ABCG1

Summary

ABCG1 (ATP binding cassette subfamily G member 1, HGNC:73) is a protein-coding gene on chromosome 21q22.3, encoding ATP-binding cassette sub-family G member 1 (P45844). Catalyzes the efflux of phospholipids such as sphingomyelin, cholesterol and its oxygenated derivatives like 7beta-hydroxycholesterol and this transport is coupled to hydrolysis of ATP.

The protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intra-cellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This protein is a member of the White subfamily. It is involved in macrophage cholesterol and phospholipids transport, and may regulate cellular lipid homeostasis in other cell types. Six alternative splice variants have been identified.

Source: NCBI Gene 9619 — RefSeq curated summary.

At a glance

• GWAS associations: 9
• Clinical variants (ClinVar): 146 total — 29 pathogenic, 2 likely-pathogenic
• MANE Select transcript: NM_016818

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:73
Approved symbol	ABCG1
Name	ATP binding cassette subfamily G member 1
Location	21q22.3
Locus type	gene with protein product
Status	Approved
Aliases	ABC8
Ensembl gene	ENSG00000160179
Ensembl biotype	protein_coding
OMIM	603076
Entrez	9619

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 11 protein_coding, 3 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000343687, ENST00000347800, ENST00000361802, ENST00000398437, ENST00000398449, ENST00000398457, ENST00000450121, ENST00000462050, ENST00000467818, ENST00000472587, ENST00000496783, ENST00000878297, ENST00000878298, ENST00000878299, ENST00000878300

RefSeq mRNA: 6 — MANE Select: NM_016818 NM_004915, NM_016818, NM_207174, NM_207627, NM_207628, NM_207629

CCDS: CCDS13681, CCDS13682, CCDS13683, CCDS42937, CCDS42938

Canonical transcript exons

ENST00000398449 — 15 exons

Exon	Start	End
ENSE00003477889	42276895	42276945
ENSE00003496464	42291498	42291656
ENSE00003505582	42285880	42285994
ENSE00003506666	42225671	42225914
ENSE00003523195	42271070	42271187
ENSE00003543273	42273303	42273435
ENSE00003544349	42288211	42288312
ENSE00003547441	42282274	42282419
ENSE00003553101	42287889	42288037
ENSE00003670239	42291092	42291192
ENSE00003674298	42294542	42294660
ENSE00003688085	42290050	42290218
ENSE00003688526	42296164	42297244
ENSE00003689634	42284560	42284683
ENSE00003900760	42219140	42219304

Expression profiles

Bgee: expression breadth ubiquitous, 270 present calls, max score 92.24.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 13.0865 / max 369.0332, expressed in 1115 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
189281	12.7984	1110
189282	0.1902	103
189280	0.0756	31
189279	0.0223	10

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right adrenal gland	UBERON:0001233	92.24	gold quality
left adrenal gland	UBERON:0001234	92.04	gold quality
right adrenal gland cortex	UBERON:0035827	91.80	gold quality
jejunal mucosa	UBERON:0000399	91.70	gold quality
left adrenal gland cortex	UBERON:0035825	91.32	gold quality
adrenal cortex	UBERON:0001235	91.30	gold quality
adrenal gland	UBERON:0002369	90.98	gold quality
spleen	UBERON:0002106	90.09	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	89.68	gold quality
lower lobe of lung	UBERON:0008949	89.59	gold quality
amniotic fluid	UBERON:0000173	89.38	gold quality
medial globus pallidus	UBERON:0002477	89.04	gold quality
upper lobe of left lung	UBERON:0008952	88.98	gold quality
upper lobe of lung	UBERON:0008948	88.86	gold quality
tendon of biceps brachii	UBERON:0008188	88.29	gold quality
right lung	UBERON:0002167	88.18	gold quality
pigmented layer of retina	UBERON:0001782	87.56	gold quality
epithelium of nasopharynx	UBERON:0001951	87.56	gold quality
lung	UBERON:0002048	87.42	gold quality
visceral pleura	UBERON:0002401	87.17	gold quality
globus pallidus	UBERON:0001875	87.01	gold quality
blood	UBERON:0000178	86.65	gold quality
islet of Langerhans	UBERON:0000006	86.59	gold quality
mucosa of paranasal sinus	UBERON:0005030	85.91	gold quality
duodenum	UBERON:0002114	85.67	gold quality
penis	UBERON:0000989	85.59	gold quality
choroid plexus epithelium	UBERON:0003911	85.50	gold quality
colonic mucosa	UBERON:0000317	85.13	gold quality
pericardium	UBERON:0002407	85.12	gold quality
lymph node	UBERON:0000029	85.10	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.82
E-MTAB-6386	no	148.29

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): NFKB, NR0B2, NR1H2, NR1H3, PPARG, RARA, RXRB, SP1, ZNF202

miRNA regulators (miRDB)

50 targeting ABCG1, 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-3662	99.99	73.82	5684
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-9-3P	99.96	70.88	2068
HSA-MIR-338-5P	99.92	72.34	2951
HSA-MIR-329-3P	99.91	66.56	1234
HSA-MIR-362-3P	99.91	66.38	1267
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-221-5P	99.86	65.45	1052
HSA-MIR-8073	99.86	65.21	1118
HSA-MIR-132-3P	99.73	70.56	1424
HSA-MIR-212-3P	99.73	70.65	1424
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-567	99.63	68.57	1219
HSA-MIR-24-3P	99.59	69.97	1934
HSA-MIR-141-5P	99.57	67.86	897
HSA-MIR-6740-3P	99.48	68.49	1392
HSA-MIR-208A-5P	99.42	70.83	1913
HSA-MIR-208B-5P	99.42	70.83	1952
HSA-MIR-185-5P	99.35	68.60	2497
HSA-MIR-4644	99.35	69.12	2514
HSA-MIR-520F-5P	99.34	70.40	1632
HSA-MIR-6505-3P	99.34	67.39	1071
HSA-MIR-1207-3P	98.99	66.22	1532
HSA-MIR-6876-3P	98.97	65.69	765
HSA-MIR-626	98.89	66.21	762
HSA-MIR-384	98.71	67.34	1229
HSA-MIR-1301-3P	98.64	68.27	1071
HSA-MIR-5047	98.64	68.62	1035
HSA-MIR-6776-5P	98.54	67.43	1304

Literature-anchored findings (GeneRIF, showing 40)

• ABCG1 is not required for apolipoprotein A-1-mediated endothelial cholesterol efflux from vascular endothelial cells. (PMID:15492319)
• Analysis of the effect of the Su(Hw) insulator on the expression of the miniwhite gene in Drosophila melanogaster. (PMID:15584507)
• ABCG1 redistributes cholesterol to cell-surface domains where it becomes accessible for removal by HDL, demonstrating its direct role of ABCG1 in cellular cholesterol transport (PMID:15994327)
• characterization of two LXR response elements in first & second introns of the ABCG1 gene & demonstrate their function in cultured macrophage & liver cells; studies clarify mechanism of upregulation of the ABCG1 gene by oxysterols in macrophages & liver (PMID:16024918)
• Abcg1 is a key gene involved in both cholesterol efflux to HDL and in tissue lipid homeostasis (PMID:16054053)
• synergistic relationship between ABCA1 and ABCG1 in peripheral tissues, where ABCA1 lipidates any lipid-poor/free apoA-I to generate nascent or pre-beta-HDL (PMID:16357317)
• ABCG1 was localized to the plasma membrane in HEK293 cells and mediate the efflux of cholesterol and choline phospholipids. (PMID:16702602)
• provides the first evidence that unsaturated fatty acids suppress ABCG1 gene expression by a mechanism which involves the binding of LXR/RXR to the promoters (PMID:16730733)
• Macrophage ABCG1 deficiency does lead to heavy lipid accumulation in macrophages of the lung, and also a moderately significant effect on atherosclerotic lesion development was observed. (PMID:16857950)
• The splice variant ABCG1(666) may be the most prominent form of functional ABCG1 expressed in the human. (PMID:16870176)
• ABCG1 and ABCG4 act in concert with ABCA1 to maximize the removal of excess cholesterol from cells and to generate cholesterol-rich lipoprotein particles (PMID:16902247)
• NPC1 protein function is non-essential for the trafficking and removal of cellular cholesterol by ApoAI if the down-stream defects in ABCA1 and ABCG1 regulation in NPC disease cells are corrected using an LXR agonist (PMID:17020879)
• Two genes of the cholesterol efflux system (ABCA1 and ABCG1) were down-regulated in HCAECs exposed to uraemic plasma. (PMID:17082211)
• ABCG1 plays a significant role in the regulation of neuronal cholesterol efflux to apolipoprotein E discs. (PMID:17121837)
• These results indicate that positional and geometrical isomers of CLAs have specific effects on gene expression of human macrophages and that t9,t11-CLA activates ABCG1 by a SREBP-1c-dependent mechanism. (PMID:17141191)
• In intermediate phenotypes of suicidal behavior,ABCG1 might act on suicidal behavior through these traits. (PMID:17187964)
• Results show that ABCG1 mRNA expression increased in response to dexamethasone in primary rat hepatocytes however, the effect was absent or inhibitory in human HepG2 cells and THP-1 macrophages due to low glucocorticoid receptor levels. (PMID:17241464)
• altered cholesterol metabolism and amyloid precursor protein trafficking mediated by ABCG1 may contribute to the accelerated onset of Alzheimer’s disease neuropathology in Down syndrome (PMID:17293612)
• ABCG1 protects against 7beta-HC-induced cell death, an important role in prevention of neurodegenerative and cardiovascular disease. (PMID:17408620)
• These results suggest that the ABCG1-mediated efflux of cholesterol and sphingomyelin (SM) is dependent on the cellular SM level and distribution of cholesterol in the plasma membrane. (PMID:17761632)
• ABCG1 deficiency in pulmonary alveolar proteinosis alveolar macrophages is attributable to the absence of a GM-CSF-mediated PPARgamma pathway. (PMID:17848583)
• No significant gender effect in the capacity of serum from nondyslipidemic subjects to mediate free cholesterol efflux via the ABCG1 transporter pathway was detected (PMID:18057374)
• ABCG1 expression and cholesterol efflux are reduced in patients with type 2 diabetes mellitus (PMID:18490524)
• Overexpression of human ABCG1 does not affect atherosclerosis in fat-fed ApoE-deficient mice. (PMID:18599800)
• Results suggest a causative relationship between ABCG1 function and apoptotic cell death in macrophages and in other cell types. (PMID:18619413)
• The reduction in ABCG1 is associated with impairment in cholesterol efflux and may contribute to accelerated foam cell formation in diabetic patients. (PMID:18640393)
• ABCG1 increases cell membrane free cholesterol pools and changes its rate of desorption into the aqueous phase without enhancing the association with the acceptor. (PMID:18827283)
• Human endothelial cells of the placental barrier efficiently deliver cholesterol to the fetal circulation via ABCA1 and ABCG1. (PMID:19168441)
• Western blot experiments demonstrate that ABCA1 and ABCG1 protein levels are synchronously suppressed by high glucose levels and the w6-unsaturated fatty acid linoleic acid. (PMID:19287193)
• Data describe the requirement of GPS2 for ABCG1 gene transcription and cholesterol efflux from macrophages, and implicate GPS2 in facilitating LXRalpha/beta recruitment to an ABCG1-specific promoter/enhancer unit upon ligand activation. (PMID:19481530)
• a novel ABCG1 -257T>G promoter polymorphism influences CAD severity in Japanese men; ABCG1 transcription activity was significantly lower in the G allele of -257T>G polymorphism (PMID:19556716)
• Results indicated that the ABCG1-mediated cell cholesterol efflux can be efficiently driven by a small discoidal phospholipid-containing particle resembling plasma pre-beta1 HDL. (PMID:19839639)
• ABCG1 mediates oxysterol efflux from oxLDL-loaded macrophages, and the exported oxysterol by ABCG1 pathway can be selectively taken up by hepatocytes. (PMID:19895785)
• results provide evidence that TGF-beta1 up-regulates expressions of ABCA1, ABCG1 and SR-BI through the LXR alpha pathway in THP-1 macrophage-derived foam cells (PMID:20057170)
• In women, significant relationships were found between rs1893590 polymorphisms (ABCG1 gene) and HDLcholesterol plasma concentrations (PMID:20170916)
• AMPK activation prevents ypercholesterolemia-mediated endothelial dysfunction and the underlying mechanism may involve an increased efflux of cholesterol and 7-oxysterols via the ABCG1 pathway. (PMID:20395595)
• ABCG1 is expressed in cultured human keratinocytes and murine epidermis (PMID:20675829)
• Postprandial lipemia enhanced SR-BI and ABCG1-dependent efflux to large HDL2 particles. (PMID:20713650)
• The promotion of cholesterol efflux via ATP-binding cassette transporter G1(ABCG1) results in a reduced inhibitory interaction of endothelial nitric oxide synthase with caveolin-1. (PMID:20798376)
• Two SNPs of the ABCG1is associated with the susceptibility and severity of coronary atherosclerotic disease in Chinese Han population. (PMID:20931526)

Cross-species orthologs

14 orthologs

Organism	Symbol	Gene ID
danio_rerio	abcg1	ENSDARG00000063475
mus_musculus	Abcg1	ENSMUSG00000024030
rattus_norvegicus	Abcg1	ENSRNOG00000001158
drosophila_melanogaster	st	FBGN0003515
drosophila_melanogaster	w	FBGN0003996
drosophila_melanogaster	Atet	FBGN0020762
drosophila_melanogaster	CG4822	FBGN0031220
drosophila_melanogaster	CG31689	FBGN0031449
drosophila_melanogaster	CG9663	FBGN0031516
drosophila_melanogaster	CG31121	FBGN0051121
drosophila_melanogaster	CG32091	FBGN0052091
caenorhabditis_elegans		WBGENE00006522
caenorhabditis_elegans		WBGENE00015479
caenorhabditis_elegans		WBGENE00017179

Paralogs (4): ABCG2 (ENSG00000118777), ABCG5 (ENSG00000138075), ABCG8 (ENSG00000143921), ABCG4 (ENSG00000172350)

Protein

Protein identifiers

ATP-binding cassette sub-family G member 1 — P45844 (reviewed: P45844)

Alternative names: ATP-binding cassette transporter 8, White protein homolog

All UniProt accessions (3): P45844, C9JKD9, E9PGV9

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the efflux of phospholipids such as sphingomyelin, cholesterol and its oxygenated derivatives like 7beta-hydroxycholesterol and this transport is coupled to hydrolysis of ATP. The lipid efflux is ALB-dependent. Is an active component of the macrophage lipid export complex. Could also be involved in intracellular lipid transport processes. The role in cellular lipid homeostasis may not be limited to macrophages. Prevents cell death by transporting cytotoxic 7beta-hydroxycholesterol.

Subunit / interactions. Homodimer; disulfide-linked. Homooligomer. May form heterodimers with several heterologous partners of the ABCG subfamily. Forms heterodimers with ABCG4. Interacts with CAV1; this interaction regulates ABCG1-mediated cholesterol efflux.

Subcellular location. Endoplasmic reticulum membrane. Golgi apparatus membrane. Cell membrane.

Tissue specificity. Expressed in several tissues. Expressed in macrophages; expression is increased in macrophages from patients with Tangier disease.

Post-translational modifications. Palmitoylation at Cys-315 seems important for trafficking from the endoplasmic reticulum.

Activity regulation. The cholesterol efflux is enhanced by APOA1.

Induction. Strongly induced in monocyte-derived macrophages during cholesterol influx. Conversely, mRNA and protein expression are suppressed by lipid efflux. Induction is mediated by the liver X receptor/retinoid X receptor (LXR/RXR) pathway. Not induced by bacterial lipopolysaccharides (LPS). Repressed by ZNF202.

Similarity. Belongs to the ABC transporter superfamily. ABCG family. Eye pigment precursor importer (TC 3.A.1.204) subfamily.

Isoforms (8)

UniProt ID	Names	Canonical?
P45844-1	1	yes
P45844-2	2, J
P45844-3	3, ABDE
P45844-4	4, G
P45844-5	5, F
P45844-6	6, HI
P45844-7	7, C
P45844-8	8

RefSeq proteins (6): NP_004906, NP_058198, NP_997057, NP_997510, NP_997511, NP_997512 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003439	ABC_transporter-like_ATP-bd	Domain
IPR003593	AAA+_ATPase	Domain
IPR005284	Pigment_permease/Abcg	Family
IPR013525	ABC2_TM	Domain
IPR017871	ABC_transporter-like_CS	Conserved_site
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR043926	ABCG_dom	Domain
IPR050352	ABCG_transporters	Family

Pfam: PF00005, PF01061, PF19055

Catalyzed reactions (Rhea), 4 shown:

• a sphingomyelin(in) + ATP + H2O = a sphingomyelin(out) + ADP + phosphate + H(+) (RHEA:38903)
• cholesterol(in) + ATP + H2O = cholesterol(out) + ADP + phosphate + H(+) (RHEA:39051)
• 7beta-hydroxycholesterol(in) + ATP + H2O = 7beta-hydroxycholesterol(out) + ADP + phosphate + H(+) (RHEA:39795)
• an N-(acyl)-sphingosylphosphocholine(in) + ATP + H2O = an N-(acyl)-sphingosylphosphocholine(out) + ADP + phosphate + H(+) (RHEA:46468)

UniProt features (95 total): helix 22, strand 17, mutagenesis site 16, topological domain 7, splice variant 7, turn 7, transmembrane region 6, lipid moiety-binding region 5, sequence conflict 3, domain 2, chain 1, binding site 1, sequence variant 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
7R8D	ELECTRON MICROSCOPY	3.2
7FDV	ELECTRON MICROSCOPY	3.26
7R8C	ELECTRON MICROSCOPY	3.7
7R8E	ELECTRON MICROSCOPY	3.7
7OZ1	ELECTRON MICROSCOPY	4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P45844-F1	81.34	0.56

Functional residue map

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

Ligand- & substrate-binding residues (1): 118–125

Post-translational modifications (5): 30, 154, 315, 394, 406

Mutagenesis-validated functional residues (16):

Position	Phenotype
30	no significant effect.
124	affects atp binding. does not affect efflux of 7beta-hydroxycholesterol. does not affect localization at plasma membrane
154	no significant effect.
315	significantly decreases abcg1-mediated cholesterol efflux.
394	no significant effect.
406	no significant effect.
491	significantly reduces interaction with cav1; when associated with a-493. significantly reduces abcg1-mediated cholestero
493	significantly reduces interaction with cav1; when associated with a-491. significantly reduces abcg1-mediated cholestero
498	significantly reduces interaction with cav1; when associated with a-499. significantly reduces abcg1-mediated cholestero
498	does not affect abcg1-mediated cholesterol efflux; when associated with i-499.
498	dramatically reduces the ability of abcg1 to mediate cholesterol efflux; when associated with i-499.
499	significantly reduces interaction with cav1; when associated with a-498. significantly reduces abcg1-mediated cholestero
499	does not affect abcg1-mediated cholesterol efflux; when associated with i-498.
499	dramatically reduces the ability of abcg1 to mediate cholesterol efflux; when associated with i-498.

Function

Pathways and Gene Ontology

Reactome pathways

10 pathways

ID	Pathway
R-HSA-1369062	ABC transporters in lipid homeostasis
R-HSA-8964058	HDL remodeling
R-HSA-9029569	NR1H3 & NR1H2 regulate gene expression linked to cholesterol transport and efflux
R-HSA-162582	Signal Transduction
R-HSA-174824	Plasma lipoprotein assembly, remodeling, and clearance
R-HSA-382551	Transport of small molecules
R-HSA-382556	ABC-family protein mediated transport
R-HSA-8963899	Plasma lipoprotein remodeling
R-HSA-9006931	Signaling by Nuclear Receptors
R-HSA-9024446	NR1H2 and NR1H3-mediated signaling

MSigDB gene sets: 437 (showing top): GOBP_CELLULAR_RESPONSE_TO_LIPOPROTEIN_PARTICLE_STIMULUS, GOBP_REGULATION_OF_LIPID_STORAGE, GOBP_STEROL_HOMEOSTASIS, YANG_BREAST_CANCER_ESR1_BULK_UP, GOBP_POSITIVE_REGULATION_OF_AMIDE_METABOLIC_PROCESS, GOBP_POSITIVE_REGULATION_OF_PROTEIN_LOCALIZATION, GOBP_POSITIVE_REGULATION_OF_CHOLESTEROL_EFFLUX, GOBP_REGULATION_OF_CHOLESTEROL_EFFLUX, GOCC_CELL_SURFACE, THEILGAARD_NEUTROPHIL_AT_SKIN_WOUND_DN, LINDGREN_BLADDER_CANCER_CLUSTER_3_DN, GOBP_POSITIVE_REGULATION_OF_STEROL_TRANSPORT, MAHADEVAN_IMATINIB_RESISTANCE_DN, GOBP_POSITIVE_REGULATION_OF_ALCOHOL_BIOSYNTHETIC_PROCESS, GOBP_REGULATION_OF_MEMBRANE_LIPID_DISTRIBUTION

GO Biological Process (26): cholesterol metabolic process (GO:0008203), negative regulation of macrophage derived foam cell differentiation (GO:0010745), positive regulation of cholesterol efflux (GO:0010875), negative regulation of cholesterol storage (GO:0010887), intracellular cholesterol transport (GO:0032367), cholesterol efflux (GO:0033344), phospholipid efflux (GO:0033700), response to lipid (GO:0033993), low-density lipoprotein particle remodeling (GO:0034374), high-density lipoprotein particle remodeling (GO:0034375), glycoprotein transport (GO:0034436), cholesterol homeostasis (GO:0042632), amyloid precursor protein catabolic process (GO:0042987), reverse cholesterol transport (GO:0043691), positive regulation of cholesterol biosynthetic process (GO:0045542), positive regulation of protein secretion (GO:0050714), transmembrane transport (GO:0055085), phospholipid homeostasis (GO:0055091), cellular response to high density lipoprotein particle stimulus (GO:0071403), regulation of cholesterol metabolic process (GO:0090181), positive regulation of amyloid-beta formation (GO:1902004), xenobiotic detoxification by transmembrane export across the plasma membrane (GO:1990961), lipid transport (GO:0006869), negative regulation of lipid storage (GO:0010888), cholesterol transport (GO:0030301), lipid translocation (GO:0034204)

GO Molecular Function (16): ATP binding (GO:0005524), phospholipid binding (GO:0005543), cholesterol binding (GO:0015485), ATP hydrolysis activity (GO:0016887), toxin transmembrane transporter activity (GO:0019534), ABC-type sterol transporter activity (GO:0034041), protein homodimerization activity (GO:0042803), ADP binding (GO:0043531), protein heterodimerization activity (GO:0046982), phosphatidylcholine floppase activity (GO:0090554), cholesterol transfer activity (GO:0120020), floppase activity (GO:0140328), nucleotide binding (GO:0000166), protein binding (GO:0005515), protein dimerization activity (GO:0046983), ABC-type transporter activity (GO:0140359)

GO Cellular Component (12): Golgi membrane (GO:0000139), nucleoplasm (GO:0005654), mitochondrion (GO:0005739), endosome (GO:0005768), endoplasmic reticulum membrane (GO:0005789), Golgi apparatus (GO:0005794), plasma membrane (GO:0005886), external side of plasma membrane (GO:0009897), recycling endosome (GO:0055037), endoplasmic reticulum (GO:0005783), endomembrane system (GO:0012505), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-7 pathways:

Category	Pathways
Transport of small molecules	2
ABC-family protein mediated transport	1
Plasma lipoprotein remodeling	1
NR1H2 and NR1H3-mediated signaling	1
Plasma lipoprotein assembly, remodeling, and clearance	1
Signal Transduction	1
Signaling by Nuclear Receptors	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cholesterol transport	3
cellular anatomical structure	3
cytoplasm	3
intracellular membrane-bounded organelle	3
endomembrane system	3
plasma lipoprotein particle remodeling	2
adenyl ribonucleotide binding	2
protein dimerization activity	2
plasma membrane	2
sterol metabolic process	1
secondary alcohol metabolic process	1
macrophage derived foam cell differentiation	1
regulation of macrophage derived foam cell differentiation	1
negative regulation of cell differentiation	1
regulation of cholesterol efflux	1
positive regulation of cholesterol transport	1
cholesterol efflux	1
cholesterol storage	1
regulation of cholesterol storage	1
negative regulation of lipid storage	1
intracellular anatomical structure	1
intracellular sterol transport	1
phospholipid transport	1
response to chemical	1
protein transport	1
carbohydrate derivative transport	1
sterol homeostasis	1
amyloid precursor protein metabolic process	1
cholesterol biosynthetic process	1
regulation of cholesterol biosynthetic process	1
positive regulation of cholesterol metabolic process	1
positive regulation of sterol biosynthetic process	1
positive regulation of alcohol biosynthetic process	1
protein secretion	1
regulation of protein secretion	1
positive regulation of protein transport	1
positive regulation of secretion by cell	1
transport	1
cellular process	1
lipid homeostasis	1

Protein interactions and networks

STRING

2106 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ABCG1	APOA1	P02647	997
ABCG1	APOE	P02649	928
ABCG1	SREBF2	Q12772	875
ABCG1	XPR1	Q9UBH6	873
ABCG1	NR1H3	Q13133	863
ABCG1	SCARB1	Q8WTV0	848
ABCG1	SREBF1	P36956	841
ABCG1	CYP7A1	P22680	813
ABCG1	SCARB2	Q14108	809
ABCG1	NR1H2	P55055	782
ABCG1	NPC1	O15118	775
ABCG1	PPARG	P37231	758
ABCG1	MYLIP	Q8WY64	741
ABCG1	CETP	P11597	737
ABCG1	APOA2	P02652	723

IntAct

3 interactions, top by confidence:

A	B	Type	Score
ABCG1	YARS1	psi-mi:“MI:0914”(association)	0.350
ADGRG5	SLC33A1	psi-mi:“MI:0914”(association)	0.350

BioGRID (69): ABCG1 (Affinity Capture-MS), ABCG1 (Affinity Capture-MS), ABCG1 (Affinity Capture-MS), Kif2c (Affinity Capture-MS), Nup214 (Affinity Capture-MS), Tyms (Affinity Capture-MS), Ppfibp1 (Affinity Capture-MS), Ap2a2 (Affinity Capture-MS), Tmem66 (Affinity Capture-MS), LOC100760824 (Affinity Capture-MS), Vps53 (Affinity Capture-MS), Pfas (Affinity Capture-MS), Usp9x (Affinity Capture-MS), Ikbkap (Affinity Capture-MS), Vps16 (Affinity Capture-MS)

ESM2 similar proteins: A0A0M3R8G1, A0A0M4FLW6, A9YWR6, B8ALI0, D3GE74, D4AYW0, H6WS93, H6WS94, O81016, O95259, P29973, P45844, P50530, P93025, Q00194, Q00195, Q03720, Q16281, Q28279, Q2PCF1, Q2QV81, Q5W274, Q5Z9S8, Q60603, Q62398, Q62927, Q63472, Q64343, Q7PC84, Q7PC86, Q7PC87, Q84K47, Q8GU83, Q8GU92, Q8H8V7, Q8RWI9, Q8RXN0, Q90805, Q93YS4, Q9C8J8

Diamond homologs: A0A059J0G5, A0A0M3R8G1, A0A0M4FLW6, A0A1U8QKX8, A2WSH0, A9YWR6, B8ALI0, B9G300, B9G5Y5, C7J6G6, D3GE74, D3ZCM3, F2PLH2, F2RSQ6, F2SHL1, H9BZ66, O24367, O80946, O81016, P10090, P25371, P45843, P45844, P58428, Q05360, Q08234, Q0JLC5, Q16928, Q17320, Q27256, Q2QV81, Q4GZT4, Q4WFQ4, Q54CG0, Q55DA0, Q55DR1, Q55DW4, Q55GB1, Q5MB13, Q64343

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
ABCG1	up-regulates	HDL_assembly

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	29
Likely pathogenic	2
Uncertain significance	68
Likely benign	12
Benign	17

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1341200	GRCh37/hg19 21q11.2-22.3(chr21:15006457-48097372)x3	Pathogenic
1458311	NC_000021.8:g.(?43160998)(47865240_?)del	Pathogenic
1526706	GRCh37/hg19 21q11.2-22.3(chr21:15285841-48097372)	Pathogenic
1526720	GRCh37/hg19 21q22.2-22.3(chr21:42410406-48097372)	Pathogenic
1703616	GRCh37/hg19 21q22.3(chr21:42679089-48097372)	Pathogenic
1705932	GRCh37/hg19 21q11.2-22.3(chr21:14420615-48080926)x3	Pathogenic
253403	GRCh37/hg19 21q11.2-22.3(chr21:15410701-48090317)x3	Pathogenic
253477	GRCh37/hg19 21q22.2-22.3(chr21:39841248-44652723)x3	Pathogenic
253512	GRCh37/hg19 21q11.2-22.3(chr21:15538655-48080926)x1	Pathogenic
2684910	GRCh37/hg19 21q11.2-22.3(chr21:15006458-45674637)x3	Pathogenic
2684914	GRCh37/hg19 21q22.11-22.3(chr21:33015681-48097372)x3	Pathogenic
3062420	GRCh37/hg19 21q21.3-22.3(chr21:30685776-48097372)x3	Pathogenic
3062421	GRCh37/hg19 21q22.3(chr21:43603041-48097372)x1	Pathogenic
3062423	GRCh37/hg19 21q21.3-22.3(chr21:26929299-48097372)x3	Pathogenic
3062426	GRCh37/hg19 21q22.3(chr21:43369956-48097372)x1	Pathogenic
3062428	GRCh37/hg19 21q22.12-22.3(chr21:35872675-48097372)x1	Pathogenic
3062429	GRCh37/hg19 21q22.11-22.3(chr21:34092685-48097372)x3	Pathogenic
3242283	GRCh37/hg19 21q11.2-22.3(chr21:15380398-48100790)x3	Pathogenic
3391864	GRCh37/hg19 21q22.11-22.3(chr21:34586759-48097372)x3	Pathogenic
394099	GRCh37/hg19 21q22.13-22.3(chr21:38790552-43619940)x1	Pathogenic
394309	GRCh37/hg19 21q11.2-22.3(chr21:14771770-48080867)x3	Pathogenic
443002	GRCh37/hg19 21q22.13-22.3(chr21:38699545-48097372)x1	Pathogenic
443072	GRCh37/hg19 21q22.2-22.3(chr21:41254101-48097372)x1	Pathogenic
443167	GRCh37/hg19 21q22.3(chr21:43498966-48097372)x1	Pathogenic
443979	GRCh37/hg19 21q11.2-22.3(chr21:15006458-48097372)	Pathogenic
59013	GRCh37/hg19 21q22.1-22.3(chr21:35527952-44298520)x1	Pathogenic
625618	GRCh37/hg19 21q22.2-22.3(chr21:41537095-46914745)	Pathogenic
816508	GRCh37/hg19 21q22.2-22.3(chr21:42044877-48100155)x3	Pathogenic
983157	GRCh37/hg19 21q11.2-22.3(chr21:14629063-48090317)x3	Pathogenic
2684917	GRCh37/hg19 21q22.3(chr21:43687354-48097372)x3	Likely pathogenic

SpliceAI

2507 predictions. Top by Δscore:

Variant	Effect	Δscore
21:42225670:GA:G	acceptor_gain	1.0000
21:42225907:G:GT	donor_gain	1.0000
21:42271064:TTGCA:T	acceptor_loss	1.0000
21:42271065:TGCA:T	acceptor_loss	1.0000
21:42271066:GCA:G	acceptor_loss	1.0000
21:42271067:CA:C	acceptor_loss	1.0000
21:42271068:A:AG	acceptor_gain	1.0000
21:42271068:AG:A	acceptor_gain	1.0000
21:42271069:G:GC	acceptor_loss	1.0000
21:42271069:G:GG	acceptor_gain	1.0000
21:42271069:GG:G	acceptor_gain	1.0000
21:42273292:T:A	acceptor_gain	1.0000
21:42273293:G:A	acceptor_gain	1.0000
21:42273298:T:TA	acceptor_gain	1.0000
21:42273299:GCA:G	acceptor_loss	1.0000
21:42273300:CAGGG:C	acceptor_gain	1.0000
21:42273301:A:AG	acceptor_gain	1.0000
21:42273301:A:AT	acceptor_loss	1.0000
21:42273301:AG:A	acceptor_gain	1.0000
21:42273301:AGG:A	acceptor_gain	1.0000
21:42273301:AGGGA:A	acceptor_gain	1.0000
21:42273302:G:C	acceptor_loss	1.0000
21:42273302:G:GA	acceptor_gain	1.0000
21:42273302:GG:G	acceptor_gain	1.0000
21:42273302:GGG:G	acceptor_gain	1.0000
21:42273302:GGGA:G	acceptor_gain	1.0000
21:42273302:GGGAG:G	acceptor_gain	1.0000
21:42273424:G:GT	donor_gain	1.0000
21:42273432:GATG:G	donor_gain	1.0000
21:42273436:G:GG	donor_gain	1.0000

AlphaMissense

4368 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
21:42271135:G:C	G118R	1.000
21:42271135:G:T	G118C	1.000
21:42271136:G:A	G118D	1.000
21:42271145:G:A	G121E	1.000
21:42271147:G:C	A122P	1.000
21:42271150:G:T	G123W	1.000
21:42271151:G:A	G123E	1.000
21:42271153:A:C	K124Q	1.000
21:42271154:A:T	K124M	1.000
21:42271156:T:C	S125P	1.000
21:42271157:C:T	S125F	1.000
21:42273390:G:C	Q164H	1.000
21:42273390:G:T	Q164H	1.000
21:42276908:T:C	L184P	1.000
21:42282354:G:C	K223N	1.000
21:42282354:G:T	K223N	1.000
21:42282359:T:C	L225P	1.000
21:42282368:C:A	A228E	1.000
21:42282377:T:C	L231P	1.000
21:42282395:T:A	V237D	1.000
21:42282407:A:C	D241A	1.000
21:42282407:A:G	D241G	1.000
21:42282407:A:T	D241V	1.000
21:42282409:G:A	E242K	1.000
21:42282410:A:G	E242G	1.000
21:42282410:A:T	E242V	1.000
21:42282411:G:C	E242D	1.000
21:42282411:G:T	E242D	1.000
21:42282413:C:A	P243H	1.000
21:42282413:C:G	P243R	1.000

dbSNP variants (sampled 300 via entrez): RS1000007851 (21:42281900 T>G), RS1000037562 (21:42274925 G>A), RS1000047950 (21:42202643 G>A,T), RS1000051995 (21:42253386 C>G,T), RS1000058752 (21:42220615 G>A), RS1000103598 (21:42244839 G>A), RS1000105698 (21:42207143 A>G), RS1000117733 (21:42217269 G>A), RS1000158577 (21:42215119 G>A), RS1000163422 (21:42253005 C>A,T), RS1000213950 (21:42220574 A>C,G), RS1000214686 (21:42212711 T>A), RS1000272592 (21:42223061 A>C), RS1000304736 (21:42255785 C>A), RS1000323056 (21:42292046 A>G)

Disease associations

OMIM: gene MIM:603076 | disease phenotypes: MIM:190685, MIM:616341, MIM:254800

GenCC curated gene-disease

Mondo (4): Down syndrome (MONDO:0008608), developmental and epileptic encephalopathy, 30 (MONDO:0014595), progressive myoclonus epilepsy (MONDO:0020074), neurodevelopmental disorder (MONDO:0700092)

Orphanet (3): Down syndrome (Orphanet:870), Progressive myoclonic epilepsy type 1 (Orphanet:308), Progressive myoclonic epilepsy (Orphanet:98261)

HPO phenotypes

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

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST001356_17	Gout	1.000000e-07
GCST002337_7	Amyotrophic lateral sclerosis (sporadic)	5.000000e-07
GCST002592_13	Neuritic plaque	8.000000e-06
GCST002592_34	Neuritic plaque	8.000000e-09
GCST002593_26	Dementia and core Alzheimer’s disease neuropathologic changes	7.000000e-06
GCST002593_50	Dementia and core Alzheimer’s disease neuropathologic changes	7.000000e-06
GCST003132_5	Eating disorder in bipolar disorder	4.000000e-07
GCST003918_1	Idiopathic osteonecrosis of the femoral head	2.000000e-07
GCST010242_121	HDL cholesterol levels	2.000000e-08

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0006798	neuritic plaque measurement
EFO:0006801	Alzheimer’s disease neuropathologic change
EFO:1001930	idiopathic osteonecrosis of the femoral head
EFO:0004612	high density lipoprotein cholesterol measurement

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D004314	Down Syndrome	C10.597.606.360.220; C16.131.077.327; C16.131.260.260; C16.320.180.260
D020191	Myoclonic Epilepsies, Progressive	C10.228.140.490.375.130.650; C10.228.140.490.493.063.650
D065886	Neurodevelopmental Disorders	F03.625

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs225440	Toxicity	3	fluorouracil;irinotecan;leucovorin	Colorectal Neoplasms

PharmGKB variants

4 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs182694	ABCG1		0.00	0
rs225440	ABCG1	3	3.25	1	fluorouracil;irinotecan;leucovorin
rs425215	ABCG1		0.00	0
rs492338	ABCG1		0.00	0

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: transporter — ABCG subfamily

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
T0901317	decreases reaction, increases expression, increases reaction, affects cotreatment	7
Valproic Acid	affects expression, affects methylation, increases expression	7
Resveratrol	affects cotreatment, decreases expression, increases expression, increases reaction, increases activity (+2 more)	5
Benzo(a)pyrene	affects methylation, decreases expression	3
Estradiol	affects cotreatment, decreases expression, increases expression	3
Progesterone	affects cotreatment, decreases expression, increases expression	3
Cyclosporine	increases expression	3
triphenyl phosphate	increases expression, affects expression, decreases reaction	2
bis(tri-n-butyltin)oxide	increases expression	2
tributyltin	increases expression	2
perfluorooctanoic acid	increases expression	2
epigallocatechin gallate	decreases expression	2
GW 3965	decreases expression, decreases reaction, increases expression	2
Alitretinoin	increases expression, affects cotreatment	2
Air Pollutants	increases abundance, increases expression	2
Cadmium	increases expression, increases response to substance, increases abundance	2
Cisplatin	affects expression, decreases expression	2
Curcumin	increases expression	2
Nickel	decreases expression	2
Rifampin	increases expression	2
Silicon Dioxide	decreases expression	2
Smoke	increases abundance, increases expression, decreases expression	2
Tobacco Smoke Pollution	decreases methylation, increases expression	2
Tretinoin	increases expression	2
Aflatoxin B1	decreases methylation, decreases expression	2
Cadmium Chloride	increases abundance, increases expression	2
GSK-J4	increases expression	1
lly-283	increases expression	1
1,2-linoleoylphosphatidylcholine	decreases expression	1
22-hydroxycholesterol	increases expression	1

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_1252	HCC1428	Cancer cell line	Female
CVCL_C9DB	HCC1428/Cas9-hyg	Cancer cell line	Female
CVCL_YX83	HCC1428-LTED	Cancer cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01112683	PHASE4	COMPLETED	Efficacy and Safety of Memantine Hydrochloride in Enhancing the Cognitive Abilities of Young Adults With Down Syndrome
NCT04219280	PHASE4	RECRUITING	Evaluating Treatment of ADHD in Children with Down Syndrome
NCT04747275	PHASE4	TERMINATED	Use of Liquid Stable Levothyroxine in Trisomy 21 Pediatric Patients
NCT05458479	PHASE4	COMPLETED	Fluoxetine Treatment of Depression in Down Syndrome
NCT06911944	PHASE4	NOT_YET_RECRUITING	Amyloid Lowering for Alzheimer’s in Down’s With Donanemab Investigation
NCT07280468	PHASE4	RECRUITING	Endotype DIrected Treatment for OSA in Down Syndrome
NCT00056329	PHASE3	UNKNOWN	Vitamin E in Aging Persons With Down Syndrome
NCT00754013	PHASE3	TERMINATED	Evaluating The Efficacy And Safety Of Donepezil Hydrochloride (Aricept) In The Treatment Of The Cognitive Dysfunction Exhibited By Children With Down Syndrome, Aged 6 To 10
NCT00754052	PHASE3	TERMINATED	Evaluating The Efficacy And Safety Of Donepezil Hydrochloride (Aricept) In The Treatment Of The Cognitive Dysfunction Exhibited By Children With Down Syndrome, Aged 11 To 17
NCT01190930	PHASE3	COMPLETED	Risk-Adapted Chemotherapy in Treating Younger Patients With Newly Diagnosed Standard-Risk Acute Lymphoblastic Leukemia or Localized B-Lineage Lymphoblastic Lymphoma
NCT01576705	PHASE3	COMPLETED	Efficacy Assessment of Systematic Treatment With Folinic Acid and Thyroid Hormone on Psychomotor Development of Down Syndrome Young Children
NCT01594346	PHASE3	COMPLETED	Multicenter Vitamin E Trial in Aging Persons With Down Syndrome
NCT02521493	PHASE3	ACTIVE_NOT_RECRUITING	Response-Based Chemotherapy in Treating Newly Diagnosed Acute Myeloid Leukemia or Myelodysplastic Syndrome in Younger Patients With Down Syndrome
NCT03914625	PHASE3	ACTIVE_NOT_RECRUITING	A Study to Investigate Blinatumomab in Combination With Chemotherapy in Patients With Newly Diagnosed B-Lymphoblastic Leukemia
NCT04801771	PHASE3	ACTIVE_NOT_RECRUITING	Effects of Hypoglossal Nerve Stimulation on Cognition and Language in Down Syndrome and Obstructive Sleep Apnea
NCT05528549	PHASE3	COMPLETED	Blood Flow and Blood Pressure Investigation in Down Syndrome
NCT06860373	PHASE3	TERMINATED	LIFE-DSR-Biomarker Sub-study of Biomarkers in Down Syndrome Related Alzheimer’s Disease (DS-AD)
NCT07135167	PHASE3	RECRUITING	Compassionate Use Study of Epi-ON Corneal Collagen Crosslinking Performed Using UVA Exposure on Eyes With Ectatic Corneal Diseases for Subjects With Down Syndrome
NCT07232134	PHASE3	RECRUITING	The Efficacy of Therapy in Patients With Acute Myeloid Leukemia and Down Syndrome in Russia
NCT07234695	PHASE3	RECRUITING	LEvetiracetam to Prevent Seizures in Symptomatic Alzheimer’s Disease in Adults With Down Syndrome
NCT07238465	PHASE3	RECRUITING	Exploring Sympathetic Nervous System Function in Individuals With Down Syndrome
NCT00570128	PHASE2	COMPLETED	Evaluating The Efficacy And Safety Of Donepezil Hydrochloride (HCl) (Aricept) In Treating Cognitive Dysfunction Exhibited By Children With Down Syndrome
NCT00675025	PHASE2	TERMINATED	Evaluating The Safety Of Donepezil Hydrochloride (Aricept) For Up To 1 Year In The Treatment Of The Cognitive Dysfunction Exhibited By Children With Down Syndrome - Follow-Up To A 10-Week, Double-Blind, Placebo-Controlled Trial
NCT00891917	PHASE2	WITHDRAWN	Liq-NOL Efficacy in Pediatric Patients With Down Syndrome
NCT00928304	PHASE2	COMPLETED	Phase II Study of Florbetaben (BAY94-9172) PET Imaging for Detection/Exclusion of Cerebral β-amyloid.
NCT01394796	PHASE2	COMPLETED	Egcg, a dyrk1a Inhibitor as Therapeutic Tool for Reversing Cognitive Deficits in Down Syndrome Individuals.
NCT01699711	PHASE2	COMPLETED	Normalization of dyrk1A and APP Function as an Approach to Improve Cognitive Performance and Decelerate AD Progression in DS Subjects: Epigallocatechin Gallate as Therapeutic Tool
NCT01791725	PHASE2	COMPLETED	A 4-Week Safety Study of Oral ELND005 in Young Adults With Down Syndrome Without Dementia
NCT01975545	PHASE2	UNKNOWN	Fluor Varnish With Silver Nanoparticles for Dental Remineralization in Patients With Trisomy 21
NCT02024789	PHASE2	COMPLETED	A Study of RG1662 in Adults and Adolescents With Down Syndrome (CLEMATIS)
NCT02094053	PHASE2	COMPLETED	A Double-blind, Placebo-controlled Comparative Study and Open-label Extension Study to Confirm the Efficacy and Safety of E2020 in Subjects With Down Syndrome Having Regression Symptoms and Disabled Activities of Daily Living.
NCT02304302	PHASE2	COMPLETED	Down Syndrome Memantine Follow-up Study
NCT02484703	PHASE2	TERMINATED	A Study of RO5186582 in Down Syndrome Among Children 6 to 11 Years of Age
NCT02971254	PHASE2	COMPLETED	The Effects of Inhalational Anaesthetics in Cognitive Functions in Down Syndrome Patients
NCT03286634	PHASE2	ACTIVE_NOT_RECRUITING	ASIA Down Syndrome Acute Lymphoblastic Leukemia 2016
NCT03538925	PHASE2	COMPLETED	Building Sentences With Preschoolers Who Use AAC
NCT04115878	PHASE2	COMPLETED	Medications for Obstructive Sleep Apnea In Children With Down Syndrome
NCT04246372	PHASE2	COMPLETED	Tofacitinib for Immune Skin Conditions in Down Syndrome
NCT04373616	PHASE2	WITHDRAWN	A Study of ACI-24 in Adults With Down Syndrome
NCT04546399	PHASE2	RECRUITING	A Study to Compare Blinatumomab Alone to Blinatumomab With Nivolumab in Patients Diagnosed With First Relapse B-Cell Acute Lymphoblastic Leukemia (B-ALL)