ZWILCH
protein-codingzwilch kinetochore protein, the group of RZZ complex
Gene summary
Involved in mitotic spindle assembly checkpoint signaling and protein localization to kinetochore. Located in kinetochore. Part of RZZ complex. [provided by Alliance of Genome Resources, Jul 2025]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~45.2 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AD
Disease ID:MONDO:0005258
Submitter: Ambry Genetics
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to ZWILCH variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_017975.5. 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 | 1 | 1 | ||||
| missense | 77 | 3 | 1 | 81 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 3 | 3 | ||||
| Total | 0 | 0 | 80 | 4 | 1 | 85 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_060445.3 | 18 | MANE Select | |
| Ensembl | ENSP00000311429.5 | 18 | MANE Select | |
| RefSeq | NP_001274750.1 | 14 | Standard | |
| RefSeq | NP_001274751.1 | 14 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Signal Transduction
- Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal
- Amplification of signal from the kinetochores
- Mitotic Spindle Checkpoint
- Cell Cycle Checkpoints
Biological Process
- mitotic cell cycle checkpoint
- cell division
Molecular Function
- protein binding
Cellular Component
- kinetochore
- condensed chromosome kinetochore
- cytosol
- RZZ complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000307897
- Coding exons
- 18
- Length
- 44819
- Individuals with no LoFs
- 125688
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 60
- Defined
- 125748
- p
- 0.000239
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.387 | 317 | 298 | 1.06 | 0.0000142 | 3911 |
| Missense (PolyPhen) | 107 | 95.743 | 1.1176 | 1348 | ||
| Synonymous | -0.626 | 110 | 102 | 1.08 | 0.00000501 | 1055 |
| Loss of Function | 1.46 | 25 | 34.2 | 0.731 | 0.00000145 | 449 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00013 | 0.00012 | rare |
| Latino/Admixed American | 0.00019 | 0.00017 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00022 | 0.00022 | rare |
| Finnish | 0.000093 | 0.000092 | rare |
| European (Non-Finnish) | 0.00026 | 0.00025 | rare |
| South Asian | 0.00047 | 0.00046 | rare |
| Other | 0.00052 | 0.00049 | 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:15824131). {ECO:0000269|PubMed:15824131}.;
Recessive Scores
- pRec
- 0.0773
Intolerance Scores
- LoFtool
- 0.914
- RVIS EVS
- 0.04
- RVIS percentile EVS
- 57.41
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- E
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.434
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |