SKA3

Chr 13

spindle and kinetochore associated complex subunit 3

Also known as: C13orf3, RAMA1

NCBI Gene: 221150ENSG00000165480UniProt: Q8IX90OMIM: 619247

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.

OMIMResearchSummary from RefSeq, UniProt
DNmechanismLOEUF 1.14
Clinical Summary— SKA3
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
44 unique Pathogenic / Likely Pathogenic· 55 VUS of 138 total submissions
Explore recent and relevant literature in Research Assistant →

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 OE0.72 (0.47–1.14)
0≤0.351.4
Missense OE1.06 (0.95–1.19)
0≤0.61.4
Synonymous OE1.08
0≤1.21.6
LoF obs/exp: 13 / 18.1Missense obs/exp: 214 / 201.8Syn Z: -0.52
DN
0.6454th %ile
GOF
0.3887th %ile
LOF
0.4628th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

138 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic42
Likely Pathogenic2
VUS55
Likely Benign10
Benign2
42
Pathogenic
2
Likely Pathogenic
55
VUS
10
Likely Benign
2
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
42
0
42
Likely Pathogenic
0
0
2
0
2
VUS
0
44
11
0
55
Likely Benign
0
4
5
1
10
Benign
0
0
2
0
2
Total048621111

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

SKA3 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients