SKA3

protein-coding

spindle and kinetochore associated complex subunit 3

Gene summary

This gene encodes a component of the spindle and kinetochore-associated protein complex that regulates microtubule attachment to the kinetochores during mitosis. The encoded protein localizes to the outer kinetechore and may be required for normal chromosome segregation and cell division. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2009]

Previous symbols:

C13orf3

MANE transcript

NM_145061.6

Inheritance

—

ClinVar variants

U:59B:5

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.72

Max pathogenic AF

—

Genomic locus

chr13:21,153,595-21,176,552

External References & Databases

Ensembl (ENSG00000165480)

Transcript & Mutation Effects

hg38 • Region Span ~23.0 kb

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GenCC 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 SKA3 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 49

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_145061.6. 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			1 clinvar	1 clinvar		2
missense			46 clinvar	4 clinvar		50
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			11 clinvar			11
Total	0	0	59	5	0	64

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 32 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_145061.6	RefSeq	NP_659498.4	9	MANE Select
ENST00000314759.6	Ensembl	ENSP00000319417.5	9	MANE Select
NM_001166017.2	RefSeq	NP_001159489.1	8	Standard
ENST00000298260.8	Ensembl	ENSP00000298260.4	2	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

mitotic cell cycle
chromosome segregation
regulation of microtubule polymerization or depolymerization
cell division

Molecular Function

protein binding

Cellular Component

kinetochore
condensed chromosome outer kinetochore
cytoplasm
spindle microtubule

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000314759
Coding exons: 8
Length: 23008
Individuals with no LoFs: 113135
Homozygous LoFs: 0
Heterozygous LoFs: 12613
Defined: 125748
p: 0.0515

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.306	214	202	1.06	0.00000972	2665
Missense (PolyPhen)		38	55.244	0.68786		791
Synonymous	-0.522	79	73.3	1.08	0.00000362	766
Loss of Function	1.11	13	18.1	0.718	8.41e-7	261

Population LoF Frequency

Population	CAF	p-value	Status
African	0.011	0.011	notable
Latino/Admixed American	0.057	0.056	notable
Ashkenazi Jewish	0.046	0.046	notable
East Asian	0.068	0.068	notable
Finnish	0.063	0.063	notable
European (Non-Finnish)	0.046	0.045	notable
South Asian	0.077	0.077	notable
Other	0.045	0.044	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Component of the SKA1 complex, a microtubule-binding subcomplex of the outer kinetochore that is essential for proper chromosome segregation (PubMed:19289083, PubMed:19360002, PubMed:23085020). The SKA1 complex is a direct component of the kinetochore-microtubule interface and directly associates with microtubules as oligomeric assemblies (PubMed:19289083, PubMed:19360002). The complex facilitates the processive movement of microspheres along a microtubule in a depolymerization-coupled manner (PubMed:19289083). In the complex, it mediates the microtubule-stimulated oligomerization (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:19289083, ECO:0000269|PubMed:19360002, ECO:0000269|PubMed:23085020}.;

Recessive Scores

pRec: 0.0782

Intolerance Scores

LoFtool: 0.823
RVIS EVS: 0.84
RVIS percentile EVS: 88.3

Essentials

Essential (CRISPR): E
Essential (CRISPR2): E
Essential (gene trap): E
Indispensability pred.: E
Indispensability score: 0.824

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium