SKOR2

Chr 18AR

SKI family transcriptional corepressor 2

NCBI Gene: 652991ENSG00000215474UniProt: Q2VWA4OMIM: 617138

SKOR2 encodes a transcriptional repressor that binds SMAD proteins and negatively regulates TGF-beta signaling in the nervous system. Mutations cause Valence-Farazi cerebellar ataxia syndrome with autosomal recessive inheritance. The gene is highly constrained against loss-of-function variants (LOEUF 0.436), consistent with its essential role in cerebellar development and function.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 0.441 OMIM phenotype
Clinical Summary— SKOR2
⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.75) — some intolerance to loss-of-function variants.
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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint
0.44LOEUF
pLI 0.754
Z-score 3.25
OE 0.17 (0.08–0.44)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.63Z-score
OE missense 0.72 (0.64–0.81)
193 obs / 268.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.17 (0.08–0.44)
0≤0.351.4
Missense OE0.72 (0.64–0.81)
0≤0.61.4
Synonymous OE1.13
0≤1.21.6
LoF obs/exp: 3 / 17.8Missense obs/exp: 193 / 268.2Syn Z: -1.09
DN
0.4190th %ile
GOF
0.3590th %ile
LOF
0.80top 5%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.44

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

SKOR2 · 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.

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Clinical Literature
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Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Biallelic Novel SKOR2 Variants in Individuals With Cerebellar Hypoplasia and Intellectual Disability, Expanding the Phenotypic Spectrum of Valence-Farazi Cerebellar Ataxia Syndrome.
Abu-El-Haija A et al.·Am J Med Genet A
2026
Identification of two novel pathogenic mutations in the SKOR2 gene linked to cerebellar hypoplasia and a broad spectrum of neurodevelopmental delay in two Iranian families.
Farazi Fard MA et al.·J Hum Genet
2025
Interactions among Merlin, Arkadia, and SKOR2 mediate NF2-associated human Schwann cell proliferation.
Tang PC et al.·Stem Cell Res Ther
2025Open Access
Identification of SKOR2 IgG as a novel biomarker of paraneoplastic neurologic syndrome.
Rezk M et al.·Front Immunol
2023Open Access
Gata2, Nkx2-2 and Skor2 form a transcription factor network regulating development of a midbrain GABAergic neuron subtype with characteristics of REM-sleep regulatory neurons.
Kirjavainen A et al.·Development
2022
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