SMC3 Gene: Function, Mutations, and Associated Diseases | NCBI, UniProt, OMIM

SMC3 encodes a core component of the cohesin complex, which mediates sister chromatid cohesion, DNA repair, and transcriptional regulation. The protein contains a hinge domain that allows dimerization with SMC1A, forming a V-shaped heterodimer. Post-translational modifications, including acetylation by ESCO1/ESCO2, regulate cohesin dynamics. Germline mutations cause Cornelia de Lange syndrome type 3 (CdLS3), while somatic alterations are implicated in colorectal, breast, and other cancers.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• Cohesin complex (Reactome: R-HSA-2470946)

• Cell cycle

• mitotic (Reactome: R-HSA-69278)

• DNA double-strand break repair (Reactome: R-HSA-5693606)

• Chromosome maintenance (KEGG: hsa04110)

SMC3 is a 1,217-amino-acid nuclear protein that forms a heterodimer with SMC1A via its hinge domain. The SMC1A-SMC3 dimer, together with RAD21 and STAG proteins, constitutes the cohesin complex. SMC3 contains an N-terminal Walker A motif and a C-terminal Walker B motif that together form an ATPase domain essential for cohesin loading onto chromatin. Acetylation of SMC3 at K105 and K106 by ESCO1/ESCO2 stabilizes cohesin on DNA. The protein also participates in DNA damage response by facilitating homologous recombination.