SGCE

Summary

SGCE (sarcoglycan epsilon, HGNC:10808) is a protein-coding gene on chromosome 7q21.3, encoding Epsilon-sarcoglycan (O43556). Component of the sarcoglycan complex, a subcomplex of the dystrophin-glycoprotein complex which forms a link between the F-actin cytoskeleton and the extracellular matrix. It is a selective cancer dependency (DepMap: 11.8% of cell lines) and haploinsufficient (ClinGen: sufficient evidence).

This gene encodes the epsilon member of the sarcoglycan family. Sarcoglycans are transmembrane proteins that are components of the dystrophin-glycoprotein complex, which link the actin cytoskeleton to the extracellular matrix. Unlike other family members which are predominantly expressed in striated muscle, the epsilon sarcoglycan is more broadly expressed. Mutations in this gene are associated with myoclonus-dystonia syndrome. This gene is imprinted, with preferential expression from the paternal allele. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. A pseudogene associated with this gene is located on chromosome 2.

Source: NCBI Gene 8910 — RefSeq curated summary.

At a glance

• Gene–disease (curated): myoclonic dystonia 11 (Definitive, GenCC) — +1 more curated relationship
• Clinical variants (ClinVar): 86 total — 14 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 26
• Cancer dependency (DepMap): dependent in 11.8% of screened cell lines
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
• MANE Select transcript: NM_003919

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10808
Approved symbol	SGCE
Name	sarcoglycan epsilon
Location	7q21.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000127990
Ensembl biotype	protein_coding
OMIM	604149
Entrez	8910

Gene structure

Transcript identifiers

Ensembl transcripts: 113 — 60 protein_coding, 25 retained_intron, 23 nonsense_mediated_decay, 5 protein_coding_CDS_not_defined

ENST00000415788, ENST00000425444, ENST00000428696, ENST00000437425, ENST00000445866, ENST00000447873, ENST00000450385, ENST00000462731, ENST00000472326, ENST00000522045, ENST00000642169, ENST00000642291, ENST00000642353, ENST00000642394, ENST00000642441, ENST00000642497, ENST00000642564, ENST00000642638, ENST00000642707, ENST00000642754, ENST00000642759, ENST00000642802, ENST00000642904, ENST00000642933, ENST00000643020, ENST00000643041, ENST00000643128, ENST00000643160, ENST00000643193, ENST00000643206, ENST00000643272, ENST00000643324, ENST00000643358, ENST00000643368, ENST00000643491, ENST00000643568, ENST00000643605, ENST00000643610, ENST00000643714, ENST00000643903, ENST00000643991, ENST00000644087, ENST00000644116, ENST00000644122, ENST00000644201, ENST00000644268, ENST00000644373, ENST00000644375, ENST00000644533, ENST00000644551, ENST00000644609, ENST00000644639, ENST00000644658, ENST00000644674, ENST00000644681, ENST00000644682, ENST00000644816, ENST00000644924, ENST00000644966, ENST00000645027, ENST00000645101, ENST00000645109, ENST00000645262, ENST00000645390, ENST00000645445, ENST00000645535, ENST00000645579, ENST00000645624, ENST00000645665, ENST00000645725, ENST00000645767, ENST00000645804, ENST00000645920, ENST00000646098, ENST00000646119, ENST00000646137, ENST00000646265, ENST00000646301, ENST00000646434, ENST00000646466, ENST00000646489, ENST00000646559, ENST00000646600, ENST00000646682, ENST00000646761, ENST00000646879, ENST00000646910, ENST00000646943, ENST00000647018, ENST00000647031, ENST00000647048, ENST00000647096, ENST00000647110, ENST00000647334, ENST00000647351, ENST00000647379, ENST00000647533, ENST00000648936, ENST00000898600, ENST00000898601, ENST00000898602, ENST00000898603, ENST00000898604, ENST00000898605, ENST00000898606, ENST00000898607, ENST00000898608, ENST00000898609, ENST00000925606, ENST00000948718, ENST00000948719, ENST00000948720, ENST00000948721

RefSeq mRNA: 12 — MANE Select: NM_003919 NM_001099400, NM_001099401, NM_001301139, NM_001346713, NM_001346715, NM_001346717, NM_001346719, NM_001346720, NM_001362807, NM_001362808, NM_001362809, NM_003919

CCDS: CCDS47642, CCDS47643, CCDS5637, CCDS75634, CCDS87519, CCDS87520, CCDS87522, CCDS87523

Canonical transcript exons

ENST00000648936 — 11 exons

Exon	Start	End
ENSE00000877301	94600646	94600857
ENSE00000877302	94603290	94603452
ENSE00000877303	94618758	94618956
ENSE00000977072	94598775	94598963
ENSE00001031760	94599697	94599723
ENSE00003580279	94623325	94623397
ENSE00003581013	94629719	94629841
ENSE00003659370	94588689	94588732
ENSE00003677921	94628202	94628359
ENSE00003833513	94584980	94585515
ENSE00003833709	94655990	94656133

Expression profiles

Bgee: expression breadth ubiquitous, 289 present calls, max score 97.79.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 11.7089 / max 90.2776, expressed in 1333 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
84929	9.6194	1314
84930	1.8171	940
84931	0.2723	116

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tendon of biceps brachii	UBERON:0008188	97.79	gold quality
left ovary	UBERON:0002119	97.61	gold quality
right ovary	UBERON:0002118	97.52	gold quality
adrenal tissue	UBERON:0018303	97.50	gold quality
calcaneal tendon	UBERON:0003701	97.05	gold quality
ovary	UBERON:0000992	96.82	gold quality
left adrenal gland	UBERON:0001234	96.74	gold quality
left adrenal gland cortex	UBERON:0035825	96.54	gold quality
tibial nerve	UBERON:0001323	96.43	gold quality
descending thoracic aorta	UBERON:0002345	96.38	gold quality
adrenal gland	UBERON:0002369	96.35	gold quality
tendon	UBERON:0000043	96.18	gold quality
right adrenal gland	UBERON:0001233	96.08	gold quality
adrenal cortex	UBERON:0001235	96.08	gold quality
thoracic aorta	UBERON:0001515	96.04	gold quality
ascending aorta	UBERON:0001496	96.03	gold quality
right adrenal gland cortex	UBERON:0035827	95.99	gold quality
left uterine tube	UBERON:0001303	95.97	gold quality
right coronary artery	UBERON:0001625	95.96	gold quality
adenohypophysis	UBERON:0002196	95.88	gold quality
body of uterus	UBERON:0009853	95.80	gold quality
tibia	UBERON:0000979	95.65	gold quality
aorta	UBERON:0000947	95.60	gold quality
endocervix	UBERON:0000458	95.56	gold quality
colonic epithelium	UBERON:0000397	95.31	gold quality
popliteal artery	UBERON:0002250	95.30	gold quality
tibial artery	UBERON:0007610	95.30	gold quality
cartilage tissue	UBERON:0002418	95.29	gold quality
ventricular zone	UBERON:0003053	95.28	gold quality
muscle layer of sigmoid colon	UBERON:0035805	95.25	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	22.03
E-CURD-114	yes	18.42
E-CURD-112	yes	9.24
E-ENAD-27	no	3.34

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

22 targeting SGCE, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-4307	99.82	70.45	3374
HSA-MIR-323A-3P	99.79	70.30	1739
HSA-MIR-5002-5P	99.76	70.84	1763
HSA-MIR-586	99.65	70.40	2051
HSA-MIR-142-5P	99.48	70.92	2416
HSA-MIR-5590-3P	99.48	70.91	2429
HSA-MIR-6507-3P	99.35	67.32	1059
HSA-MIR-194-5P	99.01	69.65	1465
HSA-MIR-5701	98.97	69.54	1502
HSA-MIR-6847-3P	96.50	67.30	582

Functional genomics

ClinGen dosage: haploinsufficiency 3 (sufficient evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map DepMap (CRISPR cell-line fitness): dependent in 11.8% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

• Mutations in the gene encoding epsilon-sarcoglycan cause myoclonus-dystonia syndrome (PMID:11528394)
• Myoclonus-dystonia syndrome: epsilon-sarcoglycan mutations and phenotype (PMID:12325078)
• Myoclonus-dystonia is a movement disorder associated with mutations in the epsilon-sarcoglycan gene (SGCE) in most families and in the DRD2 and DYT1 genes in two single families. (PMID:12402271)
• Evidence that paternal expression of the epsilon-sarcoglycan gene accounts for reduced penetrance in myoclonus-dystonia (PMID:12444570)
• placental transcription from SGCE remained unchanged throughout pregnancy (PMID:12620933)
• The epsilon-sarcoglycan gene (SGCE), mutated in myoclonus-dystonia syndrome, is maternally imprinted (PMID:12634861)
• Severe myoclonus-dystonia syndrome characterized by obsessive-compulsive disorder, depression, and anxiety was shown to be associated with a novel truncating mutation located within exon 4 of SGCE. (PMID:12707948)
• Genetic analysis of a 5-generation Dutch family with inherited myoclonus-dystonia revealed a 1-bp insertion (885Tins)in exon 7 of the SGCE gene, resulting in frameshift and subsequent protein truncation at amino acid 297. (PMID:12821748)
• We describe 3 children with a similar clinical picture of autosomal dominant M-D and an SGCE mutation in only one of them, suggesting that M-D is genetically heterogeneous. (PMID:14978685)
• Mutatoins sarse not sassociaatd with sporadic Gilles de la Tourette syndrome. (PMID:15627203)
• 3 new mutations were found in patients with essential myoclous or myoclonic dystonia:R372X, 564-576del, IVS3-3T>C. (PMID:15728306)
• onset with both myoclonus and dystonia, and axial dystonia were detected significantly more often in the epsilon-sarcoplycan mutation carriers. (PMID:16534121)
• Some Myoclonus-dystonia syndrome-associated mutations in SGCE impair trafficking of the mutant protein to the plasma membrane. (PMID:17200151)
• a heterozygous point mutation in the epsilon-sarcoglycan gene, which leads to skipping of exon 5 in a family with myoclonus-dystonia syndrome complicated with severe depression (PMID:17230465)
• Obsessive-compulsive disorder and alcohol dependence are associated with manifesting mutated SGCE. (PMID:17296918)
• Our findings are not sufficient to conclude whether different SGCE mutations could lead to different phenoytpes of myoclonus-dystonia. (PMID:17394244)
• Korean Myoclonus-dystonia syndrome family with a novel splicing mutation of the SGCE gene and a unique phenotype mimicking Moya-Moya disease. (PMID:17394247)
• Autosomal dominant myoclonus-dystonia and Tourette syndrome in a family without linkage to the SGCE gene. (PMID:17702041)
• Two additional patients carried a de novo SGCE nonsense mutation in exon 3 (R97X) and a novel SGCE missense mutation in exon 6 (G227V) in this study. (PMID:17702043)
• Genomic deletion size at the epsilon-sarcoglycan locus determines the clinical phenotype in myoclonus-dystonia. (PMID:17898012)
• intragenic deletions with SGCE and it highlights the need to include exonic copy number variation when performing mutational analysis of SGCE. (PMID:18098280)
• Real-time PCR showed that ETOH significantly altered the expression of genes involved in cell adhesion. There was an increase in the expression of alpha and beta Laminins 1, beta Integrins 3 and 5, Secreted phosphoprotein1 and Sarcoglycan epsilon. (PMID:18162078)
• Myoclonus-dystonia due to SGCE protein mutations is characterized by early onset myoclonic jerks, often associated with dystonia. (PMID:18175340)
• Two heterozygous deletions of the entire SGCE gene and flanking DNA and a heterozygous deletion of exon 2 only were detected, accounting for 33% (3/9) of the mutations found. (PMID:18205193)
• There was no association of the SCGE coding & flanking intronic region in OCD and/or GTS or CMT. The functional relevance of a newly found c.1314+172T>C 3’-untranslated region variant has yet to be determined. (PMID:18349702)
• No muscle involvement in myoclonus-dystonia caused by epsilon-sarcoglycan gene mutations. (PMID:18355305)
• We describe the myoclonus in patients with mutations in the SGCE gene and characterize the pattern of this myoclonus. This pattern may improve the sensitivity of clinical tests and to define populations suitable for therapeutic trials. (PMID:18362280)
• A new 662 + 1insG mutation in exon 5 leads to a frameshift with a downstream stop codon, maybe interfering with mRNA stability. This is the first Chinese SGCE mutation leading to myoclonus-dystonia syndrome with a varied phenotype in the same family. (PMID:18581468)
• SGCE gene deletion is associated with myoclonus-dystonia, language delay, and malformative anomalies. (PMID:18651096)
• In Inherited myoclonus dystonia family case, father and daughter were found to carry the R237X mutation in the SGCE gene in heterozygous status. (PMID:18702114)
• We identified a new genetic alteration-maternal chromosome 7 disomy-that can cause myoclonus-dystonia. This alteration results in repression of both alleles of the maternally imprinted SGCE gene and suggests SGCE loss of function as the disease mechanism. (PMID:18852357)
• Sequence analysis of the SGCE gene and screening for copy number variations were performed. (PMID:19066193)
• In this study identified heterozygous epsilon sarcoglycan (SGCE) mutations, including a novel deletion of exon 10 in patient with myoclonus-dystonia. (PMID:19117362)
• 33 month old girl & her twin brother presenting myoclonus on intentional tasks; family history was positive for paternal uncle, his 2 daughters & paternal great grandfather; sequencing revealed a novel nonsense mutation c.942C>A (p.Tyr314X) in exon 7. (PMID:19147379)
• writer’s cramp as presenting symptom is not associated with mutations in DYT11, DYT16, but it can be the sole manifestation of DYT1 GAG deletion mutation carriers. (PMID:19441135)
• Physiology and surgical response for a 63-year-old woman who underwent deep brain stimulation for myoclonus dystonia related to a SGCE mutation. (PMID:19896264)
• MMP-7 and SGCE are distinctive molecular factors in sporadic colorectal cancers from the mutator phenotype pathway (PMID:20372795)
• This study identified three novel mutations of SGCE in the respective three myoclonus-dystonia syndrome families in Taiwan. (PMID:20800530)
• loss of function of the brain-specific SGCE isoform underlies the exclusively neurological myoclonus-dystonia phenotype (PMID:21157498)
• Dystonia severity in twenty-five clinically affected DYT11 mutation carriers is strongly correlated with increased gray matter volume in bilateral putamina. (PMID:21219543)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	sgce	ENSDARG00000012138
mus_musculus	Sgce	ENSMUSG00000004631
rattus_norvegicus	Sgce	ENSRNOG00000046905
drosophila_melanogaster	Scgalpha	FBGN0032013
caenorhabditis_elegans		WBGENE00019227

Paralogs (1): SGCA (ENSG00000108823)

Protein

Protein identifiers

Epsilon-sarcoglycan — O43556 (reviewed: O43556)

All UniProt accessions (57): O43556, A0A0S2Z4P5, A0A2R8Y2R1, A0A2R8Y416, A0A2R8Y448, A0A2R8Y4E3, A0A2R8Y4P8, A0A2R8Y4X1, A0A2R8Y504, A0A2R8Y5F3, A0A2R8Y5H7, A0A2R8Y5J3, A0A2R8Y5J6, A0A2R8Y5L4, A0A2R8Y5M2, A0A2R8Y5P8, A0A2R8Y5Q3, A0A2R8Y5R7, A0A2R8Y5X0, A0A2R8Y5X5, A0A2R8Y621, A0A2R8Y628, A0A2R8Y638, A0A2R8Y652, A0A2R8Y696, A0A2R8Y6D4, A0A2R8Y6G8, A0A2R8Y6I4, A0A2R8Y6S4, A0A2R8Y6U6, A0A2R8Y6V3, A0A2R8Y6Y5, A0A2R8Y6Z8, A0A2R8Y7J1, A0A2R8Y7M6, A0A2R8Y7Q5, A0A2R8Y821, A0A2R8Y831, A0A2R8YCT2, A0A2R8YD68, A0A2R8YDK8, A0A2R8YDZ5, A0A2R8YE16, A0A2R8YE48, A0A2R8YE99, A0A2R8YEY2, A0A2R8YFA5, A0A2R8YGQ3, A0A2R8YGV6, A0A2R8YH48, A0A2R8YH84, A0A2U3TZN7, B7Z2R4, C9J4J9, C9JR67, E9PEH6, H0YC75

UniProt curated annotations — full annotation on UniProt →

Function. Component of the sarcoglycan complex, a subcomplex of the dystrophin-glycoprotein complex which forms a link between the F-actin cytoskeleton and the extracellular matrix.

Subcellular location. Cell membrane. Sarcolemma. Cytoplasm. Cytoskeleton. Cell projection. Dendrite. Golgi apparatus.

Tissue specificity. Ubiquitous.

Post-translational modifications. N-glycosylated. Ubiquitinated, leading to its degradation by the proteasome.

Disease relevance. Dystonia 11, myoclonic (DYT11) [MIM:159900] A myoclonic dystonia. Dystonia is defined by the presence of sustained involuntary muscle contractions, often leading to abnormal postures. DYT11 is characterized by involuntary lightning jerks and dystonic movements and postures alleviated by alcohol. Inheritance is autosomal dominant. The age of onset, pattern of body involvement, presence of myoclonus and response to alcohol are all variable. The disease is caused by variants affecting the gene represented in this entry.

Miscellaneous. Brain-specific.

Similarity. Belongs to the sarcoglycan alpha/epsilon family.

Isoforms (3)

UniProt ID	Names	Canonical?
O43556-1	1, epsilon-SG1	yes
O43556-3	2, epsilon-SG2
O43556-4	3

RefSeq proteins (12): NP_001092870, NP_001092871, NP_001288068, NP_001333642, NP_001333644, NP_001333646, NP_001333648, NP_001333649, NP_001349736, NP_001349737, NP_001349738, NP_003910* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006644	Cadg	Domain
IPR008908	Sarcoglycan_alpha/epsilon	Family
IPR048346	Sarcoglycan_N	Domain
IPR048347	Sarcoglycan_C	Domain

Pfam: PF05510, PF20989

UniProt features (24 total): sequence variant 15, splice variant 3, topological domain 2, chain 1, transmembrane region 1, sequence conflict 1, glycosylation site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O43556-F1	74.19	0.43

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Glycosylation sites (1): 200

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-9913351	Formation of the dystrophin-glycoprotein complex (DGC)
R-HSA-1474244	Extracellular matrix organization
R-HSA-3000171	Non-integrin membrane-ECM interactions

MSigDB gene sets: 218 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_MCMV_INFECTION_UP, MODULE_52, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, XU_GH1_AUTOCRINE_TARGETS_UP, KAAB_HEART_ATRIUM_VS_VENTRICLE_UP, YANG_BREAST_CANCER_ESR1_LASER_DN, TOMLINS_PROSTATE_CANCER_DN, GOBP_CELL_CELL_SIGNALING, MODULE_66, MODULE_118, GOBP_MUSCLE_STRUCTURE_DEVELOPMENT, DAVIES_MULTIPLE_MYELOMA_VS_MGUS_UP, SCHAEFFER_PROSTATE_DEVELOPMENT_6HR_UP, BOYAULT_LIVER_CANCER_SUBCLASS_G123_UP, TSENG_IRS1_TARGETS_DN

GO Biological Process (2): cell-matrix adhesion (GO:0007160), muscle organ development (GO:0007517)

GO Molecular Function (1): calcium ion binding (GO:0005509)

GO Cellular Component (13): Golgi membrane (GO:0000139), endoplasmic reticulum membrane (GO:0005789), Golgi apparatus (GO:0005794), cytoskeleton (GO:0005856), plasma membrane (GO:0005886), dystrophin-associated glycoprotein complex (GO:0016010), sarcoglycan complex (GO:0016012), dendrite membrane (GO:0032590), sarcolemma (GO:0042383), cytoplasm (GO:0005737), membrane (GO:0016020), dendrite (GO:0030425), cell projection (GO:0042995)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Non-integrin membrane-ECM interactions	1
Extracellular matrix organization	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
plasma membrane protein complex	2
cell-substrate adhesion	1
animal organ development	1
muscle structure development	1
metal ion binding	1
Golgi apparatus	1
bounding membrane of organelle	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
intracellular membraneless organelle	1
membrane	1
cell periphery	1
glycoprotein complex	1
dystroglycan complex	1
dendrite	1
neuron projection membrane	1
plasma membrane	1
intracellular anatomical structure	1
neuron projection	1
dendritic tree	1

Protein interactions and networks

STRING

846 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SGCE	SGCD	Q92629	941
SGCE	SSPN	Q14714	940
SGCE	TOR1A	O14656	939
SGCE	SGCB	Q16585	928
SGCE	PEG10	Q86TG7	869
SGCE	THAP1	Q9NVV9	852
SGCE	GCH1	P30793	835
SGCE	SGCZ	Q96LD1	830
SGCE	DMD	P11532	808
SGCE	DAG1	Q14118	795
SGCE	SGCG	Q13326	790
SGCE	DRD2	P14416	741
SGCE	SLITRK1	Q96PX8	726
SGCE	NNAT	Q16517	690
SGCE	UTRN	P46939	681

IntAct

26 interactions, top by confidence:

A	B	Type	Score
TMEM30B	KLRG2	psi-mi:“MI:0914”(association)	0.530
FCGRT	GOLIM4	psi-mi:“MI:0914”(association)	0.530
KEAP1	SGCE	psi-mi:“MI:0407”(direct interaction)	0.440
	TK2	psi-mi:“MI:0915”(physical association)	0.400
SGCE	CWC15	psi-mi:“MI:0915”(physical association)	0.370
PPP1CC	SGCE	psi-mi:“MI:0915”(physical association)	0.370
DAG1	AGRN	psi-mi:“MI:0914”(association)	0.350
DAG1	SGCE	psi-mi:“MI:0914”(association)	0.350
NS3	C15orf61	psi-mi:“MI:0914”(association)	0.350
	SHTN1	psi-mi:“MI:0914”(association)	0.350
	TMEM223	psi-mi:“MI:0914”(association)	0.350
	TNFRSF10A	psi-mi:“MI:0914”(association)	0.350
CACNA1C	DISP2	psi-mi:“MI:0914”(association)	0.350
HCN1	POTEF	psi-mi:“MI:0914”(association)	0.350
CTLA4	TMEM120B	psi-mi:“MI:0914”(association)	0.350
NRSN1	FAM171A2	psi-mi:“MI:0914”(association)	0.350
SCAP	UPK3BL1	psi-mi:“MI:0914”(association)	0.350
FAM234A	IFRD1	psi-mi:“MI:0914”(association)	0.350
RYK	TNFRSF10B	psi-mi:“MI:0914”(association)	0.350
IGDCC4	SGCE	psi-mi:“MI:0914”(association)	0.350
SCARB2	SGCE	psi-mi:“MI:0914”(association)	0.350
SLC10A5	STXBP3	psi-mi:“MI:0914”(association)	0.350
ARIH2	SGCE	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (37): SGCE (Affinity Capture-MS), SGCE (Affinity Capture-MS), SGCE (Two-hybrid), SGCE (Affinity Capture-MS), SGCE (Affinity Capture-MS), SGCE (Affinity Capture-MS), SGCE (Proximity Label-MS), SGCE (Proximity Label-MS), SGCE (Proximity Label-MS), SGCE (Proximity Label-MS), SGCE (Proximity Label-MS), SGCE (Proximity Label-MS), SGCE (Affinity Capture-RNA), CBL (Affinity Capture-Western), SGCE (Affinity Capture-Western)

ESM2 similar proteins: A1L2K1, A4FV27, A4IGL3, A7E2Z9, A8WFR0, B0S5G3, L7VG99, O14525, O43556, O54715, O70258, O70367, O75829, O77049, O77770, O88823, P05300, P13473, P17046, P17047, P17404, P40682, P49130, Q15904, Q29S03, Q4R5B1, Q5PPI4, Q5R5V2, Q5RAP2, Q5VW38, Q61137, Q6AXF6, Q6Q3F5, Q6YAT4, Q6ZQE4, Q8BXN9, Q8NBN3, Q8VDA1, Q90617, Q9D387

Diamond homologs: O43556, O70258, P82350, Q16586, Q28686, Q29S03, Q4R5B1, Q5RAP2, Q64255, Q6YAT4

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	14
Likely pathogenic	1
Uncertain significance	46
Likely benign	18
Benign	4

Top pathogenic / likely-pathogenic (15)

Variant ID	HGVS	Classification
1067508	NM_003919.3(SGCE):c.109+2T>C	Pathogenic
1069379	NM_003919.3(SGCE):c.109+1G>A	Pathogenic
1073071	NC_000007.13:g.(?94252627)(94252719_?)del	Pathogenic
1073072	NC_000007.13:g.(?94228081)(94232770_?)del	Pathogenic
1323587	NM_003919.3(SGCE):c.37_38insA (p.Cys13Ter)	Pathogenic
1458211	NC_000007.13:g.(?94248050)(94252729_?)del	Pathogenic
1459085	NC_000007.13:g.(?94248050)(94248288_?)del	Pathogenic
1459087	NC_000007.13:g.(?94257494)(94285410_?)del	Pathogenic
1459378	NC_000007.13:g.(?94232582)(94232784_?)del	Pathogenic
1459683	NC_000007.13:g.(?94285282)(94285410_?)del	Pathogenic
2424795	NC_000007.13:g.(?94252617)(94252729_?)del	Pathogenic
280479	NM_003919.3(SGCE):c.299G>A (p.Trp100Ter)	Pathogenic
4083497	GRCh37/hg19 7q21.3(chr7:94232602-94232764)x1	Pathogenic
4530778	NM_003919.3(SGCE):c.109+1G>T	Pathogenic
4709519	NM_003919.3(SGCE):c.109+5G>C	Likely pathogenic

SpliceAI

5088 predictions. Top by Δscore:

Variant	Effect	Δscore
7:94527155:A:AG	acceptor_gain	1.0000
7:94527155:AT:A	acceptor_gain	1.0000
7:94527156:T:G	acceptor_gain	1.0000
7:94527156:T:TA	acceptor_gain	1.0000
7:94527160:A:AG	acceptor_gain	1.0000
7:94527161:G:GG	acceptor_gain	1.0000
7:94527161:GC:G	acceptor_gain	1.0000
7:94527204:GTG:G	donor_gain	1.0000
7:94530460:G:GT	donor_gain	1.0000
7:94530460:G:T	donor_gain	1.0000
7:94533248:CA:C	donor_gain	1.0000
7:94533250:G:GG	donor_gain	1.0000
7:94533674:TTTA:T	acceptor_loss	1.0000
7:94533677:A:AG	acceptor_gain	1.0000
7:94533677:AG:A	acceptor_loss	1.0000
7:94533677:AGT:A	acceptor_gain	1.0000
7:94533678:G:GA	acceptor_gain	1.0000
7:94533678:GT:G	acceptor_gain	1.0000
7:94533678:GTG:G	acceptor_gain	1.0000
7:94533678:GTGGT:G	acceptor_gain	1.0000
7:94533798:ACAAG:A	donor_loss	1.0000
7:94533799:CAAGG:C	donor_loss	1.0000
7:94533800:AAG:A	donor_loss	1.0000
7:94533803:GT:G	donor_loss	1.0000
7:94533804:T:G	donor_loss	1.0000
7:94535389:G:GG	donor_gain	1.0000
7:94535524:G:GG	donor_gain	1.0000
7:94549630:GTTAT:G	donor_gain	1.0000
7:94549631:T:G	donor_gain	1.0000
7:94549635:G:GG	donor_gain	1.0000

AlphaMissense

2876 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:94603305:C:A	W270C	1.000
7:94603305:C:G	W270C	1.000
7:94603307:A:G	W270R	1.000
7:94603307:A:T	W270R	1.000
7:94603372:C:G	C248S	1.000
7:94603373:A:T	C248S	1.000
7:94603444:A:T	V224D	1.000
7:94618759:C:G	G221R	1.000
7:94618849:A:G	W191R	1.000
7:94618849:A:T	W191R	1.000
7:94623390:G:T	A133D	1.000
7:94628245:C:T	G116E	1.000
7:94628246:C:A	G116W	1.000
7:94628246:C:G	G116R	1.000
7:94628246:C:T	G116R	1.000
7:94628251:A:G	L114P	1.000
7:94628251:A:T	L114Q	1.000
7:94628257:C:T	G112E	1.000
7:94628290:A:G	L101P	1.000
7:94628290:A:T	L101H	1.000
7:94628292:C:A	W100C	1.000
7:94628292:C:G	W100C	1.000
7:94628294:A:G	W100R	1.000
7:94628294:A:T	W100R	1.000
7:94628331:A:C	F87L	1.000
7:94628331:A:T	F87L	1.000
7:94628332:A:G	F87S	1.000
7:94628333:A:G	F87L	1.000
7:94598913:C:G	R372P	0.999
7:94598916:A:G	L371P	0.999

dbSNP variants (sampled 300 via entrez): RS1000113706 (7:94628974 G>A), RS1000121860 (7:94622146 T>C), RS1000190043 (7:94607740 C>T), RS1000205985 (7:94611008 G>A), RS1000265210 (7:94614131 C>A), RS1000293459 (7:94647484 C>A,G,T), RS1000294650 (7:94614348 C>A), RS1000320932 (7:94599534 C>T), RS1000373854 (7:94614569 CT>C), RS1000388964 (7:94614299 A>G), RS1000399335 (7:94655006 C>T), RS1000444261 (7:94607265 A>C), RS1000472895 (7:94622433 G>C), RS1000474855 (7:94607351 A>C), RS1000558170 (7:94585479 C>T)

Disease associations

OMIM: gene MIM:604149 | disease phenotypes: MIM:159900

GenCC curated gene-disease

Disease	Classification	Inheritance
myoclonic dystonia 11	Definitive	Autosomal dominant
myoclonus-dystonia syndrome	Supportive	Autosomal dominant

Mondo (2): myoclonic dystonia 11 (MONDO:0008044), myoclonus-dystonia syndrome (MONDO:0000903)

Orphanet (1): Myoclonus-dystonia syndrome (Orphanet:36899)

HPO phenotypes

26 total (26 of 26 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000473	Torticollis
HP:0000716	Depression
HP:0000722	Compulsive behaviors
HP:0000739	Anxiety
HP:0000756	Agoraphobia
HP:0001252	Hypotonia
HP:0001332	Dystonia
HP:0001336	Myoclonus
HP:0001337	Tremor
HP:0002356	Writer’s cramp
HP:0002530	Axial dystonia
HP:0003144	Increased serum serotonin
HP:0003621	Juvenile onset
HP:0003785	Decreased CSF homovanillic acid concentration
HP:0003829	Typified by incomplete penetrance
HP:0008770	Obsessive-compulsive trait
HP:0010531	Spinal myoclonus
HP:0011463	Childhood onset
HP:0012075	Personality disorder
HP:0020020	Decreased CSF 5-hydroxyindoleacetic acid concentration
HP:0025269	Panic attack
HP:0030955	Addictive alcohol use
HP:0031959	Leg dystonia
HP:0031960	Arm dystonia
HP:0045084	Limb myoclonus

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C536096	Myoclonic dystonia (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

23 total (human), top 23 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases expression, increases methylation	4
sodium arsenite	affects cotreatment, increases abundance, increases expression, decreases expression	3
Arsenic	affects methylation, affects cotreatment, increases abundance, increases expression, decreases expression	3
Cyclosporine	decreases expression	2
aristolochic acid I	decreases expression	1
dicrotophos	decreases expression	1
trichostatin A	decreases expression	1
beta-lapachone	increases expression	1
picoxystrobin	increases expression	1
Sunitinib	decreases expression	1
Benzo(a)pyrene	affects methylation	1
Cyclophosphamide	affects response to substance	1
Doxorubicin	decreases expression	1
Fluorouracil	affects response to substance	1
Folic Acid	decreases expression	1
Gallic Acid	increases expression	1
Methotrexate	affects response to substance	1
Triclosan	increases methylation	1
Antirheumatic Agents	increases expression	1
Okadaic Acid	decreases expression	1
Copper Sulfate	decreases expression	1
tert-Butylhydroperoxide	decreases expression	1
Particulate Matter	decreases expression	1

Cellosaurus cell lines

6 cell lines: 6 induced pluripotent stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_C9QC	HPS1942	Induced pluripotent stem cell	Male
CVCL_C9QD	HPS1943	Induced pluripotent stem cell	Male
CVCL_C9QE	HPS1944	Induced pluripotent stem cell	Male
CVCL_C9QF	HPS1945	Induced pluripotent stem cell	Male
CVCL_C9QG	HPS1946	Induced pluripotent stem cell	Male
CVCL_C9QH	HPS1947	Induced pluripotent stem cell	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01806805	PHASE3	COMPLETED	Efficacy Trial of Zonisamide for Myoclonus Dystonia
NCT05671068	Not specified	COMPLETED	EMOTION & COGNITION IN MYOCLONUS DYSTONIA (AGENT10-ECODYST)
NCT03428009	Not specified	RECRUITING	Dystonia Genotype-Phenotype Correlation