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: 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: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: 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: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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