SYNE1

spectrin repeat containing nuclear envelope protein 1, the group of Spectrin repeat containing nuclear envelope family|KASH domain containing

Basic information

Region (hg38): 6:152121687-152637801

Previous symbols: [ "C6orf98" ]

Links

ENSG00000131018 ∙ NCBI:23345 ∙ OMIM:608441 ∙ HGNC:17089 ∙ Uniprot:Q8NF91 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autosomal recessive ataxia, Beauce type (Strong), mode of inheritance: AR
• autosomal recessive ataxia, Beauce type (Supportive), mode of inheritance: AR
• autosomal dominant Emery-Dreifuss muscular dystrophy (Supportive), mode of inheritance: AD
• autosomal recessive myogenic arthrogryposis multiplex congenita (Supportive), mode of inheritance: AR
• Emery-Dreifuss muscular dystrophy 4, autosomal dominant (Moderate), mode of inheritance: AD
• autosomal recessive ataxia, Beauce type (Definitive), mode of inheritance: AR
• Emery-Dreifuss muscular dystrophy 4, autosomal dominant (Limited), mode of inheritance: AD
• autosomal recessive ataxia, Beauce type (Strong), mode of inheritance: AR
• autosomal recessive ataxia, Beauce type (Strong), mode of inheritance: AR
• arthrogryposis multiplex congenita 3, myogenic type (Strong), mode of inheritance: AR
• Emery-Dreifuss muscular dystrophy 4, autosomal dominant (Limited), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Emery-Dreifuss muscular dystrophy 4, autosomal dominant	AD	Cardiovascular	One reported patient was found to have left ventricular basal and septal hypertrophy with mild diastolic dysfunction, and surveillance (eg, with echocardiogram) may allow early medical management	Cardiovascular; Musculoskeletal; Neurologic	17503513; 17159980; 17761684; 19542096; 20301553; 20301609; 24319099; 27782104

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SYNE1 gene.

• not provided (68 variants)
• Autosomal recessive ataxia, Beauce type;Emery-Dreifuss muscular dystrophy 4, autosomal dominant (46 variants)
• Autosomal recessive ataxia, Beauce type (39 variants)
• Emery-Dreifuss muscular dystrophy 4, autosomal dominant;Autosomal recessive ataxia, Beauce type (33 variants)
• Emery-Dreifuss muscular dystrophy 4, autosomal dominant (6 variants)
• SYNE1-related disorder (5 variants)
• Arthrogryposis multiplex congenita 3, myogenic type (4 variants)
• Juvenile amyotrophic lateral sclerosis (2 variants)
• Spastic ataxia (1 variants)
• Inborn genetic diseases (1 variants)
• Arthrogryposis multiplex congenita 3, myogenic type;Autosomal recessive ataxia, Beauce type;Emery-Dreifuss muscular dystrophy 4, autosomal dominant (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SYNE1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			153	887	29	1069
missense		3	2810	63	40	2916
nonsense	101	47	4	1		153
start loss			1			1
frameshift	56	41	5	2	1	105
inframe indel			22			22
splice donor/acceptor (+/-2bp)	12	34	3			49
splice region			126	118	13	257
non coding	1	1	65	608	378	1053
Total	170	126	3063	1561	448

Highest pathogenic variant AF is 0.000125

Variants in SYNE1

This is a list of pathogenic ClinVar variants found in the SYNE1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
6-152121768-CT-C		Cerebellar ataxia • Emery-Dreifuss muscular dystrophy	Uncertain significance (Jun 14, 2016)
6-152121768-CTT-C		Cerebellar ataxia • Emery-Dreifuss muscular dystrophy	Benign (Jun 14, 2016)
6-152121853-T-C		Autosomal recessive ataxia, Beauce type • Emery-Dreifuss muscular dystrophy 4, autosomal dominant	Benign (Jan 12, 2018)
6-152121855-TA-T		Cerebellar ataxia • Emery-Dreifuss muscular dystrophy	Uncertain significance (Jun 14, 2016)
6-152121921-A-G		Autosomal recessive ataxia, Beauce type • Emery-Dreifuss muscular dystrophy 4, autosomal dominant	Uncertain significance (Jan 13, 2018)
6-152121987-A-G		Emery-Dreifuss muscular dystrophy 4, autosomal dominant • Autosomal recessive ataxia, Beauce type	Uncertain significance (Jan 12, 2018)
6-152121987-A-T		Emery-Dreifuss muscular dystrophy 4, autosomal dominant • Autosomal recessive ataxia, Beauce type	Uncertain significance (Jan 12, 2018)
6-152122003-T-C		Autosomal recessive ataxia, Beauce type • Emery-Dreifuss muscular dystrophy 4, autosomal dominant	Uncertain significance (Jan 12, 2018)
6-152122068-A-G		Emery-Dreifuss muscular dystrophy 4, autosomal dominant • Autosomal recessive ataxia, Beauce type	Uncertain significance (Jan 13, 2018)
6-152122141-A-G		Emery-Dreifuss muscular dystrophy 4, autosomal dominant • Autosomal recessive ataxia, Beauce type	Uncertain significance (Jan 13, 2018)
6-152122155-C-T			Likely benign (Mar 25, 2019)
6-152122245-T-C		Emery-Dreifuss muscular dystrophy 4, autosomal dominant • Autosomal recessive ataxia, Beauce type	Conflicting classifications of pathogenicity (Aug 01, 2022)
6-152122250-C-T		Autosomal recessive ataxia, Beauce type • Emery-Dreifuss muscular dystrophy 4, autosomal dominant	Uncertain significance (Jan 12, 2018)
6-152122254-C-T		Autosomal recessive ataxia, Beauce type • Emery-Dreifuss muscular dystrophy 4, autosomal dominant	Benign (Jun 18, 2018)
6-152122255-G-A		Emery-Dreifuss muscular dystrophy 4, autosomal dominant • Autosomal recessive ataxia, Beauce type	Uncertain significance (Jan 12, 2018)
6-152122270-C-T		Autosomal recessive ataxia, Beauce type • Emery-Dreifuss muscular dystrophy 4, autosomal dominant	Uncertain significance (Jan 13, 2018)
6-152122298-T-C		Emery-Dreifuss muscular dystrophy 4, autosomal dominant • Autosomal recessive ataxia, Beauce type	Uncertain significance (Jan 13, 2018)
6-152122333-G-T		Emery-Dreifuss muscular dystrophy 4, autosomal dominant • Autosomal recessive ataxia, Beauce type	Benign (Jun 18, 2018)
6-152122335-G-A		Autosomal recessive ataxia, Beauce type • Emery-Dreifuss muscular dystrophy 4, autosomal dominant	Uncertain significance (Jan 13, 2018)
6-152122341-G-A		Emery-Dreifuss muscular dystrophy 4, autosomal dominant • Autosomal recessive ataxia, Beauce type	Benign/Likely benign (Jan 12, 2018)
6-152122439-G-A		Autosomal recessive ataxia, Beauce type;Emery-Dreifuss muscular dystrophy 4, autosomal dominant	Likely benign (Jul 29, 2023)
6-152122446-G-A			Uncertain significance (Mar 15, 2020)
6-152122454-A-G		Emery-Dreifuss muscular dystrophy 4, autosomal dominant;Autosomal recessive ataxia, Beauce type	Likely benign (Jan 19, 2022)
6-152122455-T-C		Emery-Dreifuss muscular dystrophy 4, autosomal dominant;Autosomal recessive ataxia, Beauce type	Uncertain significance (Aug 29, 2020)
6-152122457-C-T		Autosomal recessive ataxia, Beauce type;Emery-Dreifuss muscular dystrophy 4, autosomal dominant	Likely benign (Nov 01, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SYNE1	protein_coding	protein_coding	ENST00000367255	144	516118

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
3.19e-52	1.00	125312	0	436	125748	0.00174

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.291	4465	4.41e+3	1.01	0.000252	58271
Missense in Polyphen		1067	1162.1	0.91819		16036
Synonymous	-1.64	1798	1.71e+3	1.05	0.000101	16092
Loss of Function	12.8	182	487	0.374	0.0000264	5737

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00383	0.00381
Ashkenazi Jewish	0.000620	0.000595
East Asian	0.00147	0.00147
Finnish	0.00120	0.00120
European (Non-Finnish)	0.00195	0.00190
Middle Eastern	0.00147	0.00147
South Asian	0.00171	0.00170
Other	0.00180	0.00179

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Multi-isomeric modular protein which forms a linking network between organelles and the actin cytoskeleton to maintain the subcellular spatial organization. As a component of the LINC (LInker of Nucleoskeleton and Cytoskeleton) complex involved in the connection between the nuclear lamina and the cytoskeleton. The nucleocytoplasmic interactions established by the LINC complex play an important role in the transmission of mechanical forces across the nuclear envelope and in nuclear movement and positioning. May be involved in nucleus-centrosome attachment and nuclear migration in neural progenitors implicating LINC complex association with SUN1/2 and probably association with cytoplasmic dynein-dynactin motor complexes; SYNE1 and SYNE2 may act redundantly. Required for centrosome migration to the apical cell surface during early ciliogenesis. May be involved in nuclear remodeling during sperm head formation in spermatogenenis; a probable SUN3:SYNE1/KASH1 LINC complex may tether spermatid nuclei to posterior cytoskeletal structures such as the manchette. {ECO:0000250|UniProtKB:Q6ZWR6, ECO:0000269|PubMed:11792814, ECO:0000269|PubMed:18396275}.
• Disease: DISEASE: Spinocerebellar ataxia, autosomal recessive, 8 (SCAR8) [MIM:610743]: Spinocerebellar ataxia is a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCAR8 is an autosomal recessive form. {ECO:0000269|PubMed:17159980}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Emery-Dreifuss muscular dystrophy 4, autosomal dominant (EDMD4) [MIM:612998]: A form of Emery-Dreifuss muscular dystrophy, a degenerative myopathy characterized by weakness and atrophy of muscle without involvement of the nervous system, early contractures of the elbows, Achilles tendons and spine, and cardiomyopathy associated with cardiac conduction defects. {ECO:0000269|PubMed:17761684}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: miR-targeted genes in epithelium - TarBase;miR-targeted genes in lymphocytes - TarBase;miR-targeted genes in muscle cell - TarBase (Consensus)

Recessive Scores

• pRec: 0.461

Intolerance Scores

• loftool: 0.881
• rvis_EVS: -0.16
• rvis_percentile_EVS: 41.65

Haploinsufficiency Scores

• hipred: N
• hipred_score: 0.393
• ghis: 0.510

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.669

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	High	High	High
Primary Immunodeficiency	High	High	High
Cancer	High	High	High

Mouse Genome Informatics

• Gene name: Syne1
• Phenotype: immune system phenotype; skeleton phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); vision/eye phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); respiratory system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); cellular phenotype; homeostasis/metabolism phenotype; muscle phenotype; growth/size/body region phenotype

Zebrafish Information Network

• Gene name: syne1b
• Affected structure: post-vent region
• Phenotype tag: abnormal
• Phenotype quality: increased curvature

Gene ontology

• Biological process: nucleus organization;Golgi organization;spermatogenesis;muscle cell differentiation;cytoskeletal anchoring at nuclear membrane;nuclear matrix anchoring at nuclear membrane
• Cellular component: P-body;nucleus;nuclear envelope;nuclear outer membrane;nucleoplasm;nucleolus;cytoplasm;Golgi apparatus;cytoskeleton;integral component of membrane;sarcomere;nuclear membrane;meiotic nuclear membrane microtubule tethering complex;postsynaptic membrane
• Molecular function: RNA binding;actin binding;protein binding;lamin binding;enzyme binding;protein homodimerization activity;actin filament binding