SKA1

Chr 18

spindle and kinetochore associated complex subunit 1

Also known as: C18orf24

NCBI Gene: 220134 ENSG00000154839 UniProt: Q96BD8 OMIM: 616673

The SKA1 protein is a component of the SKA complex that stabilizes spindle microtubule-kinetochore attachments during cell division and assists in chromosome alignment at the mitotic spindle equator. Biallelic mutations cause microcephaly with early-onset seizures and developmental delay, following autosomal recessive inheritance. This gene is highly intolerant to loss-of-function variants in the general population, suggesting that complete loss of protein function is likely incompatible with normal development.

OMIM ResearchSummary from RefSeq, UniProt

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]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.22

LOEUF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.22LOEUF

pLI 0.000

Z-score 1.00

OE 0.70 (0.42–1.22)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

1.02Z-score

OE missense 0.75 (0.63–0.89)

95 obs / 127.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.70 (0.42–1.22)

0≤0.351.4

Missense OE?0.75 (0.63–0.89)

0≤0.61.4

Synonymous OE?0.96

0≤1.21.6

LoF obs/exp: 9 / 12.9Missense obs/exp: 95 / 127.2Syn Z: 0.22

Background carrier burden — how many people carry a rare variant somewhere in SKA1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 350

266 rare PASS variants

Rare truncating (LoF)

1 in 560

57 rare PASS variants

Rare synonymous (reference)

1 in 310

94 rare PASS variants

Rare missense and truncating variants are carried at similar rates in SKA1; this gene does not show strong loss-of-function constraint by this measure. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 320	1 in 920
South Asian	~43k	1 in 160	1 in 5,600
Remaining (unassigned)	~30k	1 in 330	1 in 390
European (Finnish)	~27k	1 in 1,200	≈ 1 in 8,900
Admixed American	~22k	1 in 440	≈ 1 in 5,900
African / African American	~21k	1 in 190	1 in 1,600
East Asian	~20k	1 in 220	≈ 1 in 9,600
Ashkenazi Jewish	~13k	1 in 500	1 in 620
Middle Eastern	~2,882	1 in 180	≈ 1 in 1,300

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 2 of 6 coding exons well covered in gnomAD exomes; exons 2, 3, 4, 6 marginal. Genomes: all 6.? see exons ↓