{"gene":"EMC9","run_date":"2026-06-09T23:54:43","timeline":{"discoveries":[{"year":2023,"finding":"EMC9 (as a component of the ER membrane protein complex, EMC) is required for correct transmembrane protein topogenesis; loss of EMC9 function in Xenopus tropicalis disrupts neural crest development and craniofacial cartilage formation, phenocopying EMC1 loss of function.","method":"Morpholino-based depletion (loss-of-function) in Xenopus tropicalis with craniofacial/neural crest phenotypic readouts","journal":"Genesis (New York, N.Y. : 2000)","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — clean loss-of-function in a vertebrate model with defined cellular phenotype (neural crest/craniofacial), single lab, single primary method","pmids":["37318954"],"is_preprint":false}],"current_model":"EMC9 is a subunit of the ER membrane protein complex (EMC) that functions in the co-translational insertion and topogenesis of transmembrane proteins; loss of EMC9 in Xenopus disrupts neural crest development and craniofacial structures, consistent with a role in proper membrane protein biogenesis across cell types."},"narrative":{"mechanistic_narrative":"EMC9 is a component of the ER membrane protein complex (EMC), which mediates correct topogenesis of transmembrane proteins; depletion of EMC9 in Xenopus tropicalis disrupts neural crest development and craniofacial cartilage formation, phenocopying loss of EMC1 [PMID:37318954]. Beyond this single loss-of-function study, no further molecular or biochemical detail of EMC9 has been characterized in the available corpus.","teleology":[{"year":2023,"claim":"It was unknown whether EMC9 contributes to a defined developmental process; morpholino depletion established that EMC9, like other EMC subunits, is required for neural crest and craniofacial development consistent with a role in membrane protein topogenesis.","evidence":"Morpholino-based loss-of-function depletion in Xenopus tropicalis with craniofacial/neural crest phenotypic readouts","pmids":["37318954"],"confidence":"Medium","gaps":["No direct biochemical demonstration of EMC9 within the EMC complex in this system","Specific transmembrane client proteins dependent on EMC9 not identified","Single lab, single method without reciprocal or rescue validation reported"]},{"year":null,"claim":"The molecular activity of EMC9 within the EMC, its direct interaction partners, structural arrangement, and the substrate proteins whose insertion it supports remain uncharacterized in the available corpus.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No defined molecular function or catalytic role assigned to EMC9","No structural or biochemical characterization of EMC9's position in the EMC","No human disease association established in the timeline"]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["EMC (ER membrane protein complex)"],"partners":[],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q9Y3B6","full_name":"ER membrane protein complex subunit 9","aliases":["Protein FAM158A"],"length_aa":208,"mass_kda":23.1,"function":"Part of the endoplasmic reticulum membrane protein complex (EMC) that enables the energy-independent insertion into endoplasmic reticulum membranes of newly synthesized membrane proteins (PubMed:29242231, PubMed:29809151, PubMed:30415835, PubMed:32459176). Preferentially accommodates proteins with transmembrane domains that are weakly hydrophobic or contain destabilizing features such as charged and aromatic residues (PubMed:29242231, PubMed:29809151, PubMed:30415835). Involved in the cotranslational insertion of multi-pass membrane proteins in which stop-transfer membrane-anchor sequences become ER membrane spanning helices (PubMed:29809151, PubMed:30415835). It is also required for the post-translational insertion of tail-anchored/TA proteins in endoplasmic reticulum membranes (PubMed:29242231, PubMed:29809151). By mediating the proper cotranslational insertion of N-terminal transmembrane domains in an N-exo topology, with translocated N-terminus in the lumen of the ER, controls the topology of multi-pass membrane proteins like the G protein-coupled receptors (PubMed:30415835). By regulating the insertion of various proteins in membranes, it is indirectly involved in many cellular processes (Probable)","subcellular_location":"Endoplasmic reticulum membrane","url":"https://www.uniprot.org/uniprotkb/Q9Y3B6/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/EMC9","classification":"Not Classified","n_dependent_lines":5,"n_total_lines":1208,"dependency_fraction":0.0041390728476821195},"opencell":{"profiled":true,"resolved_as":"","ensg_id":"ENSG00000100908","cell_line_id":"CID001794","localizations":[{"compartment":"er","grade":3}],"interactors":[{"gene":"EMC2","stoichiometry":10.0},{"gene":"EMC1","stoichiometry":10.0},{"gene":"RPL19","stoichiometry":10.0},{"gene":"RPL38","stoichiometry":10.0},{"gene":"EMC3","stoichiometry":10.0},{"gene":"EMC7","stoichiometry":10.0},{"gene":"RPL29","stoichiometry":10.0},{"gene":"SNRPE","stoichiometry":10.0},{"gene":"RPL34","stoichiometry":10.0},{"gene":"EMC4","stoichiometry":4.0}],"url":"https://opencell.sf.czbiohub.org/target/CID001794","total_profiled":1310},"omim":[{"mim_id":"621496","title":"ENDOPLASMIC RETICULUM MEMBRANE PROTEIN COMPLEX, SUBUNIT 9; EMC9","url":"https://www.omim.org/entry/621496"},{"mim_id":"614545","title":"ENDOPLASMIC RETICULUM MEMBRANE PROTEIN COMPLEX, SUBUNIT 10; EMC10","url":"https://www.omim.org/entry/614545"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"","locations":[],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/EMC9"},"hgnc":{"alias_symbol":["CGI-112"],"prev_symbol":["C14orf122","FAM158A"]},"alphafold":{"accession":"Q9Y3B6","domains":[{"cath_id":"3.40.140.10","chopping":"3-193","consensus_level":"high","plddt":93.3537,"start":3,"end":193}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9Y3B6","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q9Y3B6-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q9Y3B6-F1-predicted_aligned_error_v6.png","plddt_mean":90.81},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=EMC9","jax_strain_url":"https://www.jax.org/strain/search?query=EMC9"},"sequence":{"accession":"Q9Y3B6","fasta_url":"https://rest.uniprot.org/uniprotkb/Q9Y3B6.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q9Y3B6/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9Y3B6"}},"corpus_meta":[{"pmid":"34102206","id":"PMC_34102206","title":"Circular RNA circ-FAM158A promotes retinoblastoma progression by regulating miR-138-5p/SLC7A5 axis.","date":"2021","source":"Experimental eye research","url":"https://pubmed.ncbi.nlm.nih.gov/34102206","citation_count":20,"is_preprint":false},{"pmid":"36547723","id":"PMC_36547723","title":"Role of circular RNAs in retinoblastoma.","date":"2022","source":"Functional & integrative genomics","url":"https://pubmed.ncbi.nlm.nih.gov/36547723","citation_count":10,"is_preprint":false},{"pmid":"32188542","id":"PMC_32188542","title":"Transcriptomics-genomics data integration and expression quantitative trait loci analyses in oocyte donors and embryo recipients for improving invitro production of dairy cattle embryos.","date":"2018","source":"Reproduction, fertility, and development","url":"https://pubmed.ncbi.nlm.nih.gov/32188542","citation_count":10,"is_preprint":false},{"pmid":"37001772","id":"PMC_37001772","title":"The impact of non-coding RNAs in the pathobiology of eye disorders.","date":"2023","source":"International journal of biological macromolecules","url":"https://pubmed.ncbi.nlm.nih.gov/37001772","citation_count":7,"is_preprint":false},{"pmid":"37318954","id":"PMC_37318954","title":"Expanding EMC foldopathies: Topogenesis deficits alter the neural crest.","date":"2023","source":"Genesis (New York, N.Y. : 2000)","url":"https://pubmed.ncbi.nlm.nih.gov/37318954","citation_count":3,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":4591,"output_tokens":348,"usd":0.009496,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":6557,"output_tokens":742,"usd":0.025667,"stage2_stop_reason":"end_turn"},"total_usd":0.035163,"stage1_batch_id":"msgbatch_01AsR7g8dGTEiEw9U83bJeWn","stage2_batch_id":"msgbatch_01YV5ZyxtFNUZEjxRcpd9jzb","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2023,\n      \"finding\": \"EMC9 (as a component of the ER membrane protein complex, EMC) is required for correct transmembrane protein topogenesis; loss of EMC9 function in Xenopus tropicalis disrupts neural crest development and craniofacial cartilage formation, phenocopying EMC1 loss of function.\",\n      \"method\": \"Morpholino-based depletion (loss-of-function) in Xenopus tropicalis with craniofacial/neural crest phenotypic readouts\",\n      \"journal\": \"Genesis (New York, N.Y. : 2000)\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — clean loss-of-function in a vertebrate model with defined cellular phenotype (neural crest/craniofacial), single lab, single primary method\",\n      \"pmids\": [\"37318954\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"EMC9 is a subunit of the ER membrane protein complex (EMC) that functions in the co-translational insertion and topogenesis of transmembrane proteins; loss of EMC9 in Xenopus disrupts neural crest development and craniofacial structures, consistent with a role in proper membrane protein biogenesis across cell types.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"EMC9 is a component of the ER membrane protein complex (EMC), which mediates correct topogenesis of transmembrane proteins; depletion of EMC9 in Xenopus tropicalis disrupts neural crest development and craniofacial cartilage formation, phenocopying loss of EMC1 [#0]. Beyond this single loss-of-function study, no further molecular or biochemical detail of EMC9 has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2023,\n      \"claim\": \"It was unknown whether EMC9 contributes to a defined developmental process; morpholino depletion established that EMC9, like other EMC subunits, is required for neural crest and craniofacial development consistent with a role in membrane protein topogenesis.\",\n      \"evidence\": \"Morpholino-based loss-of-function depletion in Xenopus tropicalis with craniofacial/neural crest phenotypic readouts\",\n      \"pmids\": [\"37318954\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No direct biochemical demonstration of EMC9 within the EMC complex in this system\",\n        \"Specific transmembrane client proteins dependent on EMC9 not identified\",\n        \"Single lab, single method without reciprocal or rescue validation reported\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The molecular activity of EMC9 within the EMC, its direct interaction partners, structural arrangement, and the substrate proteins whose insertion it supports remain uncharacterized in the available corpus.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No defined molecular function or catalytic role assigned to EMC9\",\n        \"No structural or biochemical characterization of EMC9's position in the EMC\",\n        \"No human disease association established in the timeline\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [],\n    \"localization\": [],\n    \"pathway\": [],\n    \"complexes\": [\"EMC (ER membrane protein complex)\"],\n    \"partners\": [],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"loss","faith_supported":1,"faith_total":1,"faith_pct":100.0}}