SKA2
protein-codingspindle and kinetochore associated complex subunit 2, the group of MicroRNA protein coding host genes
Gene summary
Enables microtubule binding activity. Involved in attachment of mitotic spindle microtubules to kinetochore and regulation of microtubule polymerization or depolymerization. Located in kinetochore and spindle microtubule. Part of SKA complex. [provided by Alliance of Genome Resources, Jul 2025]
- FAM33A
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~45.4 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 SKA2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_182620.4. 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 | 4 | 4 | ||||
| missense | 13 | 1 | 14 | |||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 15 | 5 | 0 | 20 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_872426.1 | 4 | MANE Select | |
| Ensembl | ENSP00000333433.7 | 4 | MANE Select | |
| RefSeq | NP_001094065.1 | 3 | Standard | |
| RefSeq | NP_001317328.1 | 4 | 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
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000330137
- Coding exons
- 4
- Length
- 45319
- Individuals with no LoFs
- 124599
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 40
- Defined
- 124639
- p
- 0.000160
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.546 | 48 | 59.9 | 0.802 | 0.00000293 | 786 |
| Missense (PolyPhen) | 6 | 9.1871 | 0.65309 | 167 | ||
| Synonymous | 0.422 | 19 | 21.5 | 0.884 | 0.00000102 | 213 |
| Loss of Function | -0.787 | 9 | 6.79 | 1.33 | 3.52e-7 | 85 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000065 | 0.000065 | rare |
| Latino/Admixed American | 0.00067 | 0.00067 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000056 | 0.000056 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00012 | 0.00012 | rare |
| South Asian | 0.000035 | 0.000033 | rare |
| Other | 0.00017 | 0.00017 | 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:17093495, PubMed:19289083). In the complex, it is required for SKA1 localization (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). {ECO:0000269|PubMed:17093495, ECO:0000269|PubMed:19289083, ECO:0000269|PubMed:23085020}.;
Recessive Scores
- pRec
- 0.0876
Intolerance Scores
- LoFtool
- 0.653
- RVIS EVS
- 0.19
- RVIS percentile EVS
- 66.57
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- E
- Essential (gene trap)
- E
- Indispensability pred.
- E
- Indispensability score
- 0.960
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |