SKA1
protein-codingspindle and kinetochore associated complex subunit 1
Gene summary
Enables microtubule binding activity. Involved in attachment of mitotic spindle microtubules to kinetochore; negative regulation of mitotic spindle assembly checkpoint signaling; and positive regulation of microtubule polymerization. Located in centrosome; kinetochore; and mitotic spindle microtubule. Part of SKA complex. [provided by Alliance of Genome Resources, Jun 2026]
- C18orf24
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~19.1 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 SKA1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_145060.4. 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 | 1 | 1 | ||||
| missense | 22 | 3 | 25 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 24 | 3 | 0 | 27 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_659497.1 | 6 | MANE Select | |
| Ensembl | ENSP00000285116.3 | 6 | MANE Select | |
| RefSeq | NP_001034624.1 | 6 | Standard | |
| Ensembl | ENSP00000381470.1 | 6 | 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
- chromosome segregation
- regulation of microtubule polymerization or depolymerization
- cell division
Molecular Function
- protein binding
- microtubule binding
Cellular Component
- condensed chromosome outer kinetochore
- cytosol
- spindle microtubule
- microtubule cytoskeleton
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000285116
- Coding exons
- 6
- Length
- 19179
- Individuals with no LoFs
- 125655
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 56
- Defined
- 125711
- p
- 0.000223
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.02 | 95 | 127 | 0.747 | 0.00000643 | 1672 |
| Missense (PolyPhen) | 20 | 34.916 | 0.5728 | 503 | ||
| Synonymous | 0.219 | 42 | 43.8 | 0.958 | 0.00000217 | 452 |
| Loss of Function | 0.999 | 9 | 12.9 | 0.700 | 7.31e-7 | 179 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00019 | 0.00018 | rare |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0.00080 | 0.00079 | rare |
| East Asian | 0.00016 | 0.00016 | rare |
| Finnish | 0.000046 | 0.000046 | rare |
| European (Non-Finnish) | 0.00033 | 0.00033 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0.00068 | 0.00065 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Component of the SKA1 complex, a microtubule-binding subcomplex of the outer kinetochore that is essential for proper chromosome segregation (PubMed:17093495, PubMed:19289083, PubMed:23085020). Required for timely anaphase onset during mitosis, when chromosomes undergo bipolar attachment on spindle microtubules leading to silencing of the spindle checkpoint (PubMed:17093495). The SKA1 complex is a direct component of the kinetochore-microtubule interface and directly associates with microtubules as oligomeric assemblies (PubMed:19289083). The complex facilitates the processive movement of microspheres along a microtubule in a depolymerization-coupled manner (PubMed:19289083). Affinity for microtubules is synergistically enhanced in the presence of the ndc-80 complex and may allow the ndc-80 complex to track depolymerizing microtubules (PubMed:23085020). In the complex, it mediates the interaction with microtubules (PubMed:19289083, PubMed:23085020). {ECO:0000269|PubMed:17093495, ECO:0000269|PubMed:19289083, ECO:0000269|PubMed:23085020}.;
Recessive Scores
- pRec
- 0.0780
Intolerance Scores
- LoFtool
- 0.909
- RVIS EVS
- 0.26
- RVIS percentile EVS
- 70.26
Essentials
- Essential (CRISPR)
- E
- Essential (CRISPR2)
- E
- Essential (gene trap)
- E
- Indispensability pred.
- E
- Indispensability score
- 0.731
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |