ZWINT: ZW10 Interactor, Kinetochore Component
Essential regulator of mitotic checkpoint signaling and chromosome segregation
Gene Information Card
| Symbol | ZWINT |
|---|---|
| Full Name | ZW10 interacting kinetochore protein |
| Gene Type | Protein coding |
| Chromosomal Location | 10q21.2 |
| NCBI Gene ID | 11130 ncbi.nlm.nih.gov/gene/11130 |
| Ensembl ID | ENSG00000122952 |
| UniProt ID | O95229 |
| OMIM ID | 609177 |
| HGNC ID | 13195 |
| Aliases | ZW10IP, HZWINT, KNTC2AP, SIP30 |
Description
ZWINT encodes a zinc-finger protein that localizes to the kinetochore and interacts with ZW10, a component of the RZZ (ROD-ZW10-ZWINT) complex. This complex is essential for the spindle assembly checkpoint (SAC), ensuring accurate chromosome segregation during mitosis. ZWINT recruits ZW10 to the kinetochore and participates in the recruitment of dynein and other checkpoint proteins. Loss of ZWINT function leads to mitotic arrest, aneuploidy, and genomic instability.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Breast cancer | ZWINT overexpression correlates with poor prognosis; promotes proliferation and migration via mitotic checkpoint dysregulation | PMID: 31406129 |
| Lung adenocarcinoma | Upregulation associated with tumor progression and immune infiltration | PMID: 33365017 |
| Microcephaly (autosomal recessive) | Homozygous loss-of-function mutations impair kinetochore function, leading to microcephaly and intellectual disability | PMID: 29276005 |
| Colorectal cancer | High expression linked to chromosomal instability and poor survival | PMID: 30337557 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 25.3 | High |
| Bone marrow | 18.7 | High |
| Lymph node | 15.2 | Medium |
| Brain | 8.1 | Medium |
| Liver | 4.5 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 22.1 | Cervical cancer cell line; high expression |
| MCF7 | 19.8 | Breast cancer cell line; moderate expression |
| A549 | 17.3 | Lung cancer cell line; moderate expression |
| HEK293 | 12.6 | Embryonic kidney; moderate expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.238C>T (p.Arg80*) | Nonsense | Rare | Loss of function; associated with microcephaly |
| c.347G>A (p.Arg116His) | Missense | Rare | Impaired ZW10 binding; reduced kinetochore localization |
| c.1A>G (p.Met1?) | Start loss | Rare | Complete loss of protein; microcephaly phenotype |
Mutation functional classification
Loss of Function (LOF)
Nonsense and start-loss mutations (e.g., p.Arg80*, p.Met1?) abolish ZWINT protein expression or function, leading to mitotic checkpoint defects and microcephaly.
Gain of Function (GOF)
Not reported; overexpression in cancers is likely secondary to transcriptional dysregulation rather than activating mutations.
Dominant Negative (DN)
Not described; ZWINT mutations are typically recessive in microcephaly.
View complete mutation data：
Gene Ontology (GO)
| • mitotic spindle assembly checkpoint | • kinetochore |
| • chromosome segregation | • protein binding |
| • zinc ion binding | • cell division |
Pathways
• Spindle assembly checkpoint (SAC) signaling
• RZZ complex assembly
• Kinetochore-microtubule attachment
Protein Summary
ZWINT is a 277-amino-acid zinc-finger protein (UniProt O95229) that localizes to the outer kinetochore. It directly binds ZW10 and is required for the stable association of the RZZ complex with kinetochores. ZWINT also interacts with dynein light chains and the checkpoint protein MAD1. Through these interactions, ZWINT ensures proper SAC activation and chromosome biorientation. Structurally, it contains a C2H2-type zinc finger domain and a coiled-coil region mediating protein-protein interactions.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ZWINT Knockout HEK293 Cell Line | EDJ-KQ3495 | Human | 11130 | Details Get a Quote |
| ZWINT Knockout HCT 116 Cell Line | EDJ-KQ25290 | Human | 11130 | Details Get a Quote |
| ZWINT Knockout HeLa Cell Line | EDJ-KQ25291 | Human | 11130 | Details Get a Quote |
| ZWINT Knockout A-549 Cell Line | EDJ-KQ64074 | Human | 11130 | Details Get a Quote |
