MSH2

Human reference anchor

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/)

1. Does the registry's originating record identify human MSH2, an ortholog or a cross-species concept? provenance
2. Does vr.tr.msh2 primarily denote the gene locus or the encoded protein? boundary

Reference-qualified products

Record transcript, protein and construct references separately, including sequence versions and any engineered changes.

1. Which versioned transcript and protein accessions define the MSH2 product under examination? definition
2. Does the observed material contain a splice difference, truncation, tag or substitution relative to that reference? measurement

MSH3 and MSH6 partnerships

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/)

1. Was MSH2 measured alone, with MSH6 or with MSH3? definition
2. What evidence establishes association rather than merely detecting both proteins in the same sample? provenance

Mismatch-specific readouts

Represent DNA recognition using mismatch identity, loop size, sequence context and a matched-duplex comparison.

1. Which base mismatch or insertion/deletion loop was tested, and in what DNA sequence context? definition
2. How did binding compare with matched DNA under the same protein and buffer conditions? measurement

Binding, hydrolysis and clamping

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/)

1. Which nucleotides, concentrations and cofactors were present during the MSH2-complex assay? measurement
2. Does the readout establish nucleotide binding, ATP turnover, DNA retention or sliding-clamp formation? boundary

Expression and localization evidence

Keep RNA expression, protein abundance and subcellular distribution separate, with cell type and detection controls.

1. Was MSH2 RNA or protein measured, in which cells and with what normalization? measurement
2. What localization and detection controls distinguish reduced MSH2 from technical non-detection? provenance

Effect-specific comparison

Record whether a change affects abundance, partner association, substrate recognition, nucleotide behaviour or integrated repair, including inconclusive results.

1. Which reference-qualified MSH2 alteration was tested, and was it endogenous or engineered? provenance
2. Which functional measurements differ from the reference, with what controls and uncertainty? measurement

MSH2-specific evidence

Require evidence linking the phenotype to MSH2 rather than inferring causation from a general repair readout or a single expression result.

1. What perturbation, restoration or orthogonal assay supports assigning the observed defect to MSH2? provenance
2. Which additional observation would resolve competing explanations involving MSH2 abundance, its partners or downstream repair? action

Check these first

Recalled without web access and unsourced; every item is a lead to verify.

1. Which of these check these first hold for the sense of MSH2 this model covers, and on what evidence? provenance

Identifiers and schemes

Recalled without web access and unsourced; every item is a lead to verify.

1. Which of these identifiers and schemes hold for the sense of MSH2 this model covers, and on what evidence? provenance

Real-world use

Recalled without web access and unsourced; every item is a lead to verify.

1. Which of these real-world use hold for the sense of MSH2 this model covers, and on what evidence? provenance

Failure modes and hazards

Recalled without web access and unsourced; every item is a lead to verify.

1. Which of these failure modes and hazards hold for the sense of MSH2 this model covers, and on what evidence? provenance

Neighbouring kinds and how to tell them apart

Recalled without web access and unsourced; every item is a lead to verify.

1. Which of these neighbouring kinds and how to tell them apart hold for the sense of MSH2 this model covers, and on what evidence? provenance