KIZ
protein-codingkizuna centrosomal protein
Gene summary
The protein encoded by this gene localizes to centrosomes, strengthening and stabilizing the pericentriolar region prior to spindle formation. The encoded protein usually remains with the mother centrosome after centrosomal duplication. Sevral transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2013]
- NCRNA00153
- C20orf19
- PLK1S1
MANE transcript
Inheritance
ClinVar variants
Top phenotype
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~120.6 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0014345
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: AR
Disease ID:MONDO:0014345
Submitter: G2P
Inheritance Pattern: AR
Disease ID:MONDO:0014345
Submitter: PanelApp Australia
Inheritance Pattern: AD
Disease ID:MONDO:0019200
Submitter: Orphanet
Inheritance Pattern: AR
Disease ID:MONDO:0700232
Submitter: ClinGen
*KIZ* was first reported in relation to cases of autosomal recessive inheritance of retinitis pigmentosa (RP) in 2014 by El Shamieh et al., PMID: 24680887. KIZ is a protein necessary for centromere stabilization during mitosis. Mutations in *KIZ* are thought to cause defects in photoreceptor connecting cilium, leading to retinal disorders such as RP. There is significant heterogeneity in RP, however patients with *KIZ*-associated retinopathy have been reported to have fundus findings typical of RP, that is, vascular attenuation and peripheral retinal atrophy with pigment migration. A perifoveal ring of increased autofluorescence on fundus autofluorescence imaging and a rod-cone dystrophy have also been described. Four suspected pathogenic variants (two nonsense, one frameshift, and one found in the *KIZ* initiation codon) that have been reported in 14 probands across six publications (PMIDs: 24680887, 29057815, 32052671, 31556760, 28837078, 32098976) are included in this curation. The mechanism of pathogenicity appears to be biallelic loss of function. This gene-disease association is also supported by experimental evidence that *KIZ* is non-specifically expressed in retina tissue (PMID:25613900). Multiple RT-PCR experiments have confirmed the expression of *KIZ* in human retina samples (PMIDs: 24680887 and 29057815). Finally, using microarray and RT-PCR data, Strunnikova et al. found that *KIZ* was highly expressed in the RPE layer of the retina (PMID: 20360305). Experiments have also shown that KIZ colocalizes with the cilium markers α-tubulin and γ-tubulin in the basal body of cilia in photoreceptors in mouse retina (PMID: 29057815) and in human fibroblasts (PMID: 24680887). In summary, *KIZ* is definitively associated with KIZ-related retinopathy. This has been repeatedly demonstrated in both the research and clinical diagnostic settings and has been upheld over time. This classification was approved by the ClinGen Retina GCEP on February 2, 2023 (SOP Version 9).
Clinical Genomic Database (CGD)
Manifestation: Ophthalmologic
Intervention: General
Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to KIZ variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_018474.6. 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 | 5 | 94 | 1 | 100 | ||
| missense | 1 | 237 | 31 | 3 | 272 | |
| nonsense | 9 | 5 | 2 | 16 | ||
| start loss | 1 | 1 | ||||
| frameshift | 13 | 18 | 3 | 2 | 1 | 37 |
| splice donor/acceptor (+/-2bp) | 13 | 2 | 15 | |||
| Total | 22 | 38 | 249 | 127 | 5 | 441 |
Highest pathogenic variant AF is 0.00020728745
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_060944.3 | 13 | MANE Select | |
| Ensembl | ENSP00000479542.1 | 13 | MANE Select | |
| RefSeq | NP_001156494.1 | 11 | Standard | |
| RefSeq | NP_001156495.1 | 10 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- PLK1 signaling events
Biological Process
- spindle organization
Molecular Function
- protein binding
- protein kinase binding
Cellular Component
- cytoplasm
- centrosome
- cell projection
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Centrosomal protein required for establishing a robust mitotic centrosome architecture that can endure the forces that converge on the centrosomes during spindle formation. Required for stabilizing the expanded pericentriolar material around the centriole. {ECO:0000269|PubMed:16980960}.;
- Disease
- DISEASE: Retinitis pigmentosa 69 (RP69) [MIM:615780]: A retinal dystrophy belonging to the group of pigmentary retinopathies. Retinitis pigmentosa is characterized by retinal pigment deposits visible on fundus examination and primary loss of rod photoreceptor cells followed by secondary loss of cone photoreceptors. Patients typically have night vision blindness and loss of midperipheral visual field. As their condition progresses, they lose their far peripheral visual field and eventually central vision as well. {ECO:0000269|PubMed:24680887}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Recessive Scores
- pRec
- 0.0666