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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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ZWILCH
zwilch kinetochore protein
Chromosome 15 · 15q22.31
NCBI Gene: 55055Ensembl: ENSG00000174442.13HGNC: HGNC:25468UniProt: A8K4T3
28PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein bindingmitotic spindle assembly checkpoint signalingprotein localization to kinetochorekinetochorerenal carcinomaovarian neoplasmprostate carcinomaneurodegenerative disease
✦AI Summary

ZWILCH is an essential component of the spindle assembly checkpoint (SAC) that ensures proper chromosome 15 during mitosis 1. The protein functions as part of the Rod-Zwilch-ZW10 (RZZ) complex, which contains two copies of each subunit and has a predicted molecular mass of ~800 kDa 2. Mechanistically, ZWILCH within the RZZ complex is required for recruiting two critical kinetochore components: the dynein-dynactin complex and the Mad1-Mad2 complex 1. The RZZ complex is directly responsible for both Mad1-Mad2 recruitment to unattached kinetochores and its subsequent removal following microtubule attachment, thus participating in both checkpoint activation and inactivation 1. Specifically, Zwilch binds to the adaptor protein Spindly's C-terminal domain alongside Rod's N-terminal β-propeller, and mutations in Zwilch that abrogate this interaction prevent Spindly and dynein recruitment in vivo 3. Loss of ZWILCH function results in characteristic mitotic defects including lagging chr15 at anaphase and precocious sister chr15 separation 4. Clinically, ZWILCH upregulation correlates with poor prognosis in adrenocortical carcinoma, where enhanced expression associates with increased tumor mitotic rate and reduced patient survival 5.

Sources cited
1
ZWILCH is part of the RZZ complex essential for spindle checkpoint function and Mad1-Mad2 recruitment
PMID: 15922598
2
The RZZ complex contains two copies of each subunit with ~800 kDa molecular mass
PMID: 25849506
3
Zwilch binds Spindly and is required for dynein recruitment to kinetochores
PMID: 28320824
4
ZWILCH mutations cause lagging chromosomes and precocious sister chromatid separation
PMID: 12686595
5
ZWILCH upregulation correlates with poor survival in adrenocortical carcinoma
PMID: 37189849
Disease Associationsⓘ20
renal carcinomaOpen Targets
0.34Weak
ovarian neoplasmOpen Targets
0.31Weak
prostate carcinomaOpen Targets
0.30Weak
neurodegenerative diseaseOpen Targets
0.29Weak
Abruptio PlacentaeOpen Targets
0.27Weak
prostate cancerOpen Targets
0.22Weak
upper respiratory tract disorderOpen Targets
0.20Weak
Testicular Germ Cell TumorOpen Targets
0.20Weak
adrenal cortex carcinomaOpen Targets
0.08Suggestive
Hemoglobin E - beta-thalassemiaOpen Targets
0.06Suggestive
hemoglobin E-beta-thalassemia syndromeOpen Targets
0.06Suggestive
refractive errorOpen Targets
0.06Suggestive
microcytic anemia with liver iron overloadOpen Targets
0.06Suggestive
Adult-onset autosomal recessive sideroblastic anemiaOpen Targets
0.05Suggestive
hereditary persistence of fetal hemoglobin-sickle cell disease syndromeOpen Targets
0.05Suggestive
cancerOpen Targets
0.05Suggestive
neoplasmOpen Targets
0.05Suggestive
hemoglobin D diseaseOpen Targets
0.05Suggestive
FTH1-related iron overloadOpen Targets
0.05Suggestive
hemochromatosis type 5Open Targets
0.05Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
RINT1Protein interaction100%PLK1Protein interaction100%CDK1Protein interaction100%CCNA2Protein interaction100%CDCA8Protein interaction99%NUF2Protein interaction97%
Tissue Expression6 tissues
Bone Marrow
100%
Brain
50%
Ovary
35%
Lung
23%
Heart
22%
Liver
20%
Gene Interaction Network
Click a node to explore
ZWILCHRINT1PLK1CDK1CCNA2CDCA8NUF2
PROTEIN STRUCTURE
Preparing viewer…
PDB3IF8 · 2.55 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
1.06LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.81 [0.63–1.06]
RankingsWhere ZWILCH stands among ~20K protein-coding genes
  • #12,495of 20,598
    Most Researched28
  • #10,670of 17,882
    Most Constrained (LOEUF)1.06
Genes detectedZWILCH
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Complex assembly, crystallization and preliminary X-ray crystallographic analysis of the human Rod-Zwilch-ZW10 (RZZ) complex.
PMID: 25849506
Acta Crystallogr F Struct Biol Commun · 2015
1.00
2
Rod-Zw10-Zwilch: a key player in the spindle checkpoint.
PMID: 15922598
Trends Cell Biol · 2005
0.90
3
The Enhanced Expression of ZWILCH Predicts Poor Survival of Adrenocortical Carcinoma Patients.
PMID: 37189849
Biomedicines · 2023
0.80
4
Molecular mechanism of dynein recruitment to kinetochores by the Rod-Zw10-Zwilch complex and Spindly.
PMID: 28320824
J Cell Biol · 2017
0.70
5
Regulators of the cytoplasmic dynein motor.
PMID: 19935668
Nat Rev Mol Cell Biol · 2009
0.60