{"gene":"CKMT2","run_date":"2026-06-09T22:57:18","timeline":{"discoveries":[{"year":1993,"finding":"The CKMT2 gene (sarcomeric mitochondrial creatine kinase 2) was mapped to chromosome 5q13.3 by fluorescence in situ hybridization using YAC clones, and positioned between D5S424 and D5S428 on the multipoint map, distal to the spinal muscular atrophy locus.","method":"Fluorescence in situ hybridization (FISH) of YAC clones; genetic mapping in CEPH families","journal":"Genomics","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct chromosomal localization by FISH with genetic confirmation, single study","pmids":["8276398"],"is_preprint":false},{"year":2022,"finding":"CKMT2 protein expression was significantly downregulated in an ovariectomized female rat OSAHS model compared to control, sham, and estrogen-treatment groups, and co-regulated with ESRRG and PERM1 proteins, suggesting CKMT2 participates in a ESRRG-PERM1-CKMT2 signaling axis relevant to genioglossal muscle contractile function.","method":"Western blotting in rat OSAHS model with ovariectomy and estrogen treatment groups","journal":"Transplant immunology","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single method (western blot), single lab, no direct mechanistic interrogation of CKMT2 function","pmids":["35623593"],"is_preprint":false},{"year":2024,"finding":"CKMT2 protein is released into the plasma specifically following reperfused (but not non-reperfused) acute myocardial infarction in mice, with elevated plasma levels significantly associated with infarct size and impaired left ventricular function, indicating CKMT2 is a mitochondrial protein released upon reperfusion-specific cardiac injury.","method":"Untargeted mass spectrometry and ELISA-based validation of plasma proteins in mouse reperfused vs. non-reperfused AMI model; echocardiography and TTC staining for functional/morphological endpoints","journal":"Biomedicines","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — two orthogonal methods (MS + ELISA) in controlled animal model, single lab","pmids":["39457679"],"is_preprint":false},{"year":2025,"finding":"CKMT2 overexpression in duck myoblasts significantly promoted myoblast proliferation and myotube differentiation, while knockdown had the opposite effect, establishing CKMT2 as a functional regulator of skeletal muscle myoblast proliferation and differentiation.","method":"Gain- and loss-of-function experiments (overexpression and knockdown) in duck myoblast cells with cellular readouts of proliferation and myotube differentiation","journal":"Animals","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single lab, single cellular system (non-human avian), no mechanistic pathway placement beyond phenotypic readout","pmids":["41463801"],"is_preprint":false}],"current_model":"CKMT2 (sarcomeric mitochondrial creatine kinase 2) is a mitochondrial enzyme encoded on chromosome 5q13.3 that participates in energy homeostasis in muscle tissue; it is released into circulation specifically upon mitochondrial damage from reperfusion injury, and experimental evidence in avian myoblasts indicates it promotes myoblast proliferation and differentiation, while co-regulation with ESRRG and PERM1 has been observed in a rodent model of muscle function impairment."},"narrative":{"mechanistic_narrative":"CKMT2 (sarcomeric mitochondrial creatine kinase 2) is a mitochondrial protein implicated in muscle energy homeostasis, mapped to chromosome 5q13.3 distal to the spinal muscular atrophy locus [PMID:8276398]. In a mouse model of acute myocardial infarction, CKMT2 protein is released into plasma specifically following reperfused — but not non-reperfused — injury, with circulating levels tracking infarct size and impaired left ventricular function, identifying it as a mitochondrial protein liberated upon reperfusion-specific cardiac damage [PMID:39457679]. Beyond chromosomal localization and this injury-release phenotype, the enzymatic and signaling mechanisms of CKMT2 have not been characterized in the available corpus; lower-confidence findings link it to a putative ESRRG–PERM1–CKMT2 axis in genioglossal muscle and to control of myoblast proliferation and differentiation, but neither has been placed mechanistically.","teleology":[{"year":1993,"claim":"Establishing the genomic position of CKMT2 was the first step toward distinguishing it from neighboring disease loci on chromosome 5q.","evidence":"FISH of YAC clones with genetic mapping in CEPH families","pmids":["8276398"],"confidence":"Medium","gaps":["No functional or enzymatic characterization","Does not address tissue expression or regulation"]},{"year":2022,"claim":"CKMT2 was placed in a candidate hormone-responsive regulatory context, addressing whether its abundance tracks muscle contractile dysfunction.","evidence":"Western blotting in an ovariectomized rat OSAHS model with estrogen treatment groups","pmids":["35623593"],"confidence":"Low","gaps":["Single method (western blot), no direct interrogation of CKMT2 function","Co-regulation with ESRRG and PERM1 is correlative, not a demonstrated physical or signaling axis","Direction of causality unestablished"]},{"year":2024,"claim":"It was unknown whether CKMT2 could serve as a damage-specific marker; this work showed its plasma release is selective for reperfusion injury and correlates with cardiac dysfunction.","evidence":"Untargeted mass spectrometry plus ELISA validation of plasma in a mouse reperfused vs. non-reperfused AMI model, with echocardiography and TTC staining","pmids":["39457679"],"confidence":"Medium","gaps":["Mechanism of release upon reperfusion not defined","Whether release is cause or consequence of dysfunction unresolved","Human relevance not established"]},{"year":2025,"claim":"Direct perturbation tested whether CKMT2 actively regulates muscle cell behavior rather than merely marking it, showing it drives myoblast proliferation and differentiation.","evidence":"Gain- and loss-of-function (overexpression and knockdown) in duck myoblasts with proliferation and myotube differentiation readouts","pmids":["41463801"],"confidence":"Low","gaps":["Non-human avian system only","No mechanistic pathway placement beyond phenotypic readout","No link to its mitochondrial creatine kinase enzymatic activity"]},{"year":null,"claim":"The enzymatic mechanism, substrates, interaction partners, and the molecular basis for reperfusion-specific release of CKMT2 remain undefined.","evidence":"","pmids":[],"confidence":"Low","gaps":["No biochemical reconstitution of catalytic activity in the corpus","No validated direct protein partners","Human functional data absent"]}],"mechanism_profile":{"molecular_activity":[],"localization":[{"term_id":"GO:0005739","term_label":"mitochondrion","supporting_discovery_ids":[2]}],"pathway":[],"complexes":[],"partners":[],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"P17540","full_name":"Creatine kinase S-type, mitochondrial","aliases":["Basic-type mitochondrial creatine kinase","Mib-CK","Sarcomeric mitochondrial creatine kinase","S-MtCK"],"length_aa":419,"mass_kda":47.5,"function":"Reversibly catalyzes the transfer of phosphate between ATP and various phosphogens (e.g. creatine phosphate). Creatine kinase isoenzymes play a central role in energy transduction in tissues with large, fluctuating energy demands, such as skeletal muscle, heart, brain and spermatozoa","subcellular_location":"Mitochondrion inner membrane","url":"https://www.uniprot.org/uniprotkb/P17540/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/CKMT2","classification":"Not Classified","n_dependent_lines":0,"n_total_lines":1208,"dependency_fraction":0.0},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/CKMT2","total_profiled":1310},"omim":[{"mim_id":"123295","title":"CREATINE KINASE, MITOCHONDRIAL 2; CKMT2","url":"https://www.omim.org/entry/123295"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"","locations":[],"tissue_specificity":"Group enriched","tissue_distribution":"Detected in many","driving_tissues":[{"tissue":"heart muscle","ntpm":1157.4},{"tissue":"skeletal muscle","ntpm":1341.7},{"tissue":"tongue","ntpm":2166.2}],"url":"https://www.proteinatlas.org/search/CKMT2"},"hgnc":{"alias_symbol":["SMTCK"],"prev_symbol":[]},"alphafold":{"accession":"P17540","domains":[{"cath_id":"1.10.135.10","chopping":"41-130","consensus_level":"high","plddt":95.2926,"start":41,"end":130},{"cath_id":"3.30.590.10","chopping":"146-402","consensus_level":"medium","plddt":95.1523,"start":146,"end":402}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/P17540","model_url":"https://alphafold.ebi.ac.uk/files/AF-P17540-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-P17540-F1-predicted_aligned_error_v6.png","plddt_mean":89.44},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=CKMT2","jax_strain_url":"https://www.jax.org/strain/search?query=CKMT2"},"sequence":{"accession":"P17540","fasta_url":"https://rest.uniprot.org/uniprotkb/P17540.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/P17540/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/P17540"}},"corpus_meta":[{"pmid":"35866106","id":"PMC_35866106","title":"Long Non-Coding RNA CKMT2-AS1 Reduces the Viability of Colorectal Cancer Cells by Targeting AKT/mTOR Signaling Pathway.","date":"2022","source":"Iranian journal of public health","url":"https://pubmed.ncbi.nlm.nih.gov/35866106","citation_count":18,"is_preprint":false},{"pmid":"8276398","id":"PMC_8276398","title":"The gene for creatine kinase, mitochondrial 2 (sarcomeric; CKMT2), maps to chromosome 5q13.3.","date":"1993","source":"Genomics","url":"https://pubmed.ncbi.nlm.nih.gov/8276398","citation_count":12,"is_preprint":false},{"pmid":"39457679","id":"PMC_39457679","title":"Mitochondrial Creatine Kinase 2 (Ckmt2) as a Plasma-Based Biomarker for Evaluating Reperfusion Injury in Acute Myocardial Infarction.","date":"2024","source":"Biomedicines","url":"https://pubmed.ncbi.nlm.nih.gov/39457679","citation_count":3,"is_preprint":false},{"pmid":"41135276","id":"PMC_41135276","title":"Sulforaphane targets STAT3-CKMT2-AS1 to suppress gastric cancer via PSMB8 downregulation and AIMP1 stabilization.","date":"2025","source":"Phytomedicine : international journal of phytotherapy and phytopharmacology","url":"https://pubmed.ncbi.nlm.nih.gov/41135276","citation_count":1,"is_preprint":false},{"pmid":"41236096","id":"PMC_41236096","title":"LncRNA CKMT2-AS1 Promotes Hepatocellular Carcinoma Development Via Sponging miR-142-5p and Targeting IFITM3.","date":"2025","source":"The Turkish journal of gastroenterology : the official journal of Turkish Society of Gastroenterology","url":"https://pubmed.ncbi.nlm.nih.gov/41236096","citation_count":1,"is_preprint":false},{"pmid":"35623593","id":"PMC_35623593","title":"Molecular mechanism of the ESRRG-PERM1-CKMT2 signal axis in ovariectomized female rats with OSAHS.","date":"2022","source":"Transplant immunology","url":"https://pubmed.ncbi.nlm.nih.gov/35623593","citation_count":1,"is_preprint":false},{"pmid":"41463801","id":"PMC_41463801","title":"CKMT2 Promotes Breast Muscle Growth in Qiangying Ducks via Enhancing Myoblast Proliferation and Differentiation.","date":"2025","source":"Animals : an open access journal from MDPI","url":"https://pubmed.ncbi.nlm.nih.gov/41463801","citation_count":0,"is_preprint":false},{"pmid":"41878336","id":"PMC_41878336","title":"Metabolic profiling of the TME uncovers the contrasting impacts of CKMT2 and PDE2A in CRC progression and therapeutic response.","date":"2026","source":"Frontiers in pharmacology","url":"https://pubmed.ncbi.nlm.nih.gov/41878336","citation_count":0,"is_preprint":false},{"pmid":"42226299","id":"PMC_42226299","title":"Long non-coding RNA CKMT2-AS1 serves as a biomarker for osteoarthritis and participates in chondrocyte injury via miR-6720-5p.","date":"2026","source":"Journal of orthopaedic surgery and research","url":"https://pubmed.ncbi.nlm.nih.gov/42226299","citation_count":0,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":7190,"output_tokens":1028,"usd":0.018495,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":7537,"output_tokens":1480,"usd":0.037343,"stage2_stop_reason":"end_turn"},"total_usd":0.055838,"stage1_batch_id":"msgbatch_01ACAxJQabDsht39JXeWG22d","stage2_batch_id":"msgbatch_01QEU22A9U5sbPTgsMzTmvSf","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 1993,\n      \"finding\": \"The CKMT2 gene (sarcomeric mitochondrial creatine kinase 2) was mapped to chromosome 5q13.3 by fluorescence in situ hybridization using YAC clones, and positioned between D5S424 and D5S428 on the multipoint map, distal to the spinal muscular atrophy locus.\",\n      \"method\": \"Fluorescence in situ hybridization (FISH) of YAC clones; genetic mapping in CEPH families\",\n      \"journal\": \"Genomics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct chromosomal localization by FISH with genetic confirmation, single study\",\n      \"pmids\": [\"8276398\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"CKMT2 protein expression was significantly downregulated in an ovariectomized female rat OSAHS model compared to control, sham, and estrogen-treatment groups, and co-regulated with ESRRG and PERM1 proteins, suggesting CKMT2 participates in a ESRRG-PERM1-CKMT2 signaling axis relevant to genioglossal muscle contractile function.\",\n      \"method\": \"Western blotting in rat OSAHS model with ovariectomy and estrogen treatment groups\",\n      \"journal\": \"Transplant immunology\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single method (western blot), single lab, no direct mechanistic interrogation of CKMT2 function\",\n      \"pmids\": [\"35623593\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"CKMT2 protein is released into the plasma specifically following reperfused (but not non-reperfused) acute myocardial infarction in mice, with elevated plasma levels significantly associated with infarct size and impaired left ventricular function, indicating CKMT2 is a mitochondrial protein released upon reperfusion-specific cardiac injury.\",\n      \"method\": \"Untargeted mass spectrometry and ELISA-based validation of plasma proteins in mouse reperfused vs. non-reperfused AMI model; echocardiography and TTC staining for functional/morphological endpoints\",\n      \"journal\": \"Biomedicines\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — two orthogonal methods (MS + ELISA) in controlled animal model, single lab\",\n      \"pmids\": [\"39457679\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"CKMT2 overexpression in duck myoblasts significantly promoted myoblast proliferation and myotube differentiation, while knockdown had the opposite effect, establishing CKMT2 as a functional regulator of skeletal muscle myoblast proliferation and differentiation.\",\n      \"method\": \"Gain- and loss-of-function experiments (overexpression and knockdown) in duck myoblast cells with cellular readouts of proliferation and myotube differentiation\",\n      \"journal\": \"Animals\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single lab, single cellular system (non-human avian), no mechanistic pathway placement beyond phenotypic readout\",\n      \"pmids\": [\"41463801\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"CKMT2 (sarcomeric mitochondrial creatine kinase 2) is a mitochondrial enzyme encoded on chromosome 5q13.3 that participates in energy homeostasis in muscle tissue; it is released into circulation specifically upon mitochondrial damage from reperfusion injury, and experimental evidence in avian myoblasts indicates it promotes myoblast proliferation and differentiation, while co-regulation with ESRRG and PERM1 has been observed in a rodent model of muscle function impairment.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"CKMT2 (sarcomeric mitochondrial creatine kinase 2) is a mitochondrial protein implicated in muscle energy homeostasis, mapped to chromosome 5q13.3 distal to the spinal muscular atrophy locus [#0]. In a mouse model of acute myocardial infarction, CKMT2 protein is released into plasma specifically following reperfused — but not non-reperfused — injury, with circulating levels tracking infarct size and impaired left ventricular function, identifying it as a mitochondrial protein liberated upon reperfusion-specific cardiac damage [#2]. Beyond chromosomal localization and this injury-release phenotype, the enzymatic and signaling mechanisms of CKMT2 have not been characterized in the available corpus; lower-confidence findings link it to a putative ESRRG–PERM1–CKMT2 axis in genioglossal muscle and to control of myoblast proliferation and differentiation, but neither has been placed mechanistically.\",\n  \"teleology\": [\n    {\n      \"year\": 1993,\n      \"claim\": \"Establishing the genomic position of CKMT2 was the first step toward distinguishing it from neighboring disease loci on chromosome 5q.\",\n      \"evidence\": \"FISH of YAC clones with genetic mapping in CEPH families\",\n      \"pmids\": [\"8276398\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No functional or enzymatic characterization\", \"Does not address tissue expression or regulation\"]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"CKMT2 was placed in a candidate hormone-responsive regulatory context, addressing whether its abundance tracks muscle contractile dysfunction.\",\n      \"evidence\": \"Western blotting in an ovariectomized rat OSAHS model with estrogen treatment groups\",\n      \"pmids\": [\"35623593\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"Single method (western blot), no direct interrogation of CKMT2 function\", \"Co-regulation with ESRRG and PERM1 is correlative, not a demonstrated physical or signaling axis\", \"Direction of causality unestablished\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"It was unknown whether CKMT2 could serve as a damage-specific marker; this work showed its plasma release is selective for reperfusion injury and correlates with cardiac dysfunction.\",\n      \"evidence\": \"Untargeted mass spectrometry plus ELISA validation of plasma in a mouse reperfused vs. non-reperfused AMI model, with echocardiography and TTC staining\",\n      \"pmids\": [\"39457679\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Mechanism of release upon reperfusion not defined\", \"Whether release is cause or consequence of dysfunction unresolved\", \"Human relevance not established\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Direct perturbation tested whether CKMT2 actively regulates muscle cell behavior rather than merely marking it, showing it drives myoblast proliferation and differentiation.\",\n      \"evidence\": \"Gain- and loss-of-function (overexpression and knockdown) in duck myoblasts with proliferation and myotube differentiation readouts\",\n      \"pmids\": [\"41463801\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"Non-human avian system only\", \"No mechanistic pathway placement beyond phenotypic readout\", \"No link to its mitochondrial creatine kinase enzymatic activity\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The enzymatic mechanism, substrates, interaction partners, and the molecular basis for reperfusion-specific release of CKMT2 remain undefined.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"No biochemical reconstitution of catalytic activity in the corpus\", \"No validated direct protein partners\", \"Human functional data absent\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [],\n    \"localization\": [\n      {\"term_id\": \"GO:0005739\", \"supporting_discovery_ids\": [2]}\n    ],\n    \"pathway\": [],\n    \"complexes\": [],\n    \"partners\": [],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"tie","faith_supported":2,"faith_total":2,"faith_pct":100.0}}