{"id":"24d0afc8-c7ab-5de7-a7fe-ca75ba5eb01e","stable_key":"08ce9896-9d1c-5bbf-b705-5bfe771091d5:b7-hlcs-t610","predicate":"has_reduced_affinity_for","statement":"The human HLCS Thr610-deletion variant had a biotin Km approximately three times the wild-type value.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"19fc5f51-12d3-57c8-b89b-52f3209ff68c","mechanism_event_label":"Different HLCS variants impair biotin use by different amounts.","subject":{"id":"8d43478a-3e89-5bdd-a841-3e09035c5064","slug":"hlcs-del-t610","display_name":"Human HLCS Thr610 deletion variant","entity_type_key":"protein_state"},"object":{"id":"37a8e96b-f95b-5ba7-a0bc-8ed3cfaf5fd8","slug":"biotin","display_name":"Biotin","entity_type_key":"small_molecule"},"evidence_count":1,"mechanism_event":{"id":"19fc5f51-12d3-57c8-b89b-52f3209ff68c","stable_key":"08ce9896-9d1c-5bbf-b705-5bfe771091d5:b7-hlcs-t610-event","event_type":"biochemical_relationship","label":"Different HLCS variants impair biotin use by different amounts.","description":"The human HLCS Thr610-deletion variant had a biotin Km approximately three times the wild-type value.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"518c7af6-7e78-59ed-a9cb-3de53c9a39c8","slug":"hlcs","display_name":"Human holocarboxylase synthetase / HLCS","entity_type_key":"protein"},"role":"wild-type comparator","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"8d43478a-3e89-5bdd-a841-3e09035c5064","slug":"hlcs-del-t610","display_name":"Human HLCS Thr610 deletion variant","entity_type_key":"protein_state"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"37a8e96b-f95b-5ba7-a0bc-8ed3cfaf5fd8","slug":"biotin","display_name":"Biotin","entity_type_key":"small_molecule"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""}]},"contexts":[{"dimension":"availability_state","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null},{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/biotin-research/10590022.abstract.txt\", \"locator\": \"Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"bbdc1b8fa77a6935ced529e847093935cf4c8c9e056470e81aa3473968b980c5\", \"start_char\": 0, \"end_char\": 1628, \"text_sha256\": \"bbdc1b8fa77a6935ced529e847093935cf4c8c9e056470e81aa3473968b980c5\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Kinetics of seven human HLCS variants, patient cells and clinical response comparison","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Genetic variants and biotin supplementation","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Biotin responsiveness varied with residual enzyme capacity. Genotype effects must not be equated with ordinary dietary biotin deficiency.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Biotin research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"biotin","display_name":"Biotin","entity_type_key":"small_molecule"}},{"dimension":"organism","value_text":"Homo sapiens","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Different HLCS variants impair biotin use by different amounts.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[b7-p10590022] Relationship between kinetic properties of mutant enzyme and biochemical and clinical responsiveness to biotin in holocarboxylase synthetase deficiency. (1999). https://pubmed.ncbi.nlm.nih.gov/10590022/ DOI: 10.1203/00006450-199912000-00004","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Purified variants and cultured patient cells","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"trigger_kind","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null}],"evidence":[{"id":"dfb7a7fd-7303-5793-9438-76540cc0aa29","evidence_kind":"source_excerpt","locator":"Lines 507-518","start_line":507,"end_line":518,"excerpt":"### b7-hlcs-t610\nThe human HLCS Thr610-deletion variant had a biotin Km approximately three times the wild-type value.\nCondition category: machinery_impairment\nnutrient_topic: Biotin research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: Different HLCS variants impair biotin use by different amounts.\norganism: Homo sapiens\ntissue_or_cell_type: Purified variants and cultured patient cells\nexperimental_model: Kinetics of seven human HLCS variants, patient cells and clinical response comparison\nlimitations: Biotin responsiveness varied with residual enzyme capacity. Genotype effects must not be equated with ordinary dietary biotin deficiency.\nexposure: Genetic variants and biotin supplementation\nevidence_span: {\"source_cache\": \"artifacts/biotin-research/10590022.abstract.txt\", \"locator\": \"Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"bbdc1b8fa77a6935ced529e847093935cf4c8c9e056470e81aa3473968b980c5\", \"start_char\": 0, \"end_char\": 1628, \"text_sha256\": \"bbdc1b8fa77a6935ced529e847093935cf4c8c9e056470e81aa3473968b980c5\"}\n[b7-p10590022] Relationship between kinetic properties of mutant enzyme and biochemical and clinical responsiveness to biotin in holocarboxylase synthetase deficiency. (1999). https://pubmed.ncbi.nlm.nih.gov/10590022/ DOI: 10.1203/00006450-199912000-00004","model_system":"Kinetics of seven human HLCS variants, patient cells and clinical response comparison","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [b7-p10590022] Relationship between kinetic properties of mutant enzyme and biochemical and clinical responsiveness to biotin in holocarboxylase synthetase deficiency. 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