SKOR1

Summary

SKOR1 (SKI family transcriptional corepressor 1, HGNC:21326) is a protein-coding gene on chromosome 15q23, encoding SKI family transcriptional corepressor 1 (P84550). Acts as a transcriptional corepressor of LBX1.

Enables SMAD binding activity and sequence-specific double-stranded DNA binding activity. Involved in negative regulation of BMP signaling pathway. Located in dendrite and neuronal cell body.

Source: NCBI Gene 390598 — RefSeq curated summary.

At a glance

• GWAS associations: 7
• Clinical variants (ClinVar): 8 total
• MANE Select transcript: NM_001365915

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21326
Approved symbol	SKOR1
Name	SKI family transcriptional corepressor 1
Location	15q23
Locus type	gene with protein product
Status	Approved
Aliases	CORL1, FUSSEL15
Ensembl gene	ENSG00000188779
Ensembl biotype	protein_coding
OMIM	611273
Entrez	390598

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 4 protein_coding

ENST00000341418, ENST00000380035, ENST00000554054, ENST00000554240

RefSeq mRNA: 1 — MANE Select: NM_001365915 NM_001365915

CCDS: CCDS92030

Canonical transcript exons

ENST00000380035 — 9 exons

Exon	Start	End
ENSE00001371636	67832607	67832681
ENSE00001372784	67830191	67830298
ENSE00001380759	67829179	67829269
ENSE00001381353	67832274	67832348
ENSE00001386576	67830818	67830889
ENSE00001483503	67825509	67825709
ENSE00003498060	67833192	67833257
ENSE00003530821	67825936	67828144
ENSE00003892728	67833742	67834582

Expression profiles

Bgee: expression breadth ubiquitous, 119 present calls, max score 76.57.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.1095 / max 42.2955, expressed in 29 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
147364	0.0604	23
147366	0.0295	3
147367	0.0162	5
147365	0.0034	1

Top tissues by expression

127 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
right hemisphere of cerebellum	UBERON:0014890	76.57	gold quality
cerebellum	UBERON:0002037	75.15	gold quality
cerebellar cortex	UBERON:0002129	75.06	gold quality
cerebellar hemisphere	UBERON:0002245	74.96	gold quality
mucosa of stomach	UBERON:0001199	63.70	gold quality
primary visual cortex	UBERON:0002436	62.03	gold quality
ventricular zone	UBERON:0003053	61.77	gold quality
bone marrow cell	CL:0002092	60.59	gold quality
right frontal lobe	UBERON:0002810	59.36	gold quality
Brodmann (1909) area 9	UBERON:0013540	58.71	gold quality
cortical plate	UBERON:0005343	58.53	gold quality
brain	UBERON:0000955	58.18	gold quality
frontal cortex	UBERON:0001870	58.14	gold quality
right ovary	UBERON:0002118	57.93	gold quality
ganglionic eminence	UBERON:0004023	57.74	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	57.66	gold quality
prefrontal cortex	UBERON:0000451	57.47	gold quality
superior frontal gyrus	UBERON:0002661	57.45	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	57.30	gold quality
pituitary gland	UBERON:0000007	57.25	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	57.09	gold quality
tibial artery	UBERON:0007610	56.92	gold quality
popliteal artery	UBERON:0002250	56.89	gold quality
muscle layer of sigmoid colon	UBERON:0035805	56.84	gold quality
left ovary	UBERON:0002119	56.78	gold quality
cerebral cortex	UBERON:0000956	56.54	gold quality
ovary	UBERON:0000992	56.16	gold quality
adenohypophysis	UBERON:0002196	56.03	gold quality
skin of leg	UBERON:0001511	55.89	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	55.85	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.63

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 6)

• a novel gene, fussel-15 (functional smad suppressing element on chromosome 15) with high homology to the recently discovered Fussel-18 protein. (PMID:17292623)
• MEIS1 and LBXCOR1 are developmental factors and raise new pathophysiologic questions for RLS. (PMID:18541116)
• Permanent expression of Fussel-15 in keloid and skin sclerosis fibroblasts could be involved in the pathogenesis of these conditions. (PMID:21641385)
• MAP2K5/SKOR1 may be associated with Chinese essential tremor patients. (PMID:29798820)
• SKOR1 has a transcriptional regulatory role on genes involved in pathways related to restless legs syndrome. (PMID:32572201)
• Human alpha-synuclein overexpression upregulates SKOR1 in a rat model of simulated nigrostriatal ageing. (PMID:38529808)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	skor1b	ENSDARG00000062448
danio_rerio	skor1a	ENSDARG00000069030
mus_musculus	Skor1	ENSMUSG00000022245
rattus_norvegicus	Skor1	ENSRNOG00000013959

Paralogs (3): SKIL (ENSG00000136603), SKI (ENSG00000157933), SKOR2 (ENSG00000215474)

Protein

Protein identifiers

SKI family transcriptional corepressor 1 — P84550 (reviewed: P84550)

Alternative names: Functional Smad-suppressing element on chromosome 15, LBX1 corepressor 1, Ladybird homeobox corepressor 1

All UniProt accessions (3): G3V3E1, G3V5H7, P84550

UniProt curated annotations — full annotation on UniProt →

Function. Acts as a transcriptional corepressor of LBX1. Inhibits BMP signaling.

Subunit / interactions. Interacts with LBX1. Interacts with SMAD1, SMAD2 and SMAD3.

Subcellular location. Nucleus.

Tissue specificity. Present specifically in cerebellar Purkinje cells (at protein level).

Similarity. Belongs to the SKI family.

Isoforms (3)

UniProt ID	Names	Canonical?
P84550-1	1	yes
P84550-2	2
P84550-3	3

RefSeq proteins (1): NP_001352844* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003380	SKI/SNO/DAC	Domain
IPR009061	DNA-bd_dom_put_sf	Homologous_superfamily
IPR010919	SAND-like_dom_sf	Homologous_superfamily
IPR014890	c-SKI_SMAD4-bd_dom	Domain
IPR023216	Tscrpt_reg_SKI_SnoN	Family
IPR037000	Ski_DNA-bd_sf	Homologous_superfamily

Pfam: PF02437, PF08782

UniProt features (26 total): compositionally biased region 10, region of interest 6, splice variant 6, sequence variant 2, chain 1, coiled-coil region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P84550-F1	55.96	0.21

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 55 (showing top): GOBP_REGULATION_OF_CELLULAR_RESPONSE_TO_GROWTH_FACTOR_STIMULUS, MARTORIATI_MDM4_TARGETS_NEUROEPITHELIUM_DN, GOBP_NEGATIVE_REGULATION_OF_CELLULAR_RESPONSE_TO_GROWTH_FACTOR_STIMULUS, GOBP_REGULATION_OF_TRANSMEMBRANE_RECEPTOR_PROTEIN_SERINE_THREONINE_KINASE_SIGNALING_PATHWAY, GOBP_NEGATIVE_REGULATION_OF_BMP_SIGNALING_PATHWAY, GOBP_RESPONSE_TO_BMP, TANAKA_METHYLATED_IN_ESOPHAGEAL_CARCINOMA, GOBP_RESPONSE_TO_GROWTH_FACTOR, GOBP_REGULATION_OF_BMP_SIGNALING_PATHWAY, GOCC_NEURON_PROJECTION, chr15q23, GOMF_SMAD_BINDING, GOBP_NEGATIVE_REGULATION_OF_TRANSMEMBRANE_RECEPTOR_PROTEIN_SERINE_THREONINE_KINASE_SIGNALING_PATHWAY, LEE_TARGETS_OF_PTCH1_AND_SUFU_DN, GOCC_TRANSCRIPTION_REGULATOR_COMPLEX

GO Biological Process (5): negative regulation of transcription by RNA polymerase II (GO:0000122), regulation of DNA-templated transcription (GO:0006355), negative regulation of BMP signaling pathway (GO:0030514), negative regulation of DNA-templated transcription (GO:0045892), negative regulation of transmembrane receptor protein serine/threonine kinase signaling pathway (GO:0090101)

GO Molecular Function (4): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), SMAD binding (GO:0046332), sequence-specific double-stranded DNA binding (GO:1990837)

GO Cellular Component (5): nucleus (GO:0005634), transcription regulator complex (GO:0005667), cytoplasm (GO:0005737), dendrite (GO:0030425), neuronal cell body (GO:0043025)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of transcription by RNA polymerase II	2
DNA-templated transcription	2
RNA polymerase II transcription regulatory region sequence-specific DNA binding	2
transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
BMP signaling pathway	1
regulation of BMP signaling pathway	1
negative regulation of transmembrane receptor protein serine/threonine kinase signaling pathway	1
negative regulation of cellular response to growth factor stimulus	1
regulation of DNA-templated transcription	1
negative regulation of RNA biosynthetic process	1
cell surface receptor protein serine/threonine kinase signaling pathway	1
negative regulation of signal transduction	1
regulation of transmembrane receptor protein serine/threonine kinase signaling pathway	1
cis-regulatory region sequence-specific DNA binding	1
chromatin	1
DNA-binding transcription factor activity	1
protein binding	1
double-stranded DNA binding	1
sequence-specific DNA binding	1
intracellular membrane-bounded organelle	1
protein-containing complex	1
intracellular anatomical structure	1
cellular anatomical structure	1
neuron projection	1
dendritic tree	1
somatodendritic compartment	1
cell body	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

3 interactions, top by confidence:

A	B	Type	Score
SKOR1	TRIM27	psi-mi:“MI:0914”(association)	0.350
CD247	RSL1D1	psi-mi:“MI:0914”(association)	0.350

BioGRID (5): HDAC6 (Affinity Capture-MS), DYRK1B (Affinity Capture-MS), TRIM27 (Affinity Capture-MS), PRKAA1 (Affinity Capture-MS), SKOR1 (Proximity Label-MS)

ESM2 similar proteins: A1L020, A1L3F4, A7X8B3, A7X8B5, A7X8B7, A7X8B9, A7X8C2, A7X8C4, A7X8C7, A7X8C9, A7X8D2, A7X8D4, A7XW25, O97775, O97776, O97952, O97960, P06401, P10275, P84550, P84551, P89463, Q01JD1, Q05A36, Q0VDT2, Q3UE17, Q5PQQ7, Q5U5Q3, Q69Z36, Q6QT55, Q6ZK57, Q6ZN04, Q71FD5, Q7RTV3, Q7TSJ6, Q7XQN1, Q7XT42, Q84SL2, Q86XN8, Q8BQ89

Diamond homologs: A7M7C7, P12755, P12757, P17863, P49140, P84550, P84551, Q02225, Q1LXZ9, Q2VWA4, Q5R431, Q60665, Q60698, Q8BX46, Q9TUG2, Q925Q8, Q96NX9, H2KY91, Q9QYB2, Q9UI36

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
SKOR1	“down-regulates activity”	LBX1	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

8 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	0
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1781 predictions. Top by Δscore:

Variant	Effect	Δscore
15:67830169:AATTC:A	acceptor_gain	1.0000
15:67830173:C:CA	acceptor_gain	1.0000
15:67830189:A:G	acceptor_gain	1.0000
15:67832270:ACAG:A	acceptor_loss	1.0000
15:67832271:C:G	acceptor_gain	1.0000
15:67832271:CAGA:C	acceptor_loss	1.0000
15:67832272:A:AG	acceptor_gain	1.0000
15:67832272:AGAG:A	acceptor_gain	1.0000
15:67832272:AGAGG:A	acceptor_loss	1.0000
15:67832273:G:GA	acceptor_gain	1.0000
15:67832273:GA:G	acceptor_gain	1.0000
15:67832273:GAGG:G	acceptor_gain	1.0000
15:67832273:GAGGA:G	acceptor_gain	1.0000
15:67832344:CAAAG:C	donor_loss	1.0000
15:67832345:AAAG:A	donor_loss	1.0000
15:67832346:AAGGT:A	donor_loss	1.0000
15:67832348:GGT:G	donor_loss	1.0000
15:67832350:T:A	donor_loss	1.0000
15:67832604:C:G	acceptor_gain	1.0000
15:67832606:GA:G	acceptor_gain	1.0000
15:67832606:GAT:G	acceptor_gain	1.0000
15:67832606:GATA:G	acceptor_gain	1.0000
15:67832606:GATAA:G	acceptor_gain	1.0000
15:67833182:T:TA	acceptor_gain	1.0000
15:67833188:CCAG:C	acceptor_loss	1.0000
15:67833189:CAGAT:C	acceptor_loss	1.0000
15:67833190:A:AG	acceptor_gain	1.0000
15:67833191:G:GA	acceptor_gain	1.0000
15:67833191:GA:G	acceptor_gain	1.0000
15:67833191:GAT:G	acceptor_gain	1.0000

AlphaMissense

6222 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:67826073:T:C	L82P	1.000
15:67826078:G:T	G84W	1.000
15:67826088:T:A	I87N	1.000
15:67826088:T:G	I87S	1.000
15:67826097:T:C	L90P	1.000
15:67826117:C:A	R97S	1.000
15:67826118:G:C	R97P	1.000
15:67826121:T:A	L98Q	1.000
15:67826121:T:C	L98P	1.000
15:67826123:T:C	C99R	1.000
15:67826124:G:A	C99Y	1.000
15:67826125:C:G	C99W	1.000
15:67826127:T:A	L100Q	1.000
15:67826127:T:C	L100P	1.000
15:67826136:T:A	I103N	1.000
15:67826136:T:C	I103T	1.000
15:67826136:T:G	I103S	1.000
15:67826138:T:C	S104P	1.000
15:67826139:C:A	S104Y	1.000
15:67826139:C:T	S104F	1.000
15:67826143:C:A	N105K	1.000
15:67826143:C:G	N105K	1.000
15:67826148:T:A	L107H	1.000
15:67826148:T:C	L107P	1.000
15:67826151:T:A	L108H	1.000
15:67826151:T:C	L108P	1.000
15:67826162:A:C	S112R	1.000
15:67826164:C:A	S112R	1.000
15:67826164:C:G	S112R	1.000
15:67826165:T:C	Y113H	1.000

dbSNP variants (sampled 300 via entrez): RS1000520570 (15:67824103 TCGAGAAAC>T), RS1000585256 (15:67825355 C>G,T), RS1001078886 (15:67831095 A>G), RS1001079378 (15:67829979 G>A), RS1001079651 (15:67825237 G>A), RS1001424872 (15:67827044 T>A,C,G), RS1001560064 (15:67827433 C>G), RS1002939418 (15:67833920 C>A,T), RS1003075130 (15:67834138 G>C), RS1003096782 (15:67828317 G>A,T), RS1003129090 (15:67828085 G>A), RS1003407783 (15:67833564 C>T), RS1003438833 (15:67826042 C>G), RS1003669418 (15:67831686 G>A), RS1003870479 (15:67829299 T>C)

Disease associations

OMIM: gene MIM:611273 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST000056_3	Restless legs syndrome	1.000000e-15
GCST000830_6	Body mass index	1.000000e-18
GCST001159_4	Restless legs syndrome	1.000000e-22
GCST002701_14	Verbal declarative memory	1.000000e-06
GCST005042_16	Restless legs syndrome	5.000000e-69
GCST007280_1	Number of twin births	3.000000e-08
GCST010917_12	Proportion of activated microglia (midfrontal cortex)	2.000000e-07

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0004874	memory performance
EFO:0006805	word list delayed recall measurement
EFO:0009439	multiple births measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

15 total (human), top 15 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
propionaldehyde	decreases expression	1
bisphenol A	affects cotreatment, decreases methylation	1
arsenite	increases methylation	1
CGP 52608	affects binding, increases reaction	1
2-palmitoylglycerol	increases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Cadmium	decreases expression, increases abundance	1
Smoke	increases expression	1
Triclosan	increases expression	1
Valproic Acid	increases methylation	1
Vanadium	increases abundance, increases methylation	1
Fluorescein-5-isothiocyanate	affects binding	1
Metals, Heavy	increases abundance, increases methylation	1
Cadmium Chloride	increases abundance, decreases expression	1
S-Nitrosoglutathione	increases expression	1

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_TL38	HAP1 SKOR1 (-) 1	Cancer cell line	Male
CVCL_XS82	HAP1 SKOR1 (-) 2	Cancer cell line	Male
CVCL_XS83	HAP1 SKOR1 (-) 3	Cancer cell line	Male

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.