Proteomic Investigation of Differential Interactomes of Glypican 1 and a Putative Disease-Modifying Variant of Ataxia.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:37585105", "kind": "science-record", "revision": 4, "content_hash": "sha256:73788cab41d9ad89bcc68991b63bcd805e04b9254552068a2e128d972b0e9aa6", "created_at": "2026-11-01T19:02:23Z", "updated_at": "2026-11-01T22:10:06Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Proteomic Investigation of Differential Interactomes of Glypican 1 and a Putative Disease-Modifying Variant of Ataxia.", "doi": "10.1021/acs.jproteome.3c00402", "pmid": "37585105", "authors": ["Nur Cengiz Winter", "Mert Karakaya", "Peter Mosen", "Isabell Brusius", "Banu Anlar", "Goknur Haliloglu", "Dominic Winter", "Brunhilde Wirth"], "journal": "Journal of proteome research", "year": 2023, "abstract": "In a currently 13-year-old girl of consanguineous Turkish parents, who developed unsteady gait and polyneuropathy at the ages of 3 and 6 years, respectively, we performed whole genome sequencing and identified a biallelic missense variant c.424C>T, p.R142W in glypican 1 (GPC1) as a putative disease-associated variant. Up to date, GPC1 has not been associated with a neuromuscular disorder, and we hypothesized that this variant, predicted as deleterious, may be causative for the disease. Using mass spectrometry-based proteomics, we investigated the interactome of GPC1 WT and the missense variant. We identified 198 proteins interacting with GPC1, of which 16 were altered for the missense variant. This included CANX as well as vacuolar ATPase (V-ATPase) and the mammalian target of rapamycin complex 1 (mTORC1) complex members, whose dysregulation could have a potential impact on disease severity in the patient. Importantly, these proteins are novel interaction partners of GPC1. At 10.5 years, the patient developed dilated cardiomyopathy and kyphoscoliosis, and Friedreich's ataxia (FRDA) was suspected. Given the unusually severe phenotype in a patient with FRDA carrying only 104 biallelic GAA repeat expansions in FXN, we currently speculate that disturbed GPC1 function may have exacerbated the disease phenotype. LC-MS/MS data are accessible in the ProteomeXchange Consortium (PXD040023).", "claims": [{"id": "claim-data-access", "statement": "The mass spectrometry proteomics data have been deposited in the ProteomeXchange Consortium (http://proteomecentral.proteomexchange.org) via PRIDE partner repository, with the dataset identifier PXD040023. The NGS genome data of the family are stored in the EGA database under access numbers EGAR00001408420 and EGAN00001366913. Uncropped images of the Western blots can be found under File S1.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37585105", "locator": "sections[22] \"Data Availability Statement\" paragraph 2", "quote": "The mass spectrometry proteomics data have been deposited in the ProteomeXchange Consortium (http://proteomecentral.proteomexchange.org) via PRIDE partner repository, with the dataset identifier PXD040023. The NGS genome data of the family are stored in the EGA database under access numbers EGAR00001408420 and EGAN00001366913. Uncropped images of the Western blots can be found under File S1."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The study identified 198 GPC1-interacting proteins, 16 of which showed altered interaction levels for the GPC1 R142W missense variant.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:37585105", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "We identified 198 proteins interacting with GPC1, of which 16 were altered for the missense variant."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The study identified 198 GPC1-interacting proteins, 16 of which showed altered interaction levels for the GPC1 R142W missense variant.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:37585105"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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Using mass spectrometry-based proteomics, we investigated the interactome of GPC1 WT", "ations (co-IPs) in combination with MS-based proteomic analyses. Proteomic Analysis of the GPC1 Int", "ombination with MS-based proteomic analyses. Proteomic Analysis of the GPC1 Interactome First, we f"], "order_basis": "paper_text_order:0", "id": "assay:1"}, {"role": "data_generation", "definition_id": "cell_culture", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.77, "evidence": ["the number 13-022. Cell Culture HEK293T and HeLa cells, as well as patient-derived primary fi"], "order_basis": "paper_text_order:2021", "id": "assay:2"}, {"role": "data_generation", "definition_id": "clinical_cohort", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["l Culture HEK293T and HeLa cells, as well as patient-derived primary fibroblasts, were maintained at 37 °", "e,f) Western blot analysis of GPC1 levels in patient-derived fibroblasts. A significant increase in inten", "vestigated GPC1 protein abundance in primary patient-derived skin fibroblasts, using Western blot analysi"], "order_basis": "paper_text_order:2043", "id": "assay:3"}, {"role": "data_generation", "definition_id": "transfection", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["y (Figure S1). GPC1 expression plasmids were transfected using Lipofectamine 2000 (Thermo Fisher), an", "red the signal intensities between GFP (mock transfected control group) and GPC1 analyses. After remo", "e label-free quantification for GPC1 and GFP-transfected HEK293T cells. GPC1 interacting proteins pas", "ation of HA-tagged GPC1 WT and GPC1 R142W in transfected HEK293T cells. (a) Investigation of ER local"], "order_basis": "paper_text_order:2370", "id": "assay:4"}, {"role": "data_generation", "definition_id": "western_blot", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["species shown by amino acid alignment. (e,f) Western blot analysis of GPC1 levels in patient-derived f", "mary patient-derived skin fibroblasts, using Western blot analysis. As controls, skin biopsy-derived f", "f the obtained primary fibroblast lines. The Western blot analysis revealed an increased band intensit", "ractionation experiments in combination with Western blot analysis, which revealed a significant enric"], "order_basis": "paper_text_order:6271", "id": "assay:5"}, {"role": "data_generation", "definition_id": "animal_model", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["y in cerebellar and NMJ development as shown in mice and D. melanogasterGpc1 knockout models,3,8", "n recognizing GPI-anchored cargoes in yeast, mouse, and human cell lines.30 Furthermore, we det"], "order_basis": "paper_text_order:7891", "id": "assay:6"}, {"role": "data_generation", "definition_id": "ihc", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.85, "evidence": ["nd GPC1 R142W in HEK293T cells. 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