{"gene":"NBAS","run_date":"2026-06-10T05:19:52","timeline":{"discoveries":[{"year":2015,"finding":"NBAS protein is involved in retrograde vesicular transport between the endoplasmic reticulum and Golgi; loss-of-function mutations reduce protein levels of NBAS and its interaction partner p31 (USE1), as shown by immunoblot analysis of patient fibroblasts.","method":"Immunoblot analysis of patient-derived fibroblasts; genetic identification of biallelic loss-of-function mutations","journal":"American journal of human genetics","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal protein-level evidence in patient fibroblasts with functional context, single lab but consistent with pathway","pmids":["26073778"],"is_preprint":false},{"year":2015,"finding":"The syntaxin 18 complex (of which NBAS is a component) is thermally susceptible, providing the molecular basis for fever-triggered acute liver failure episodes in NBAS deficiency; patient fibroblasts showed increased sensitivity to high temperature at both protein and functional levels, and a disturbed tethering of vesicles indicating a defect in ER-to-Golgi retrograde transport.","method":"Functional studies on patient fibroblasts: heat sensitivity assays, vesicle tethering assays","journal":"Journal of inherited metabolic disease","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct functional assays in patient cells with two orthogonal readouts (protein stability and vesicle tethering), single lab","pmids":["26541327"],"is_preprint":false},{"year":2011,"finding":"Zebrafish NBAS (NAG/NBAS) is required for nonsense-mediated mRNA decay (NMD): morpholino-induced depletion of zebrafish Nbas results in failure to degrade PTC-containing mRNAs, severe developmental defects, and reduced embryonic viability, phenotypes similar to those caused by depletion of core NMD factors Upf1, Smg-5, and Smg-6.","method":"Morpholino knockdown in zebrafish embryos; NMD reporter assays for PTC-containing mRNA degradation; phenotypic analysis","journal":"Nucleic acids research","confidence":"High","confidence_rationale":"Tier 2 / Strong — loss-of-function with defined molecular phenotype (NMD substrate stabilization), epistasis with core NMD factors, replicated across multiple NMD factors in same study","pmids":["21227923"],"is_preprint":false},{"year":2013,"finding":"DHX34 and NBAS co-regulate a large set of endogenous NMD target transcripts in human cells, zebrafish, and C. elegans; depletion of either factor stabilizes transcripts encoding NMD factors themselves, demonstrating participation in a conserved NMD negative feedback autoregulatory loop. NMD also modulates cellular stress response and membrane trafficking pathways.","method":"Microarray expression profiling after RNAi-mediated depletion of DHX34 or NBAS in human cells, zebrafish embryos, and C. elegans; comparison with core NMD factor depletions","journal":"Nucleic acids research","confidence":"High","confidence_rationale":"Tier 2 / Strong — cross-species validation in three organisms with genome-wide expression profiling, multiple orthogonal depletions, independently replicated pathway placement","pmids":["23828042"],"is_preprint":false},{"year":2022,"finding":"NBAS deficiency impairs NK cell cytotoxic degranulation: knockdown of NBAS in the NK cell line IMC-1 via shRNA resulted in loss of lytic granule polarization and a decreased number of cytotoxic vesicles near the Golgi apparatus, placing NBAS upstream of the degranulation pathway in a Golgi-to-ER retrograde transport context.","method":"shRNA knockdown of NBAS in NK cell line (IMC-1); immunofluorescence for lytic granule polarization; quantification of cytotoxic vesicles near Golgi","journal":"Journal of hematology & oncology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct loss-of-function with defined cellular phenotype (granule polarization), single lab, two orthogonal readouts","pmids":["35902954"],"is_preprint":false},{"year":2021,"finding":"NBAS-deficient patient NK cells show reduced absolute numbers of mature CD56dim NK cells, lower activation and degranulation in response to K562 target cells; this functional impairment was reversible upon pre-activation with IL-2 in vitro, indicating an NK cell-intrinsic role for NBAS in cytotoxic granule release.","method":"Multi-parametric immunophenotyping; functional degranulation assays (CD107a) with K562 target cells; IL-2 rescue experiment in patient-derived NK cells","journal":"Journal of clinical immunology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — functional assays in patient cells with rescue experiment, single lab, multiple orthogonal readouts","pmids":["34386911"],"is_preprint":false},{"year":2022,"finding":"C. elegans SMGL-1 (NBAS ortholog) acts as a guanine nucleotide exchange factor (GEF) for RAB-8, activating RAB-8 to drive unconventional Golgi-bypassing protein secretion (UPS) of integral membrane proteins. SMGL-1 resides in the ER-Golgi intermediate compartment and adjacent RAB-8-positive structures, and its localization there requires the NRZ complex component CZW-1/ZW10.","method":"C. elegans genetics; GEF activity assay for RAB-8; live imaging and co-localization; loss-of-function (smgl-1 and rab-8 mutants); epistasis with NRZ complex (czw-1/ZW10)","journal":"The Journal of cell biology","confidence":"High","confidence_rationale":"Tier 1 / Strong — in vitro GEF activity assay, reconstitution, localization with functional validation, epistasis with NRZ complex, multiple orthogonal methods in one study","pmids":["35604368"],"is_preprint":false},{"year":2019,"finding":"The NBAS protein contains structurally and functionally distinct domains (β-propeller, Sec39, C-terminal) that correspond to distinct clinical subgroups; protein modeling refined the β-propeller domain structure, and missense variants/in-frame deletions in different domains produce non-overlapping clinical phenotypes (combined, ILFS2, SOPH), implying domain-specific molecular functions.","method":"Computational protein structure prediction/modeling; genotype-phenotype correlation analysis in 110 patients with biallelic variants","journal":"Genetics in medicine","confidence":"Low","confidence_rationale":"Tier 4 / Moderate — computational structural modeling with genotype-phenotype correlation, no direct biochemical validation of domain function","pmids":["31761904"],"is_preprint":false},{"year":2020,"finding":"Mutant NBAS protein (carrying variants in the Sec39 domain) is thermally unstable and reduces expression of MGP (a regulator of bone homeostasis) in patient fibroblasts; additionally, reduced collagen secretion was observed, suggesting NBAS variants impair ER-to-Golgi retrograde transport needed for collagen secretion.","method":"Functional studies in patient fibroblasts: protein stability assays at elevated temperature, MGP expression analysis, collagen secretion assay","journal":"Molecular genetics and metabolism","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct functional assays in patient fibroblasts with multiple readouts (thermostability, MGP, collagen), single lab","pmids":["33707149"],"is_preprint":false},{"year":2020,"finding":"A novel NBAS missense substitution causes altered Golgi-to-ER retrograde vesicular trafficking and reduced collagen secretion in patient fibroblasts, directly linking NBAS function to collagen secretion and bone phenotype.","method":"In vitro functional studies on patient fibroblasts: vesicular trafficking assay; collagen secretion assay","journal":"Bone","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct functional assays in patient-derived cells with two orthogonal readouts, single lab","pmids":["32768688"],"is_preprint":false},{"year":2019,"finding":"Reduced protein levels of NBAS interaction partner p31 (USE1) serve as a functional biomarker for NBAS deficiency; Western blot of patient fibroblasts showed reduced p31 levels even in cases where NBAS protein itself was not decreased (two missense variants), demonstrating that p31 stability depends on NBAS function.","method":"Western blotting for NBAS and p31 protein levels in patient-derived fibroblasts","journal":"Human genome variation","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct protein quantification in patient cells; p31 reduction consistently observed across multiple patients/families including those with preserved NBAS protein levels","pmids":["30622725"],"is_preprint":false},{"year":2022,"finding":"p31 (USE1) protein levels were reduced in all three patient families tested by Western blotting, including an individual with two missense variants where NBAS protein levels were preserved, further confirming that p31 stability is dependent on NBAS function and that p31 level is a more sensitive functional readout than NBAS level alone.","method":"Western blotting for NBAS and p31 protein levels in patient fibroblasts from three families","journal":"JIMD reports","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct protein quantification across multiple families with consistent result, single lab","pmids":["35433172"],"is_preprint":false},{"year":2023,"finding":"A missense variant p.C448R in NBAS produces a protein with reduced mRNA and protein expression upon ectopic expression compared to wild-type, and induces increased intracellular reactive oxygen species, apoptosis, and ER stress marker expression in cultured cells, suggesting the mutant protein causes ER stress and is less stable than wild-type.","method":"Ectopic overexpression of wild-type vs. p.C448R NBAS; RT-qPCR and Western blot for expression; ROS assay; apoptosis assay; Western blot for ER stress markers","journal":"Human genome variation","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct comparison of wild-type and mutant protein with multiple functional readouts, single lab","pmids":["37055399"],"is_preprint":false},{"year":2025,"finding":"Molecular dynamics simulations of NBAS Sec39 domain missense variants (p.Leu744Pro and p.Arg756Cys) demonstrate that wild-type NBAS is thermostable at both 37°C and 42°C, while mutant NBAS shows pronounced conformational fluctuations, disrupted hydrogen-bonding networks, and secondary structural reorganization specifically under thermal stress (42°C), providing a structural mechanism for fever-triggered acute liver failure.","method":"Molecular dynamics simulation (MDS) of wild-type and mutant NBAS Sec39 domain at 37°C and 42°C","journal":"Human molecular genetics","confidence":"Low","confidence_rationale":"Tier 4 / Weak — computational simulation only, no direct biochemical or structural validation of thermostability difference","pmids":["40680151"],"is_preprint":false},{"year":2023,"finding":"NBAS and UPF1 proteins co-localize in human lung epithelial cells (Calu3), and NBAS co-localizes with p31 (USE1); co-localization of NBAS with UPF1 and with p31 was not altered by SARS-CoV-2 infection within 24 h, and both NBAS and UPF1 were found to co-localize with SARS-CoV-2 S and N proteins.","method":"Immunofluorescence co-localization in SARS-CoV-2-infected Calu3 cells","journal":"International journal of molecular sciences","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single co-localization experiment, single lab, no functional consequence demonstrated for NBAS specifically","pmids":["36768954"],"is_preprint":false}],"current_model":"NBAS is a multifunctional 'moonlighting' protein that participates in at least two distinct molecular processes: (1) retrograde vesicular trafficking from the Golgi to the ER as a component of the syntaxin 18/NRZ complex (interacting with p31/USE1 and ZW10), where its Sec39 domain is thermally susceptible and mutations cause fever-triggered ER stress and hepatocytolysis; and (2) nonsense-mediated mRNA decay (NMD), where it cooperates with DHX34 and core NMD factors (UPF1, SMG5/6/7) to degrade PTC-containing transcripts and regulate a conserved NMD autoregulatory feedback loop; additionally, in NK cells, NBAS is required for lytic granule polarization and degranulation via a Golgi-associated vesicular transport mechanism, and its C. elegans ortholog SMGL-1 acts as a GEF for RAB-8 to drive unconventional protein secretion."},"narrative":{"mechanistic_narrative":"NBAS is a moonlighting protein that operates in two largely separable cellular processes: ER-to-Golgi retrograde vesicular trafficking and nonsense-mediated mRNA decay (NMD) [PMID:26073778, PMID:21227923]. In the trafficking arm, NBAS functions as a component of the syntaxin 18/NRZ tethering complex, where it stabilizes its interaction partner p31/USE1—loss of NBAS function reduces p31 protein levels even when NBAS itself is preserved, making p31 a sensitive functional readout of NBAS activity [PMID:26073778, PMID:30622725, PMID:35433172]. The syntaxin 18 complex containing NBAS is thermally susceptible, and its Sec39-domain variants destabilize the protein under elevated temperature while disturbing vesicle tethering, providing the molecular basis for fever-triggered ER stress and acute liver failure [PMID:26541327, PMID:33707149]. Defective retrograde transport in NBAS-mutant fibroblasts impairs collagen secretion and reduces expression of the bone regulator MGP, linking NBAS to skeletal phenotypes [PMID:33707149, PMID:32768688]. In parallel, NBAS is required for NMD: its depletion stabilizes PTC-containing transcripts and, together with DHX34, co-regulates a conserved set of endogenous NMD targets including transcripts encoding NMD factors themselves, marking NBAS as part of an autoregulatory feedback loop alongside core factors UPF1 and SMG5/6 [PMID:21227923, PMID:23828042]. NBAS also supports immune cytotoxicity, being required in NK cells for lytic granule polarization and degranulation through a Golgi-associated vesicular transport mechanism [PMID:35902954, PMID:34386911]. Biallelic NBAS variants cause a spectrum of human disease in which distinct protein domains correlate with non-overlapping clinical subgroups [PMID:31761904].","teleology":[{"year":2011,"claim":"Established that NBAS is not solely a trafficking protein but is functionally required for nonsense-mediated mRNA decay, an unexpected second role.","evidence":"Morpholino knockdown in zebrafish embryos with NMD reporter assays and phenotypic comparison to core NMD factors","pmids":["21227923"],"confidence":"High","gaps":["Does not define the biochemical step in NMD at which NBAS acts","No human cell validation in this study"]},{"year":2013,"claim":"Defined NBAS as a co-regulator with DHX34 of a conserved NMD autoregulatory feedback loop, placing it within the regulatory architecture rather than just substrate degradation.","evidence":"Microarray profiling after RNAi depletion of NBAS or DHX34 across human cells, zebrafish, and C. elegans","pmids":["23828042"],"confidence":"High","gaps":["Does not establish direct physical interaction of NBAS with DHX34 or UPF1","Mechanism connecting NMD role to trafficking role unresolved"]},{"year":2015,"claim":"Identified NBAS as a component of ER-to-Golgi retrograde transport whose loss destabilizes its partner p31/USE1, anchoring the trafficking function.","evidence":"Immunoblot of patient fibroblasts with biallelic loss-of-function mutations","pmids":["26073778"],"confidence":"Medium","gaps":["Direct binding interface between NBAS and p31 not mapped","Stoichiometry within the syntaxin 18/NRZ complex not defined"]},{"year":2015,"claim":"Explained fever-triggered acute liver failure mechanistically by showing the NBAS-containing syntaxin 18 complex is thermally susceptible and that vesicle tethering fails.","evidence":"Heat-sensitivity and vesicle tethering assays in patient fibroblasts","pmids":["26541327"],"confidence":"Medium","gaps":["Which subunit confers thermal lability not isolated","Liver-specific vulnerability not explained at cellular level"]},{"year":2019,"claim":"Linked distinct NBAS protein domains to non-overlapping clinical subgroups, implying domain-specific molecular functions.","evidence":"Computational structure modeling with genotype-phenotype correlation across 110 patients","pmids":["31761904"],"confidence":"Low","gaps":["No direct biochemical validation of domain-specific function","Structural model not experimentally confirmed"]},{"year":2019,"claim":"Refined the functional readout for NBAS deficiency by showing p31 reduction occurs even when NBAS protein is preserved, indicating p31 stability strictly depends on NBAS.","evidence":"Western blot of NBAS and p31 in patient fibroblasts including missense-variant cases","pmids":["30622725"],"confidence":"Medium","gaps":["Does not determine whether NBAS directly protects p31 from degradation","Generality across all variant classes not established"]},{"year":2020,"claim":"Connected NBAS retrograde transport function to collagen secretion and bone homeostasis via reduced MGP expression and impaired secretion.","evidence":"Thermostability, MGP expression, and collagen secretion assays in patient fibroblasts (two studies)","pmids":["33707149","32768688"],"confidence":"Medium","gaps":["Mechanism by which retrograde defect lowers collagen secretion not resolved","MGP downregulation pathway not mapped"]},{"year":2021,"claim":"Demonstrated an NK cell-intrinsic role for NBAS in cytotoxic granule release, reversible by IL-2 pre-activation.","evidence":"Immunophenotyping and CD107a degranulation assays with IL-2 rescue in patient NK cells","pmids":["34386911"],"confidence":"Medium","gaps":["Molecular step in degranulation requiring NBAS not defined","Single-lab patient cohort"]},{"year":2022,"claim":"Placed NBAS upstream of NK degranulation through a Golgi-associated retrograde transport mechanism affecting lytic granule polarization.","evidence":"shRNA knockdown in IMC-1 NK cell line with immunofluorescence quantification of granules near Golgi","pmids":["35902954"],"confidence":"Medium","gaps":["Direct trafficking cargo for granule polarization not identified","Link to the syntaxin 18 complex in NK cells not shown"]},{"year":2022,"claim":"Revealed a GEF activity for the NBAS ortholog SMGL-1 toward RAB-8 driving unconventional protein secretion, the most direct biochemical mechanism yet for an NBAS-family protein.","evidence":"C. elegans genetics, in vitro RAB-8 GEF assay, co-localization, and epistasis with NRZ component CZW-1/ZW10","pmids":["35604368"],"confidence":"High","gaps":["Whether human NBAS retains RAB-8 GEF activity not demonstrated","Relationship between GEF function and retrograde tethering not integrated"]},{"year":2023,"claim":"Showed a specific missense variant destabilizes NBAS and induces ROS, apoptosis, and ER stress, supporting a stress-driven pathomechanism.","evidence":"Ectopic expression of wild-type versus p.C448R NBAS with ROS, apoptosis, and ER stress marker assays","pmids":["37055399"],"confidence":"Medium","gaps":["Overexpression system may not reflect physiological context","Causality between ER stress and tissue phenotype not established"]},{"year":2023,"claim":"Documented co-localization of NBAS with UPF1 and with p31 in lung epithelial cells, and association with SARS-CoV-2 proteins.","evidence":"Immunofluorescence co-localization in infected Calu3 cells","pmids":["36768954"],"confidence":"Low","gaps":["Single co-localization experiment without functional consequence","No reciprocal validation of NBAS-UPF1 physical interaction"]},{"year":2025,"claim":"Provided a structural rationale for thermal instability by simulating Sec39-domain variants under fever-range temperature.","evidence":"Molecular dynamics simulation of wild-type and mutant Sec39 domain at 37°C and 42°C","pmids":["40680151"],"confidence":"Low","gaps":["Computational only, no biochemical thermostability measurement","Predicted conformational changes not experimentally confirmed"]},{"year":null,"claim":"How NBAS coordinates or partitions its trafficking and NMD functions, and whether human NBAS possesses the RAB-8 GEF activity seen in its ortholog, remains unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No reconstituted human NBAS GEF assay","Mechanistic link between NMD and retrograde transport roles undefined","Tissue-specific basis of distinct clinical subgroups not mechanistically explained"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0140098","term_label":"catalytic activity, acting on RNA","supporting_discovery_ids":[2,3]},{"term_id":"GO:0098772","term_label":"molecular function regulator activity","supporting_discovery_ids":[6]}],"localization":[{"term_id":"GO:0005783","term_label":"endoplasmic reticulum","supporting_discovery_ids":[0,1,8]},{"term_id":"GO:0005794","term_label":"Golgi apparatus","supporting_discovery_ids":[4,6]}],"pathway":[{"term_id":"R-HSA-8953854","term_label":"Metabolism of RNA","supporting_discovery_ids":[2,3]},{"term_id":"R-HSA-5653656","term_label":"Vesicle-mediated transport","supporting_discovery_ids":[0,1]},{"term_id":"R-HSA-168256","term_label":"Immune System","supporting_discovery_ids":[4,5]}],"complexes":["syntaxin 18/NRZ complex"],"partners":["USE1","ZW10","DHX34","UPF1","RAB8A"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"A2RRP1","full_name":"NBAS subunit of NRZ tethering complex","aliases":["Neuroblastoma-amplified gene protein","Neuroblastoma-amplified sequence"],"length_aa":2371,"mass_kda":268.6,"function":"Involved in Golgi-to-endoplasmic reticulum (ER) retrograde transport; the function is proposed to depend on its association in the NRZ complex which is believed to play a role in SNARE assembly at the ER (PubMed:19369418). Required for normal embryonic development (By similarity). May play a role in the nonsense-mediated decay pathway of mRNAs containing premature stop codons (By similarity)","subcellular_location":"Cytoplasm; Endoplasmic reticulum; Endoplasmic reticulum membrane","url":"https://www.uniprot.org/uniprotkb/A2RRP1/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/NBAS","classification":"Not Classified","n_dependent_lines":713,"n_total_lines":1208,"dependency_fraction":0.5902317880794702},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[{"gene":"STX18","stoichiometry":4.0},{"gene":"ANKRD46","stoichiometry":0.2},{"gene":"BNIP1","stoichiometry":0.2},{"gene":"COPA","stoichiometry":0.2},{"gene":"COPB2","stoichiometry":0.2},{"gene":"COPE","stoichiometry":0.2},{"gene":"GOLT1B","stoichiometry":0.2},{"gene":"GOSR1","stoichiometry":0.2},{"gene":"PGRMC1","stoichiometry":0.2},{"gene":"SCFD1","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/search/NBAS","total_profiled":1310},"omim":[{"mim_id":"616483","title":"INFANTILE LIVER FAILURE SYNDROME 2; ILFS2","url":"https://www.omim.org/entry/616483"},{"mim_id":"615438","title":"INFANTILE LIVER FAILURE SYNDROME 1; ILFS1","url":"https://www.omim.org/entry/615438"},{"mim_id":"614800","title":"SHORT STATURE, OPTIC NERVE ATROPHY, AND PELGER-HUET ANOMALY; SOPH","url":"https://www.omim.org/entry/614800"},{"mim_id":"610089","title":"RAD50-INTERACTING PROTEIN 1; RINT1","url":"https://www.omim.org/entry/610089"},{"mim_id":"608025","title":"NBAS SUBUNIT OF NRZ TETHERING COMPLEX; NBAS","url":"https://www.omim.org/entry/608025"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Approved","locations":[{"location":"Golgi apparatus","reliability":"Approved"},{"location":"Nuclear membrane","reliability":"Additional"},{"location":"Nucleoli","reliability":"Additional"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/NBAS"},"hgnc":{"alias_symbol":["NAG"],"prev_symbol":[]},"alphafold":{"accession":"A2RRP1","domains":[{"cath_id":"-","chopping":"588-632_671-722","consensus_level":"medium","plddt":81.8163,"start":588,"end":722},{"cath_id":"-","chopping":"724-877","consensus_level":"medium","plddt":86.8425,"start":724,"end":877},{"cath_id":"-","chopping":"1568-1654","consensus_level":"medium","plddt":73.9113,"start":1568,"end":1654},{"cath_id":"-","chopping":"1977-2079","consensus_level":"medium","plddt":82.7811,"start":1977,"end":2079},{"cath_id":"-","chopping":"2279-2371","consensus_level":"medium","plddt":81.0541,"start":2279,"end":2371}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/A2RRP1","model_url":"https://alphafold.ebi.ac.uk/files/AF-A2RRP1-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-A2RRP1-F1-predicted_aligned_error_v6.png","plddt_mean":74.06},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=NBAS","jax_strain_url":"https://www.jax.org/strain/search?query=NBAS"},"sequence":{"accession":"A2RRP1","fasta_url":"https://rest.uniprot.org/uniprotkb/A2RRP1.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/A2RRP1/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/A2RRP1"}},"corpus_meta":[{"pmid":"26073778","id":"PMC_26073778","title":"Biallelic Mutations in NBAS Cause Recurrent Acute Liver Failure with Onset in Infancy.","date":"2015","source":"American journal of human genetics","url":"https://pubmed.ncbi.nlm.nih.gov/26073778","citation_count":99,"is_preprint":false},{"pmid":"26541327","id":"PMC_26541327","title":"Recurrent acute liver failure due to NBAS deficiency: phenotypic spectrum, disease mechanisms, and therapeutic concepts.","date":"2015","source":"Journal of inherited metabolic disease","url":"https://pubmed.ncbi.nlm.nih.gov/26541327","citation_count":80,"is_preprint":false},{"pmid":"23828042","id":"PMC_23828042","title":"DHX34 and NBAS form part of an autoregulatory NMD circuit that regulates endogenous RNA targets in human cells, zebrafish and Caenorhabditis elegans.","date":"2013","source":"Nucleic acids research","url":"https://pubmed.ncbi.nlm.nih.gov/23828042","citation_count":76,"is_preprint":false},{"pmid":"26286438","id":"PMC_26286438","title":"NBAS mutations cause a multisystem disorder involving bone, connective tissue, liver, immune system, and retina.","date":"2015","source":"American journal of medical genetics. 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pediatrics","url":"https://pubmed.ncbi.nlm.nih.gov/36594124","citation_count":2,"is_preprint":false},{"pmid":"40215727","id":"PMC_40215727","title":"RNA sequencing driven diagnosis expands the phenotypic spectrum of NBAS deficiency.","date":"2025","source":"Molecular genetics and metabolism","url":"https://pubmed.ncbi.nlm.nih.gov/40215727","citation_count":2,"is_preprint":false},{"pmid":"29369590","id":"PMC_29369590","title":"[Population frequency and age of mutation G5741→A in gene NBAS which is a cause of SOPH syndrome in Sakha (Yakutia) Republic].","date":"2016","source":"Genetika","url":"https://pubmed.ncbi.nlm.nih.gov/29369590","citation_count":2,"is_preprint":false},{"pmid":"30845840","id":"PMC_30845840","title":"Oculofacial alterations in NBAS-SOPH like mutations: Case report.","date":"2019","source":"European journal of ophthalmology","url":"https://pubmed.ncbi.nlm.nih.gov/30845840","citation_count":2,"is_preprint":false},{"pmid":"39641476","id":"PMC_39641476","title":"Protein-Variant-Phenotype Study of NBAS Using AlphaFold in the Aspect of SOPH Syndrome.","date":"2024","source":"Proteins","url":"https://pubmed.ncbi.nlm.nih.gov/39641476","citation_count":1,"is_preprint":false},{"pmid":"38517998","id":"PMC_38517998","title":"Autoimmune hemolytic anemia and thrombocytopenia in a Chinese patient with heterozygous NBAS mutations: Case report.","date":"2024","source":"Medicine","url":"https://pubmed.ncbi.nlm.nih.gov/38517998","citation_count":1,"is_preprint":false},{"pmid":"37151364","id":"PMC_37151364","title":"Pregnancy, delivery, and postpartum period in infantile liver failure syndrome type 2 due to variants in NBAS.","date":"2023","source":"JIMD reports","url":"https://pubmed.ncbi.nlm.nih.gov/37151364","citation_count":1,"is_preprint":false},{"pmid":"33542026","id":"PMC_33542026","title":"Novel compound heterozygous variants in the NBAS gene in a child with osteogenesis imperfecta and recurrent acute liver failure.","date":"2021","source":"BMJ case reports","url":"https://pubmed.ncbi.nlm.nih.gov/33542026","citation_count":1,"is_preprint":false},{"pmid":"39606973","id":"PMC_39606973","title":"[Clinical features and genetic study of four cases of pediatric acute liver failure caused by NBAS gene variants].","date":"2025","source":"Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology","url":"https://pubmed.ncbi.nlm.nih.gov/39606973","citation_count":1,"is_preprint":false},{"pmid":"39779337","id":"PMC_39779337","title":"[Clinical features and genetic analysis of three patients with Infantile liver failure syndrome type 2 due to variants of NBAS gene].","date":"2025","source":"Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical 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NMD also modulates cellular stress response and membrane trafficking pathways.\",\n      \"method\": \"Microarray expression profiling after RNAi-mediated depletion of DHX34 or NBAS in human cells, zebrafish embryos, and C. elegans; comparison with core NMD factor depletions\",\n      \"journal\": \"Nucleic acids research\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — cross-species validation in three organisms with genome-wide expression profiling, multiple orthogonal depletions, independently replicated pathway placement\",\n      \"pmids\": [\"23828042\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"NBAS deficiency impairs NK cell cytotoxic degranulation: knockdown of NBAS in the NK cell line IMC-1 via shRNA resulted in loss of lytic granule polarization and a decreased number of cytotoxic vesicles near the Golgi apparatus, placing NBAS upstream of the degranulation pathway in a Golgi-to-ER retrograde transport context.\",\n      \"method\": \"shRNA knockdown of NBAS in NK cell line (IMC-1); immunofluorescence for lytic granule polarization; quantification of cytotoxic vesicles near Golgi\",\n      \"journal\": \"Journal of hematology & oncology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct loss-of-function with defined cellular phenotype (granule polarization), single lab, two orthogonal readouts\",\n      \"pmids\": [\"35902954\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"NBAS-deficient patient NK cells show reduced absolute numbers of mature CD56dim NK cells, lower activation and degranulation in response to K562 target cells; this functional impairment was reversible upon pre-activation with IL-2 in vitro, indicating an NK cell-intrinsic role for NBAS in cytotoxic granule release.\",\n      \"method\": \"Multi-parametric immunophenotyping; functional degranulation assays (CD107a) with K562 target cells; IL-2 rescue experiment in patient-derived NK cells\",\n      \"journal\": \"Journal of clinical immunology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — functional assays in patient cells with rescue experiment, single lab, multiple orthogonal readouts\",\n      \"pmids\": [\"34386911\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"C. elegans SMGL-1 (NBAS ortholog) acts as a guanine nucleotide exchange factor (GEF) for RAB-8, activating RAB-8 to drive unconventional Golgi-bypassing protein secretion (UPS) of integral membrane proteins. SMGL-1 resides in the ER-Golgi intermediate compartment and adjacent RAB-8-positive structures, and its localization there requires the NRZ complex component CZW-1/ZW10.\",\n      \"method\": \"C. elegans genetics; GEF activity assay for RAB-8; live imaging and co-localization; loss-of-function (smgl-1 and rab-8 mutants); epistasis with NRZ complex (czw-1/ZW10)\",\n      \"journal\": \"The Journal of cell biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — in vitro GEF activity assay, reconstitution, localization with functional validation, epistasis with NRZ complex, multiple orthogonal methods in one study\",\n      \"pmids\": [\"35604368\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"The NBAS protein contains structurally and functionally distinct domains (β-propeller, Sec39, C-terminal) that correspond to distinct clinical subgroups; protein modeling refined the β-propeller domain structure, and missense variants/in-frame deletions in different domains produce non-overlapping clinical phenotypes (combined, ILFS2, SOPH), implying domain-specific molecular functions.\",\n      \"method\": \"Computational protein structure prediction/modeling; genotype-phenotype correlation analysis in 110 patients with biallelic variants\",\n      \"journal\": \"Genetics in medicine\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 4 / Moderate — computational structural modeling with genotype-phenotype correlation, no direct biochemical validation of domain function\",\n      \"pmids\": [\"31761904\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"Mutant NBAS protein (carrying variants in the Sec39 domain) is thermally unstable and reduces expression of MGP (a regulator of bone homeostasis) in patient fibroblasts; additionally, reduced collagen secretion was observed, suggesting NBAS variants impair ER-to-Golgi retrograde transport needed for collagen secretion.\",\n      \"method\": \"Functional studies in patient fibroblasts: protein stability assays at elevated temperature, MGP expression analysis, collagen secretion assay\",\n      \"journal\": \"Molecular genetics and metabolism\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct functional assays in patient fibroblasts with multiple readouts (thermostability, MGP, collagen), single lab\",\n      \"pmids\": [\"33707149\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"A novel NBAS missense substitution causes altered Golgi-to-ER retrograde vesicular trafficking and reduced collagen secretion in patient fibroblasts, directly linking NBAS function to collagen secretion and bone phenotype.\",\n      \"method\": \"In vitro functional studies on patient fibroblasts: vesicular trafficking assay; collagen secretion assay\",\n      \"journal\": \"Bone\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct functional assays in patient-derived cells with two orthogonal readouts, single lab\",\n      \"pmids\": [\"32768688\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"Reduced protein levels of NBAS interaction partner p31 (USE1) serve as a functional biomarker for NBAS deficiency; Western blot of patient fibroblasts showed reduced p31 levels even in cases where NBAS protein itself was not decreased (two missense variants), demonstrating that p31 stability depends on NBAS function.\",\n      \"method\": \"Western blotting for NBAS and p31 protein levels in patient-derived fibroblasts\",\n      \"journal\": \"Human genome variation\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct protein quantification in patient cells; p31 reduction consistently observed across multiple patients/families including those with preserved NBAS protein levels\",\n      \"pmids\": [\"30622725\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"p31 (USE1) protein levels were reduced in all three patient families tested by Western blotting, including an individual with two missense variants where NBAS protein levels were preserved, further confirming that p31 stability is dependent on NBAS function and that p31 level is a more sensitive functional readout than NBAS level alone.\",\n      \"method\": \"Western blotting for NBAS and p31 protein levels in patient fibroblasts from three families\",\n      \"journal\": \"JIMD reports\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct protein quantification across multiple families with consistent result, single lab\",\n      \"pmids\": [\"35433172\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"A missense variant p.C448R in NBAS produces a protein with reduced mRNA and protein expression upon ectopic expression compared to wild-type, and induces increased intracellular reactive oxygen species, apoptosis, and ER stress marker expression in cultured cells, suggesting the mutant protein causes ER stress and is less stable than wild-type.\",\n      \"method\": \"Ectopic overexpression of wild-type vs. p.C448R NBAS; RT-qPCR and Western blot for expression; ROS assay; apoptosis assay; Western blot for ER stress markers\",\n      \"journal\": \"Human genome variation\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct comparison of wild-type and mutant protein with multiple functional readouts, single lab\",\n      \"pmids\": [\"37055399\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"Molecular dynamics simulations of NBAS Sec39 domain missense variants (p.Leu744Pro and p.Arg756Cys) demonstrate that wild-type NBAS is thermostable at both 37°C and 42°C, while mutant NBAS shows pronounced conformational fluctuations, disrupted hydrogen-bonding networks, and secondary structural reorganization specifically under thermal stress (42°C), providing a structural mechanism for fever-triggered acute liver failure.\",\n      \"method\": \"Molecular dynamics simulation (MDS) of wild-type and mutant NBAS Sec39 domain at 37°C and 42°C\",\n      \"journal\": \"Human molecular genetics\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 4 / Weak — computational simulation only, no direct biochemical or structural validation of thermostability difference\",\n      \"pmids\": [\"40680151\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"NBAS and UPF1 proteins co-localize in human lung epithelial cells (Calu3), and NBAS co-localizes with p31 (USE1); co-localization of NBAS with UPF1 and with p31 was not altered by SARS-CoV-2 infection within 24 h, and both NBAS and UPF1 were found to co-localize with SARS-CoV-2 S and N proteins.\",\n      \"method\": \"Immunofluorescence co-localization in SARS-CoV-2-infected Calu3 cells\",\n      \"journal\": \"International journal of molecular sciences\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single co-localization experiment, single lab, no functional consequence demonstrated for NBAS specifically\",\n      \"pmids\": [\"36768954\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"NBAS is a multifunctional 'moonlighting' protein that participates in at least two distinct molecular processes: (1) retrograde vesicular trafficking from the Golgi to the ER as a component of the syntaxin 18/NRZ complex (interacting with p31/USE1 and ZW10), where its Sec39 domain is thermally susceptible and mutations cause fever-triggered ER stress and hepatocytolysis; and (2) nonsense-mediated mRNA decay (NMD), where it cooperates with DHX34 and core NMD factors (UPF1, SMG5/6/7) to degrade PTC-containing transcripts and regulate a conserved NMD autoregulatory feedback loop; additionally, in NK cells, NBAS is required for lytic granule polarization and degranulation via a Golgi-associated vesicular transport mechanism, and its C. elegans ortholog SMGL-1 acts as a GEF for RAB-8 to drive unconventional protein secretion.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"NBAS is a moonlighting protein that operates in two largely separable cellular processes: ER-to-Golgi retrograde vesicular trafficking and nonsense-mediated mRNA decay (NMD) [#0, #2]. In the trafficking arm, NBAS functions as a component of the syntaxin 18/NRZ tethering complex, where it stabilizes its interaction partner p31/USE1—loss of NBAS function reduces p31 protein levels even when NBAS itself is preserved, making p31 a sensitive functional readout of NBAS activity [#0, #10, #11]. The syntaxin 18 complex containing NBAS is thermally susceptible, and its Sec39-domain variants destabilize the protein under elevated temperature while disturbing vesicle tethering, providing the molecular basis for fever-triggered ER stress and acute liver failure [#1, #8]. Defective retrograde transport in NBAS-mutant fibroblasts impairs collagen secretion and reduces expression of the bone regulator MGP, linking NBAS to skeletal phenotypes [#8, #9]. In parallel, NBAS is required for NMD: its depletion stabilizes PTC-containing transcripts and, together with DHX34, co-regulates a conserved set of endogenous NMD targets including transcripts encoding NMD factors themselves, marking NBAS as part of an autoregulatory feedback loop alongside core factors UPF1 and SMG5/6 [#2, #3]. NBAS also supports immune cytotoxicity, being required in NK cells for lytic granule polarization and degranulation through a Golgi-associated vesicular transport mechanism [#4, #5]. Biallelic NBAS variants cause a spectrum of human disease in which distinct protein domains correlate with non-overlapping clinical subgroups [#7].\",\n  \"teleology\": [\n    {\n      \"year\": 2011,\n      \"claim\": \"Established that NBAS is not solely a trafficking protein but is functionally required for nonsense-mediated mRNA decay, an unexpected second role.\",\n      \"evidence\": \"Morpholino knockdown in zebrafish embryos with NMD reporter assays and phenotypic comparison to core NMD factors\",\n      \"pmids\": [\"21227923\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Does not define the biochemical step in NMD at which NBAS acts\", \"No human cell validation in this study\"]\n    },\n    {\n      \"year\": 2013,\n      \"claim\": \"Defined NBAS as a co-regulator with DHX34 of a conserved NMD autoregulatory feedback loop, placing it within the regulatory architecture rather than just substrate degradation.\",\n      \"evidence\": \"Microarray profiling after RNAi depletion of NBAS or DHX34 across human cells, zebrafish, and C. elegans\",\n      \"pmids\": [\"23828042\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Does not establish direct physical interaction of NBAS with DHX34 or UPF1\", \"Mechanism connecting NMD role to trafficking role unresolved\"]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"Identified NBAS as a component of ER-to-Golgi retrograde transport whose loss destabilizes its partner p31/USE1, anchoring the trafficking function.\",\n      \"evidence\": \"Immunoblot of patient fibroblasts with biallelic loss-of-function mutations\",\n      \"pmids\": [\"26073778\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct binding interface between NBAS and p31 not mapped\", \"Stoichiometry within the syntaxin 18/NRZ complex not defined\"]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"Explained fever-triggered acute liver failure mechanistically by showing the NBAS-containing syntaxin 18 complex is thermally susceptible and that vesicle tethering fails.\",\n      \"evidence\": \"Heat-sensitivity and vesicle tethering assays in patient fibroblasts\",\n      \"pmids\": [\"26541327\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Which subunit confers thermal lability not isolated\", \"Liver-specific vulnerability not explained at cellular level\"]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Linked distinct NBAS protein domains to non-overlapping clinical subgroups, implying domain-specific molecular functions.\",\n      \"evidence\": \"Computational structure modeling with genotype-phenotype correlation across 110 patients\",\n      \"pmids\": [\"31761904\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"No direct biochemical validation of domain-specific function\", \"Structural model not experimentally confirmed\"]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Refined the functional readout for NBAS deficiency by showing p31 reduction occurs even when NBAS protein is preserved, indicating p31 stability strictly depends on NBAS.\",\n      \"evidence\": \"Western blot of NBAS and p31 in patient fibroblasts including missense-variant cases\",\n      \"pmids\": [\"30622725\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Does not determine whether NBAS directly protects p31 from degradation\", \"Generality across all variant classes not established\"]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Connected NBAS retrograde transport function to collagen secretion and bone homeostasis via reduced MGP expression and impaired secretion.\",\n      \"evidence\": \"Thermostability, MGP expression, and collagen secretion assays in patient fibroblasts (two studies)\",\n      \"pmids\": [\"33707149\", \"32768688\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Mechanism by which retrograde defect lowers collagen secretion not resolved\", \"MGP downregulation pathway not mapped\"]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Demonstrated an NK cell-intrinsic role for NBAS in cytotoxic granule release, reversible by IL-2 pre-activation.\",\n      \"evidence\": \"Immunophenotyping and CD107a degranulation assays with IL-2 rescue in patient NK cells\",\n      \"pmids\": [\"34386911\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Molecular step in degranulation requiring NBAS not defined\", \"Single-lab patient cohort\"]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Placed NBAS upstream of NK degranulation through a Golgi-associated retrograde transport mechanism affecting lytic granule polarization.\",\n      \"evidence\": \"shRNA knockdown in IMC-1 NK cell line with immunofluorescence quantification of granules near Golgi\",\n      \"pmids\": [\"35902954\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct trafficking cargo for granule polarization not identified\", \"Link to the syntaxin 18 complex in NK cells not shown\"]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Revealed a GEF activity for the NBAS ortholog SMGL-1 toward RAB-8 driving unconventional protein secretion, the most direct biochemical mechanism yet for an NBAS-family protein.\",\n      \"evidence\": \"C. elegans genetics, in vitro RAB-8 GEF assay, co-localization, and epistasis with NRZ component CZW-1/ZW10\",\n      \"pmids\": [\"35604368\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Whether human NBAS retains RAB-8 GEF activity not demonstrated\", \"Relationship between GEF function and retrograde tethering not integrated\"]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Showed a specific missense variant destabilizes NBAS and induces ROS, apoptosis, and ER stress, supporting a stress-driven pathomechanism.\",\n      \"evidence\": \"Ectopic expression of wild-type versus p.C448R NBAS with ROS, apoptosis, and ER stress marker assays\",\n      \"pmids\": [\"37055399\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Overexpression system may not reflect physiological context\", \"Causality between ER stress and tissue phenotype not established\"]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Documented co-localization of NBAS with UPF1 and with p31 in lung epithelial cells, and association with SARS-CoV-2 proteins.\",\n      \"evidence\": \"Immunofluorescence co-localization in infected Calu3 cells\",\n      \"pmids\": [\"36768954\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"Single co-localization experiment without functional consequence\", \"No reciprocal validation of NBAS-UPF1 physical interaction\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Provided a structural rationale for thermal instability by simulating Sec39-domain variants under fever-range temperature.\",\n      \"evidence\": \"Molecular dynamics simulation of wild-type and mutant Sec39 domain at 37°C and 42°C\",\n      \"pmids\": [\"40680151\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"Computational only, no biochemical thermostability measurement\", \"Predicted conformational changes not experimentally confirmed\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How NBAS coordinates or partitions its trafficking and NMD functions, and whether human NBAS possesses the RAB-8 GEF activity seen in its ortholog, remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No reconstituted human NBAS GEF assay\", \"Mechanistic link between NMD and retrograde transport roles undefined\", \"Tissue-specific basis of distinct clinical subgroups not mechanistically explained\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0140098\", \"supporting_discovery_ids\": [2, 3]},\n      {\"term_id\": \"GO:0098772\", \"supporting_discovery_ids\": [6]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005783\", \"supporting_discovery_ids\": [0, 1, 8]},\n      {\"term_id\": \"GO:0005794\", \"supporting_discovery_ids\": [4, 6]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-8953854\", \"supporting_discovery_ids\": [2, 3]},\n      {\"term_id\": \"R-HSA-5653656\", \"supporting_discovery_ids\": [0, 1]},\n      {\"term_id\": \"R-HSA-168256\", \"supporting_discovery_ids\": [4, 5]}\n    ],\n    \"complexes\": [\"syntaxin 18/NRZ complex\"],\n    \"partners\": [\"USE1\", \"ZW10\", \"DHX34\", \"UPF1\", \"RAB8A\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":7,"faith_total":7,"faith_pct":100.0}}