GABARAPL1

Summary

GABARAPL1 (GABA type A receptor associated protein like 1, HGNC:4068) is a protein-coding gene on chromosome 12p13.2, encoding Gamma-aminobutyric acid receptor-associated protein-like 1 (Q9H0R8). Ubiquitin-like modifier that increases cell-surface expression of kappa-type opioid receptor through facilitating anterograde intracellular trafficking of the receptor.

Enables Tat protein binding activity; phospholipid binding activity; and ubiquitin protein ligase binding activity. Predicted to be involved in cellular response to nitrogen starvation and macroautophagy. Located in several cellular components, including autophagosome; ciliary basal body; and mitochondrion.

Source: NCBI Gene 23710 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 15 total
• Druggable target: yes
• MANE Select transcript: NM_031412

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4068
Approved symbol	GABARAPL1
Name	GABA type A receptor associated protein like 1
Location	12p13.2
Locus type	gene with protein product
Status	Approved
Aliases	gec1, APG8L, ATG8L, ATG8B
Ensembl gene	ENSG00000139112
Ensembl biotype	protein_coding
OMIM	607420
Entrez	23710

Gene structure

Transcript identifiers

Ensembl transcripts: 20 — 13 protein_coding, 6 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000266458, ENST00000421801, ENST00000535576, ENST00000537201, ENST00000539170, ENST00000539289, ENST00000539408, ENST00000540424, ENST00000541453, ENST00000541960, ENST00000542722, ENST00000543602, ENST00000544284, ENST00000545047, ENST00000545290, ENST00000545859, ENST00000545887, ENST00000546017, ENST00000629504, ENST00000929818

RefSeq mRNA: 2 — MANE Select: NM_031412 NM_001363598, NM_031412

CCDS: CCDS8620, CCDS86280

Canonical transcript exons

ENST00000266458 — 4 exons

Exon	Start	End
ENSE00002236538	10212877	10213219
ENSE00003513231	10221787	10223128
ENSE00003579148	10218063	10218141
ENSE00003609796	10220440	10220558

Expression profiles

Bgee: expression breadth ubiquitous, 299 present calls, max score 99.96.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 58.1726 / max 1321.8607, expressed in 1779 samples.

FANTOM5 promoters (11 alternative TSS)

Promoter ID	TPM avg	Samples expressed
124145	50.5240	1770
124148	1.9341	666
124147	1.1506	550
124144	1.0656	520
124151	0.9448	351
124152	0.9104	299
124149	0.6980	285
124143	0.4202	159
124153	0.3431	138
124150	0.1250	64

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
Brodmann (1909) area 23	UBERON:0013554	99.96	gold quality
endothelial cell	CL:0000115	99.93	gold quality
middle temporal gyrus	UBERON:0002771	99.92	gold quality
pons	UBERON:0000988	99.64	gold quality
parotid gland	UBERON:0001831	99.63	gold quality
primary visual cortex	UBERON:0002436	99.61	gold quality
medial globus pallidus	UBERON:0002477	99.61	gold quality
lateral nuclear group of thalamus	UBERON:0002736	99.61	gold quality
occipital lobe	UBERON:0002021	99.56	gold quality
superior frontal gyrus	UBERON:0002661	99.56	gold quality
nephron tubule	UBERON:0001231	99.55	gold quality
orbitofrontal cortex	UBERON:0004167	99.50	gold quality
superior vestibular nucleus	UBERON:0007227	99.49	gold quality
parietal lobe	UBERON:0001872	99.46	gold quality
tendon of biceps brachii	UBERON:0008188	99.46	gold quality
globus pallidus	UBERON:0001875	99.45	gold quality
substantia nigra pars compacta	UBERON:0001965	99.44	gold quality
postcentral gyrus	UBERON:0002581	99.43	gold quality
Brodmann (1909) area 46	UBERON:0006483	99.43	gold quality
frontal pole	UBERON:0002795	99.40	gold quality
prefrontal cortex	UBERON:0000451	99.39	gold quality
renal glomerulus	UBERON:0000074	99.37	gold quality
Brodmann (1909) area 10	UBERON:0013541	99.37	gold quality
kidney epithelium	UBERON:0004819	99.35	gold quality
entorhinal cortex	UBERON:0002728	99.34	gold quality
metanephric glomerulus	UBERON:0004736	99.32	gold quality
dorsal root ganglion	UBERON:0000044	99.26	gold quality
frontal cortex	UBERON:0001870	99.26	gold quality
frontal lobe	UBERON:0016525	99.26	gold quality
renal medulla	UBERON:0000362	99.22	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-3929	yes	1142.61
E-MTAB-6701	yes	37.85
E-CURD-122	yes	22.45
E-MTAB-6678	yes	8.56
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): E2F1

Literature-anchored findings (GeneRIF, showing 26)

• Gec1/GABARAPL1 was more expressed than GABARAP in the central nervous system (CNS), while GABARAP was more expressed in endocrine glands. (PMID:14625090)
• GEC1 interacts with the kappa opioid receptor and enhances expression of the receptor (PMID:16431922)
• GEC1-kappa opioid receptor binding involves hydrophobic interactions: GEC1 has chaperone-like effect. (PMID:19001416)
• Caspase cleavage of Atg4D stimulates GABARAP-L1 processing and triggers mitochondrial targeting and apoptosis. (PMID:19549685)
• Gabarapl1 mRNA expression in breast tumours is a good indicator of the risk of recurrence, specifically in lymph nodes positive patients. (PMID:20197771)
• analysis of specific functions of GABARAPL1 [review] (PMID:21597319)
• Results indicate that the presence of a tryptophan residue in the LIR motif increases the binding affinity of GABARAPL-1/NBR1-LIR complex. (PMID:21620860)
• Atg8 interacting motif (AIM) in Stbd1 is necessary for GABARAPL1 binding. (PMID:21893048)
• Data demonstrate that HSP90 interacts and protects GABARAPL1 from its degradation by the proteasome. (PMID:22120110)
• Results showed that the mRNA and protein levels of GABARAPL1 and GATE-16 were decreased in the cerebellum of multiple system atrophy relative to controls (PMID:22959883)
• Kaplan-Meier survival analysis showed a significant association between low GABARAPL1 expression and poor prognosis of HCC patients. (PMID:24647565)
• Lipidation of the LC3/GABARAP family of autophagy proteins relies on a membrane-curvature-sensing domain in Atg3. (PMID:24747438)
• GABARAPL1 plays an important role in cell proliferation, invasion, and autophagic flux, as well as in mitochondrial homeostasis and cellular metabolic programs in a breast cancer cell line. (PMID:24879149)
• Androgen deprivation downregulates Gabarapl1 in an AR dependent manner, resulting in the increase of autophagy flux (PMID:26050226)
• Our data demonstrated that a specific decrease of GABARAPL1 expression in breast cancers was associated with both DNA methylation and histone deacetylation and that CREB-1 recruitment on GABARAPL1 (PMID:26474850)
• these results indicate that miR-195 regulates cell proliferation, migration, angiogenesis and autophagy of hEPCs by targeting GABARAPL1 (PMID:27623937)
• GABARAPs are identified as the first known direct interaction partners of Nef that are essential for its plasma membrane localization. (PMID:28729737)
• Knockdown of p62 or GABARAPL1 reduced cell survival upon proteasome inhibition. (PMID:29535191)
• PIK3C3, BECN1 and ATG14 contain functional LIR motifs and interact with the Atg8-family proteins with a preference for GABARAP and GABARAPL1. (PMID:30767700)
• Autophagic Network Analysis of the Dual Effect of Sevoflurane on Neurons Associated with GABARAPL1 and 2. (PMID:32685442)
• Lack of GABARAP-Type Proteins Is Accompanied by Altered Golgi Morphology and Surfaceome Composition. (PMID:33374830)
• Non-canonical autophagy drives alternative ATG8 conjugation to phosphatidylserine. (PMID:33909989)
• Loss of GABARAPL1 confers ferroptosis resistance to cancer stem-like cells in hepatocellular carcinoma. (PMID:36062307)
• ATG8-dependent LMX1B-autophagy crosstalk shapes human midbrain dopaminergic neuronal resilience. (PMID:37014324)
• METTL3 promotes hyperoxia-induced pyroptosis in neonatal bronchopulmonary dysplasia by inhibiting ATG8-mediated autophagy. (PMID:37478627)
• The transcription factor NRF1 (NFE2L1) activates aggrephagy by inducing p62 and GABARAPL1 after proteasome inhibition to maintain proteostasis. (PMID:37658135)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	map1lc3cl	ENSDARG00000075727
mus_musculus	Gabarapl1	ENSMUSG00000030161
rattus_norvegicus	Gabarapl1	ENSRNOG00000053362
caenorhabditis_elegans		WBGENE00002981

Paralogs (6): GABARAPL2 (ENSG00000034713), MAP1LC3A (ENSG00000101460), MAP1LC3B (ENSG00000140941), GABARAP (ENSG00000170296), MAP1LC3C (ENSG00000197769), MAP1LC3B2 (ENSG00000258102)

Protein

Protein identifiers

Gamma-aminobutyric acid receptor-associated protein-like 1 — Q9H0R8 (reviewed: Q9H0R8)

Alternative names: Early estrogen-regulated protein, GABA(A) receptor-associated protein-like 1, Glandular epithelial cell protein 1

All UniProt accessions (7): Q9H0R8, A0A0G2JKT8, F5GX12, F5GYD9, F5GZY7, F5H007, G3V1T7

UniProt curated annotations — full annotation on UniProt →

Function. Ubiquitin-like modifier that increases cell-surface expression of kappa-type opioid receptor through facilitating anterograde intracellular trafficking of the receptor. Involved in formation of autophagosomal vacuoles. 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. Interacts with ATG13, OPRK1, RB1CC1 and ULK1. Interacts with TP53INP1 and TP53INP2. Directly interacts with SQSTM1. Interacts with ATG3, ATG7 and MAP15. Interacts with TECPR2. Interacts with TBC1D5. Interacts with MAPK15. Interacts with TRIM5. Interacts with MEFV and TRIM21. Interacts with WDFY3. Interacts with the reticulophagy receptor TEX264. Interacts with UBA5. Interacts with KBTBD6 and KBTBD7; the interaction is direct. Interacts with reticulophagy regulators RETREG1, RETREG2 and RETREG3. Interacts with IRGM. Interacts with DNM2. Interacts with NCOA4 (via C-terminus). (Microbial infection) Interacts with Kaposi’s sarcoma-associated herpesvirus protein VIRF-1.

Subcellular location. Cytoplasmic vesicle. Autophagosome. Cytoplasmic vesicle membrane. Cytoplasm. Cytoskeleton. Endoplasmic reticulum. Golgi apparatus.

Tissue specificity. Ubiquitous. Expressed at very high levels in the brain, heart, peripheral blood leukocytes, liver, kidney, placenta and skeletal muscle. Expressed at very low levels in thymus and small intestine. In the brain, expression is particularly intense in motoneurons in the embryo and in neurons involved in somatomotor and neuroendocrine functions in the adult, particularly in the substantia nigra pars compacta.

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, GABARAPL1-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, GABARAPL1-II. During non-canonical autophagy, the processed form is conjugated to phosphatidylserine (PS) phospholipid. ATG4 proteins also mediate the delipidation of PE-conjugated forms required for GABARAPL1 recycling when autophagosomes fuse with lysosomes. 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).

Similarity. Belongs to the ATG8 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9H0R8-1	1	yes
Q9H0R8-2	2

RefSeq proteins (2): NP_001350527, NP_113600* (*=MANE)

Domains & families (InterPro)

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

Pfam: PF02991

UniProt features (21 total): mutagenesis site 5, strand 5, helix 4, site 2, lipid moiety-binding region 2, chain 1, propeptide 1, splice variant 1

Structure

Experimental structures (PDB)

14 structures.

PDB	Method	Resolution (Å)
6YOO	X-RAY DIFFRACTION	1.06
6HOI	X-RAY DIFFRACTION	1.14
6HOL	X-RAY DIFFRACTION	1.4
5LXI	X-RAY DIFFRACTION	1.44
7AA7	X-RAY DIFFRACTION	1.45
8X8A	X-RAY DIFFRACTION	1.53
5LXH	X-RAY DIFFRACTION	1.58
2R2Q	X-RAY DIFFRACTION	1.65
7AA9	X-RAY DIFFRACTION	1.72
9JF2	X-RAY DIFFRACTION	1.76
7JHX	X-RAY DIFFRACTION	1.91
9HGC	X-RAY DIFFRACTION	2.52
5DPT	X-RAY DIFFRACTION	2.9
2L8J	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H0R8-F1	95.05	0.92

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 (2): 115–116 ((microbial infection) cleavage; by ravz); 116–117 (cleavage; by atg4b)

Post-translational modifications (2): 116, 116

Mutagenesis-validated functional residues (5):

Position	Phenotype
67	abolished interaction with atg4b.
116	no processing of precursor.
9	abolished interaction with atg4b.
28	does not affect interaction with atg4b.
47	abolished interaction with atg4b.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-1632852	Macroautophagy

MSigDB gene sets: 404 (showing top): GGGACCA_MIR133A_MIR133B, AP1_01, HNF3ALPHA_Q6, GOBP_VACUOLE_ORGANIZATION, RORA1_01, GOCC_VACUOLAR_MEMBRANE, GOZGIT_ESR1_TARGETS_DN, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, DACOSTA_UV_RESPONSE_VIA_ERCC3_UP, TGACCTY_ERR1_Q2, GOBP_VESICLE_MEDIATED_TRANSPORT, RODWELL_AGING_KIDNEY_NO_BLOOD_DN, GOBP_MACROAUTOPHAGY, LINDGREN_BLADDER_CANCER_CLUSTER_2A_DN, HINATA_NFKB_TARGETS_KERATINOCYTE_UP

GO Biological Process (6): autophagosome assembly (GO:0000045), mitophagy (GO:0000423), cellular response to nitrogen starvation (GO:0006995), glycophagy (GO:0061723), autophagosome maturation (GO:0097352), autophagy (GO:0006914)

GO Molecular Function (8): phospholipid binding (GO:0005543), phosphatidylethanolamine binding (GO:0008429), Tat protein binding (GO:0030957), ubiquitin protein ligase binding (GO:0031625), beta-tubulin binding (GO:0048487), GABA receptor binding (GO:0050811), cargo adaptor activity (GO:0140312), protein binding (GO:0005515)

GO Cellular Component (15): autophagosome membrane (GO:0000421), autophagosome (GO:0005776), endoplasmic reticulum (GO:0005783), Golgi apparatus (GO:0005794), cytosol (GO:0005829), microtubule (GO:0005874), plasma membrane (GO:0005886), cilium (GO:0005929), cytoplasmic vesicle membrane (GO:0030659), ciliary basal body (GO:0036064), cytoplasm (GO:0005737), mitochondrion (GO:0005739), cytoskeleton (GO:0005856), membrane (GO:0016020), cytoplasmic vesicle (GO:0031410)

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	5
macroautophagy	3
intracellular membrane-bounded organelle	3
cellular anatomical structure	3
endomembrane system	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 starvation	1
cellular response to nitrogen levels	1
glycogen catabolic process	1
protein-containing complex disassembly	1
catabolic process	1
transmembrane transport	1
process utilizing autophagic mechanism	1
lipid binding	1
phospholipid binding	1
RNA polymerase II-specific DNA-binding transcription factor binding	1
ubiquitin-like protein ligase binding	1
tubulin binding	1
signaling receptor binding	1
vesicle-mediated transport	1
protein-macromolecule adaptor activity	1
binding	1
vacuolar membrane	1
autophagosome	1
vacuole	1
microtubule cytoskeleton	1
polymeric cytoskeletal fiber	1
membrane	1
cell periphery	1
intraciliary transport particle	1
membrane-bounded organelle	1
plasma membrane bounded cell projection	1
vesicle membrane	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

300 interactions, top by confidence:

A	B	Type	Score
SQSTM1	GABARAPL1	psi-mi:“MI:0915”(physical association)	0.950
RETREG3	GABARAPL1	psi-mi:“MI:0915”(physical association)	0.830
GABARAPL1	RETREG3	psi-mi:“MI:0915”(physical association)	0.830
GABARAPL1	ATG4B	psi-mi:“MI:0915”(physical association)	0.830
ATG4B	GABARAPL1	psi-mi:“MI:0407”(direct interaction)	0.830
GABARAPL1	KBTBD7	psi-mi:“MI:0915”(physical association)	0.820
KBTBD7	GABARAPL1	psi-mi:“MI:0915”(physical association)	0.820
KBTBD7	GABARAPL1	psi-mi:“MI:0407”(direct interaction)	0.820
GABARAPL1	CALCOCO2	psi-mi:“MI:0915”(physical association)	0.780
GABARAPL1	TNIP1	psi-mi:“MI:0915”(physical association)	0.780
TNIP1	GABARAPL1	psi-mi:“MI:0915”(physical association)	0.780
CALCOCO2	GABARAPL1	psi-mi:“MI:0915”(physical association)	0.780
KBTBD6	GABARAPL1	psi-mi:“MI:0407”(direct interaction)	0.760
TBC1D25	GABARAPL1	psi-mi:“MI:0915”(physical association)	0.740
ATG4A	GABARAPL1	psi-mi:“MI:0915”(physical association)	0.720
GABARAPL1	ATG4A	psi-mi:“MI:0915”(physical association)	0.720

BioGRID (274): GABARAPL1 (Two-hybrid), GABARAPL1 (Two-hybrid), GABARAPL1 (Two-hybrid), GABARAPL1 (Two-hybrid), SCYL3 (Two-hybrid), KBTBD7 (Two-hybrid), AHNAK2 (Two-hybrid), ATG4A (Two-hybrid), FUNDC1 (Two-hybrid), FAM134C (Two-hybrid), KRTAP10-7 (Two-hybrid), KRTAP10-9 (Two-hybrid), KRTAP10-3 (Two-hybrid), GABARAPL1 (Affinity Capture-RNA), GABARAPL1 (Affinity Capture-RNA)

ESM2 similar proteins: A1CQS1, A1D3N4, A2QPN1, A2YS06, A4IGN3, A4LA70, A7KAL9, C4B4E4, I1S1W5, M2SQA5, N4X184, O14037, O95166, P0CO54, P0CO55, P60517, P60518, Q09490, Q0C804, Q0VGK0, Q1JQD4, Q2GVL1, Q498D9, Q4P2U6, Q4WJ27, Q5B2U9, Q5BIZ2, Q5QFG1, Q5RF21, Q66IB8, Q6C794, Q6DJH5, Q6GQ27, Q6Z1D5, Q755X2, Q8HYB6, Q8J282, Q8LEM4, Q8MK68, Q8NJJ4

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

3 interactions.

A	Effect	B	Mechanism
GABARAPL1	“up-regulates activity”	SQSTM1	binding
NBR1	up-regulates	GABARAPL1	binding
TFE3	“up-regulates quantity by expression”	GABARAPL1	“transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 71 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
Autophagy	10	34.5×	2e-11
Macroautophagy	12	32.2×	3e-13

GO biological processes:

GO term	Partners	Fold	FDR
piecemeal microautophagy of the nucleus	5	74.3×	5e-07
mitophagy	10	50.5×	9e-13
autophagosome assembly	11	39.2×	9e-13
macroautophagy	7	26.8×	6e-07
positive regulation of autophagy	6	19.8×	3e-05
autophagy	9	15.7×	5e-07
protein transport	10	7.0×	7e-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	11
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

574 predictions. Top by Δscore:

Variant	Effect	Δscore
12:10213178:G:GT	donor_gain	1.0000
12:10213179:A:T	donor_gain	1.0000
12:10213195:G:GT	donor_gain	1.0000
12:10213220:G:GG	donor_gain	1.0000
12:10218057:TTCCA:T	acceptor_loss	1.0000
12:10218058:TCCA:T	acceptor_loss	1.0000
12:10218059:CCA:C	acceptor_loss	1.0000
12:10218060:CAG:C	acceptor_loss	1.0000
12:10218061:A:AT	acceptor_loss	1.0000
12:10218062:G:C	acceptor_loss	1.0000
12:10218113:G:GT	donor_gain	1.0000
12:10218138:ACTG:A	donor_loss	1.0000
12:10218140:TGG:T	donor_loss	1.0000
12:10218143:T:A	donor_loss	1.0000
12:10220414:T:A	acceptor_gain	1.0000
12:10220431:A:AG	acceptor_gain	1.0000
12:10220432:T:G	acceptor_gain	1.0000
12:10220434:A:AG	acceptor_gain	1.0000
12:10220435:T:G	acceptor_gain	1.0000
12:10220436:CCA:C	acceptor_loss	1.0000
12:10220437:CAGTT:C	acceptor_loss	1.0000
12:10220438:A:AG	acceptor_gain	1.0000
12:10220438:AGTT:A	acceptor_gain	1.0000
12:10220438:AGTTG:A	acceptor_gain	1.0000
12:10220439:G:A	acceptor_loss	1.0000
12:10220439:G:GA	acceptor_gain	1.0000
12:10220439:GT:G	acceptor_gain	1.0000
12:10220439:GTT:G	acceptor_gain	1.0000
12:10220439:GTTG:G	acceptor_gain	1.0000
12:10220439:GTTGG:G	acceptor_gain	1.0000

AlphaMissense

774 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:10218136:T:C	L55P	1.000
12:10213181:G:A	G18R	0.999
12:10213181:G:C	G18R	0.999
12:10213182:G:A	G18E	0.999
12:10213215:T:A	V29D	0.999
12:10213218:C:A	P30H	0.999
12:10218116:G:C	K48N	0.999
12:10218116:G:T	K48N	0.999
12:10218121:T:A	L50Q	0.999
12:10218121:T:C	L50P	0.999
12:10218124:T:A	V51E	0.999
12:10220442:G:C	G58R	0.999
12:10220443:G:A	G58D	0.999
12:10220464:G:C	R65P	0.999
12:10220499:T:C	F77L	0.999
12:10220501:C:A	F77L	0.999
12:10220501:C:G	F77L	0.999
12:10221808:T:C	F104L	0.999
12:10221810:T:A	F104L	0.999
12:10221810:T:G	F104L	0.999
12:10213170:G:C	R14P	0.998
12:10213194:G:C	R22P	0.998
12:10213212:G:T	R28M	0.998
12:10213213:G:C	R28S	0.998
12:10213213:G:T	R28S	0.998
12:10218064:T:A	V31E	0.998
12:10218067:T:A	I32N	0.998
12:10218070:T:A	V33E	0.998
12:10218110:G:C	K46N	0.998
12:10218110:G:T	K46N	0.998

dbSNP variants (sampled 300 via entrez): RS1000200132 (12:10212188 G>T), RS1000249384 (12:10212379 C>T), RS1000548211 (12:10210983 G>A,C), RS1000692444 (12:10216905 T>C,G), RS1000723120 (12:10216691 T>A,C), RS1001357563 (12:10215816 G>A), RS1001377800 (12:10219912 G>A), RS1001404759 (12:10213547 G>T), RS1001408792 (12:10219758 G>A), RS1001431192 (12:10215344 G>A), RS1001772340 (12:10213903 C>T), RS1002213024 (12:10223480 T>C), RS1002373022 (12:10215783 C>A), RS1002380441 (12:10221415 G>A), RS1002837904 (12:10216724 G>A)

Disease associations

OMIM: gene MIM:607420 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4879515 (SINGLE PROTEIN)

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

ChEMBL bioactivities

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

pChembl	Type	Value	Unit	Molecule
5.46	IC50	3430	nM	CHEMBL5556385

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
5-(5,6-dichloro-1H-indol-4-yl)-2-[2-(dimethylamino)ethyliminomethyl]-3-hydroxycyclohex-2-en-1-one	2086253: Inhibition of GABARAPL1 (unknown origin) by Alphascreen assay	ic50	3.4300	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	increases expression	4
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	3
Tobacco Smoke Pollution	increases expression	3
Tretinoin	increases expression	3
Cyclosporine	increases expression	3
cobaltous chloride	increases expression	2
Rosiglitazone	increases expression	2
Decitabine	affects expression, increases expression	2
Zoledronic Acid	decreases expression	2
Air Pollutants	decreases expression, affects expression, increases abundance	2
Cisplatin	increases expression	2
Doxorubicin	increases expression	2
Hydrogen Peroxide	increases expression, affects expression, affects cotreatment	2
Tetrachlorodibenzodioxin	increases expression	2
Tunicamycin	increases expression	2
Valproic Acid	increases expression	2
Cadmium Chloride	decreases expression, increases expression	2
dicrotophos	decreases expression	1
chloroacetaldehyde	decreases expression	1
methylmercuric chloride	increases expression	1
triphenyl phosphate	affects expression	1
pirinixic acid	affects binding, increases activity, increases expression	1
bisphenol A	affects expression	1
methylselenic acid	increases expression	1
2-methyl-4-isothiazolin-3-one	increases expression	1
2-butenal	increases expression	1
beta-lapachone	increases expression	1
sulforaphane	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4835345	Binding	Binding affinity to human GABARAPL1 expressed in Escherichia coli T7 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_SP37	HAP1 GABARAPL1 (-) 1	Cancer cell line	Male
CVCL_SP38	HAP1 GABARAPL1 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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