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Protein / target

DNA mismatch repair protein Msh3

Encoded byMSH3P20585Homo sapiensSwiss-Prot
UniProt: P20585Ensembl: ENSG00000113318HGNC: HGNC:7326NCBI Gene: 4437
Small-molecule tractable
Druggability
Structure with Ligand
1
Research papers

Protein at a glance

Biological role

ATP-dependent DNA damage sensor

Strongest disease association

Neoplastic Syndromes, Hereditary

Via encoding gene MSH3 · Genetic evidence · score 0.95

Research activity

Emerging research

1 papers · latest 2025

Derived from structured UniProt, Open Targets and literature data on this page.

Protein profile

UniProt 2026_02

Canonical identity and biological annotation from UniProt.

Function overview

Component of the post-replicative DNA mismatch repair system (MMR).

View complete UniProt function annotation

Component of the post-replicative DNA mismatch repair system (MMR). Heterodimerizes with MSH2 to form MutS beta which binds to DNA mismatches thereby initiating DNA repair. When bound, the MutS beta heterodimer bends the DNA helix and shields approximately 20 base pairs. MutS beta recognizes large insertion-deletion loops (IDL) up to 13 nucleotides long. After mismatch binding, forms a ternary complex with the MutL alpha heterodimer, which is thought to be responsible for directing the downstream MMR events, including strand discrimination, excision, and resynthesis

Domains and Gene Ontology detail (15)

Gene Ontology

  • Cmembrane
  • CMutSbeta complex
  • Cnucleoplasm
  • Cnucleus
  • FATP binding
  • FATP-dependent DNA damage sensor activity
  • Fdouble-stranded DNA binding
  • Fenzyme binding
  • Fmismatched DNA binding
  • PDNA repair
  • Pmaintenance of DNA repeat elements
  • Pmismatch repair

1137 aa · 127 kDa

Translational evidence

Open Targets 26

Why this target matters therapeutically, strongest evidence first. Disease associations are gene-level (via the gene that encodes this protein) and open into the full confidence synthesis; the development universe, tractability and safety annotations are target-level, from Open Targets.

Strongest disease associations · via encoding gene MSH3

Gene-level evidence surfaced through the gene MSH3that encodes this protein — not a direct protein–disease relationship. Ranked by Forefront's causal-directness weighting, so genetically- and clinically-evidenced diseases lead over ones that merely share the literature.

Endometrial Neoplasms
0.95Well supported

Genetic evidence dominant · Open Targets 0.65

Neoplastic Syndromes, Hereditary
0.95Well supported

Genetic evidence dominant · Open Targets 0.58

Inherited cancer-predisposing syndrome
0.95Well supported

Genetic evidence dominant · Open Targets 0.57

Neurodegenerative Diseases
0.19Preliminary

Pathway evidence dominant · Open Targets 0.28 · no direct causal or clinical evidence

View evidence synthesis (4)
Endometrial NeoplasmsWell supported
0.95
agreement 0.84–1.00
Genetic70%Somatic mutation28%Literature2%Genetic literaturedup

Open Targets aggregate 0.65 · 3 independent evidence families · 1 not counted as duplicate

Neoplastic Syndromes, HereditaryWell supported
0.95
agreement 0.81–1.00
Genetic100%Literature0%

Open Targets aggregate 0.58 · 2 independent evidence families

Inherited cancer-predisposing syndromeWell supported
0.95
agreement 0.83–1.00
Genetic100%

Open Targets aggregate 0.57 · 1 independent evidence family

Neurodegenerative DiseasesPreliminary
0.19
agreement 0.01–0.36
Pathway98%Literature2%

Open Targets aggregate 0.28 · 2 independent evidence families · no direct causal or clinical evidence

The evidence agreement range shows how closely the independent evidence families agree — it is not a statistical confidence interval, and nothing here is fitted to outcome data. Derived from Open Targets evidence types under Forefront weighting; the per-type scores above show the calculation.

Show all associations
Endometrial Neoplasms0.65
Neoplastic Syndromes, Hereditary0.58
Inherited cancer-predisposing syndrome0.57
Neurodegenerative Diseases0.28

Tractability

Small molecules — Emerging

Feasibility evidence (structure with ligand) — no clinical-stage drug of this modality recorded.

Protein degraders — Emerging

Feasibility evidence (database ubiquitination and half-life data) — no clinical-stage drug of this modality recorded.

View underlying tractability evidence (3)
SM · Structure with LigandPR · Database UbiquitinationPR · Half-life Data

Raw Open Targets tractability assessment buckets, by modality.

Safety-related annotations

leukopeniaClinPGxfatigueClinPGxoverall survivalClinPGxevent-free survivalClinPGxdrug toxicityClinPGxoverall survival ratesClinPGx

Terms indexed against this target in Open Targets' safety data, with their datasource. These are annotations, not causal claims: the direction of effect (whether activation or inhibition is implicated), species and evidence strength are not captured here, so an entry does not mean that modulating this target is known to cause that condition.

Research activity

1 papers · to 2025

Papers linked directly to this protein. This is the protein's own literature — descriptor-derived papers are kept separate below.

Most cited

Distinct mismatch-repair complex genes set neuronal CAG-repeat expansion rate to drive selective pathogenesis in HD mice.46 cites

Wang N · Cell · 2025

Recent

Distinct mismatch-repair complex genes set neuronal CAG-repeat expansion rate to drive selective pathogenesis in HD mice.

Wang N · Cell · 2025

Europe PMC papers linked directly to this protein.