GPC4

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0016477 cell migration	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: IBA annotation based on phylogenetic inference from other glypican family members. Glypicans can modulate cell migration through their interactions with growth factors and morphogens that regulate cell motility. However, direct experimental evidence for GPC4-specific roles in cell migration is limited compared to its well-established roles in synaptogenesis and Wnt signaling. Reason: While glypicans broadly influence cell migration through growth factor modulation, this is not a defining core function of GPC4. The phylogenetic inference is reasonable but GPC4's primary characterized functions are in synapse formation and Wnt signaling co-receptor activity. Supporting Evidence: GO_REF:0000033
GO:0031012 extracellular matrix	IBA GO_REF:0000033	ACCEPT	Summary: IBA annotation indicating GPC4 localization to extracellular matrix. As a GPI-anchored proteoglycan bearing heparan sulfate chains, GPC4 can interact with ECM components. However, GPC4 is primarily described as a cell surface protein with a GPI anchor. Reason: Glypicans are known to interact with the extracellular matrix through their heparan sulfate chains. While GPC4 is primarily GPI-anchored at the cell surface, it can also be shed and found in extracellular spaces including the synaptic cleft. Supporting Evidence: GO_REF:0000033
GO:0098696 regulation of neurotransmitter receptor localization to postsynaptic specialization membrane	IBA GO_REF:0000033	ACCEPT	Summary: IBA annotation reflecting GPC4's established role in regulating AMPA receptor localization at synapses. This is a well-characterized function of GPC4 in the CNS where astrocyte-derived GPC4 promotes GluA1/AMPA receptor clustering at postsynaptic sites. Reason: This annotation accurately captures a core function of GPC4. The deep research literature confirms that GPC4 promotes excitatory synapse maturation by increasing surface clustering of GluA1-containing AMPA receptors via a LRRTM-GPC4-PTPsigma pathway and by inducing neuronal pentraxin-1 (NPTX1) release. Supporting Evidence: GO_REF:0000033 file:human/GPC4/GPC4-deep-research-falcon.md It promotes excitatory synapse maturation by increasing surface clustering of GluA1-containing AMPA receptors via a LRRTM-GPC4-PTPsigma pathway and by inducing neuronal pentraxin-1 (NPTX1) release from axons.
GO:0009986 cell surface	IBA GO_REF:0000033	ACCEPT	Summary: IBA annotation for cell surface localization. GPC4 is GPI-anchored to the outer leaflet of the plasma membrane, making the cell surface its primary functional location. Reason: This is a core localization for GPC4. UniProt confirms cell membrane localization via GPI anchor at position Ser-529. The protein is tethered to the external side of the plasma membrane where it acts as a co-receptor for signaling molecules. Supporting Evidence: GO_REF:0000033 PMID:10585884 Expression of glypican-4 in haematopoietic-progenitor and bone-marrow-stromal cells.
GO:0045202 synapse	IBA GO_REF:0000033	ACCEPT	Summary: IBA annotation for synapse localization. GPC4 is released by astrocytes into the synaptic cleft where it functions in synaptogenesis and AMPA receptor recruitment. Reason: This annotation accurately reflects GPC4's role as an astrocyte-derived synaptogenic factor that functions at synapses to promote excitatory synapse formation and maturation. This is a core function supported by extensive literature. Supporting Evidence: GO_REF:0000033
GO:0099560 synaptic membrane adhesion	IBA GO_REF:0000033	ACCEPT	Summary: IBA annotation reflecting GPC4's role in synaptic membrane adhesion. GPC4 interacts with LRRTMs and presynaptic PTPsigma to coordinate pre- and postsynaptic assembly, functioning as a trans-synaptic organizer. Reason: GPC4 functions as a synaptic organizer that bridges pre- and postsynaptic membranes through interactions with synaptic adhesion molecules. The LRRTM-GPC4-PTPsigma complex mediates trans-synaptic signaling that coordinates synapse development. Supporting Evidence: GO_REF:0000033
GO:1905606 regulation of presynapse assembly	IBA GO_REF:0000033	ACCEPT	Summary: IBA annotation for regulation of presynapse assembly. GPC4's interactions with presynaptic PTPsigma contribute to presynaptic differentiation and organization. Reason: This annotation captures GPC4's role in coordinating presynaptic development through its trans-synaptic signaling function. The LRRTM-GPC4-PTPsigma pathway involves engagement of presynaptic receptor protein tyrosine phosphatase sigma to promote presynaptic differentiation. Supporting Evidence: GO_REF:0000033
GO:0005576 extracellular region	IEA GO_REF:0000044	ACCEPT	Summary: IEA annotation based on UniProtKB subcellular location mapping. GPC4 can be shed from the cell surface and secreted into extracellular spaces. Reason: UniProt confirms that secreted glypican-4 is released into the extracellular space. The protein contains a GPI-anchoring signal that can be cleaved to release soluble forms. Soluble GPC4 has been detected in serum and other biofluids. Supporting Evidence: GO_REF:0000044
GO:0005886 plasma membrane	IEA GO_REF:0000120	ACCEPT	Summary: IEA annotation based on InterPro glypican domain and UniProtKB subcellular location data. GPC4 is GPI-anchored to the plasma membrane. Reason: This is correct and well-supported. UniProt confirms GPC4 contains a GPI-anchor signal with the amidated serine at position 529, tethering it to the plasma membrane outer leaflet. Supporting Evidence: GO_REF:0000120
GO:0009966 regulation of signal transduction	IEA GO_REF:0000002	ACCEPT	Summary: IEA annotation from InterPro glypican domain mapping. Glypicans regulate signal transduction by acting as co-receptors for morphogens and growth factors. Reason: This accurately captures a core function of GPC4. The glypican family modulates signaling by binding ligands (Wnt, FGF, Hedgehog) through heparan sulfate chains and presenting them to receptors. GPC4 has experimentally demonstrated roles in Wnt signaling. Supporting Evidence: GO_REF:0000002 PMID:29276006 2017 Dec 21. WNT Signaling Perturbations Underlie the Genetic Heterogeneity of Robinow Syndrome.
GO:0031012 extracellular matrix	IEA GO_REF:0000002	ACCEPT	Summary: IEA annotation from InterPro glypican domain mapping. Duplicate of the IBA annotation for the same term. Reason: Consistent with the IBA annotation for the same term. Glypicans with heparan sulfate chains interact with ECM components. This IEA provides additional support. Supporting Evidence: GO_REF:0000002
GO:0043202 lysosomal lumen	IEA GO_REF:0000117	ACCEPT	Summary: IEA annotation from ARBA machine learning models suggesting lysosomal lumen localization. This likely reflects GPC4's presence in the degradation pathway for heparan sulfate proteoglycans. Reason: Heparan sulfate proteoglycans are degraded in lysosomes. Reactome pathways confirm that HSPGs including GPC4 are translocated to lysosomes for degradation, and heparanase cleaves heparan sulfate in the lysosomal lumen. Supporting Evidence: GO_REF:0000117
GO:0098552 side of membrane	IEA GO_REF:0000043	MODIFY	Summary: IEA annotation based on UniProtKB GPI-anchor keyword mapping. GPC4 is on the extracellular side of the membrane. Reason: The term 'side of membrane' is too general. GPC4 is specifically located on the external side of the plasma membrane via its GPI anchor. A more specific term should be used. Proposed replacements: external side of plasma membrane Supporting Evidence: GO_REF:0000043 PMID:10585884 Expression of glypican-4 in haematopoietic-progenitor and bone-marrow-stromal cells.
GO:0005515 protein binding	IPI PMID:28514442 Architecture of the human interactome defines protein commun...	MODIFY	Summary: IPI annotation from IntAct based on high-throughput interactome study. Interaction with GPC6 (Q9Y625) detected. Reason: The term 'protein binding' is too general and uninformative. GPC4 interacts with GPC6, another glypican family member. More specific molecular function terms describing GPC4's co-receptor or signaling adapter activities would be more informative. Proposed replacements: coreceptor activity Supporting Evidence: PMID:28514442 Architecture of the human interactome defines protein communities and disease networks.
GO:0005515 protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	MARK AS OVER ANNOTATED	Summary: IPI annotation from HuRI reference interactome study. Interaction with PICK1 (Q9NRD5) detected. Reason: While the protein-protein interaction is likely valid (from the HuRI reference interactome), the term 'protein binding' does not provide functional insight. PICK1 is a PDZ domain protein involved in AMPA receptor trafficking, which could be relevant to GPC4's synaptic function, but the annotation as currently stated is uninformative. Supporting Evidence: PMID:32296183 Apr 8. A reference map of the human binary protein interactome.
GO:0005515 protein binding	IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling...	MARK AS OVER ANNOTATED	Summary: IPI annotation from BioPlex 3.0 AP-MS study. Interaction with GPC6 (Q9Y625) detected. Reason: Duplicate evidence for GPC4-GPC6 interaction. Same concern as above - 'protein binding' is too general. The interaction between glypican family members may reflect their organization in membrane microdomains or functional cooperation. Supporting Evidence: PMID:33961781 2021 May 6. Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.
GO:0005515 protein binding	IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func...	MARK AS OVER ANNOTATED	Summary: IPI annotation from recent interactome study. Interaction with GPC6 (Q9Y625) detected. Reason: Third independent detection of GPC4-GPC6 interaction strengthens confidence in this interaction. However, 'protein binding' remains uninformative. Supporting Evidence: PMID:40205054 Apr 9. Multimodal cell maps as a foundation for structural and functional genomics.
GO:0045202 synapse	IEA GO_REF:0000107	ACCEPT	Summary: IEA annotation transferred from mouse ortholog based on Ensembl Compara analysis. Consistent with IBA annotation for same term. Reason: This annotation is consistent with the well-established role of GPC4 at synapses. The transfer from mouse ortholog is appropriate as mouse GPC4 function in synaptogenesis is well characterized. Supporting Evidence: GO_REF:0000107
GO:0098978 glutamatergic synapse	IEA GO_REF:0000107	ACCEPT	Summary: IEA annotation transferred from mouse ortholog indicating localization at glutamatergic synapses. GPC4 promotes excitatory (glutamatergic) synapse formation. Reason: This annotation is consistent with GPC4's role in promoting GluA1-containing AMPA receptor clustering at excitatory synapses. GPC4 specifically promotes excitatory synapse maturation. Supporting Evidence: GO_REF:0000107
GO:0099560 synaptic membrane adhesion	IEA GO_REF:0000107	ACCEPT	Summary: IEA annotation transferred from mouse ortholog. Consistent with IBA annotation for same term. Reason: Provides additional support for GPC4's role in synaptic membrane adhesion through ortholog transfer. Consistent with established LRRTM-GPC4-PTPsigma trans-synaptic complex. Supporting Evidence: GO_REF:0000107
GO:0005796 Golgi lumen	TAS Reactome:R-HSA-9940993	ACCEPT	Summary: TAS annotation from Reactome pathway indicating GPC4 presence in Golgi lumen during glycosaminoglycan biosynthesis. PXYLP1 dephosphorylates xylose moiety. Reason: GPC4 transits through the Golgi during biosynthesis where its heparan sulfate chains are assembled. This is part of the normal processing of all HSPGs. Supporting Evidence: Reactome:R-HSA-9940993
GO:0005796 Golgi lumen	TAS Reactome:R-HSA-9941039	ACCEPT	Summary: TAS annotation from Reactome pathway. FAM20B phosphorylates xylose moiety during GAG chain assembly. Reason: Part of the HS-GAG biosynthesis pathway in the Golgi. Multiple Reactome references support GPC4's transit through Golgi during biosynthesis. Supporting Evidence: Reactome:R-HSA-9941039
GO:0015026 coreceptor activity	NAS PMID:24431302 Wnt signaling in midbrain dopaminergic neuron development an...	ACCEPT	Summary: NAS annotation for coreceptor activity based on review discussing Wnt signaling in dopaminergic neuron development. Glypicans act as co-receptors for Wnt ligands. Reason: This is a core molecular function of GPC4. The glypican family functions as co-receptors for morphogens including Wnts, presenting them to Frizzled receptors through HS-dependent binding. This annotation accurately captures GPC4's primary molecular function. Supporting Evidence: PMID:24431302 Wnt signaling in midbrain dopaminergic neuron development and regenerative medicine for Parkinson's disease. PMID:29276006 2017 Dec 21. WNT Signaling Perturbations Underlie the Genetic Heterogeneity of Robinow Syndrome.
GO:0016055 Wnt signaling pathway	IMP PMID:29276006 WNT Signaling Perturbations Underlie the Genetic Heterogenei...	ACCEPT	Summary: IMP annotation based on finding pathogenic GPC4 variants in patients with Robinow syndrome, a disorder caused by Wnt/PCP pathway perturbation. Functional studies supported GPC4's role in Wnt signaling. Reason: This annotation is well-supported by experimental evidence. The study identified GPC4 as a candidate gene for Robinow syndrome and demonstrated its connection to the Wnt signaling pathway. GPC4's role in Wnt signaling is a core function of this co-receptor. Supporting Evidence: PMID:29276006 2017 Dec 21. WNT Signaling Perturbations Underlie the Genetic Heterogeneity of Robinow Syndrome.
GO:0005634 nucleus	HDA PMID:21630459 Proteomic characterization of the human sperm nucleus	MARK AS OVER ANNOTATED	Summary: HDA annotation from proteomic characterization of human sperm nucleus. GPC4 was identified among proteins in isolated sperm nuclei. Reason: This is likely a false positive from the high-throughput proteomics study. GPC4 is a GPI-anchored cell surface proteoglycan with no known nuclear function. The sperm nucleus preparation may have contained contaminating membrane fragments or this represents an artifact. Nuclear localization contradicts all known biology of glypicans. Supporting Evidence: PMID:21630459 Jun 1. Proteomic characterization of the human sperm nucleus.
GO:0070062 extracellular exosome	HDA PMID:19199708 Proteomic analysis of human parotid gland exosomes by multid...	ACCEPT	Summary: HDA annotation from proteomic analysis of parotid gland exosomes. GPC4 was identified among exosomal proteins by MudPIT mass spectrometry. Reason: This annotation is plausible. GPC4 can be shed from the cell surface and released in extracellular vesicles. The study identified GPC4 among 491 proteins in parotid exosomes. GPI-anchored proteins including glypicans are known to be incorporated into exosomes. Supporting Evidence: PMID:19199708 Proteomic analysis of human parotid gland exosomes by multidimensional protein identification technology (MudPIT).
GO:0005796 Golgi lumen	TAS Reactome:R-HSA-1878002	ACCEPT	Summary: TAS annotation from Reactome. XYLTs transfer xylose to core protein during GAG synthesis. Reason: Part of the tetrasaccharide linker synthesis pathway required for GAG chain assembly. GPC4 transits through Golgi during biosynthesis. Supporting Evidence: Reactome:R-HSA-1878002
GO:0005796 Golgi lumen	TAS Reactome:R-HSA-1889955	ACCEPT	Summary: TAS annotation from Reactome. B3GAT dimers transfer glucuronic acid during linker synthesis. Reason: Part of HS-GAG biosynthesis pathway. All TAS Golgi lumen annotations from Reactome reflect GPC4's transit through secretory pathway during biosynthesis and modification. Supporting Evidence: Reactome:R-HSA-1889955
GO:0005796 Golgi lumen	TAS Reactome:R-HSA-1889978	ACCEPT	Summary: TAS annotation from Reactome. B3GALT6 transfers galactose during linker synthesis. Reason: Part of HS-GAG biosynthesis. Golgi localization during processing is expected. Supporting Evidence: Reactome:R-HSA-1889978
GO:0005796 Golgi lumen	TAS Reactome:R-HSA-2022851	ACCEPT	Summary: TAS annotation from Reactome. EXT1:EXT2 complex transfers GlcNAc to heparan chain. Reason: Part of heparan sulfate chain elongation in Golgi. Supporting Evidence: Reactome:R-HSA-2022851
GO:0005796 Golgi lumen	TAS Reactome:R-HSA-2022856	ACCEPT	Summary: TAS annotation from Reactome. EXT1:EXT2 complex transfers glucuronic acid to heparan. Reason: Part of HS chain elongation pathway. Supporting Evidence: Reactome:R-HSA-2022856
GO:0005796 Golgi lumen	TAS Reactome:R-HSA-2022860	ACCEPT	Summary: TAS annotation from Reactome. NDSTs sulfate glucosamine residues forming heparan sulfate. Reason: Part of HS chain modification in Golgi. Critical for generating sulfated heparan sulfate. Supporting Evidence: Reactome:R-HSA-2022860
GO:0005796 Golgi lumen	TAS Reactome:R-HSA-2022887	ACCEPT	Summary: TAS annotation from Reactome. NDSTs N-deacetylate GlcNAc residues. Reason: Part of HS chain modification pathway. Supporting Evidence: Reactome:R-HSA-2022887
GO:0005796 Golgi lumen	TAS Reactome:R-HSA-2024108	ACCEPT	Summary: TAS annotation from Reactome. HSPGs are secreted to plasma membrane. Reason: Represents transport of mature GPC4 from Golgi to plasma membrane. Supporting Evidence: Reactome:R-HSA-2024108
GO:0005796 Golgi lumen	TAS Reactome:R-HSA-2076383	ACCEPT	Summary: TAS annotation from Reactome. HS3ST1 sulfates glucosamine at C3. Reason: Part of HS chain modification pathway in Golgi. Supporting Evidence: Reactome:R-HSA-2076383
GO:0005796 Golgi lumen	TAS Reactome:R-HSA-2076392	ACCEPT	Summary: TAS annotation from Reactome. EXT1:EXT2 transfers glucuronic acid. Reason: Duplicate pathway reference for HS chain elongation. Supporting Evidence: Reactome:R-HSA-2076392
GO:0005796 Golgi lumen	TAS Reactome:R-HSA-2076419	ACCEPT	Summary: TAS annotation from Reactome. HS6STs sulfate glucosamine at C6. Reason: Part of HS chain modification in Golgi. Supporting Evidence: Reactome:R-HSA-2076419
GO:0005796 Golgi lumen	TAS Reactome:R-HSA-2076508	ACCEPT	Summary: TAS annotation from Reactome. HS2ST1 sulfates iduronic acid at C2. Reason: Part of HS chain modification. Supporting Evidence: Reactome:R-HSA-2076508
GO:0005796 Golgi lumen	TAS Reactome:R-HSA-2076611	ACCEPT	Summary: TAS annotation from Reactome. HS3ST2-6 sulfate glucosamine at C3. Reason: Part of HS chain modification pathway. Supporting Evidence: Reactome:R-HSA-2076611
GO:0005796 Golgi lumen	TAS Reactome:R-HSA-3560802	ACCEPT	Summary: TAS annotation from Reactome disease pathway. Defective B3GAT3 affecting linker synthesis. Reason: GPC4 is substrate for GAG biosynthesis machinery, including in disease contexts. Supporting Evidence: Reactome:R-HSA-3560802
GO:0005796 Golgi lumen	TAS Reactome:R-HSA-3656254	ACCEPT	Summary: TAS annotation from Reactome disease pathway. Defective EXT2 in EXT1:EXT2 complex. Reason: GPC4 is affected in exostoses syndromes caused by EXT mutations. Supporting Evidence: Reactome:R-HSA-3656254
GO:0005796 Golgi lumen	TAS Reactome:R-HSA-3656257	ACCEPT	Summary: TAS annotation from Reactome disease pathway. Defective EXT1. Reason: Part of disease pathway affecting HSPG biosynthesis. Supporting Evidence: Reactome:R-HSA-3656257
GO:0005796 Golgi lumen	TAS Reactome:R-HSA-3656261	ACCEPT	Summary: TAS annotation from Reactome disease pathway. Reason: Part of disease pathway affecting HSPG biosynthesis. Supporting Evidence: Reactome:R-HSA-3656261
GO:0005796 Golgi lumen	TAS Reactome:R-HSA-3656267	ACCEPT	Summary: TAS annotation from Reactome disease pathway. Reason: Part of disease pathway affecting HSPG biosynthesis. Supporting Evidence: Reactome:R-HSA-3656267
GO:0005886 plasma membrane	TAS Reactome:R-HSA-1678694	ACCEPT	Summary: TAS annotation from Reactome. Heparanase 2 binds heparan sulfate proteoglycans at plasma membrane. Reason: GPC4 is targeted by heparanase 2 at the cell surface. Supporting Evidence: Reactome:R-HSA-1678694
GO:0005886 plasma membrane	TAS Reactome:R-HSA-2024084	ACCEPT	Summary: TAS annotation from Reactome. HS-GAGs translocate to lysosome for degradation. Reason: GPC4 at plasma membrane is internalized for degradation. Supporting Evidence: Reactome:R-HSA-2024084
GO:0005886 plasma membrane	TAS Reactome:R-HSA-2024108	ACCEPT	Summary: TAS annotation from Reactome. HSPGs secreted to plasma membrane. Reason: GPC4 is transported to and functions at the plasma membrane. Supporting Evidence: Reactome:R-HSA-2024108
GO:0005886 plasma membrane	TAS Reactome:R-HSA-2404131	ACCEPT	Summary: TAS annotation from Reactome. LRPs transport retinol-HSPG complexes. Reason: HSPGs including GPC4 participate in retinoid metabolism at cell surface. Supporting Evidence: Reactome:R-HSA-2404131
GO:0005886 plasma membrane	TAS Reactome:R-HSA-2423785	ACCEPT	Summary: TAS annotation from Reactome. Retinol-ester complexes bind apoE and HSPG. Reason: GPC4 as HSPG involved in retinoid transport pathway. Supporting Evidence: Reactome:R-HSA-2423785
GO:0005886 plasma membrane	TAS Reactome:R-HSA-2429643	ACCEPT	Summary: TAS annotation from Reactome. NREH hydrolyzes retinol esters from HSPG complexes. Reason: Part of retinoid metabolism pathway involving HSPGs. Supporting Evidence: Reactome:R-HSA-2429643
GO:0005886 plasma membrane	TAS Reactome:R-HSA-9694579	KEEP AS NON CORE	Summary: TAS annotation from Reactome. SARS-CoV-2 spike glycoprotein binds ACE2 on host cells. HSPGs can act as co-receptors for viral entry. Reason: While HSPGs including GPC4 may facilitate SARS-CoV-2 binding, this is not a core biological function but rather reflects pathogen exploitation of cell surface proteoglycans. Supporting Evidence: Reactome:R-HSA-9694579
GO:0005886 plasma membrane	TAS Reactome:R-HSA-9694661	KEEP AS NON CORE	Summary: TAS annotation from Reactome. TMPRSS2 mediated spike protein cleavage. Reason: Part of viral entry pathway. Not a core function of GPC4. Supporting Evidence: Reactome:R-HSA-9694661
GO:0005886 plasma membrane	TAS Reactome:R-HSA-9698988	KEEP AS NON CORE	Summary: TAS annotation from Reactome. SARS-CoV-2 membrane fusion. Reason: Viral entry pathway. Not a core GPC4 function. Supporting Evidence: Reactome:R-HSA-9698988
GO:0005886 plasma membrane	TAS Reactome:R-HSA-9699007	KEEP AS NON CORE	Summary: TAS annotation from Reactome. FURIN mediated spike cleavage. Reason: Viral entry pathway. Not a core GPC4 function. Supporting Evidence: Reactome:R-HSA-9699007
GO:0005886 plasma membrane	TAS Reactome:R-HSA-9836899	KEEP AS NON CORE	Summary: TAS annotation from Reactome. RSV sG binds to HSPGs. Reason: Viral attachment pathway. HSPGs serve as attachment factors for many pathogens but this is not a core biological function. Supporting Evidence: Reactome:R-HSA-9836899
GO:0043202 lysosomal lumen	TAS Reactome:R-HSA-1667005	ACCEPT	Summary: TAS annotation from Reactome. Heparanase cleaves heparan sulfate in lysosome. Reason: GPC4 is degraded in lysosomes where heparanase cleaves HS chains. Supporting Evidence: Reactome:R-HSA-1667005
GO:0043202 lysosomal lumen	TAS Reactome:R-HSA-2024084	ACCEPT	Summary: TAS annotation from Reactome. HS-GAGs translocate to lysosome. Reason: Part of HSPG degradation pathway. Supporting Evidence: Reactome:R-HSA-2024084
GO:0005796 Golgi lumen	TAS Reactome:R-HSA-1889981	ACCEPT	Summary: TAS annotation from Reactome. B4GALT7 transfers galactose to xylosyl unit. Reason: Part of GAG linker synthesis in Golgi. Supporting Evidence: Reactome:R-HSA-1889981
GO:0005796 Golgi lumen	TAS Reactome:R-HSA-3560804	ACCEPT	Summary: TAS annotation from Reactome disease pathway. Defective B4GALT7. Reason: Disease pathway affecting GAG synthesis on GPC4. Supporting Evidence: Reactome:R-HSA-3560804
GO:0005796 Golgi lumen	TAS Reactome:R-HSA-9036285	ACCEPT	Summary: TAS annotation from Reactome disease pathway. Reason: Disease pathway affecting GPC4 biosynthesis. Supporting Evidence: Reactome:R-HSA-9036285
GO:0005796 Golgi lumen	TAS Reactome:R-HSA-9036289	ACCEPT	Summary: TAS annotation from Reactome disease pathway. Reason: Disease pathway affecting GPC4 biosynthesis. Supporting Evidence: Reactome:R-HSA-9036289
GO:0005796 Golgi lumen	TAS Reactome:R-HSA-9953259	ACCEPT	Summary: TAS annotation from Reactome. EXTL3 transfers GlcNAc to GAG linker. Reason: Part of HS chain initiation in Golgi. Supporting Evidence: Reactome:R-HSA-9953259
GO:0005796 Golgi lumen	TAS Reactome:R-HSA-1667005	ACCEPT	Summary: TAS annotation from Reactome. Note this reference is for lysosomal heparanase activity, may be a pathway data entry issue. Reason: While the reference describes lysosomal processing, GPC4 transits through Golgi. Supporting Evidence: Reactome:R-HSA-1667005
GO:0005796 Golgi lumen	TAS Reactome:R-HSA-4420365	ACCEPT	Summary: TAS annotation from Reactome disease pathway. Defective B3GALT6. Reason: Disease pathway affecting GAG linker synthesis. Supporting Evidence: Reactome:R-HSA-4420365
GO:0009897 external side of plasma membrane	IDA PMID:10585884 Expression of glypican-4 in haematopoietic-progenitor and bo...	ACCEPT	Summary: IDA annotation based on direct experimental evidence. FACS analysis and confocal laser-scanning microscopy demonstrated GPC4 on the cell surface of haematopoietic progenitor cells and bone marrow stromal cells. Reason: Direct experimental evidence for external plasma membrane localization. The study showed GPC4 expression on the surface of TF-1 cells by FACS analysis and confirmed localization by confocal microscopy. This is consistent with GPC4's GPI-anchored structure placing it on the extracellular side of the membrane. Supporting Evidence: PMID:10585884 Expression of glypican-4 in haematopoietic-progenitor and bone-marrow-stromal cells.
GO:0030674 protein-macromolecule adaptor activity	NAS file:human/GPC4/GPC4-deep-research-falcon.md	NEW	Summary: GPC4 functions as a synaptic adaptor that bridges pre- and postsynaptic membranes through the LRRTM-GPC4-PTPsigma trans-synaptic complex. This adaptor function is critical for recruiting and clustering AMPA receptors at glutamatergic synapses. Reason: This annotation captures GPC4's well-characterized role as a trans-synaptic organizer that mediates protein complex assembly at synapses. The deep research literature confirms GPC4 bridges LRRTMs with presynaptic PTPsigma to coordinate synapse development and AMPA receptor recruitment. This molecular function term accurately describes GPC4's adaptor role in assembling synaptic protein complexes. Supporting Evidence: file:human/GPC4/GPC4-deep-research-falcon.md A defining role of GPC4 is as an astrocyte-derived synaptogenic factor. It promotes excitatory synapse maturation by increasing surface clustering of GluA1-containing AMPA receptors via a LRRTM-GPC4-PTPsigma pathway

Gene Description

Existing Annotations Review

Core Functions

References

Deep Research

Falcon

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