MIS12: A Key Component of the Kinetochore and Chromosome Segregation Machinery
Essential for accurate chromosome segregation; implicated in cancer and developmental disorders.
Gene Information Card
| Symbol | MIS12 |
|---|---|
| Full Name | MIS12 kinetochore complex component |
| Gene Type | Protein coding |
| Chromosomal Location | 17p13.2 |
| NCBI Gene ID | 79003 ncbi.nlm.nih.gov/gene/79003 |
| Ensembl ID | ENSG00000167842 |
| UniProt ID | Q9H081 |
| OMIM ID | 609178 |
| HGNC ID | 17965 |
| Aliases | MIS12, hMis12, MGC8407, KNTC2AP |
Description
The MIS12 gene encodes a core component of the MIS12 kinetochore complex (also known as the MIND complex), which is essential for proper kinetochore assembly and chromosome segregation during mitosis. The MIS12 complex directly links centromeric chromatin to microtubule-binding proteins, ensuring accurate chromosome attachment and spindle checkpoint signaling. Loss of MIS12 function leads to chromosome missegregation, aneuploidy, and genomic instability, which are hallmarks of cancer. MIS12 is also implicated in developmental disorders and has been studied in the context of cellular senescence and aging.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Breast cancer | MIS12 overexpression correlates with poor prognosis; promotes aneuploidy and tumor progression | PMID: 25686126; COSMIC |
| Colorectal cancer | Mutations in MIS12 lead to chromosome instability and tumorigenesis | PMID: 24755471; COSMIC |
| Lung cancer | Altered MIS12 expression associated with metastasis and drug resistance | PMID: 29367642; COSMIC |
| Developmental disorders (microcephaly, intellectual disability) | Biallelic loss-of-function mutations in MIS12 cause MCPH (autosomal recessive primary microcephaly) | OMIM #609178; PMID: 28191891 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 15.2 | Medium |
| Bone marrow | 12.8 | Medium |
| Lymph node | 11.5 | Medium |
| Spleen | 10.9 | Medium |
| Brain | 6.3 | Low |
| Heart | 5.1 | Low |
| Liver | 4.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa (cervical carcinoma) | 18.5 | High expression; used in kinetochore studies |
| K562 (leukemia) | 16.2 | High expression |
| A549 (lung carcinoma) | 14.7 | High expression |
| MCF7 (breast carcinoma) | 12.3 | Medium expression |
| HEK293 (embryonic kidney) | 10.1 | Medium expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G (p.Met1?) | Missense | <0.01% | Loss of start codon; predicted loss of function |
| c.106C>T (p.Arg36Trp) | Missense | <0.01% | Impaired kinetochore localization; associated with microcephaly |
| c.238G>A (p.Glu80Lys) | Missense | <0.01% | Reduced complex stability; linked to chromosome missegregation |
| c.334C>T (p.Arg112*) | Nonsense | <0.01% | Premature stop; loss of function; reported in cancer |
Mutation functional classification
Loss of Function (LOF)
Mutations that disrupt MIS12 protein expression or its ability to assemble into the kinetochore complex (e.g., start-loss, nonsense, missense at conserved residues) lead to chromosome segregation defects and aneuploidy.
Gain of Function (GOF)
Not well characterized; overexpression of wild-type MIS12 in cancer may act as a gain-of-function by promoting kinetochore assembly and proliferation.
Dominant Negative (DN)
Missense mutations that allow protein expression but impair complex function (e.g., p.Arg36Trp) can act in a dominant-negative manner by incorporating into the complex and disrupting its activity.
View complete mutation data：
Gene Ontology (GO)
| • chromosome (GO:0000775) | • kinetochore (GO:0000776) |
| • condensed chromosome kinetochore (GO:0000777) | • chromosome segregation (GO:0007059) |
| • cell division (GO:0051301) | • spindle (GO:0005819) |
| • cytosol (GO:0005829) | • nucleus (GO:0005634) |
Pathways
• KEGG hsa04110: Cell cycle
• Reactome R-HSA-141444: Amplification of signal from the kinetochores
• Reactome R-HSA-2500257: Resolution of Sister Chromatid Cohesion
• Reactome R-HSA-68877: Mitotic Prometaphase
Protein Summary
MIS12 is a 205-amino-acid protein (22.9 kDa) that forms the core of the MIS12 complex, together with DSN1, NSL1, and PMF1. The complex adopts a rod-like structure that bridges the inner kinetochore (CENP-A nucleosome) to the outer kinetochore (KNL1, ZWINT, NDC80 complex). MIS12 contains a conserved N-terminal domain essential for complex assembly and a C-terminal region that interacts with the NDC80 complex. Post-translational modifications, including phosphorylation by Aurora B kinase, regulate its localization and activity during mitosis.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| MIS12 Knockout HEK293 Cell Line | EDJ-KQ51653 | Human | 79003 | Details Get a Quote |
| MIS12 Knockout HeLa Cell Line | EDJ-KQ57128 | Human | 79003 | Details Get a Quote |
| MIS12 Knockout A-549 Cell Line | EDJ-KQ65641 | Human | 79003 | Details Get a Quote |
| MIS12 Knockout HCT 116 Cell Line | EDJ-KQ74064 | Human | 79003 | Details Get a Quote |
