{"gene":"SLC35A5","run_date":"2026-06-10T07:46:33","timeline":{"discoveries":[{"year":2019,"finding":"SLC35A5 localizes exclusively to the Golgi apparatus, with its C-terminus directed toward the cytosol, as determined by subcellular fractionation/immunofluorescence and topology experiments.","method":"Immunofluorescence localization and experimental topology assay in HepG2 cells","journal":"International journal of molecular sciences","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct localization experiment with topology validation, single lab, two orthogonal methods","pmids":["30641943"],"is_preprint":false},{"year":2019,"finding":"Inactivation of SLC35A5 in HepG2 cells decreased Golgi uptake of UDP-glucuronic acid, UDP-N-acetylglucosamine, and UDP-N-acetylgalactosamine, but did not affect UDP-galactose transport, indicating SLC35A5 contributes to selective nucleotide sugar transport into the Golgi.","method":"CRISPR-Cas9 gene knockout in HepG2 cells followed by nucleotide sugar Golgi uptake assays","journal":"International journal of molecular sciences","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — clean KO with defined biochemical phenotype, single lab, multiple substrates tested","pmids":["30641943"],"is_preprint":false},{"year":2019,"finding":"SLC35A5 forms homomers as well as heteromers with other members of the SLC35A subfamily, suggesting it functions as part of a multiprotein complex.","method":"In vivo protein interaction analysis (FLIM-FRET and/or co-immunoprecipitation) in HepG2 cells","journal":"International journal of molecular sciences","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — interaction shown by FLIM-FRET, single lab, replicated across multiple SLC35A partners","pmids":["30641943"],"is_preprint":false},{"year":2019,"finding":"SLC35A5 knockout caused a slight increase in the level of chondroitin sulfate proteoglycans, implicating SLC35A5 in proteoglycan biosynthesis.","method":"CRISPR-Cas9 knockout in HepG2 cells followed by glycan analysis","journal":"International journal of molecular sciences","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single lab, single method, only a slight change observed","pmids":["30641943"],"is_preprint":false},{"year":2017,"finding":"SLC35A4 (a close SLC35A subfamily member) associates with SLC35A5 but not with SLC35A2 or SLC35A3, as demonstrated by FLIM-FRET in vivo interaction analysis.","method":"FLIM-FRET in vivo interaction analysis","journal":"Biochimica et biophysica acta. Molecular cell research","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single lab, single method; SLC35A5 is a secondary finding in a paper primarily about SLC35A4","pmids":["28167211"],"is_preprint":false},{"year":2012,"finding":"RNA interference knockdown of SLC35A5 in lymphoblastoid cell lines increased cellular susceptibility to paclitaxel-induced cytotoxicity, indicating SLC35A5 mediates cellular resistance to paclitaxel.","method":"RNA interference knockdown in HapMap lymphoblastoid cell lines with paclitaxel cytotoxicity assay","journal":"Pharmacogenetics and genomics","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single method (RNAi + cytotoxicity), no direct molecular mechanism established, single study","pmids":["22437668"],"is_preprint":false}],"current_model":"SLC35A5 is a Golgi-resident multiprotein complex member (with a cytosol-facing C-terminus bearing acidic DXEE/DXD/DXXD motifs) that forms homomers and heteromers with other SLC35A proteins and selectively facilitates Golgi uptake of UDP-glucuronic acid, UDP-N-acetylglucosamine, and UDP-N-acetylgalactosamine, thereby contributing to chondroitin sulfate proteoglycan biosynthesis and modulating cellular resistance to paclitaxel."},"narrative":{"mechanistic_narrative":"SLC35A5 is a Golgi-resident nucleotide sugar transporter that contributes to the selective import of UDP-sugars required for glycoconjugate biosynthesis [PMID:30641943]. It localizes exclusively to the Golgi apparatus with its C-terminus facing the cytosol [PMID:30641943], and its inactivation in HepG2 cells reduces Golgi uptake of UDP-glucuronic acid, UDP-N-acetylglucosamine, and UDP-N-acetylgalactosamine while leaving UDP-galactose transport intact, defining a substrate-selective transport role [PMID:30641943]. SLC35A5 functions within a multiprotein assembly, forming homomers and heteromers with other SLC35A subfamily members [PMID:30641943]. Beyond these features, the downstream consequences of SLC35A5 transport activity—including its links to chondroitin sulfate proteoglycan biosynthesis and to cellular paclitaxel resistance—have only been characterized at low confidence in the available corpus.","teleology":[{"year":2012,"claim":"Before any biochemical role was known, a functional genomics screen first connected SLC35A5 to a cellular phenotype, implicating it in drug response.","evidence":"RNAi knockdown in HapMap lymphoblastoid cell lines with paclitaxel cytotoxicity assay","pmids":["22437668"],"confidence":"Low","gaps":["Single method (RNAi + cytotoxicity) with no molecular mechanism linking SLC35A5 to paclitaxel handling","No connection drawn at this stage to transport activity or Golgi function","Not independently confirmed"]},{"year":2017,"claim":"Interaction mapping began to place SLC35A5 within the SLC35A subfamily by showing it associates selectively with SLC35A4 but not other members.","evidence":"FLIM-FRET in vivo interaction analysis (SLC35A5 a secondary finding in an SLC35A4-focused study)","pmids":["28167211"],"confidence":"Low","gaps":["Single lab, single method; SLC35A5 was a secondary observation","Functional consequence of the SLC35A4–SLC35A5 interaction not established","No reciprocal or biochemical validation of the complex"]},{"year":2019,"claim":"A focused study established SLC35A5's core identity—its Golgi localization, membrane topology, substrate-selective transport activity, and oligomeric state—answering what the protein physically is and does.","evidence":"Immunofluorescence and topology assays, CRISPR-Cas9 knockout with nucleotide sugar uptake assays, and FLIM-FRET/co-IP interaction analysis in HepG2 cells","pmids":["30641943"],"confidence":"Medium","gaps":["Direct transport by purified SLC35A5 not reconstituted; uptake measured in a knockout cell context","Stoichiometry and composition of the SLC35A multiprotein complex undefined","Whether SLC35A5 is the direct transporter or a regulatory complex subunit not resolved"]},{"year":2019,"claim":"Knockout linked SLC35A5 transport activity to a downstream glycan output, connecting it to proteoglycan biosynthesis.","evidence":"CRISPR-Cas9 knockout in HepG2 cells followed by glycan analysis","pmids":["30641943"],"confidence":"Low","gaps":["Only a slight change in chondroitin sulfate proteoglycan levels observed","Single lab, single method","Causal chain from substrate transport to proteoglycan change not directly demonstrated"]},{"year":null,"claim":"The mechanism linking SLC35A5's nucleotide sugar transport to drug resistance and to its specific complex partners remains open.","evidence":"","pmids":[],"confidence":"Low","gaps":["No molecular mechanism connects SLC35A5 transport to paclitaxel resistance","The functional role of SLC35A5 heteromers with specific SLC35A members is undefined","No structural model or reconstituted transport assay exists"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0005215","term_label":"transporter activity","supporting_discovery_ids":[1]}],"localization":[{"term_id":"GO:0005794","term_label":"Golgi apparatus","supporting_discovery_ids":[0]}],"pathway":[],"complexes":[],"partners":["SLC35A4"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q9BS91","full_name":"UDP-sugar transporter protein SLC35A5","aliases":["Solute carrier family 35 member A5"],"length_aa":424,"mass_kda":48.5,"function":"Probable UDP-sugar:UMP transmembrane antiporter involved in UDP-alpha-D-glucuronate/UDP-GlcA, UDP-GlcNAc/UDP-N-acetyl-alpha-D-glucosamine and UDP-N-acetyl-alpha-D-galactosamine/UDP-GalNAc transport from the cytosol to the lumen of the Golgi","subcellular_location":"Golgi apparatus membrane","url":"https://www.uniprot.org/uniprotkb/Q9BS91/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/SLC35A5","classification":"Not Classified","n_dependent_lines":2,"n_total_lines":1208,"dependency_fraction":0.0016556291390728477},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[{"gene":"CANX","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/search/SLC35A5","total_profiled":1310},"omim":[{"mim_id":"620298","title":"SOLUTE CARRIER FAMILY 35, MEMBER A5; SLC35A5","url":"https://www.omim.org/entry/620298"},{"mim_id":"620297","title":"SOLUTE CARRIER FAMILY 35, MEMBER A4; SLC35A4","url":"https://www.omim.org/entry/620297"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Approved","locations":[{"location":"Golgi apparatus","reliability":"Approved"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/SLC35A5"},"hgnc":{"alias_symbol":["FLJ20730"],"prev_symbol":[]},"alphafold":{"accession":"Q9BS91","domains":[{"cath_id":"-","chopping":"12-78_88-205_228-403","consensus_level":"high","plddt":82.3049,"start":12,"end":403}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9BS91","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q9BS91-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q9BS91-F1-predicted_aligned_error_v6.png","plddt_mean":76.81},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=SLC35A5","jax_strain_url":"https://www.jax.org/strain/search?query=SLC35A5"},"sequence":{"accession":"Q9BS91","fasta_url":"https://rest.uniprot.org/uniprotkb/Q9BS91.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q9BS91/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9BS91"}},"corpus_meta":[{"pmid":"22437668","id":"PMC_22437668","title":"Whole-genome studies identify solute carrier transporters in cellular susceptibility to paclitaxel.","date":"2012","source":"Pharmacogenetics and genomics","url":"https://pubmed.ncbi.nlm.nih.gov/22437668","citation_count":31,"is_preprint":false},{"pmid":"28167211","id":"PMC_28167211","title":"An insight into the orphan nucleotide sugar transporter SLC35A4.","date":"2017","source":"Biochimica et biophysica acta. Molecular cell research","url":"https://pubmed.ncbi.nlm.nih.gov/28167211","citation_count":21,"is_preprint":false},{"pmid":"30641943","id":"PMC_30641943","title":"SLC35A5 Protein-A Golgi Complex Member with Putative Nucleotide Sugar Transport Activity.","date":"2019","source":"International journal of molecular sciences","url":"https://pubmed.ncbi.nlm.nih.gov/30641943","citation_count":19,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":3854,"output_tokens":1283,"usd":0.015404,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":7915,"output_tokens":1718,"usd":0.041263,"stage2_stop_reason":"end_turn"},"total_usd":0.056667,"stage1_batch_id":"msgbatch_013LWZZT6MWaqB9qyTSeQBmU","stage2_batch_id":"msgbatch_0194ZzQaTGNpruoNJBbEMbt3","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2019,\n      \"finding\": \"SLC35A5 localizes exclusively to the Golgi apparatus, with its C-terminus directed toward the cytosol, as determined by subcellular fractionation/immunofluorescence and topology experiments.\",\n      \"method\": \"Immunofluorescence localization and experimental topology assay in HepG2 cells\",\n      \"journal\": \"International journal of molecular sciences\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct localization experiment with topology validation, single lab, two orthogonal methods\",\n      \"pmids\": [\"30641943\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"Inactivation of SLC35A5 in HepG2 cells decreased Golgi uptake of UDP-glucuronic acid, UDP-N-acetylglucosamine, and UDP-N-acetylgalactosamine, but did not affect UDP-galactose transport, indicating SLC35A5 contributes to selective nucleotide sugar transport into the Golgi.\",\n      \"method\": \"CRISPR-Cas9 gene knockout in HepG2 cells followed by nucleotide sugar Golgi uptake assays\",\n      \"journal\": \"International journal of molecular sciences\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — clean KO with defined biochemical phenotype, single lab, multiple substrates tested\",\n      \"pmids\": [\"30641943\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"SLC35A5 forms homomers as well as heteromers with other members of the SLC35A subfamily, suggesting it functions as part of a multiprotein complex.\",\n      \"method\": \"In vivo protein interaction analysis (FLIM-FRET and/or co-immunoprecipitation) in HepG2 cells\",\n      \"journal\": \"International journal of molecular sciences\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — interaction shown by FLIM-FRET, single lab, replicated across multiple SLC35A partners\",\n      \"pmids\": [\"30641943\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"SLC35A5 knockout caused a slight increase in the level of chondroitin sulfate proteoglycans, implicating SLC35A5 in proteoglycan biosynthesis.\",\n      \"method\": \"CRISPR-Cas9 knockout in HepG2 cells followed by glycan analysis\",\n      \"journal\": \"International journal of molecular sciences\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single lab, single method, only a slight change observed\",\n      \"pmids\": [\"30641943\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"SLC35A4 (a close SLC35A subfamily member) associates with SLC35A5 but not with SLC35A2 or SLC35A3, as demonstrated by FLIM-FRET in vivo interaction analysis.\",\n      \"method\": \"FLIM-FRET in vivo interaction analysis\",\n      \"journal\": \"Biochimica et biophysica acta. Molecular cell research\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single lab, single method; SLC35A5 is a secondary finding in a paper primarily about SLC35A4\",\n      \"pmids\": [\"28167211\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"RNA interference knockdown of SLC35A5 in lymphoblastoid cell lines increased cellular susceptibility to paclitaxel-induced cytotoxicity, indicating SLC35A5 mediates cellular resistance to paclitaxel.\",\n      \"method\": \"RNA interference knockdown in HapMap lymphoblastoid cell lines with paclitaxel cytotoxicity assay\",\n      \"journal\": \"Pharmacogenetics and genomics\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single method (RNAi + cytotoxicity), no direct molecular mechanism established, single study\",\n      \"pmids\": [\"22437668\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"SLC35A5 is a Golgi-resident multiprotein complex member (with a cytosol-facing C-terminus bearing acidic DXEE/DXD/DXXD motifs) that forms homomers and heteromers with other SLC35A proteins and selectively facilitates Golgi uptake of UDP-glucuronic acid, UDP-N-acetylglucosamine, and UDP-N-acetylgalactosamine, thereby contributing to chondroitin sulfate proteoglycan biosynthesis and modulating cellular resistance to paclitaxel.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"SLC35A5 is a Golgi-resident nucleotide sugar transporter that contributes to the selective import of UDP-sugars required for glycoconjugate biosynthesis [#0, #1]. It localizes exclusively to the Golgi apparatus with its C-terminus facing the cytosol [#0], and its inactivation in HepG2 cells reduces Golgi uptake of UDP-glucuronic acid, UDP-N-acetylglucosamine, and UDP-N-acetylgalactosamine while leaving UDP-galactose transport intact, defining a substrate-selective transport role [#1]. SLC35A5 functions within a multiprotein assembly, forming homomers and heteromers with other SLC35A subfamily members [#2]. Beyond these features, the downstream consequences of SLC35A5 transport activity—including its links to chondroitin sulfate proteoglycan biosynthesis and to cellular paclitaxel resistance—have only been characterized at low confidence in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2012,\n      \"claim\": \"Before any biochemical role was known, a functional genomics screen first connected SLC35A5 to a cellular phenotype, implicating it in drug response.\",\n      \"evidence\": \"RNAi knockdown in HapMap lymphoblastoid cell lines with paclitaxel cytotoxicity assay\",\n      \"pmids\": [\"22437668\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Single method (RNAi + cytotoxicity) with no molecular mechanism linking SLC35A5 to paclitaxel handling\",\n        \"No connection drawn at this stage to transport activity or Golgi function\",\n        \"Not independently confirmed\"\n      ]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"Interaction mapping began to place SLC35A5 within the SLC35A subfamily by showing it associates selectively with SLC35A4 but not other members.\",\n      \"evidence\": \"FLIM-FRET in vivo interaction analysis (SLC35A5 a secondary finding in an SLC35A4-focused study)\",\n      \"pmids\": [\"28167211\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Single lab, single method; SLC35A5 was a secondary observation\",\n        \"Functional consequence of the SLC35A4–SLC35A5 interaction not established\",\n        \"No reciprocal or biochemical validation of the complex\"\n      ]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"A focused study established SLC35A5's core identity—its Golgi localization, membrane topology, substrate-selective transport activity, and oligomeric state—answering what the protein physically is and does.\",\n      \"evidence\": \"Immunofluorescence and topology assays, CRISPR-Cas9 knockout with nucleotide sugar uptake assays, and FLIM-FRET/co-IP interaction analysis in HepG2 cells\",\n      \"pmids\": [\"30641943\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Direct transport by purified SLC35A5 not reconstituted; uptake measured in a knockout cell context\",\n        \"Stoichiometry and composition of the SLC35A multiprotein complex undefined\",\n        \"Whether SLC35A5 is the direct transporter or a regulatory complex subunit not resolved\"\n      ]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Knockout linked SLC35A5 transport activity to a downstream glycan output, connecting it to proteoglycan biosynthesis.\",\n      \"evidence\": \"CRISPR-Cas9 knockout in HepG2 cells followed by glycan analysis\",\n      \"pmids\": [\"30641943\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Only a slight change in chondroitin sulfate proteoglycan levels observed\",\n        \"Single lab, single method\",\n        \"Causal chain from substrate transport to proteoglycan change not directly demonstrated\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The mechanism linking SLC35A5's nucleotide sugar transport to drug resistance and to its specific complex partners remains open.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No molecular mechanism connects SLC35A5 transport to paclitaxel resistance\",\n        \"The functional role of SLC35A5 heteromers with specific SLC35A members is undefined\",\n        \"No structural model or reconstituted transport assay exists\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0005215\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005794\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"pathway\": [],\n    \"complexes\": [],\n    \"partners\": [\"SLC35A4\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":3,"faith_total":3,"faith_pct":100.0}}