KIF22
protein-codingkinesin family member 22, the group of Kinesins
Gene summary
The protein encoded by this gene is a member of the kinesin-like protein family. The family members are microtubule-dependent molecular motors that transport organelles within cells and move chromosomes during cell division. The C-terminal half of this protein has been shown to bind DNA. Studies with the Xenopus homolog suggests its essential role in metaphase chromosome alignment and maintenance. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2012]
- KNSL4
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~14.7 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AD
Disease ID:MONDO:0011335
Submitter: Orphanet
Inheritance Pattern: AD
Disease ID:MONDO:0011335
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: AD
Disease ID:MONDO:0011335
Submitter: PanelApp Australia
Inheritance Pattern: AD
Disease ID:MONDO:0011335
Submitter: Ambry Genetics
Inheritance Pattern: AD
Disease ID:MONDO:0011335
Submitter: G2P
Clinical Genomic Database (CGD)
Manifestation: Audiologic/Otolaryngologic; Craniofacial; Musculoskeletal
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 KIF22 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_007317.3. 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 | 4 | 73 | 3 | 80 | ||
| missense | 2 | 6 | 201 | 56 | 13 | 278 |
| nonsense | 8 | 1 | 9 | |||
| start loss | 0 | |||||
| frameshift | 8 | 1 | 9 | |||
| splice donor/acceptor (+/-2bp) | 8 | 8 | ||||
| Total | 2 | 6 | 229 | 131 | 16 | 384 |
Highest pathogenic variant AF is 0.0000037173754
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_015556.1 | 14 | MANE Select | |
| Ensembl | ENSP00000160827.5 | 14 | MANE Select | |
| RefSeq | NP_001243198.1 | 13 | Standard | |
| RefSeq | NP_001243199.1 | 13 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| kif22 | Danio rerio | Structure: post-vent region Quality: decreased length abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Progesterone-mediated oocyte maturation - Homo sapiens (human)
- Vesicle-mediated transport
- Membrane Trafficking
- Kinesins
- Factors involved in megakaryocyte development and platelet production
Biological Process
- mitotic cell cycle
- DNA repair
- retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum
- microtubule-based movement
- sister chromatid cohesion
Molecular Function
- DNA binding
- microtubule motor activity
- protein binding
- ATP binding
- microtubule binding
Cellular Component
- kinetochore
- chromatin
- nucleus
- cytosol
- kinesin complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000160827
- Coding exons
- 14
- Length
- 14667
- Individuals with no LoFs
- 125702
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 46
- Defined
- 125748
- p
- 0.000183
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.141 | 398 | 406 | 0.980 | 0.0000249 | 4254 |
| Missense (PolyPhen) | 145 | 198.99 | 0.72867 | 2090 | ||
| Synonymous | -1.82 | 185 | 156 | 1.18 | 0.00000807 | 1418 |
| Loss of Function | 2.24 | 20 | 34.2 | 0.586 | 0.00000200 | 355 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00012 | 0.00012 | rare |
| Latino/Admixed American | 0.00012 | 0.00012 | rare |
| Ashkenazi Jewish | 0.00020 | 0.00020 | rare |
| East Asian | 0.00022 | 0.00022 | rare |
| Finnish | 0.00014 | 0.00014 | rare |
| European (Non-Finnish) | 0.00018 | 0.00018 | rare |
| South Asian | 0.00033 | 0.00033 | rare |
| Other | 0.00016 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Kinesin family member that is involved in spindle formation and the movements of chromosomes during mitosis and meiosis. Binds to microtubules and to DNA (By similarity). Plays a role in congression of laterally attached chromosomes in NDC80- depleted cells (PubMed:25743205). {ECO:0000250|UniProtKB:Q9I869, ECO:0000269|PubMed:25743205}.;
- Disease
- DISEASE: Spondyloepimetaphyseal dysplasia with joint laxity, 2 (SEMDJL2) [MIM:603546]: A bone disease characterized by short stature, distinctive midface retrusion, progressive knee malalignment (genu valgum and/or varum), generalized ligamentous laxity, and mild spinal deformity. Intellectual development is not impaired. Radiographic characteristics include significantly retarded epiphyseal ossification that evolves into epiphyseal dysplasia and precocious osteoarthritis, metaphyseal irregularities and vertical striations, constricted femoral neck, slender metacarpals and metatarsals, and mild thoracolumbar kyphosis or scoliosis with normal or mild platyspondyly. The most distinctive features for differential diagnosis of SEMDJL2 are the slender metacarpals and phalanges and the progressive degeneration of carpal bones; however, these 2 features are evident only in older children and young adults. The soft consistency of cartilage in the airways leads to laryngotracheomalacia with proneness to respiratory obstruction and inspiratory stridor in infancy and childhood. {ECO:0000269|PubMed:22152677, ECO:0000269|PubMed:22152678}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Recessive Scores
- pRec
- 0.191
Intolerance Scores
- LoFtool
- 0.800
- RVIS EVS
- -0.26
- RVIS percentile EVS
- 34.88
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.864
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |