ZW10
protein-codingzw10 kinetochore protein, the group of RZZ complex|NRZ tethering complex
Gene summary
This gene encodes a protein that is one of many involved in mechanisms to ensure proper chromosome segregation during cell division. This protein is an essential component of the mitotic checkpoint, which prevents cells from prematurely exiting mitosis. [provided by RefSeq, Aug 2011]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~40.5 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to ZW10 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_004724.4. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 0 | |||||
| missense | 101 | 4 | 105 | |||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 4 | 4 | ||||
| Total | 0 | 0 | 106 | 4 | 0 | 110 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_004715.1 | 16 | MANE Select | |
| Ensembl | ENSP00000200135.3 | 16 | MANE Select | |
| Ensembl | ENSP00000440879.1 | 15 | Standard | |
| Ensembl | ENSP00000439197.1 | 4 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Signal Transduction
- Vesicle-mediated transport
- Membrane Trafficking
- Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal
- Amplification of signal from the kinetochores
Biological Process
- mitotic sister chromatid segregation
- establishment of mitotic spindle orientation
- endoplasmic reticulum to Golgi vesicle-mediated transport
- retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum
- Golgi organization
Molecular Function
- protein binding
- centromeric DNA binding
Cellular Component
- kinetochore
- condensed chromosome kinetochore
- spindle pole
- nucleus
- endoplasmic reticulum
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000200135
- Coding exons
- 16
- Length
- 40625
- Individuals with no LoFs
- 125673
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 75
- Defined
- 125748
- p
- 0.000298
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.441 | 385 | 410 | 0.939 | 0.0000204 | 5141 |
| Missense (PolyPhen) | 97 | 118.49 | 0.81861 | 1554 | ||
| Synonymous | 0.967 | 135 | 150 | 0.900 | 0.00000746 | 1453 |
| Loss of Function | 3.81 | 12 | 37.1 | 0.324 | 0.00000157 | 512 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00019 | 0.00018 | rare |
| Latino/Admixed American | 0.000059 | 0.000058 | rare |
| Ashkenazi Jewish | 0.0015 | 0.0015 | notable |
| East Asian | 0.00022 | 0.00022 | rare |
| Finnish | 0.0010 | 0.0010 | notable |
| European (Non-Finnish) | 0.00019 | 0.00019 | rare |
| South Asian | 0.00017 | 0.00016 | rare |
| Other | 0.00033 | 0.00033 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Essential component of the mitotic checkpoint, which prevents cells from prematurely exiting mitosis. Required for the assembly of the dynein-dynactin and MAD1-MAD2 complexes onto kinetochores. Its function related to the spindle assembly machinery is proposed to depend on its association in the mitotic RZZ complex (PubMed:11590237, PubMed:15485811, PubMed:15824131). Involved in regulation of membrane traffic between the Golgi and the endoplasmic reticulum (ER); the function is proposed to depend on its association in the interphase NRZ complex which is believed to play a role in SNARE assembly at the ER (PubMed:15029241). {ECO:0000269|PubMed:11590237, ECO:0000269|PubMed:15029241, ECO:0000269|PubMed:15094189, ECO:0000269|PubMed:15485811, ECO:0000269|PubMed:15824131, ECO:0000305}.;
Recessive Scores
- pRec
- 0.126
Intolerance Scores
- LoFtool
- 0.757
- RVIS EVS
- -0.97
- RVIS percentile EVS
- 8.9
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- E
- Indispensability pred.
- E
- Indispensability score
- 0.988
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |