{"schema":"https://ver.cy/schemas/card/1.0.0","id":"vr.tr.msh2","code":"thing-q14911688","url":"https://ver.cy/models/thing/q14911688/","name":"MSH2","alternateNames":[],"kind":"thing","status":"published","version":"0.1.0-research.1","language":"en","classifiers":{"family":"Thing Registry","category":"Physical world and living systems","entryKind":"thing","plane":"PHY","domain":["PHY.OBJ"],"industry":[],"navPath":"","tags":[],"facets":{}},"whatItIs":"MSH2 is a human protein-coding gene whose product recognizes DNA replication errors in complexes with MSH6 or MSH3 and initiates DNA mismatch repair.","purpose":"Enable an agent to identify MSH2, distinguish its gene and protein referents, and assess evidence about its molecular state and contribution to DNA mismatch repair.","scope":{"in":["Species-qualified MSH2 identity and reference accessions","Relationships among the MSH2 locus, transcripts, protein isoforms and observed variants","MSH2 participation in MSH6-containing and MSH3-containing complexes","DNA-substrate recognition and nucleotide-dependent functional states","MSH2-specific expression, localization and functional-assay evidence"],"out":["Independent models of MSH3, MSH6 and downstream repair proteins","The complete DNA mismatch-repair pathway","Individual patients, pedigrees and tumour specimens","Diagnosis, surveillance and treatment of hereditary cancer syndromes","Laboratory instruments, reagent inventories and generic assay procedures"],"boundaries":[]},"distinguishingFeatures":["Resolve the symbol against a species-qualified accession: human MSH2 is represented by NCBI Gene 4436, whereas a protein requires a protein accession. [NCBI Gene](https://www.ncbi.nlm.nih.gov/gene/4436/)","Distinguish MSH2 from its binding partners: human MSH2 forms complexes with MSH3 or MSH6, so identification of a partner alone does not identify MSH2. [Primary study](https://pmc.ncbi.nlm.nih.gov/articles/PMC19374/)","Distinguish the MSH2 subunit from the complete MSH2-MSH6 or MSH2-MSH3 complex by recording the experimentally identified constituents.","Require a sequence and reference mapping to distinguish an MSH2 variant or engineered construct from the reference product and from other MutS-family proteins.","Treat MSH2 abundance, mismatch binding and successful repair as separate observations; one measurement does not establish all three."],"structure":{"bundles":[{"id":"msh2-reference-identity","name":"MSH2 reference identity","description":"Establish what molecular entity the registry name denotes.","layers":[{"id":"species-and-referent","name":"Species and referent","description":"Resolve organism and gene-versus-protein identity before attaching biological claims.","findings":[{"id":"human-reference-anchor","name":"Human reference anchor","description":"NCBI identifies human MSH2 as a protein-coding gene with Gene ID 4436; this supports the provisional human interpretation but does not establish the registry's intended referent. [NCBI Gene](https://www.ncbi.nlm.nih.gov/gene/4436/)","questions":[{"text":"Does the registry's originating record identify human MSH2, an ortholog or a cross-species concept?","id":"human-reference-anchor-q01","kind":"provenance"},{"text":"Does vr.tr.msh2 primarily denote the gene locus or the encoded protein?","id":"human-reference-anchor-q02","kind":"boundary"}]}]},{"id":"sequence-and-product-mapping","name":"Sequence and product mapping","description":"Connect each molecular observation to an explicit reference.","findings":[{"id":"reference-qualified-products","name":"Reference-qualified products","description":"Record transcript, protein and construct references separately, including sequence versions and any engineered changes.","questions":[{"text":"Which versioned transcript and protein accessions define the MSH2 product under examination?","id":"reference-qualified-products-q01","kind":"definition"},{"text":"Does the observed material contain a splice difference, truncation, tag or substitution relative to that reference?","id":"reference-qualified-products-q02","kind":"measurement"}]}]}]},{"id":"msh2-repair-assemblies","name":"MSH2 repair assemblies","description":"Describe MSH2 through its experimentally supported partner and substrate relationships.","layers":[{"id":"partner-defined-complexes","name":"Partner-defined complexes","description":"Identify the assembly present in each functional observation.","findings":[{"id":"msh3-and-msh6-partnerships","name":"MSH3 and MSH6 partnerships","description":"Human MSH2 forms specific mispair-binding complexes with MSH3 and MSH6; record the partner as part of the experimental context. [Primary study](https://pmc.ncbi.nlm.nih.gov/articles/PMC19374/)","questions":[{"text":"Was MSH2 measured alone, with MSH6 or with MSH3?","id":"msh3-and-msh6-partnerships-q01","kind":"definition"},{"text":"What evidence establishes association rather than merely detecting both proteins in the same sample?","id":"msh3-and-msh6-partnerships-q02","kind":"provenance"}]}]},{"id":"substrate-resolved-recognition","name":"Substrate-resolved recognition","description":"Attach binding observations to the exact DNA substrate and complex.","findings":[{"id":"mismatch-specific-readouts","name":"Mismatch-specific readouts","description":"Represent DNA recognition using mismatch identity, loop size, sequence context and a matched-duplex comparison.","questions":[{"text":"Which base mismatch or insertion/deletion loop was tested, and in what DNA sequence context?","id":"mismatch-specific-readouts-q01","kind":"definition"},{"text":"How did binding compare with matched DNA under the same protein and buffer conditions?","id":"mismatch-specific-readouts-q02","kind":"measurement"}]}]}]},{"id":"msh2-functional-state","name":"MSH2 functional state","description":"Separate nucleotide-dependent molecular behaviour from cellular availability.","layers":[{"id":"nucleotide-coupled-behaviour","name":"Nucleotide-coupled behaviour","description":"Record nucleotide conditions and the molecular transition actually observed.","findings":[{"id":"binding-hydrolysis-and-clamping","name":"Binding, hydrolysis and clamping","description":"Experiments on human MSH2-MSH6 support ATP-bound sliding-clamp behaviour; ATP binding, hydrolysis and clamp formation require distinct evidence. [Primary study](https://pubmed.ncbi.nlm.nih.gov/10078208/)","questions":[{"text":"Which nucleotides, concentrations and cofactors were present during the MSH2-complex assay?","id":"binding-hydrolysis-and-clamping-q01","kind":"measurement"},{"text":"Does the readout establish nucleotide binding, ATP turnover, DNA retention or sliding-clamp formation?","id":"binding-hydrolysis-and-clamping-q02","kind":"boundary"}]}]},{"id":"cellular-availability","name":"Cellular availability","description":"Locate and quantify the relevant MSH2 product in its biological context.","findings":[{"id":"expression-and-localization-evidence","name":"Expression and localization evidence","description":"Keep RNA expression, protein abundance and subcellular distribution separate, with cell type and detection controls.","questions":[{"text":"Was MSH2 RNA or protein measured, in which cells and with what normalization?","id":"expression-and-localization-evidence-q01","kind":"measurement"},{"text":"What localization and detection controls distinguish reduced MSH2 from technical non-detection?","id":"expression-and-localization-evidence-q02","kind":"provenance"}]}]}]},{"id":"msh2-variation-and-inference","name":"MSH2 variation and inference","description":"Relate molecular changes to measured consequences without exceeding the evidence.","layers":[{"id":"variant-to-function","name":"Variant to function","description":"Compare a specified altered MSH2 product with an appropriate reference.","findings":[{"id":"effect-specific-comparison","name":"Effect-specific comparison","description":"Record whether a change affects abundance, partner association, substrate recognition, nucleotide behaviour or integrated repair, including inconclusive results.","questions":[{"text":"Which reference-qualified MSH2 alteration was tested, and was it endogenous or engineered?","id":"effect-specific-comparison-q01","kind":"provenance"},{"text":"Which functional measurements differ from the reference, with what controls and uncertainty?","id":"effect-specific-comparison-q02","kind":"measurement"}]}]},{"id":"causal-attribution","name":"Causal attribution","description":"Assess whether an observed repair phenotype can be assigned to MSH2.","findings":[{"id":"msh2-specific-evidence","name":"MSH2-specific evidence","description":"Require evidence linking the phenotype to MSH2 rather than inferring causation from a general repair readout or a single expression result.","questions":[{"text":"What perturbation, restoration or orthogonal assay supports assigning the observed defect to MSH2?","id":"msh2-specific-evidence-q01","kind":"provenance"},{"text":"Which additional observation would resolve competing explanations involving MSH2 abundance, its partners or downstream repair?","id":"msh2-specific-evidence-q02","kind":"action"}]}]}]},{"id":"evidence-and-external-alignment","name":"Evidence and external alignment","description":"What the world already says about this thing, gathered so the model can be checked against it.","layers":[{"id":"reported-evidence","name":"Reported evidence","description":"Findings from the breadth pass, kept separate from the structural claims.","findings":[{"id":"evidence-confidence-notes","name":"Check these first","description":"Recalled without web access and unsourced; every item is a lead to verify.","questions":[{"text":"Which of these check these first hold for the sense of MSH2 this model covers, and on what evidence?","id":"evidence-confidence-notes-q01","kind":"provenance"}]},{"id":"evidence-identifiers","name":"Identifiers and schemes","description":"Recalled without web access and unsourced; every item is a lead to verify.","questions":[{"text":"Which of these identifiers and schemes hold for the sense of MSH2 this model covers, and on what evidence?","id":"evidence-identifiers-q01","kind":"provenance"}]},{"id":"evidence-real-world-use","name":"Real-world use","description":"Recalled without web access and unsourced; every item is a lead to verify.","questions":[{"text":"Which of these real-world use hold for the sense of MSH2 this model covers, and on what evidence?","id":"evidence-real-world-use-q01","kind":"provenance"}]},{"id":"evidence-failure-modes-and-hazards","name":"Failure modes and hazards","description":"Recalled without web access and unsourced; every item is a lead to verify.","questions":[{"text":"Which of these failure modes and hazards hold for the sense of MSH2 this model covers, and on what evidence?","id":"evidence-failure-modes-and-hazards-q01","kind":"provenance"}]},{"id":"evidence-neighbours","name":"Neighbouring kinds and how to tell them apart","description":"Recalled without web access and unsourced; every item is a lead to verify.","questions":[{"text":"Which of these neighbouring kinds and how to tell them apart hold for the sense of MSH2 this model covers, and on what evidence?","id":"evidence-neighbours-q01","kind":"provenance"}]}]}]}]},"agentConduct":{"may":["Describe MSH2 and its role in DNA mismatch repair, citing sources.","Explain in general terms that inherited variants can raise cancer risk and that genetic counselling is available."],"mustNot":["Tell a person they have a hereditary cancer syndrome from a variant without clinical review.","Share a person's genetic result with relatives, employers or insurers without consent.","Classify a variant of uncertain significance as harmful or harmless without evidence.","Recommend screening or surgery for a person."],"requiresHuman":["Returning genetic results to a person or family.","Any decision on screening or preventive surgery."]},"ethics":{"considerations":["Hereditary cancer results affect whole families and can lead to discrimination.","People have a right to decide whether to learn their genetic risk."],"affectedParties":["People with tested variants","Relatives","Clinicians and counsellors"]},"owners":{"steward":"The person whose genome carries it; laboratories and clinical variant databases hold records.","roles":[],"masterSystems":["Clinical variant databases","Gene and variant databases"]},"relations":[{"target":"Q20747295","type":"parent","note":"registry parent class"}],"interaction":{"identity":{"applicability":"required","items":["Vercy registry: vr.tr.msh2","Wikidata: Q14911688 (https://www.wikidata.org/wiki/Q14911688)"]},"properties":{"applicability":"required","items":["Molecular referent: gene locus | transcript | protein | engineered construct","Species and reference identity: taxon identifier plus versioned gene, transcript or protein accession","Sequence alteration: reference-qualified DNA, RNA or protein change; endogenous or engineered origin","Complex membership: MSH6-associated | MSH3-associated | unbound | other observed association | unresolved","Nucleotide condition: ATP-bound | ADP-bound | nucleotide-free | mixed | unmeasured","DNA substrate: matched duplex | specified base mismatch | insertion/deletion loop with size in nucleotides","MSH2 abundance: assay-specific concentration or normalized abundance, with denominator and detection limit","Subcellular distribution: observed compartment, cell type, method and sampling condition","Repair-related activity: binding affinity in mol/L, ATP turnover in s^-1, or repair fraction relative to specified controls"]},"recognition":{"applicability":"required","items":["Not visible; known from sequence data or tumour staining for the protein.","Loss of protein staining in tumour tissue is reported by pathologists."]},"capabilities":{"applicability":"required","items":["Resolve an MSH2-labelled record to a species and molecular reference.","Map an observed sequence alteration to the relevant transcript and protein product.","Compare MSH2 observations only after aligning partner, substrate and assay conditions.","Identify which measurement could distinguish reduced abundance from impaired complex formation or activity.","Link a functional interpretation to its experimental evidence and record conflicting results."]},"hazards":{"applicability":"required","items":["Misclassification of variants.","Genetic discrimination after disclosure."]},"interfaces":{"applicability":"required","items":["Human gene nomenclature, HUGO Gene Nomenclature Committee (HGNC), which approves the gene symbol."]},"context":{"applicability":"required","items":["The human MSH2 gene is encountered in studies of DNA mismatch repair, genome stability and inherited cancer susceptibility.","Its sequence and expression are examined to investigate repair defects, with findings about the gene distinguished from measurements of its encoded protein."]}},"sources":[{"title":"Wikidata item Q14911688: MSH2","url":"https://www.wikidata.org/wiki/Q14911688","note":"identity and sense of the item"},{"title":"Wikipedia: MSH2","url":"https://en.wikipedia.org/wiki/MSH2","note":"general description of the item"}],"openQuestions":["What original registry source establishes the species and gene-versus-protein meaning of MSH2?","Does an existing Vercy model already own this molecular concept and require a registry link instead of a separate publication?","Which reference transcripts and protein isoforms should anchor this entry, and which have direct functional evidence?","Which assay conditions and controls support reproducible comparisons of MSH2 activity across studies?","Which proposed MSH2 functions beyond mismatch repair have sufficient direct evidence to justify extending this draft?"],"resources":{"spec":"/models/things/publications/thing-q14911688/spec.json"},"provenance":{"origin":"thing registry research (pass 2)","builtFrom":["models/things/publications/thing-q14911688/spec.json"],"providers":["Codex"],"researchStatus":"unreviewed","generatedAt":"2026-09-12T11:25:53Z","builder":"tools/build_cards.py@1.0.0"},"completeness":{"sections":{"classifiers":"filled","whatItIs":"filled","purpose":"filled","distinguishingFeatures":"filled","structure":"filled","agentConduct":"filled","ethics":"filled","owners":"filled","relations":"filled","interaction.identity":"filled","interaction.properties":"filled","interaction.recognition":"filled","interaction.capabilities":"filled","interaction.hazards":"filled","interaction.interfaces":"filled","interaction.context":"filled","sources":"filled"},"notes":{"_gate":"Published through the thing publication gate 1.0 on 2026-10-07T10:10:26+00:00: completeness 1.00; sense: Wikidata description; 2 live sources; review by codex: pass"},"score":1.0}}