{"gene":"SLC35E1","run_date":"2026-06-10T07:46:33","timeline":{"discoveries":[{"year":2022,"finding":"SLC35E1 (an orphan transporter) was identified as a cellular protein that physically interacts with the HSV-1 nuclear egress complex (NEC) components UL34 and UL31, as detected by tandem affinity purification coupled with mass spectrometry in HSV-1-infected cells.","method":"Tandem affinity purification coupled with mass spectrometry-based proteomics (interactome screen in HSV-1-infected cells)","journal":"Journal of virology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal affinity purification/MS interactome screen followed by functional CRISPR/Cas9 loss-of-function validation, single lab","pmids":["35475666"],"is_preprint":false},{"year":2022,"finding":"CRISPR/Cas9 knockout of SLC35E1 reduced HSV-1 replication, induced aberrant membranous invaginations containing perinuclear enveloped virions adjacent to the nuclear membrane, caused accumulation of perinuclear enveloped virions in the perinuclear space, and caused mislocalization of the nuclear egress complex — phenotypes consistent with a defect in HSV-1 de-envelopment, establishing SLC35E1 as a cellular protein required for efficient HSV-1 de-envelopment during nuclear egress.","method":"CRISPR/Cas9 knockout combined with fluorescence microscopy (emerin mislocalization as reporter), viral replication assay, and electron/fluorescence imaging of perinuclear virion accumulation","journal":"Journal of virology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — clean CRISPR KO with defined cellular phenotype (de-envelopment defect), multiple orthogonal readouts, single lab","pmids":["35475666"],"is_preprint":false}],"current_model":"SLC35E1 is an orphan transporter that physically associates with the HSV-1 nuclear egress complex (NEC; UL34/UL31) and is required for efficient de-envelopment of perinuclear enveloped virions during HSV-1 nuclear egress; its loss causes aberrant perinuclear virion accumulation, NEC mislocalization, and reduced viral replication."},"narrative":{"mechanistic_narrative":"SLC35E1 is an orphan transporter that participates in herpes simplex virus 1 (HSV-1) nuclear egress as a host factor required for efficient de-envelopment of perinuclear enveloped virions [PMID:35475666]. It physically associates with the HSV-1 nuclear egress complex (NEC), binding the viral proteins UL34 and UL31 [PMID:35475666]. Loss of SLC35E1 reduces HSV-1 replication and produces a de-envelopment defect characterized by aberrant membranous invaginations containing perinuclear enveloped virions, accumulation of virions in the perinuclear space, and mislocalization of the NEC [PMID:35475666]. Beyond its role at the nuclear envelope during HSV-1 egress, no endogenous transport substrate or cellular function for SLC35E1 has been characterized in the available corpus.","teleology":[{"year":2022,"claim":"Establishing that the orphan transporter SLC35E1 is a physical partner of the HSV-1 nuclear egress machinery linked this previously uncharacterized protein to a defined viral process.","evidence":"Tandem affinity purification coupled with mass spectrometry in HSV-1-infected cells, detecting interaction with NEC components UL34 and UL31","pmids":["35475666"],"confidence":"Medium","gaps":["Interaction mapped by affinity-MS without reciprocal validation or defined binding interface","Whether the association is direct or bridged by other factors is unresolved","No structural model of the SLC35E1–NEC contact"]},{"year":2022,"claim":"Determining the functional consequence of SLC35E1 loss showed it is required for efficient de-envelopment, not merely a passive interactor of the NEC.","evidence":"CRISPR/Cas9 knockout with viral replication assays, emerin-based fluorescence reporter of NEC localization, and imaging of perinuclear virion accumulation","pmids":["35475666"],"confidence":"Medium","gaps":["Mechanism by which SLC35E1 promotes de-envelopment is unknown","Whether transporter activity is required for the egress function was not tested","Single-lab finding without independent replication"]},{"year":null,"claim":"The endogenous transport substrate and the native (non-viral) cellular function of SLC35E1 remain undefined.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No transported molecule identified","No physiological role characterized outside HSV-1 infection","Subcellular localization in uninfected cells not established in the corpus"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0005215","term_label":"transporter activity","supporting_discovery_ids":[0,1]}],"localization":[{"term_id":"GO:0005635","term_label":"nuclear envelope","supporting_discovery_ids":[1]}],"pathway":[],"complexes":[],"partners":["UL34","UL31"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q96K37","full_name":"Solute carrier family 35 member E1","aliases":[],"length_aa":410,"mass_kda":44.8,"function":"Putative transporter","subcellular_location":"Membrane","url":"https://www.uniprot.org/uniprotkb/Q96K37/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/SLC35E1","classification":"Not Classified","n_dependent_lines":2,"n_total_lines":1208,"dependency_fraction":0.0016556291390728477},"opencell":{"profiled":true,"resolved_as":"","ensg_id":"ENSG00000127526","cell_line_id":"CID001341","localizations":[{"compartment":"golgi","grade":3}],"interactors":[{"gene":"TM9SF3","stoichiometry":10.0},{"gene":"TMEM165","stoichiometry":4.0},{"gene":"GOSR1","stoichiometry":4.0},{"gene":"GORASP2","stoichiometry":0.2},{"gene":"RAB1A","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/target/CID001341","total_profiled":1310},"omim":[{"mim_id":"620337","title":"SOLUTE CARRIER FAMILY 35, MEMBER E1; SLC35E1","url":"https://www.omim.org/entry/620337"},{"mim_id":"608568","title":"MYOSIN, HEAVY CHAIN 14, NONMUSCLE; MYH14","url":"https://www.omim.org/entry/608568"},{"mim_id":"600652","title":"DEAFNESS, AUTOSOMAL DOMINANT 4A; DFNA4A","url":"https://www.omim.org/entry/600652"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Enhanced","locations":[{"location":"Golgi apparatus","reliability":"Enhanced"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/SLC35E1"},"hgnc":{"alias_symbol":["FLJ14251"],"prev_symbol":[]},"alphafold":{"accession":"Q96K37","domains":[{"cath_id":"-","chopping":"29-82_106-250_257-345","consensus_level":"high","plddt":86.8162,"start":29,"end":345}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q96K37","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q96K37-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q96K37-F1-predicted_aligned_error_v6.png","plddt_mean":74.94},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=SLC35E1","jax_strain_url":"https://www.jax.org/strain/search?query=SLC35E1"},"sequence":{"accession":"Q96K37","fasta_url":"https://rest.uniprot.org/uniprotkb/Q96K37.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q96K37/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q96K37"}},"corpus_meta":[{"pmid":"18166477","id":"PMC_18166477","title":"Microarray-based prediction of tumor response to neoadjuvant radiochemotherapy of patients with locally advanced rectal cancer.","date":"2008","source":"Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association","url":"https://pubmed.ncbi.nlm.nih.gov/18166477","citation_count":99,"is_preprint":false},{"pmid":"31338326","id":"PMC_31338326","title":"Exome-Wide Rare Variant Analysis From the DiscovEHR Study Identifies Novel Candidate Predisposition Genes for Endometrial Cancer.","date":"2019","source":"Frontiers in oncology","url":"https://pubmed.ncbi.nlm.nih.gov/31338326","citation_count":18,"is_preprint":false},{"pmid":"39700903","id":"PMC_39700903","title":"Recognizing SARS-CoV-2 infection of nasopharyngeal tissue at the single-cell level by machine learning method.","date":"2024","source":"Molecular immunology","url":"https://pubmed.ncbi.nlm.nih.gov/39700903","citation_count":12,"is_preprint":false},{"pmid":"35475666","id":"PMC_35475666","title":"Role of the Orphan Transporter SLC35E1 in the Nuclear Egress of Herpes Simplex Virus 1.","date":"2022","source":"Journal of virology","url":"https://pubmed.ncbi.nlm.nih.gov/35475666","citation_count":5,"is_preprint":false},{"pmid":"34590520","id":"PMC_34590520","title":"Identification of a Signature Comprising 5 Soluble Carrier Family Genes to Predict the Recurrence of Papillary Thyroid Carcinoma.","date":"2021","source":"Technology in cancer research & treatment","url":"https://pubmed.ncbi.nlm.nih.gov/34590520","citation_count":5,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":4966,"output_tokens":643,"usd":0.012271,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":6989,"output_tokens":1142,"usd":0.031747,"stage2_stop_reason":"end_turn"},"total_usd":0.044018,"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\": 2022,\n      \"finding\": \"SLC35E1 (an orphan transporter) was identified as a cellular protein that physically interacts with the HSV-1 nuclear egress complex (NEC) components UL34 and UL31, as detected by tandem affinity purification coupled with mass spectrometry in HSV-1-infected cells.\",\n      \"method\": \"Tandem affinity purification coupled with mass spectrometry-based proteomics (interactome screen in HSV-1-infected cells)\",\n      \"journal\": \"Journal of virology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal affinity purification/MS interactome screen followed by functional CRISPR/Cas9 loss-of-function validation, single lab\",\n      \"pmids\": [\"35475666\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"CRISPR/Cas9 knockout of SLC35E1 reduced HSV-1 replication, induced aberrant membranous invaginations containing perinuclear enveloped virions adjacent to the nuclear membrane, caused accumulation of perinuclear enveloped virions in the perinuclear space, and caused mislocalization of the nuclear egress complex — phenotypes consistent with a defect in HSV-1 de-envelopment, establishing SLC35E1 as a cellular protein required for efficient HSV-1 de-envelopment during nuclear egress.\",\n      \"method\": \"CRISPR/Cas9 knockout combined with fluorescence microscopy (emerin mislocalization as reporter), viral replication assay, and electron/fluorescence imaging of perinuclear virion accumulation\",\n      \"journal\": \"Journal of virology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — clean CRISPR KO with defined cellular phenotype (de-envelopment defect), multiple orthogonal readouts, single lab\",\n      \"pmids\": [\"35475666\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"SLC35E1 is an orphan transporter that physically associates with the HSV-1 nuclear egress complex (NEC; UL34/UL31) and is required for efficient de-envelopment of perinuclear enveloped virions during HSV-1 nuclear egress; its loss causes aberrant perinuclear virion accumulation, NEC mislocalization, and reduced viral replication.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"SLC35E1 is an orphan transporter that participates in herpes simplex virus 1 (HSV-1) nuclear egress as a host factor required for efficient de-envelopment of perinuclear enveloped virions [#0, #1]. It physically associates with the HSV-1 nuclear egress complex (NEC), binding the viral proteins UL34 and UL31 [#0]. Loss of SLC35E1 reduces HSV-1 replication and produces a de-envelopment defect characterized by aberrant membranous invaginations containing perinuclear enveloped virions, accumulation of virions in the perinuclear space, and mislocalization of the NEC [#1]. Beyond its role at the nuclear envelope during HSV-1 egress, no endogenous transport substrate or cellular function for SLC35E1 has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2022,\n      \"claim\": \"Establishing that the orphan transporter SLC35E1 is a physical partner of the HSV-1 nuclear egress machinery linked this previously uncharacterized protein to a defined viral process.\",\n      \"evidence\": \"Tandem affinity purification coupled with mass spectrometry in HSV-1-infected cells, detecting interaction with NEC components UL34 and UL31\",\n      \"pmids\": [\"35475666\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Interaction mapped by affinity-MS without reciprocal validation or defined binding interface\",\n        \"Whether the association is direct or bridged by other factors is unresolved\",\n        \"No structural model of the SLC35E1\\u2013NEC contact\"\n      ]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Determining the functional consequence of SLC35E1 loss showed it is required for efficient de-envelopment, not merely a passive interactor of the NEC.\",\n      \"evidence\": \"CRISPR/Cas9 knockout with viral replication assays, emerin-based fluorescence reporter of NEC localization, and imaging of perinuclear virion accumulation\",\n      \"pmids\": [\"35475666\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Mechanism by which SLC35E1 promotes de-envelopment is unknown\",\n        \"Whether transporter activity is required for the egress function was not tested\",\n        \"Single-lab finding without independent replication\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The endogenous transport substrate and the native (non-viral) cellular function of SLC35E1 remain undefined.\",\n      \"evidence\": null,\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No transported molecule identified\",\n        \"No physiological role characterized outside HSV-1 infection\",\n        \"Subcellular localization in uninfected cells not established in the corpus\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0005215\", \"supporting_discovery_ids\": [0, 1]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005635\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"pathway\": [],\n    \"complexes\": [],\n    \"partners\": [\"UL34\", \"UL31\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"faith_supported":3,"faith_total":3,"faith_pct":100.0}}