	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-HCAD-10	yes	44.57
E-ANND-3	yes	21.83
E-CURD-114	yes	10.05
E-GEOD-84465	yes	6.52
E-CURD-112	no	2.92

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): E2F1, EGR1, HBP1, PEG3

miRNA regulators (miRDB)

18 targeting MAP1LC3A, 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-6721-5P	99.93	68.92	2981
HSA-MIR-7845-5P	99.88	64.88	771
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-3158-5P	99.65	67.51	1763
HSA-MIR-486-3P	99.51	66.82	1901
HSA-MIR-4688	99.48	64.68	828
HSA-MIR-6743-5P	99.48	63.60	721
HSA-MIR-940	99.37	66.14	2064
HSA-MIR-6808-5P	99.31	66.23	2150
HSA-MIR-6893-5P	99.31	66.25	2119
HSA-MIR-423-5P	98.69	67.48	1522
HSA-MIR-2467-3P	98.65	67.18	1969
HSA-MIR-3184-5P	98.56	67.13	1491
HSA-MIR-3126-5P	96.87	65.83	912
HSA-MIR-6875-5P	96.87	65.49	958
HSA-MIR-5194	96.77	63.91	1021
HSA-MIR-6782-5P	96.45	64.42	612

Literature-anchored findings (GeneRIF, showing 40)

• localization of LC3 to a membrane compartment by delipidation is negatively regulated by HsAtg4B (PMID:15187094)
• NMR structure of human microtubule-associated protein light chain-3 (PMID:15213446)
• MAP-LC3 can act as an adaptor protein between microtubules and autophagosomes (PMID:15857831)
• Phosphatidylserine and phosphatidylethanolamine are targets of the mammalian Atg8 modifiers, LC3, GABARAP, and GATE-16 (PMID:16303767)
• LC3 residues Phe80 and Leu82, the equivalents of Phe77 and Phe79 in Atg8, are essential for its C-terminal cleavage. (PMID:17102583)
• Muscle fibers of patients with inclusion body myositis show increased frequencies of Atg8/LC3(+) autophagosomes and that intracellular amyloid beta-protein colocalized with Atg8/LC3 in degenerating muscle fibers. (PMID:17438365)
• The specific interaction between p62 and LC3, mediated by a 22-residue sequence of p62 containing an evolutionarily conserved motif, is instrumental in mediating autophagic degradation of the p62-positive bodies. (PMID:17580304)
• Modification of LC3 occurs both during poliovirus infection and following expression of a single viral protein, a stable precursor termed 2BC. (PMID:17804493)
• LC3 is responsible for recruiting p62 into autophagosomes, a process mediated by phenylalanine 52, located within the ubiquitin core, and the N-terminal region of the protein. (PMID:18653543)
• 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)
• LC3 is upregulated in various gastrointestinal cancers and partly associated with Ki-67 inde; results suggest that LC3 expression is advantageous to cancer development especially in early-phase carcinogenesis (PMID:18695874)
• The crystal structures of catalytically inert human Atg4B in complex with processed and unprocessed forms of LC3 showed that, on LC3 binding, the regulatory loop and the N-terminal tail of HsAtg4B undergo large conformational changes. (PMID:19322194)
• A large number of MAP1LC3A and MAP1LC3B positive breast cancer tissues cores have high proportion of stained cells (81-100%) as compared with normal breast tissues. (PMID:19623642)
• Data suggest that LC3 binding maintains AKAP-Lbc in an inactive state that displays a reduced ability to promote downstream signaling. (PMID:19696020)
• A hint for an autophagic fusion event is given by the autophagosome marker green fluorescent protein(GFP)-LC3 that first localizes to autophagic vesicles and then redistributes to Yersinia-containing phagosomes. (PMID:19812190)
• beclin 1 and LC3 II autophagic gene expression is altered also in melanocytic neoplasms. (PMID:20004946)
• The presence of LC3 in cytoplasmic puncta does not necessarily reveal their participation in the formation of phagophores or their accumulation on the membranes from autophagosomes. (PMID:20023420)
• Processing of autophagic protein LC3 by the 20S proteasome. (PMID:20061800)
• analysis of nucleocytoplasmic distribution and dynamics of the autophagosome marker EGFP-LC3 (PMID:20352102)
• LC3A is expressed in operable breast carcinomas (PMID:20382705)
• PKC regulates autophagy through a mechanism independent of LC3 phosphorylation. (PMID:20398630)
• Pin1 induces LC-3 expression and mediates tamoxifen resistance in breast cancer (PMID:20479004)
• A role for WIPI2 in the progression of omegasomes into autophagosomes, is reported. (PMID:20505359)
• Binding of Dvl2 to p62 facilitates the aggregation and the LC3-mediated autophagosome recruitment of Dvl2 under starvation; the ubiquitylated Dvl2 aggregates are ultimately degraded through the autophagy-lysosome pathway. (PMID:20639871)
• These data demonstrate a role for phosphorylation in regulating LC3 activity. (PMID:20713600)
• In HCT116 colorectal cancer cells exposed to prolonged nutrient deprivation, the endogenous wt p53 posttranscriptionally down-regulates LC3, a pivotal component of the autophagic machinery. (PMID:20937856)
• p62 can be efficiently localized to autophagic compartments via preferential binding with LC3-II form. (PMID:21045561)
• LC3 regulates cardiomyocyte autophagy by hypoxia-reoxygenation. (PMID:21316776)
• Immunoblot analysis demonstrated specific accumulation of the autophagosomal LC3-II isoform in detergent-insoluble fractions from Lewy body disease brains (PMID:21412173)
• Data show that the expression of LC3, rather than beclin-1, was strongly associated with metastasis and poor clinical prognosis of human melanoma. (PMID:21415575)
• The fusion activity of LC3 is mediated by positively charged amino acids, whereas the activity of GATE-16 is mediated by hydrophobic interactions. (PMID:21497758)
• SHBs (HBV small surface protein) partially colocalized and interacted with autophagy protein LC3. (PMID:21507968)
• Low LC3A expression was related to ulceration, but not to other histopathological features nor prognosis in cutaneous melanoma. (PMID:21537144)
• Both mRNA and protein levels of Beclin-1 and LC3-II were significantly decreased in lung cancer tissues which suggested that autophagy may be involved in the pathogenesis of lung cancer. (PMID:21556768)
• inhibition of proteasomal degradation results in increased oligomerization and activation of caspase-8 on intracellular membranes; enhanced caspase-8 oligomerization and activation are promoted through interaction with SQSTM1/p62 and (LC3) (PMID:21628531)
• All cases of granular cell tumor (GCT) showed granule LC3 in cytoplasm of tumor cells, indicating that formation of intracytoplasmic granules in GCT is closely related to autophagy. In schwannoma small number of tumor cells showed granule LC3. (PMID:21674156)
• Biochemical and pathological properties of LC3 are altered; the level of LC3 is increased in an insoluble fraction from the brains of patients with Lewy body disease. (PMID:21684337)
• Data show that luminal P-PERK and LC3 levels are reduced in PERK-deficient mammary glands, whereas they are increased in human breast ductal carcinoma in situ. (PMID:21709020)
• Up-regulation of autophagic activity and expression of Beclin1 and MAPLC3 mRNA in refractory or relapse acute leukemia patients is especially significant. (PMID:21729531)
• LC3 gene expression in the peripheral leucocytes was significantly decreased in patients with coronary artery disease, indicating that autophagosome formation is decreased. (PMID:21812771)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	map1lc3a	ENSDARG00000033609
mus_musculus	Map1lc3a	ENSMUSG00000027602
rattus_norvegicus	Map1lc3a	ENSRNOG00000025443
caenorhabditis_elegans		WBGENE00002981

Paralogs (6): GABARAPL2 (ENSG00000034713), GABARAPL1 (ENSG00000139112), MAP1LC3B (ENSG00000140941), GABARAP (ENSG00000170296), MAP1LC3C (ENSG00000197769), MAP1LC3B2 (ENSG00000258102)

Protein

Protein identifiers

Microtubule-associated protein 1 light chain 3 alpha — Q9H492 (reviewed: Q9H492)

Alternative names: Autophagy-related protein LC3 A, Autophagy-related ubiquitin-like modifier LC3 A, MAP1 light chain 3-like protein 1, Microtubule-associated proteins 1A/1B light chain 3A

All UniProt accessions (1): Q9H492

UniProt curated annotations — full annotation on UniProt →

Function. Ubiquitin-like modifier involved in formation of autophagosomal vacuoles (autophagosomes). While LC3s are involved in elongation of the phagophore membrane, the GABARAP/GATE-16 subfamily is essential for a later stage in autophagosome maturation. Through its interaction with the reticulophagy receptor TEX264, participates in the remodeling of subdomains of the endoplasmic reticulum into autophagosomes upon nutrient stress, which then fuse with lysosomes for endoplasmic reticulum turnover.

Subunit / interactions. 3 different light chains, LC1 (a cleavage product of MAP1B), LC2 (a cleavage product of MAP1A) and LC3 (produced by one of the MAP1LC3 genes), can associate with the MAP1A or MAP1B heavy chains. Interacts with TP53INP1 and TP53INP2. Directly interacts with SQSTM1; this interaction leads to MAP1LC3A recruitment to inclusion bodies containing polyubiquitinated protein aggregates and to inclusion body degradation by autophagy. Interacts with ATG13. Interacts with ULK1. Interacts with TBC1D5. Found in a complex with UBQLN1 and UBQLN2. Interacts with UBQLN4 (via STI1 1 and 2 domains). Interacts with UBQLN1 in the presence of UBQLN4. Interacts with TRIM5. Interacts with MEFV. Interacts with reticulophagy regulators RETREG1, RETREG2 and RETREG3. Interacts with PICALM. Interacts with the reticulophagy receptor TEX264. Interacts with MOAP1 (via LIR motif). Interacts with IRGM. Interacts with SPART. (Microbial infection) Interacts with NS1-2 of human norovirus GII.4; this interaction does not seem to be linked to autophagy, but rather plays a role in the formation of viral factories.

Subcellular location. Cytoplasmic vesicle. Autophagosome membrane. Endomembrane system. Cytoplasm. Cytoskeleton.

Tissue specificity. Most abundant in heart, brain, liver, skeletal muscle and testis but absent in thymus and peripheral blood leukocytes.

Post-translational modifications. The precursor molecule is cleaved by ATG4 (ATG4A, ATG4B, ATG4C or ATG4D) to expose the glycine at the C-terminus and form the cytosolic form, LC3-I. The processed form is then activated by APG7L/ATG7, transferred to ATG3 and conjugated to phosphatidylethanolamine (PE) phospholipid to form the membrane-bound form, LC3-II. During non-canonical autophagy, the processed form is conjugated to phosphatidylserine (PS) phospholipid. ATG4 proteins also mediate the delipidation of PE-conjugated forms. In addition, ATG4B and ATG4D mediate delipidation of ATG8 proteins conjugated to PS during non-canonical autophagy. ATG4B constitutes the major protein for proteolytic activation. ATG4D is the main enzyme for delipidation activity. (Microbial infection) The Legionella effector RavZ is a deconjugating enzyme that hydrolyzes the amide bond between the C-terminal glycine residue and an adjacent aromatic residue in ATG8 proteins conjugated to phosphatidylethanolamine (PE), producing an ATG8 protein that is resistant to reconjugation by the host machinery due to the cleavage of the reactive C-terminal glycine. RavZ is also able to mediate delipidation of ATG8 proteins conjugated to phosphatidylserine (PS). Phosphorylation at Ser-12 by PKA inhibits conjugation to phosphatidylethanolamine (PE).

Similarity. Belongs to the ATG8 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9H492-1	1	yes
Q9H492-2	2

RefSeq proteins (2): NP_115903, NP_852610 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004241	Atg8-like	Family
IPR029071	Ubiquitin-like_domsf	Homologous_superfamily

Pfam: PF02991

UniProt features (38 total): mutagenesis site 16, strand 7, helix 6, lipid moiety-binding region 2, chain 1, propeptide 1, region of interest 1, site 1, turn 1, modified residue 1, splice variant 1

Structure

Experimental structures (PDB)

14 structures.

PDB	Method	Resolution (Å)
7RA0	X-RAY DIFFRACTION	1.36
6TBE	X-RAY DIFFRACTION	1.67
7R9Z	X-RAY DIFFRACTION	1.72
7R9W	X-RAY DIFFRACTION	1.75
3WAN	X-RAY DIFFRACTION	1.77
4ZDV	X-RAY DIFFRACTION	1.8
8T36	X-RAY DIFFRACTION	1.85
8T35	X-RAY DIFFRACTION	1.9
3WAL	X-RAY DIFFRACTION	2
8T2L	X-RAY DIFFRACTION	2.24
5CX3	X-RAY DIFFRACTION	2.3
8T4T	X-RAY DIFFRACTION	2.36
5DPR	X-RAY DIFFRACTION	2.5
3ECI	X-RAY DIFFRACTION	2.65

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H492-F1	91.46	0.79

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): 120–121 (cleavage; by atg4b)

Post-translational modifications (3): 12, 120, 120

Mutagenesis-validated functional residues (16):

Position	Phenotype
49	increases interaction with atg13 and strongly reduces autophagosome formation.
51	decreases interaction with atg13 and strongly reduces autophagosome formation.
53	decreases interaction with atg13.
57	enhances binding to retreg1.
65	enhances binding to retreg1.
116–119	abolished deconjugation of phosphatidylethanolamine (pe) by both legionella ravz and atg4b.
116–118	abolished deconjugation of phosphatidylethanolamine (pe) by both legionella ravz and atg4b.
116–117	abolished deconjugation of phosphatidylethanolamine (pe) by atg4b, without affecting deconjugation by legionella ravz.
116	abolished deconjugation of phosphatidylethanolamine (pe) by atg4b, without affecting deconjugation by legionella ravz.
117	abolished deconjugation of phosphatidylethanolamine (pe) by legionella ravz, without affecting deconjugation by atg4b.
118	does not affect deconjugation of phosphatidylethanolamine (pe).
119	abolished deconjugation of phosphatidylethanolamine (pe) by both legionella ravz and atg4b.
120	no processing of precursor.
120	abolished deconjugation of phosphatidylethanolamine (pe) by both legionella ravz and atg4b.
27	enhances binding to retreg1.
30	enhances binding to retreg1.

Function

Pathways and Gene Ontology

Reactome pathways

6 pathways

ID	Pathway
R-HSA-1632852	Macroautophagy
R-HSA-5205685	PINK1-PRKN Mediated Mitophagy
R-HSA-8934903	Receptor Mediated Mitophagy
R-HSA-5205647	Mitophagy
R-HSA-9612973	Autophagy
R-HSA-9663891	Selective autophagy

MSigDB gene sets: 253 (showing top): ATF_B, GOBP_SMAD_PROTEIN_SIGNAL_TRANSDUCTION, GOBP_VACUOLE_ORGANIZATION, GOCC_VACUOLAR_MEMBRANE, NIKOLSKY_BREAST_CANCER_20Q11_AMPLICON, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_DN, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, DARWICHE_SKIN_TUMOR_PROMOTER_UP, DARWICHE_PAPILLOMA_RISK_LOW_DN, DARWICHE_PAPILLOMA_RISK_HIGH_DN, CREBP1_Q2, RACCACAR_AML_Q6, DARWICHE_SQUAMOUS_CELL_CARCINOMA_DN, GOBP_RESPONSE_TO_COPPER_ION

GO Biological Process (18): autophagosome assembly (GO:0000045), autophagy of mitochondrion (GO:0000422), mitophagy (GO:0000423), cellular response to nitrogen starvation (GO:0006995), JNK cascade (GO:0007254), cellular response to starvation (GO:0009267), response to iron(II) ion (GO:0010040), response to lead ion (GO:0010288), macroautophagy (GO:0016236), cellular response to amino acid starvation (GO:0034198), p38MAPK cascade (GO:0038066), SMAD protein signal transduction (GO:0060395), cellular response to hydrogen peroxide (GO:0070301), cellular response to copper ion (GO:0071280), cellular response to oxygen-glucose deprivation (GO:0090650), autophagosome maturation (GO:0097352), autophagy (GO:0006914), response to nutrient levels (GO:0031667)

GO Molecular Function (5): phospholipid binding (GO:0005543), microtubule binding (GO:0008017), phosphatidylethanolamine binding (GO:0008429), ubiquitin protein ligase binding (GO:0031625), protein binding (GO:0005515)

GO Cellular Component (14): autophagosome membrane (GO:0000421), late endosome (GO:0005770), autophagosome (GO:0005776), cytosol (GO:0005829), microtubule (GO:0005874), organelle membrane (GO:0031090), autolysosome (GO:0044754), glutamatergic synapse (GO:0098978), cytoplasm (GO:0005737), cytoskeleton (GO:0005856), endomembrane system (GO:0012505), membrane (GO:0016020), cytoplasmic vesicle (GO:0031410), synapse (GO:0045202)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Mitophagy	2
Autophagy	1
Selective autophagy	1
Macroautophagy	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
autophagy	2
macroautophagy	2
cellular response to starvation	2
MAPK cascade	2
cellular response to nutrient levels	2
vacuole	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
cellular response to nitrogen levels	1
cellular response to stress	1
response to starvation	1
response to iron ion	1
response to metal ion	1
autophagosome assembly	1
response to amino acid starvation	1
cell surface receptor protein serine/threonine kinase signaling pathway	1
intracellular signaling cassette	1
cellular response to reactive oxygen species	1
response to hydrogen peroxide	1
response to copper ion	1
cellular response to metal ion	1
cellular response to decreased oxygen levels	1
response to oxygen-glucose deprivation	1
protein-containing complex disassembly	1
catabolic process	1
transmembrane transport	1
process utilizing autophagic mechanism	1
response to stimulus	1
lipid binding	1
tubulin binding	1
phospholipid binding	1
ubiquitin-like protein ligase binding	1

Protein interactions and networks

STRING

2922 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MAP1LC3A	FKBP8	Q14318	989
MAP1LC3A	SQSTM1	Q13501	969
MAP1LC3A	ATG7	O95352	968
MAP1LC3A	ATG3	Q9NT62	954
MAP1LC3A	ATG12	O94817	945
MAP1LC3A	ATG5	Q9H1Y0	944
MAP1LC3A	BECN1	Q14457	927
MAP1LC3A	ATG4B	Q9Y4P1	912
MAP1LC3A	CD300C	Q08708	906
MAP1LC3A	MAP1B	P46821	891
MAP1LC3A	MAP1S	Q66K74	886
MAP1LC3A	ATG10	Q9H0Y0	879
MAP1LC3A	ULK1	O75385	868
MAP1LC3A	ATG9A	Q7Z3C6	864
MAP1LC3A	FUNDC1	Q8IVP5	852

IntAct

157 interactions, top by confidence:

A	B	Type	Score
SQSTM1	MAP1LC3A	psi-mi:“MI:0915”(physical association)	0.950
MAP1LC3A	SQSTM1	psi-mi:“MI:0915”(physical association)	0.950
SQSTM1	MAP1LC3A	psi-mi:“MI:0407”(direct interaction)	0.950
MAP1LC3A	SQSTM1	psi-mi:“MI:0407”(direct interaction)	0.950
SQSTM1	MAP1LC3A	psi-mi:“MI:0403”(colocalization)	0.950
TNIP1	MAP1LC3A	psi-mi:“MI:0915”(physical association)	0.780
RETREG3	MAP1LC3A	psi-mi:“MI:0915”(physical association)	0.780
MAP1LC3A	RETREG3	psi-mi:“MI:0915”(physical association)	0.780
MAP1LC3A	TNIP1	psi-mi:“MI:0915”(physical association)	0.780
MAP1LC3A	KXD1	psi-mi:“MI:0915”(physical association)	0.720
KXD1	MAP1LC3A	psi-mi:“MI:0915”(physical association)	0.720
MAP1LC3A	NBR1	psi-mi:“MI:0915”(physical association)	0.680
MAP1LC3A	NBR1	psi-mi:“MI:0407”(direct interaction)	0.680
MAP1LC3A	NBR1	psi-mi:“MI:0403”(colocalization)	0.680
FUNDC1	MAP1LC3A	psi-mi:“MI:0915”(physical association)	0.670

BioGRID (466): MAP1LC3A (Co-crystal Structure), MAP1LC3A (Reconstituted Complex), tat (Reconstituted Complex), MAP1LC3A (Two-hybrid), MAP1LC3A (Two-hybrid), FUNDC1 (Two-hybrid), FAM134C (Two-hybrid), CBX5 (Co-localization), CBX5 (Affinity Capture-Western), MAP1LC3A (Two-hybrid), MAP1LC3A (Reconstituted Complex), MAP1LC3A (Affinity Capture-Western), AKAP13 (Reconstituted Complex), MAP1LC3A (Reconstituted Complex), MAP1LC3A (Reconstituted Complex)

ESM2 similar proteins: A1CQS1, A1D3N4, A2XXR7, A2YAG8, A2YS06, A6NCE7, A6RPU4, A7KAL9, I1S1W5, J4UTT5, M1C146, M2SQA5, N4X184, O41515, P0CM28, P0CM29, P60519, P60520, P60521, P60522, Q0C804, Q0V3Y9, Q1E4K5, Q1SF86, Q2HJ23, Q2RBS4, Q2UBH5, Q2XPP5, Q4P2U6, Q4WJ27, Q69NP0, Q69RC4, Q6XVN8, Q6Z1D5, Q7XPR1, Q86CR8, Q8J282, Q8LEM4, Q8S924, Q8S925

Diamond homologs: A0A1B7XV12, A1CQS1, A1D3N4, A2QPN1, A2XXR7, A2YS06, A3GFU8, A4LA70, A5DWI6, A6NCE7, A6RPU4, A6ZKM4, A7E8H4, A7KAL9, A7TDU7, C4B4E4, I1S1W5, J4UTT5, M1C146, M2SQA5, N4X184, O41515, O94272, O95166, P0C075, P0CO54, P0CO55, P38182, P60517, P60518, P60519, P60520, P60521, P60522, P87068, Q09490, Q0C804, Q0V3Y9, Q0VGK0, Q1E4K5

SIGNOR signaling

10 interactions.

A	Effect	B	Mechanism
MAP1LC3A	up-regulates	SQSTM1	binding
TP53INP2	up-regulates	MAP1LC3A	binding
NBR1	up-regulates	MAP1LC3A	binding
MAP1LC3A	up-regulates	ATG3	binding
MAP1LC3A	up-regulates	O-phosphoethanolamine	binding
ATG7	up-regulates	MAP1LC3A	binding
TP53INP1	up-regulates	MAP1LC3A	binding
MAP1LC3A	up-regulates	Autophagosome_formation
FYCO1	“up-regulates activity”	MAP1LC3A	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 90 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
Selective autophagy	6	25.7×	2e-05
Autophagy	9	20.5×	2e-07
Macroautophagy	9	16.0×	1e-06
SARS-CoV-1 Infection	5	11.0×	5e-03
Cellular response to chemical stress	5	11.0×	5e-03
KEAP1-NFE2L2 pathway	5	9.2×	9e-03
Diseases of signal transduction by growth factor receptors and second messengers	7	6.1×	7e-03

GO biological processes:

GO term	Partners	Fold	FDR
mitophagy	8	31.0×	1e-07
macroautophagy	7	20.6×	1e-05
positive regulation of autophagy	7	17.8×	2e-05
autophagosome assembly	6	16.4×	2e-04
autophagy	9	12.1×	1e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	9
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

622 predictions. Top by Δscore:

Variant	Effect	Δscore
20:34559342:CCCAG:C	acceptor_loss	1.0000
20:34559343:CCAG:C	acceptor_loss	1.0000
20:34559344:CAG:C	acceptor_loss	1.0000
20:34559345:AGG:A	acceptor_loss	1.0000
20:34559346:G:GA	acceptor_loss	1.0000
20:34559432:GCGA:G	donor_gain	1.0000
20:34559436:G:GG	donor_gain	1.0000
20:34559441:TC:T	donor_gain	1.0000
20:34559452:CGG:C	donor_loss	1.0000
20:34559454:G:GG	donor_gain	1.0000
20:34559454:GTGC:G	donor_loss	1.0000
20:34559455:T:G	donor_loss	1.0000
20:34559476:G:GT	donor_gain	1.0000
20:34559727:C:CA	acceptor_gain	1.0000
20:34559734:A:AG	acceptor_gain	1.0000
20:34559735:G:GG	acceptor_gain	1.0000
20:34559882:A:T	donor_gain	1.0000
20:34559206:A:AG	acceptor_gain	0.9900
20:34559206:AGCC:A	acceptor_gain	0.9900
20:34559207:G:GG	acceptor_gain	0.9900
20:34559207:GCCG:G	acceptor_gain	0.9900
20:34559259:TCCCG:T	donor_gain	0.9900
20:34559263:GGTG:G	donor_loss	0.9900
20:34559264:G:C	donor_loss	0.9900
20:34559264:G:GG	donor_gain	0.9900
20:34559265:T:A	donor_loss	0.9900
20:34559266:GAGTC:G	donor_loss	0.9900
20:34559338:T:TA	acceptor_gain	0.9900
20:34559341:TCCCA:T	acceptor_loss	0.9900
20:34559345:A:AG	acceptor_gain	0.9900

AlphaMissense

807 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:34559404:T:C	F52L	1.000
20:34559405:T:C	F52S	1.000
20:34559406:T:A	F52L	1.000
20:34559406:T:G	F52L	1.000
20:34559213:C:A	R16S	0.999
20:34559262:C:A	P32Q	0.999
20:34559348:T:A	V33E	0.999
20:34559351:T:A	I34N	0.999
20:34559354:T:A	I35N	0.999
20:34559359:C:A	R37S	0.999
20:34559381:T:A	L44Q	0.999
20:34559381:T:C	L44P	0.999
20:34559403:G:C	K51N	0.999
20:34559403:G:T	K51N	0.999
20:34559405:T:G	F52C	0.999
20:34559408:T:C	L53S	0.999
20:34559408:T:G	L53W	0.999
20:34559411:T:A	V54D	0.999
20:34559453:G:C	R68P	0.999
20:34559740:C:A	R70S	0.999
20:34559744:T:C	L71P	0.999
20:34559750:T:C	L73P	0.999
20:34559770:T:C	F80L	0.999
20:34559772:C:A	F80L	0.999
20:34559772:C:G	F80L	0.999
20:34559848:G:C	D106H	0.999
20:34559854:T:C	F108L	0.999
20:34559856:C:A	F108L	0.999
20:34559856:C:G	F108L	0.999
20:34559858:T:C	L109P	0.999

dbSNP variants (sampled 300 via entrez): RS1000140497 (20:34553805 C>T), RS1000356100 (20:34556878 G>A), RS1000785166 (20:34545016 C>T), RS1000795569 (20:34549566 C>G,T), RS1000834405 (20:34556318 G>A), RS1000939129 (20:34553176 G>A), RS1000989436 (20:34560114 G>A,T), RS1001195972 (20:34545206 A>G), RS1001202955 (20:34553005 A>G), RS1001253856 (20:34553175 C>A,T), RS1001448962 (20:34547588 C>T), RS1002069667 (20:34550372 T>C), RS1002259403 (20:34552142 C>T), RS1002428246 (20:34558324 C>T), RS1002463497 (20:34546440 C>G)

Disease associations

OMIM: gene MIM:601242 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST007856_83	Colorectal cancer or advanced adenoma	3.000000e-07
GCST008103_149	Bipolar disorder	3.000000e-06
GCST010135_33	Oily fish consumption	7.000000e-09
GCST010140_23	Pork consumption	7.000000e-09
GCST010142_10	Fish- and plant-related diet	8.000000e-12
GCST012227_1083	Hip circumference adjusted for BMI	5.000000e-09
GCST012227_1085	Hip circumference adjusted for BMI	4.000000e-08
GCST90011898_163	Alanine aminotransferase levels	1.000000e-18

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0008111	diet measurement
EFO:0008039	BMI-adjusted hip circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (6): CHEMBL4879518 (SINGLE PROTEIN), CHEMBL6066861 (PROTEIN-PROTEIN INTERACTION), CHEMBL6193844 (PROTEIN-PROTEIN INTERACTION), CHEMBL6193845 (PROTEIN-PROTEIN INTERACTION), CHEMBL6195681 (PROTEIN-PROTEIN INTERACTION), CHEMBL6195682 (PROTEIN-PROTEIN INTERACTION)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 11,401 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL36506	NOVOBIOCIN	4	11,401

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

ChEMBL bioactivities

9 potent at pChembl≥5 of 65 total, top 9 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.48	IC50	32.8	nM	CHEMBL5556385
5.55	Kd	2800	nM	CHEMBL4851364
5.48	Ki	3300	nM	CHEMBL4851364
5.19	Ki	6400	nM	CHEMBL4852281
5.14	Ki	7200	nM	CHEMBL4861964
5.12	Ki	7500	nM	CHEMBL4878621
5.12	Kd	7500	nM	NOVOBIOCIN
5.06	Ki	8800	nM	NOVOBIOCIN
5.06	Ki	8800	nM	CHEMBL4878719

PubChem BioAssay actives

9 with measured affinity, of 111 total; 7 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
5-(5,6-dichloro-1H-indol-4-yl)-2-[2-(dimethylamino)ethyliminomethyl]-3-hydroxycyclohex-2-en-1-one	2086249: Inhibition of LC3A (unknown origin) by Alphascreen assay	ic50	0.0328	uM
[(3R,4S,5R,6R)-5-hydroxy-6-[4-hydroxy-3-[[4-hydroxy-3-(3-methylbutyl)benzoyl]amino]-8-methyl-2-oxochromen-7-yl]oxy-3-methoxy-2,2-dimethyloxan-4-yl] carbamate	1775855: Binding affinity to human LC3A expressed in Escherichia coli BL21-(DE3) by isothermal titration calorimetry	kd	2.8000	uM
N-[4-hydroxy-7-(naphthalen-1-ylsulfonylamino)-2-oxochromen-3-yl]-3-(3-methylbutyl)benzamide	1775854: Displacement of sGFP-p62-LIR peptide from human N-terminal SNAP-fused LC3A by time-resolved FRET assay	ki	6.4000	uM
3-[4-hydroxy-3-[[3-(3-methylbutyl)benzoyl]amino]-2-oxochromen-7-yl]benzoic acid	1775854: Displacement of sGFP-p62-LIR peptide from human N-terminal SNAP-fused LC3A by time-resolved FRET assay	ki	7.2000	uM
N-[4-hydroxy-2-oxo-7-(2-phenylethylsulfonylamino)chromen-3-yl]-3-(3-methylbutyl)benzamide	1775854: Displacement of sGFP-p62-LIR peptide from human N-terminal SNAP-fused LC3A by time-resolved FRET assay	ki	7.5000	uM
[(3R,4S,5R,6R)-5-hydroxy-6-[4-hydroxy-3-[[4-hydroxy-3-(3-methylbut-2-enyl)benzoyl]amino]-8-methyl-2-oxochromen-7-yl]oxy-3-methoxy-2,2-dimethyloxan-4-yl] carbamate	1775855: Binding affinity to human LC3A expressed in Escherichia coli BL21-(DE3) by isothermal titration calorimetry	kd	7.5000	uM
N-(4-hydroxy-7-naphthalen-1-yl-2-oxochromen-3-yl)-3-(3-methylbutyl)benzamide	1775854: Displacement of sGFP-p62-LIR peptide from human N-terminal SNAP-fused LC3A by time-resolved FRET assay	ki	8.8000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Chloroquine	increases expression, decreases reaction, increases degradation	3
Cisplatin	affects expression, decreases expression, decreases response to substance, increases expression	3
Valproic Acid	increases methylation, affects expression, increases expression	3
sodium arsenite	increases abundance, increases lipidation, increases expression	2
3-methyladenine	increases expression, affects metabolic processing, decreases reaction	2
bafilomycin A	affects cotreatment, increases reaction, affects reaction, increases cleavage, increases lipidation	2
apilimod	increases expression	2
dorsomorphin	affects localization, decreases reaction, increases expression	2
Benzo(a)pyrene	increases expression, increases methylation	2
Nickel	decreases expression	2
Particulate Matter	affects expression, increases abundance, increases expression	2
aristolochic acid I	increases expression	1
4-(4-fluorophenyl)sulfonyl-5-methylthio-2-phenyloxazole	increases lipidation, affects reaction	1
thymoquinone	increases lipidation	1
triphenyl phosphate	affects expression	1
acadesine	increases reaction, affects localization	1
dihydrocapsaicin	decreases reaction, increases expression, increases reaction, affects reaction	1
arsenite	increases abundance, increases lipidation	1
cypermethrin	increases expression	1
butyraldehyde	increases expression	1
perfluorooctanoic acid	increases expression	1
resorcinol	increases lipidation	1
hydroquinone	decreases reaction, increases degradation, affects localization	1
cadmium sulfide	decreases expression	1
bafilomycin A1	increases expression	1
3,3’,4,5’-tetrahydroxystilbene	increases expression	1
epigallocatechin gallate	increases expression	1
cordycepin	increases expression	1
fangchinoline	increases lipidation	1
di-n-butylphosphoric acid	affects expression	1

ChEMBL screening assays

33 unique, capped per target: 33 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4835341	Binding	Binding affinity to human LC3A expressed in Escherichia coli BL21-(DE3) by single site binding model based isothermal titration calorimetry	Demonstrating Ligandability of the LC3A and LC3B Adapter Interface. — J Med Chem

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_A9LY	MHCC97H-GFP-LC3	Cancer cell line	Male
CVCL_WJ13	HCCLM3-GFP-LC3	Cancer cell line	Male

Clinical trials (associated diseases)

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