SKA2

Chr 17

spindle and kinetochore associated complex subunit 2

Also known as: FAM33A

NCBI Gene: 348235ENSG00000182628UniProt: Q8WVK7

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]

0
Active trials
14
Pathogenic / LP
42
ClinVar variants
2
Pubs (1 yr)
0.5
Missense Z
1.90
LOEUF
Clinical Summary— SKA2
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
14 Pathogenic / Likely Pathogenic· 21 VUS of 42 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.90LOEUF
pLI 0.000
Z-score -0.79
OE 1.33 (0.78–1.90)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.55Z-score
OE missense 0.80 (0.64–1.02)
48 obs / 59.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.1.33 (0.78–1.90)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.80 (0.64–1.02)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.88
0≤1.21.6
LoF obs/exp: 9 / 6.8Missense obs/exp: 48 / 59.9Syn Z: 0.42
DN
0.6260th %ile
GOF
0.5758th %ile
LOF
0.3939th %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

42 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic12
Likely Pathogenic2
VUS21
Likely Benign6
Benign1
12
Pathogenic
2
Likely Pathogenic
21
VUS
6
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
12
0
12
Likely Pathogenic
0
0
2
0
2
VUS
0
13
8
0
21
Likely Benign
0
4
1
1
6
Benign
0
0
1
0
1
Total01724142

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

View in ClinVar →

Protein Context — Lollipop Plot

SKA2 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Landmark / reviewRecent case evidence
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
Overexpressed PRR11-SKA2-miR301a/454 bidirectional transcription unit essentially and coordinately promotes PI3K-AKT pathway activation and lung cancer progression.
Liu T et al.·Oncogene
2026
Genetic association between SKA2 rs7208505 and preterm birth in Korean women.
Lee EJ et al.·Mol Biol Rep
2025
SKA2 enhances stress-related glucocorticoid receptor signaling through FKBP4-FKBP5 interactions in neurons.
Hartmann J et al.·Proc Natl Acad Sci U S A
2024Open Access
Oncogenic role of SKA2 and its ceRNA network in hepatocellular carcinoma based on a comprehensive analysis.
Hu W et al.·Transl Cancer Res
2024Open Access
The role of SKA2 on affective disorder, post-traumatic stress disorder and suicide behavior: systematic review and in silico analysis.
González-Castro TB et al.·Metab Brain Dis
2024Review
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