ABCA7 encodes an ATP-binding cassette subfamily A lipid transporter that couples ATP hydrolysis to intramembrane phospholipid movement, with strong substrate support for phosphatidylserine, phosphatidylcholine, and lysophosphatidylcholine. The canonical protein localizes to plasma membrane, Golgi/endosomal membranes, ruffle membranes, and phagocytic cups in myeloid and other cells. ABCA7 binds apolipoprotein A-I and supports apolipoprotein-mediated phospholipid efflux, while cholesterol efflux and HDL assembly are more context-dependent. In macrophages and microglia, ABCA7 contributes to membrane trafficking, phagocytosis, apoptotic-cell engulfment, and amyloid-beta clearance/processing pathways relevant to Alzheimer disease risk.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0042626 ATPase-coupled transmembrane transporter activity | IBA GO_REF:0000033 | ACCEPT | Summary: This molecular-function annotation captures the core ABCA7 activity: ATP-coupled intramembrane phospholipid transport/floppase activity and apoA-I-associated phospholipid efflux. Reason: The term aligns with direct biochemical evidence or well-supported cellular consequences of ABCA7 lipid transport and membrane-trafficking activity. |
| GO:0033344 cholesterol efflux | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: ABCA7 can support apoA-I-associated cholesterol/HDL-like outputs in overexpression systems, but phospholipid/lysoPC transport is the better-supported core activity. Reason: Retain the annotation as non-core because it is plausible or experimentally observed, but not the primary evolved molecular role of ABCA7. |
| GO:0033700 phospholipid efflux | IBA GO_REF:0000033 | ACCEPT | Summary: This annotation is part of the core lipid transport, phospholipid efflux, or membrane-trafficking function of ABCA7. Reason: The term aligns with direct biochemical evidence or well-supported cellular consequences of ABCA7 lipid transport and membrane-trafficking activity. |
| GO:0034188 apolipoprotein A-I receptor activity | IBA GO_REF:0000033 | ACCEPT | Summary: This molecular-function annotation captures the core ABCA7 activity: ATP-coupled intramembrane phospholipid transport/floppase activity and apoA-I-associated phospholipid efflux. Reason: The term aligns with direct biochemical evidence or well-supported cellular consequences of ABCA7 lipid transport and membrane-trafficking activity. |
| GO:0090554 phosphatidylcholine floppase activity | IBA GO_REF:0000033 | ACCEPT | Summary: This molecular-function annotation captures the core ABCA7 activity: ATP-coupled intramembrane phospholipid transport/floppase activity and apoA-I-associated phospholipid efflux. Reason: The term aligns with direct biochemical evidence or well-supported cellular consequences of ABCA7 lipid transport and membrane-trafficking activity. |
| GO:0090556 phosphatidylserine floppase activity | IBA GO_REF:0000033 | ACCEPT | Summary: This molecular-function annotation captures the core ABCA7 activity: ATP-coupled intramembrane phospholipid transport/floppase activity and apoA-I-associated phospholipid efflux. Reason: The term aligns with direct biochemical evidence or well-supported cellular consequences of ABCA7 lipid transport and membrane-trafficking activity. |
| GO:0000139 Golgi membrane | IEA GO_REF:0000044 | ACCEPT | Summary: This location fits ABCA7 function as a multipass membrane lipid transporter active at plasma, Golgi/endosomal, ruffle, and phagocytic-cup membranes. Reason: The term aligns with direct biochemical evidence or well-supported cellular consequences of ABCA7 lipid transport and membrane-trafficking activity. |
| GO:0001891 phagocytic cup | IEA GO_REF:0000044 | ACCEPT | Summary: This location fits ABCA7 function as a multipass membrane lipid transporter active at plasma, Golgi/endosomal, ruffle, and phagocytic-cup membranes. Reason: The term aligns with direct biochemical evidence or well-supported cellular consequences of ABCA7 lipid transport and membrane-trafficking activity. |
| GO:0005524 ATP binding | IEA GO_REF:0000002 | ACCEPT | Summary: This molecular-function annotation captures the core ABCA7 activity: ATP-coupled intramembrane phospholipid transport/floppase activity and apoA-I-associated phospholipid efflux. Reason: The term aligns with direct biochemical evidence or well-supported cellular consequences of ABCA7 lipid transport and membrane-trafficking activity. |
| GO:0005737 cytoplasm | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: This annotation may reflect a valid cell-state, localization, or signaling consequence, but it is peripheral to ABCA7 core lipid transporter/phagocytic function. Reason: Retain the annotation as non-core because it is plausible or experimentally observed, but not the primary evolved molecular role of ABCA7. |
| GO:0005783 endoplasmic reticulum | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: UniProt places isoform 2 (type II ABCA7), not the canonical transporter, in the endoplasmic reticulum; the mapping transfers that isoform-level location to the gene. Reason: Retain the annotation as non-core because it is plausible or experimentally observed, but not the primary evolved molecular role of ABCA7. ORGANELLES check (2026-11-04): the IEA maps the UniProt line "[Isoform 2]: ... Endoplasmic reticulum {ECO:0000269|PubMed:14592415}", while the canonical isoform 1 is curated to the cell membrane, Golgi and early endosome membranes. The organelle claim is real for the type II splice variant expressed in HEK293 cells (same paper as the EXP row), and canonical ABCA7 passes through the ER as any polytopic plasma-membrane transporter does, so the ER is a minor, isoform-restricted pool rather than the site of ABCA7 lipid export; KEEP_AS_NON_CORE, consistent with the EXP row. No ER membrane row is added: the only ER evidence is one abstract-only study of an N-terminally altered isoform (residues 1-138 missing, which removes the first predicted TM segment, 22-42), so its topology in the ER is not established, and the ER pool is not where the canonical protein acts. Supporting Evidence: file:human/ABCA7/ABCA7-uniprot.txt SUBCELLULAR LOCATION: [Isoform 2]: Cytoplasm {ECO:0000269|PubMed:14592415}. Endoplasmic reticulum {ECO:0000269|PubMed:14592415}. PMID:14592415 In contrast, type II ABCA7 appeared to be localized mainly in endoplasmic reticulum and did not show apoA-I-dependent cholesterol and phospholipid release. |
| GO:0005886 plasma membrane | IEA GO_REF:0000120 | ACCEPT | Summary: This location fits ABCA7 function as a multipass membrane lipid transporter active at plasma, Golgi/endosomal, ruffle, and phagocytic-cup membranes. Reason: The term aligns with direct biochemical evidence or well-supported cellular consequences of ABCA7 lipid transport and membrane-trafficking activity. |
| GO:0016020 membrane | IEA GO_REF:0000002 | ACCEPT | Summary: This location fits ABCA7 function as a multipass membrane lipid transporter active at plasma, Golgi/endosomal, ruffle, and phagocytic-cup membranes. Reason: The term aligns with direct biochemical evidence or well-supported cellular consequences of ABCA7 lipid transport and membrane-trafficking activity. |
| GO:0016887 ATP hydrolysis activity | IEA GO_REF:0000002 | ACCEPT | Summary: This molecular-function annotation captures the core ABCA7 activity: ATP-coupled intramembrane phospholipid transport/floppase activity and apoA-I-associated phospholipid efflux. Reason: The term aligns with direct biochemical evidence or well-supported cellular consequences of ABCA7 lipid transport and membrane-trafficking activity. |
| GO:0031901 early endosome membrane | IEA GO_REF:0000044 | ACCEPT | Summary: This location fits ABCA7 function as a multipass membrane lipid transporter active at plasma, Golgi/endosomal, ruffle, and phagocytic-cup membranes. Reason: The term aligns with direct biochemical evidence or well-supported cellular consequences of ABCA7 lipid transport and membrane-trafficking activity. |
| GO:0032587 ruffle membrane | IEA GO_REF:0000044 | ACCEPT | Summary: This location fits ABCA7 function as a multipass membrane lipid transporter active at plasma, Golgi/endosomal, ruffle, and phagocytic-cup membranes. Reason: The term aligns with direct biochemical evidence or well-supported cellular consequences of ABCA7 lipid transport and membrane-trafficking activity. |
| GO:0033344 cholesterol efflux | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: ABCA7 can support apoA-I-associated cholesterol/HDL-like outputs in overexpression systems, but phospholipid/lysoPC transport is the better-supported core activity. Reason: Retain the annotation as non-core because it is plausible or experimentally observed, but not the primary evolved molecular role of ABCA7. |
| GO:0033700 phospholipid efflux | IEA GO_REF:0000117 | ACCEPT | Summary: This annotation is part of the core lipid transport, phospholipid efflux, or membrane-trafficking function of ABCA7. Reason: The term aligns with direct biochemical evidence or well-supported cellular consequences of ABCA7 lipid transport and membrane-trafficking activity. |
| GO:0034188 apolipoprotein A-I receptor activity | IEA GO_REF:0000117 | ACCEPT | Summary: This molecular-function annotation captures the core ABCA7 activity: ATP-coupled intramembrane phospholipid transport/floppase activity and apoA-I-associated phospholipid efflux. Reason: The term aligns with direct biochemical evidence or well-supported cellular consequences of ABCA7 lipid transport and membrane-trafficking activity. |
| GO:0034205 amyloid-beta formation | IEA GO_REF:0000117 | MODIFY | Summary: ABCA7 loss increases APP endocytosis and amyloid-beta production, so the evidence supports regulation, especially negative regulation by functional ABCA7, rather than simple involvement in amyloid-beta formation. Reason: Use directional regulation terms to avoid implying ABCA7 is a positive component of amyloid-beta formation. |
| GO:0055085 transmembrane transport | IEA GO_REF:0000002 | ACCEPT | Summary: This annotation is part of the core lipid transport, phospholipid efflux, or membrane-trafficking function of ABCA7. Reason: The term aligns with direct biochemical evidence or well-supported cellular consequences of ABCA7 lipid transport and membrane-trafficking activity. |
| GO:0090554 phosphatidylcholine floppase activity | IEA GO_REF:0000116 | ACCEPT | Summary: This molecular-function annotation captures the core ABCA7 activity: ATP-coupled intramembrane phospholipid transport/floppase activity and apoA-I-associated phospholipid efflux. Reason: The term aligns with direct biochemical evidence or well-supported cellular consequences of ABCA7 lipid transport and membrane-trafficking activity. |
| GO:0090556 phosphatidylserine floppase activity | IEA GO_REF:0000116 | ACCEPT | Summary: This molecular-function annotation captures the core ABCA7 activity: ATP-coupled intramembrane phospholipid transport/floppase activity and apoA-I-associated phospholipid efflux. Reason: The term aligns with direct biochemical evidence or well-supported cellular consequences of ABCA7 lipid transport and membrane-trafficking activity. |
| GO:0140326 ATPase-coupled intramembrane lipid carrier activity | IEA GO_REF:0000003 | ACCEPT | Summary: This molecular-function annotation captures the core ABCA7 activity: ATP-coupled intramembrane phospholipid transport/floppase activity and apoA-I-associated phospholipid efflux. Reason: The term aligns with direct biochemical evidence or well-supported cellular consequences of ABCA7 lipid transport and membrane-trafficking activity. |
| GO:0140328 floppase activity | IEA GO_REF:0000117 | ACCEPT | Summary: This molecular-function annotation captures the core ABCA7 activity: ATP-coupled intramembrane phospholipid transport/floppase activity and apoA-I-associated phospholipid efflux. Reason: The term aligns with direct biochemical evidence or well-supported cellular consequences of ABCA7 lipid transport and membrane-trafficking activity. |
| GO:0140359 ABC-type transporter activity | IEA GO_REF:0000002 | ACCEPT | Summary: This molecular-function annotation captures the core ABCA7 activity: ATP-coupled intramembrane phospholipid transport/floppase activity and apoA-I-associated phospholipid efflux. Reason: The term aligns with direct biochemical evidence or well-supported cellular consequences of ABCA7 lipid transport and membrane-trafficking activity. |
| GO:1902991 regulation of amyloid precursor protein catabolic process | IEA GO_REF:0000117 | ACCEPT | Summary: ABCA7 loss-of-function data support a role in regulating APP endocytosis/processing and limiting amyloid-beta formation. Reason: The term aligns with direct biochemical evidence or well-supported cellular consequences of ABCA7 lipid transport and membrane-trafficking activity. |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MARK AS OVER ANNOTATED | Summary: The PDZ/motif interaction evidence is real but generic protein binding is not informative for ABCA7 core biology. Reason: ABCA7 function is better captured by ATP-coupled lipid carrier/floppase activity, apoA-I receptor activity, and phagocytic/endocytic lipid-trafficking processes. |
| GO:0006869 lipid transport | TAS Reactome:R-HSA-1369062 | ACCEPT | Summary: This annotation is part of the core lipid transport, phospholipid efflux, or membrane-trafficking function of ABCA7. Reason: The term aligns with direct biochemical evidence or well-supported cellular consequences of ABCA7 lipid transport and membrane-trafficking activity. |
| GO:0033344 cholesterol efflux | IGI PMID:28373057 Lysophosphatidylcholine export by human ABCA7. | KEEP AS NON CORE | Summary: ABCA7 can support apoA-I-associated cholesterol/HDL-like outputs in overexpression systems, but phospholipid/lysoPC transport is the better-supported core activity. Reason: Retain the annotation as non-core because it is plausible or experimentally observed, but not the primary evolved molecular role of ABCA7. |
| GO:0120014 phospholipid transfer activity | IGI PMID:28373057 Lysophosphatidylcholine export by human ABCA7. | ACCEPT | Summary: This molecular-function annotation captures the core ABCA7 activity: ATP-coupled intramembrane phospholipid transport/floppase activity and apoA-I-associated phospholipid efflux. Reason: The term aligns with direct biochemical evidence or well-supported cellular consequences of ABCA7 lipid transport and membrane-trafficking activity. |
| GO:0140326 ATPase-coupled intramembrane lipid carrier activity | IDA PMID:28373057 Lysophosphatidylcholine export by human ABCA7. | ACCEPT | Summary: This molecular-function annotation captures the core ABCA7 activity: ATP-coupled intramembrane phospholipid transport/floppase activity and apoA-I-associated phospholipid efflux. Reason: The term aligns with direct biochemical evidence or well-supported cellular consequences of ABCA7 lipid transport and membrane-trafficking activity. |
| GO:0120014 phospholipid transfer activity | TAS Reactome:R-HSA-382553 | ACCEPT | Summary: This molecular-function annotation captures the core ABCA7 activity: ATP-coupled intramembrane phospholipid transport/floppase activity and apoA-I-associated phospholipid efflux. Reason: The term aligns with direct biochemical evidence or well-supported cellular consequences of ABCA7 lipid transport and membrane-trafficking activity. |
| GO:0005794 Golgi apparatus | IDA GO_REF:0000052 | ACCEPT | Summary: This location fits ABCA7 function as a multipass membrane lipid transporter active at plasma, Golgi/endosomal, ruffle, and phagocytic-cup membranes. Reason: The term aligns with direct biochemical evidence or well-supported cellular consequences of ABCA7 lipid transport and membrane-trafficking activity. |
| GO:0005886 plasma membrane | IDA GO_REF:0000052 | ACCEPT | Summary: This location fits ABCA7 function as a multipass membrane lipid transporter active at plasma, Golgi/endosomal, ruffle, and phagocytic-cup membranes. Reason: The term aligns with direct biochemical evidence or well-supported cellular consequences of ABCA7 lipid transport and membrane-trafficking activity. |
| GO:0030054 cell junction | IDA GO_REF:0000052 | KEEP AS NON CORE | Summary: This annotation may reflect a valid cell-state, localization, or signaling consequence, but it is peripheral to ABCA7 core lipid transporter/phagocytic function. Reason: Retain the annotation as non-core because it is plausible or experimentally observed, but not the primary evolved molecular role of ABCA7. |
| GO:0000139 Golgi membrane | ISS GO_REF:0000024 | ACCEPT | Summary: This location fits ABCA7 function as a multipass membrane lipid transporter active at plasma, Golgi/endosomal, ruffle, and phagocytic-cup membranes. Reason: The term aligns with direct biochemical evidence or well-supported cellular consequences of ABCA7 lipid transport and membrane-trafficking activity. |
| GO:0005737 cytoplasm | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: This annotation may reflect a valid cell-state, localization, or signaling consequence, but it is peripheral to ABCA7 core lipid transporter/phagocytic function. Reason: Retain the annotation as non-core because it is plausible or experimentally observed, but not the primary evolved molecular role of ABCA7. |
| GO:0005737 cytoplasm | EXP PMID:14592415 Posttranscriptional regulation of human ABCA7 and its functi... | KEEP AS NON CORE | Summary: This annotation may reflect a valid cell-state, localization, or signaling consequence, but it is peripheral to ABCA7 core lipid transporter/phagocytic function. Reason: Retain the annotation as non-core because it is plausible or experimentally observed, but not the primary evolved molecular role of ABCA7. |
| GO:0005783 endoplasmic reticulum | EXP PMID:14592415 Posttranscriptional regulation of human ABCA7 and its functi... | KEEP AS NON CORE | Summary: The splice variant type II ABCA7 (isoform 2) expressed in HEK293 cells appeared mainly in the endoplasmic reticulum, whereas type I (canonical) ABCA7 reached the plasma membrane. Reason: Retain the annotation as non-core because it is plausible or experimentally observed, but not the primary evolved molecular role of ABCA7. ORGANELLES check (2026-11-04): the cached record of PMID:14592415 is abstract-only; the abstract attributes the ER localization to the type II splice variant (Q8IZY2-2), expressed in HEK293 cells and inactive in apoA-I-dependent lipid release, while type I localized to the plasma membrane. The experiment is whole-organelle immunostaining and cannot resolve membrane from lumen, so under the organelle policy the row stays at the root and is kept as a real, non-core, isoform-restricted location. The GOA row carries no isoform qualifier although the abstract ties the ER finding to isoform 2. Supporting Evidence: PMID:14592415 In contrast, type II ABCA7 appeared to be localized mainly in endoplasmic reticulum and did not show apoA-I-dependent cholesterol and phospholipid release. PMID:14592415 Immunostaining revealed that the type I ABCA7, expressed in HEK293 cells, was localized to the plasma membrane |
| GO:0005886 plasma membrane | EXP PMID:12917409 ATP-binding cassette transporter A7 (ABCA7) binds apolipopro... | ACCEPT | Summary: This location fits ABCA7 function as a multipass membrane lipid transporter active at plasma, Golgi/endosomal, ruffle, and phagocytic-cup membranes. Reason: The term aligns with direct biochemical evidence or well-supported cellular consequences of ABCA7 lipid transport and membrane-trafficking activity. |
| GO:0005886 plasma membrane | EXP PMID:14592415 Posttranscriptional regulation of human ABCA7 and its functi... | ACCEPT | Summary: This location fits ABCA7 function as a multipass membrane lipid transporter active at plasma, Golgi/endosomal, ruffle, and phagocytic-cup membranes. Reason: The term aligns with direct biochemical evidence or well-supported cellular consequences of ABCA7 lipid transport and membrane-trafficking activity. |
| GO:0031901 early endosome membrane | ISS GO_REF:0000024 | ACCEPT | Summary: This location fits ABCA7 function as a multipass membrane lipid transporter active at plasma, Golgi/endosomal, ruffle, and phagocytic-cup membranes. Reason: The term aligns with direct biochemical evidence or well-supported cellular consequences of ABCA7 lipid transport and membrane-trafficking activity. |
| GO:0140326 ATPase-coupled intramembrane lipid carrier activity | EXP PMID:24097981 Differential phospholipid substrates and directional transpo... | ACCEPT | Summary: This molecular-function annotation captures the core ABCA7 activity: ATP-coupled intramembrane phospholipid transport/floppase activity and apoA-I-associated phospholipid efflux. Reason: The term aligns with direct biochemical evidence or well-supported cellular consequences of ABCA7 lipid transport and membrane-trafficking activity. |
| GO:0001891 phagocytic cup | ISS GO_REF:0000024 | ACCEPT | Summary: This location fits ABCA7 function as a multipass membrane lipid transporter active at plasma, Golgi/endosomal, ruffle, and phagocytic-cup membranes. Reason: The term aligns with direct biochemical evidence or well-supported cellular consequences of ABCA7 lipid transport and membrane-trafficking activity. |
| GO:0032587 ruffle membrane | ISS GO_REF:0000024 | ACCEPT | Summary: This location fits ABCA7 function as a multipass membrane lipid transporter active at plasma, Golgi/endosomal, ruffle, and phagocytic-cup membranes. Reason: The term aligns with direct biochemical evidence or well-supported cellular consequences of ABCA7 lipid transport and membrane-trafficking activity. |
| GO:0005886 plasma membrane | IDA PMID:28373057 Lysophosphatidylcholine export by human ABCA7. | ACCEPT | Summary: This location fits ABCA7 function as a multipass membrane lipid transporter active at plasma, Golgi/endosomal, ruffle, and phagocytic-cup membranes. Reason: The term aligns with direct biochemical evidence or well-supported cellular consequences of ABCA7 lipid transport and membrane-trafficking activity. |
| GO:0008542 visual learning | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Learning and memory phenotypes are downstream organismal consequences, not direct ABCA7 molecular functions. Reason: Retain the annotation as non-core because it is plausible or experimentally observed, but not the primary evolved molecular role of ABCA7. |
| GO:0019216 regulation of lipid metabolic process | ISS GO_REF:0000024 | ACCEPT | Summary: This annotation is part of the core lipid transport, phospholipid efflux, or membrane-trafficking function of ABCA7. Reason: The term aligns with direct biochemical evidence or well-supported cellular consequences of ABCA7 lipid transport and membrane-trafficking activity. |
| GO:0033700 phospholipid efflux | IGI PMID:28373057 Lysophosphatidylcholine export by human ABCA7. | ACCEPT | Summary: This annotation is part of the core lipid transport, phospholipid efflux, or membrane-trafficking function of ABCA7. Reason: The term aligns with direct biochemical evidence or well-supported cellular consequences of ABCA7 lipid transport and membrane-trafficking activity. |
| GO:0043409 negative regulation of MAPK cascade | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: This annotation may reflect a valid cell-state, localization, or signaling consequence, but it is peripheral to ABCA7 core lipid transporter/phagocytic function. Reason: Retain the annotation as non-core because it is plausible or experimentally observed, but not the primary evolved molecular role of ABCA7. |
| GO:1902430 negative regulation of amyloid-beta formation | ISS GO_REF:0000024 | ACCEPT | Summary: ABCA7 loss-of-function data support a role in regulating APP endocytosis/processing and limiting amyloid-beta formation. Reason: The term aligns with direct biochemical evidence or well-supported cellular consequences of ABCA7 lipid transport and membrane-trafficking activity. |
| GO:1903898 negative regulation of PERK-mediated unfolded protein response | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: This annotation may reflect a valid cell-state, localization, or signaling consequence, but it is peripheral to ABCA7 core lipid transporter/phagocytic function. Reason: Retain the annotation as non-core because it is plausible or experimentally observed, but not the primary evolved molecular role of ABCA7. |
| GO:0090554 phosphatidylcholine floppase activity | IDA PMID:24097981 Differential phospholipid substrates and directional transpo... | ACCEPT | Summary: This molecular-function annotation captures the core ABCA7 activity: ATP-coupled intramembrane phospholipid transport/floppase activity and apoA-I-associated phospholipid efflux. Reason: The term aligns with direct biochemical evidence or well-supported cellular consequences of ABCA7 lipid transport and membrane-trafficking activity. |
| GO:0090556 phosphatidylserine floppase activity | IDA PMID:24097981 Differential phospholipid substrates and directional transpo... | ACCEPT | Summary: This molecular-function annotation captures the core ABCA7 activity: ATP-coupled intramembrane phospholipid transport/floppase activity and apoA-I-associated phospholipid efflux. Reason: The term aligns with direct biochemical evidence or well-supported cellular consequences of ABCA7 lipid transport and membrane-trafficking activity. |
| GO:1900223 positive regulation of amyloid-beta clearance | ISS GO_REF:0000024 | ACCEPT | Summary: This process is consistent with ABCA7-dependent membrane trafficking and phagocytic cup biology in macrophage/microglial contexts. Reason: The term aligns with direct biochemical evidence or well-supported cellular consequences of ABCA7 lipid transport and membrane-trafficking activity. |
| GO:0140328 floppase activity | IDA PMID:24097981 Differential phospholipid substrates and directional transpo... | ACCEPT | Summary: This molecular-function annotation captures the core ABCA7 activity: ATP-coupled intramembrane phospholipid transport/floppase activity and apoA-I-associated phospholipid efflux. Reason: The term aligns with direct biochemical evidence or well-supported cellular consequences of ABCA7 lipid transport and membrane-trafficking activity. |
| GO:0044857 plasma membrane raft organization | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: This annotation may reflect a valid cell-state, localization, or signaling consequence, but it is peripheral to ABCA7 core lipid transporter/phagocytic function. Reason: Retain the annotation as non-core because it is plausible or experimentally observed, but not the primary evolved molecular role of ABCA7. |
| GO:2000010 positive regulation of protein localization to cell surface | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: This annotation may reflect a valid cell-state, localization, or signaling consequence, but it is peripheral to ABCA7 core lipid transporter/phagocytic function. Reason: Retain the annotation as non-core because it is plausible or experimentally observed, but not the primary evolved molecular role of ABCA7. |
| GO:0097386 glial cell projection | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: This annotation may reflect a valid cell-state, localization, or signaling consequence, but it is peripheral to ABCA7 core lipid transporter/phagocytic function. Reason: Retain the annotation as non-core because it is plausible or experimentally observed, but not the primary evolved molecular role of ABCA7. |
| GO:0150094 amyloid-beta clearance by cellular catabolic process | ISS GO_REF:0000024 | ACCEPT | Summary: This process is consistent with ABCA7-dependent membrane trafficking and phagocytic cup biology in macrophage/microglial contexts. Reason: The term aligns with direct biochemical evidence or well-supported cellular consequences of ABCA7 lipid transport and membrane-trafficking activity. |
| GO:0034205 amyloid-beta formation | IMP PMID:26260791 ATP-binding cassette transporter A7 (ABCA7) loss of function... | MODIFY | Summary: ABCA7 loss increases APP endocytosis and amyloid-beta production, so the evidence supports regulation, especially negative regulation by functional ABCA7, rather than simple involvement in amyloid-beta formation. Reason: Use directional regulation terms to avoid implying ABCA7 is a positive component of amyloid-beta formation. |
| GO:0045806 negative regulation of endocytosis | ISS GO_REF:0000024 | ACCEPT | Summary: This process is consistent with ABCA7-dependent membrane trafficking and phagocytic cup biology in macrophage/microglial contexts. Reason: The term aligns with direct biochemical evidence or well-supported cellular consequences of ABCA7 lipid transport and membrane-trafficking activity. |
| GO:1902991 regulation of amyloid precursor protein catabolic process | IMP PMID:26260791 ATP-binding cassette transporter A7 (ABCA7) loss of function... | ACCEPT | Summary: ABCA7 loss-of-function data support a role in regulating APP endocytosis/processing and limiting amyloid-beta formation. Reason: The term aligns with direct biochemical evidence or well-supported cellular consequences of ABCA7 lipid transport and membrane-trafficking activity. |
| GO:0045332 phospholipid translocation | IDA PMID:24097981 Differential phospholipid substrates and directional transpo... | ACCEPT | Summary: This annotation is part of the core lipid transport, phospholipid efflux, or membrane-trafficking function of ABCA7. Reason: The term aligns with direct biochemical evidence or well-supported cellular consequences of ABCA7 lipid transport and membrane-trafficking activity. |
| GO:0007613 memory | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Learning and memory phenotypes are downstream organismal consequences, not direct ABCA7 molecular functions. Reason: Retain the annotation as non-core because it is plausible or experimentally observed, but not the primary evolved molecular role of ABCA7. |
| GO:0009986 cell surface | ISS GO_REF:0000024 | ACCEPT | Summary: This location fits ABCA7 function as a multipass membrane lipid transporter active at plasma, Golgi/endosomal, ruffle, and phagocytic-cup membranes. Reason: The term aligns with direct biochemical evidence or well-supported cellular consequences of ABCA7 lipid transport and membrane-trafficking activity. |
| GO:0010875 positive regulation of cholesterol efflux | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: ABCA7 can support apoA-I-associated cholesterol/HDL-like outputs in overexpression systems, but phospholipid/lysoPC transport is the better-supported core activity. Reason: Retain the annotation as non-core because it is plausible or experimentally observed, but not the primary evolved molecular role of ABCA7. |
| GO:0034504 protein localization to nucleus | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: Protein localization to nucleus is not a clear ABCA7 core function and appears to be a downstream or indirect inference. Reason: For a multipass membrane lipid transporter, nuclear protein-localization terms are not supported as a direct molecular function from the available evidence. |
| GO:0042985 negative regulation of amyloid precursor protein biosynthetic process | ISS GO_REF:0000024 | MODIFY | Summary: ABCA7 affects APP processing and amyloid-beta output, but the available evidence is about APP catabolic/endocytic processing rather than APP biosynthesis. Reason: Represent the biology with APP catabolic-process and amyloid-beta formation regulation terms instead of APP biosynthesis. |
| GO:0050766 positive regulation of phagocytosis | ISS GO_REF:0000024 | ACCEPT | Summary: This process is consistent with ABCA7-dependent membrane trafficking and phagocytic cup biology in macrophage/microglial contexts. Reason: The term aligns with direct biochemical evidence or well-supported cellular consequences of ABCA7 lipid transport and membrane-trafficking activity. |
| GO:0070374 positive regulation of ERK1 and ERK2 cascade | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: This annotation may reflect a valid cell-state, localization, or signaling consequence, but it is peripheral to ABCA7 core lipid transporter/phagocytic function. Reason: Retain the annotation as non-core because it is plausible or experimentally observed, but not the primary evolved molecular role of ABCA7. |
| GO:1901076 positive regulation of engulfment of apoptotic cell | ISS GO_REF:0000024 | ACCEPT | Summary: This process is consistent with ABCA7-dependent membrane trafficking and phagocytic cup biology in macrophage/microglial contexts. Reason: The term aligns with direct biochemical evidence or well-supported cellular consequences of ABCA7 lipid transport and membrane-trafficking activity. |
| GO:1902995 positive regulation of phospholipid efflux | ISS GO_REF:0000024 | ACCEPT | Summary: This annotation is part of the core lipid transport, phospholipid efflux, or membrane-trafficking function of ABCA7. Reason: The term aligns with direct biochemical evidence or well-supported cellular consequences of ABCA7 lipid transport and membrane-trafficking activity. |
| GO:0005886 plasma membrane | IDA PMID:14570867 Human ABCA7 supports apolipoprotein-mediated release of cell... | ACCEPT | Summary: This location fits ABCA7 function as a multipass membrane lipid transporter active at plasma, Golgi/endosomal, ruffle, and phagocytic-cup membranes. Reason: The term aligns with direct biochemical evidence or well-supported cellular consequences of ABCA7 lipid transport and membrane-trafficking activity. |
| GO:0033344 cholesterol efflux | IDA PMID:14570867 Human ABCA7 supports apolipoprotein-mediated release of cell... | KEEP AS NON CORE | Summary: ABCA7 can support apoA-I-associated cholesterol/HDL-like outputs in overexpression systems, but phospholipid/lysoPC transport is the better-supported core activity. Reason: Retain the annotation as non-core because it is plausible or experimentally observed, but not the primary evolved molecular role of ABCA7. |
| GO:0033700 phospholipid efflux | IDA PMID:14570867 Human ABCA7 supports apolipoprotein-mediated release of cell... | ACCEPT | Summary: This annotation is part of the core lipid transport, phospholipid efflux, or membrane-trafficking function of ABCA7. Reason: The term aligns with direct biochemical evidence or well-supported cellular consequences of ABCA7 lipid transport and membrane-trafficking activity. |
| GO:0034188 apolipoprotein A-I receptor activity | IDA PMID:14570867 Human ABCA7 supports apolipoprotein-mediated release of cell... | ACCEPT | Summary: This molecular-function annotation captures the core ABCA7 activity: ATP-coupled intramembrane phospholipid transport/floppase activity and apoA-I-associated phospholipid efflux. Reason: The term aligns with direct biochemical evidence or well-supported cellular consequences of ABCA7 lipid transport and membrane-trafficking activity. |
| GO:0034380 high-density lipoprotein particle assembly | IDA PMID:14570867 Human ABCA7 supports apolipoprotein-mediated release of cell... | KEEP AS NON CORE | Summary: ABCA7 can support apoA-I-associated cholesterol/HDL-like outputs in overexpression systems, but phospholipid/lysoPC transport is the better-supported core activity. Reason: Retain the annotation as non-core because it is plausible or experimentally observed, but not the primary evolved molecular role of ABCA7. |
| GO:0038027 apolipoprotein A-I-mediated signaling pathway | IDA PMID:14570867 Human ABCA7 supports apolipoprotein-mediated release of cell... | MODIFY | Summary: The supporting experiment describes apoA-I binding and lipid efflux/HDL-like particle generation, not a signaling pathway as the primary function. Reason: Replace with apoA-I receptor activity and phospholipid efflux/HDL assembly terms that match the experimental readout. Proposed replacements: apolipoprotein A-I receptor activity phospholipid efflux high-density lipoprotein particle assembly |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-382553 | ACCEPT | Summary: This location fits ABCA7 function as a multipass membrane lipid transporter active at plasma, Golgi/endosomal, ruffle, and phagocytic-cup membranes. Reason: The term aligns with direct biochemical evidence or well-supported cellular consequences of ABCA7 lipid transport and membrane-trafficking activity. |
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Download this section (compressed HTML)Q: Which ABCA7 Alzheimer-risk variants impair phospholipid transport directly, and which primarily disrupt localization, apoA-I interaction, phagocytic-cup recruitment, or APP endocytic regulation?
Suggested experts: ABC transporter experts, Alzheimer genetics experts
Q: Should cholesterol efflux and HDL assembly remain curated for ABCA7 as context-specific outputs, or should they be deemphasized in favor of phospholipid/lysophospholipid efflux?
Suggested experts: lipid transport curators, GO lipid biology curators
Q: How should GO distinguish ABCA7-dependent amyloid-beta clearance from ABCA7-dependent regulation of APP endocytosis and amyloid-beta production?
Suggested experts: microglia biology experts, APP processing experts
Q: Is ABCA7's effect on mitochondria-related phospholipids (phosphatidylglycerol and cardiolipin) a direct consequence of its lipid-transport activity or an indirect downstream effect, and does it warrant a distinct process annotation? ABCA7 knockout iPSC-derived neurons/organoids show reduced phosphatidylglycerol and cardiolipin, mitochondrial dysfunction, and impaired respiration, rescued by phosphatidylglycerol or NMN [PMID:38135757].
Suggested experts: mitochondrial lipid biology experts, Alzheimer genetics experts
Experiment: Measure phosphatidylserine, phosphatidylcholine, lysoPC, cholesterol, and apoA-I-dependent efflux in endogenous ABCA7 wild-type, knockout, and Alzheimer-risk variant human microglia and macrophages.
Hypothesis: ABCA7 risk variants primarily impair phospholipid/lysophospholipid transport rather than canonical cholesterol efflux.
Type: endogenous variant lipid efflux and floppase assay
Experiment: Track ABCA7, LRP1, APP, and amyloid-beta cargo localization during apoptotic-cell engulfment and amyloid uptake using live imaging and compartment-resolved proteomics.
Hypothesis: ABCA7 regulates amyloid outcomes through phagocytic/endocytic membrane organization and APP endocytosis rather than by directly binding amyloid-beta as a receptor.
Type: live-cell phagocytosis and APP trafficking assay
Experiment: Compare canonical isoform 1 and ER-localized isoform 2 for apoA-I-dependent efflux, ATPase-coupled phospholipid transport, and phagocytic-cup recruitment.
Hypothesis: Isoform-specific localization explains differences between cell-surface lipid efflux activity and ER-retained inactive or lower-activity ABCA7 pools.
Type: isoform-resolved localization and lipid transport assay
Experiment: Perform compartment-resolved lipidomics (mitochondrial vs plasma-membrane fractions) in ABCA7-knockout and isogenic-control human neurons to determine whether the loss of mitochondrial phosphatidylglycerol/cardiolipin reflects altered transport of a specific lipid species versus a secondary metabolic adaptation, and test rescue by targeted phosphatidylglycerol supplementation.
Hypothesis: ABCA7 loss reduces mitochondrial phosphatidylglycerol and cardiolipin and thereby impairs oxidative phosphorylation, contributing to neuronal dysfunction in Alzheimer risk.
Type: subcellular lipidomics and mitochondrial respirometry
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