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10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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SKOR1
SKI family transcriptional corepressor 1
Chromosome 15 · 15q23
NCBI Gene: 390598Ensembl: ENSG00000188779.12HGNC: HGNC:21326UniProt: P84550
17PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Transcription Factor
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
neuronal cell bodySMAD bindingsequence-specific double-stranded DNA bindingnegative regulation of BMP signaling pathwayAbnormality of the skeletal systemmorbid obesityrestless legs syndromesmoking behavior
✦AI Summary

SKOR1 is a transcriptional corepressor that regulates gene expression through sequence-specific DNA binding and interaction with transcription factor complexes 1. It acts as a corepressor of the LBX1 transcription factor and plays a critical role in regulating interneuron cell fate in the dorsal spinal cord 1. SKOR1 inhibits BMP-SMAD-dependent signaling, a pathway essential for dopaminergic neuronal survival and growth 2. SKOR1 dysregulation is strongly associated with restless legs syndrome (RLS), a common sleep-related sensory-motor disorder 134. Multiple GWAS have identified RLS-associated variants in SKOR1 noncoding regions across diverse populations 145. Gene expression studies demonstrate that SKOR1 regulates pathways relevant to RLS pathogenesis, including neurodevelopment and iron metabolism 1. Notably, MEIS1, another RLS-associated gene, positively regulates SKOR1 expression through direct promoter binding 6. In Parkinson's disease models, α-synuclein overexpression upregulates SKOR1, which impairs neurite growth and reduces mitochondrial respiration capacity 2. However, RLS genetic variants do not confer increased Parkinson's disease risk, suggesting these disorders are genetically distinct entities 7. SKOR1 is highly expressed in the central nervous system and localizes to neuronal cell bodies and dendrites 1.

Sources cited
1
SKOR1 acts as a corepressor of LBX1, is highly expressed in CNS, regulates neurodevelopment and iron metabolism pathways relevant to RLS, and is dysregulated in RLS pathogenesis
PMID: 32572201
2
α-synuclein overexpression upregulates SKOR1; SKOR1 overexpression reduces mitochondrial respiration, impairs neurite growth, and inhibits BMP-SMAD signaling that promotes dopaminergic neuronal survival
PMID: 38529808
3
MAP2K5/SKOR1 variants are associated with RLS risk in Chinese population
PMID: 28329290
4
MAP2K5/SKOR1 variants confer significant RLS risk in US population through family-based and case-control association studies
PMID: 21925394
5
RLS genetic markers including MAP2K5/SKOR1 are not associated with increased Parkinson's disease risk or subtype
PMID: 25817513
6
MEIS1 positively regulates SKOR1 expression through direct binding to SKOR1 promoter regions, and RLS-associated SNPs modify this regulation
PMID: 30111810
7
MAP2K5/SKOR1 variants show genetic association with RLS in end-stage renal disease patients
PMID: 21572129
8
SKOR1 genetic variant (rs428022) is associated with multiple births in GWAS analysis
PMID: 30760885
Disease Associationsⓘ20
Abnormality of the skeletal systemOpen Targets
0.46Moderate
morbid obesityOpen Targets
0.38Weak
restless legs syndromeOpen Targets
0.30Weak
smoking behaviorOpen Targets
0.26Weak
obesityOpen Targets
0.25Weak
type 2 diabetes mellitusOpen Targets
0.22Weak
colorectal cancerOpen Targets
0.22Weak
heart failureOpen Targets
0.20Weak
hypertensionOpen Targets
0.19Weak
Increased blood pressureOpen Targets
0.18Weak
metabolic syndromeOpen Targets
0.18Weak
smoking initiationOpen Targets
0.17Weak
endometrial cancerOpen Targets
0.17Weak
vascular diseaseOpen Targets
0.17Weak
insomniaOpen Targets
0.17Weak
bipolar disorderOpen Targets
0.16Weak
osteoarthritisOpen Targets
0.15Weak
osteoarthritis, hipOpen Targets
0.15Weak
osteoarthritis, kneeOpen Targets
0.15Weak
psoriasisOpen Targets
0.15Weak
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
VWC2LShared pathway100%LBX1Protein interaction89%MEIS1Protein interaction84%BTBD9Protein interaction78%MAP2K5Protein interaction75%TLE1Protein interaction75%
Tissue Expression6 tissues
Ovary
100%
Bone Marrow
48%
Brain
47%
Lung
33%
Liver
17%
Heart
14%
Gene Interaction Network
Click a node to explore
SKOR1VWC2LLBX1MEIS1BTBD9MAP2K5TLE1
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt P84550
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
0.81LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.61 [0.47–0.81]
RankingsWhere SKOR1 stands among ~20K protein-coding genes
  • #15,113of 20,598
    Most Researched17
  • #6,729of 17,882
    Most Constrained (LOEUF)0.81
Genes detectedSKOR1
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
SKOR1 has a transcriptional regulatory role on genes involved in pathways related to restless legs syndrome.
PMID: 32572201
Eur J Hum Genet · 2020
1.00
2
Human α-synuclein overexpression upregulates SKOR1 in a rat model of simulated nigrostriatal ageing.
PMID: 38529808
Aging Cell · 2024
0.90
3
Association of BTBD9 and MAP2K5/SKOR1 With Restless Legs Syndrome in Chinese Population.
PMID: 28329290
Sleep · 2017
0.80
4
Association studies of variants in MEIS1, BTBD9, and MAP2K5/SKOR1 with restless legs syndrome in a US population.
PMID: 21925394
Sleep Med · 2011
0.70
5
Genetic markers of Restless Legs Syndrome in Parkinson disease.
PMID: 25817513
Parkinsonism Relat Disord · 2015
0.60