SKA3

Chr 13

spindle and kinetochore associated complex subunit 3

Also known as: C13orf3, RAMA1

NCBI Gene: 221150 ENSG00000165480 UniProt: Q8IX90

The protein is a component of the spindle and kinetochore-associated complex that regulates microtubule attachment to kinetochores and is essential for proper chromosome segregation during cell division. Mutations cause microcephaly with early-onset seizures and developmental delay, inherited in an autosomal recessive pattern. The gene shows minimal constraint against loss-of-function variants, consistent with the recessive inheritance pattern observed in affected individuals.

ResearchSummary from RefSeq, UniProt

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]

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.14

LOEUF

Mechanism· predicted

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.14LOEUF

pLI 0.000

Z-score 1.11

OE 0.72 (0.47–1.14)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.31Z-score

OE missense 1.06 (0.95–1.19)

214 obs / 201.8 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.72 (0.47–1.14)

0≤0.351.4

Missense OE?1.06 (0.95–1.19)

0≤0.61.4

Synonymous OE?1.08

0≤1.21.6

LoF obs/exp: 13 / 18.1Missense obs/exp: 214 / 201.8Syn Z: -0.52

Background carrier burden — how many people carry a rare variant somewhere in SKA3?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 140

555 rare PASS variants

Rare truncating (LoF)

1 in 65

153 rare PASS variants

Rare synonymous (reference)

1 in 250

209 rare PASS variants

Rare missense and truncating variants are carried at similar rates in SKA3; 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 160	1 in 67
South Asian	~43k	1 in 81	1 in 74
Remaining (unassigned)	~30k	1 in 180	1 in 51
European (Finnish)	~27k	1 in 460	1 in 69
Admixed American	~22k	1 in 140	1 in 70
African / African American	~21k	1 in 100	1 in 50
East Asian	~20k	1 in 83	1 in 61
Ashkenazi Jewish	~13k	1 in 1,400	1 in 86
Middle Eastern	~2,884	1 in 140	≈ 1 in 950

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): 5 of 9 coding exons well covered in gnomAD exomes; exons 2, 3, 8, 9 marginal. Genomes: 8 of 9 (exon 9 below).? see exons ↓