SYNE2

spectrin repeat containing nuclear envelope protein 2, the group of KASH domain containing|Spectrin repeat containing nuclear envelope family

Basic information

Region (hg38): 14:63761898-64226433

Links

ENSG00000054654 ∙ NCBI:23224 ∙ OMIM:608442 ∙ HGNC:17084 ∙ Uniprot:Q8WXH0 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autosomal dominant Emery-Dreifuss muscular dystrophy (Supportive), mode of inheritance: AD
• Emery-Dreifuss muscular dystrophy 5, autosomal dominant (Limited), mode of inheritance: AD
• left ventricular noncompaction (Limited), mode of inheritance: AD
• Emery-Dreifuss muscular dystrophy 5, autosomal dominant (No Known Disease Relationship), mode of inheritance: AD
• Emery-Dreifuss muscular dystrophy 5, autosomal dominant (Limited), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Emery-Dreifuss muscular dystrophy 5, autosomal dominant	AD	Cardiovascular	Reported patients had cardiac findings such as arrhythmia, left ventricular hypertrophy, and dilated cardiomyopathy, and surveillance may allow early diagnosis and treatment; Heart transplantation has been reported	Cardiovascular; Musculoskeletal	17761684

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SYNE2 gene.

• Emery-Dreifuss muscular dystrophy 5, autosomal dominant (2946 variants)
• not provided (659 variants)
• Inborn genetic diseases (280 variants)
• not specified (190 variants)
• SYNE2-related condition (17 variants)
• Emery-Dreifuss muscular dystrophy (10 variants)
• See cases (2 variants)
• Restrictive cardiomyopathy;Long QT syndrome (1 variants)
• Cerebral palsy (1 variants)
• Spastic ataxia (1 variants)
• 10 conditions (1 variants)
• Primary dilated cardiomyopathy (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SYNE2 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			45	527	76	648
missense		1	1574	107	68	1750
nonsense	2	2	22		1	27
start loss						0
frameshift			27	1		28
inframe indel			24	2		26
splice donor/acceptor (+/-2bp)		1	22	1	2	26
splice region			81	77	19	177
non coding			40	218	259	517
Total	2	4	1754	856	406

Variants in SYNE2

This is a list of pathogenic ClinVar variants found in the SYNE2 region.

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

Position	Type	Phenotype	Significance	ClinVar
14-63852971-C-T		Emery-Dreifuss muscular dystrophy 5, autosomal dominant	Benign (Jan 12, 2018)
14-63852986-A-T		Emery-Dreifuss muscular dystrophy 5, autosomal dominant	Uncertain significance (Jan 13, 2018)
14-63852993-G-C		Emery-Dreifuss muscular dystrophy 5, autosomal dominant	Benign (Jan 12, 2018)
14-63853026-C-T		Emery-Dreifuss muscular dystrophy 5, autosomal dominant	Uncertain significance (Jan 13, 2018)
14-63853046-G-A		Emery-Dreifuss muscular dystrophy 5, autosomal dominant	Uncertain significance (Jan 12, 2018)
14-63853067-A-T		Emery-Dreifuss muscular dystrophy 5, autosomal dominant	Uncertain significance (Jan 13, 2018)
14-63853088-G-A		Emery-Dreifuss muscular dystrophy 5, autosomal dominant	Uncertain significance (Jan 12, 2018)
14-63853143-G-A		Emery-Dreifuss muscular dystrophy 5, autosomal dominant	Uncertain significance (Mar 16, 2018)
14-63853152-G-A		Emery-Dreifuss muscular dystrophy 5, autosomal dominant	Benign (Jan 12, 2018)
14-63909154-A-G		Emery-Dreifuss muscular dystrophy 5, autosomal dominant	Likely benign (Apr 03, 2022)
14-63909159-G-A		Emery-Dreifuss muscular dystrophy 5, autosomal dominant	Uncertain significance (Dec 12, 2019)
14-63909163-T-C		Emery-Dreifuss muscular dystrophy 5, autosomal dominant	Likely benign (Sep 11, 2019)
14-63909166-G-C		Emery-Dreifuss muscular dystrophy 5, autosomal dominant	Uncertain significance (Aug 31, 2022)
14-63909170-C-T		Emery-Dreifuss muscular dystrophy 5, autosomal dominant • SYNE2-related disorder	Benign/Likely benign (Nov 10, 2022)
14-63909175-C-T		Emery-Dreifuss muscular dystrophy 5, autosomal dominant	Likely benign (Oct 29, 2021)
14-63909176-G-A		Emery-Dreifuss muscular dystrophy 5, autosomal dominant	Uncertain significance (Apr 07, 2022)
14-63909176-G-C		Emery-Dreifuss muscular dystrophy 5, autosomal dominant	Uncertain significance (Dec 18, 2019)
14-63909180-A-C		See cases	Uncertain significance (May 19, 2021)
14-63909187-G-T		Emery-Dreifuss muscular dystrophy 5, autosomal dominant	Uncertain significance (Jul 17, 2023)
14-63909202-C-T		Emery-Dreifuss muscular dystrophy 5, autosomal dominant	Likely benign (May 31, 2022)
14-63909203-G-A		Emery-Dreifuss muscular dystrophy 5, autosomal dominant • not specified	Uncertain significance (Sep 29, 2023)
14-63909205-C-T		Emery-Dreifuss muscular dystrophy 5, autosomal dominant	Likely benign (Aug 06, 2021)
14-63909206-G-A		Emery-Dreifuss muscular dystrophy 5, autosomal dominant	Uncertain significance (Jan 19, 2024)
14-63909206-G-T		Emery-Dreifuss muscular dystrophy 5, autosomal dominant	Uncertain significance (Nov 27, 2023)
14-63909214-T-C		Emery-Dreifuss muscular dystrophy 5, autosomal dominant	Likely benign (Jan 19, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SYNE2	protein_coding	protein_coding	ENST00000358025	115	373483

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.65e-25	1.00	125492	0	256	125748	0.00102

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-1.45	3624	3.39e+3	1.07	0.000181	45902
Missense in Polyphen		1055	1103.7	0.95587		16065
Synonymous	-2.15	1390	1.29e+3	1.08	0.0000736	12293
Loss of Function	12.1	118	369	0.320	0.0000183	4692

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00226	0.00218
Ashkenazi Jewish	0.00129	0.00129
East Asian	0.00171	0.00169
Finnish	0.000509	0.000508
European (Non-Finnish)	0.000963	0.000950
Middle Eastern	0.00171	0.00169
South Asian	0.00102	0.00101
Other	0.000986	0.000978

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. Specifically, SYNE2 and SUN2 assemble in arrays of transmembrane actin-associated nuclear (TAN) lines which are bound to F-actin cables and couple the nucleus to retrograde actin flow during actin-dependent nuclear movement. May be involved in nucleus-centrosome attachment. During interkinetic nuclear migration (INM) at G2 phase and nuclear migration in neural progenitors its LINC complex association with SUN1/2 and probable association with cytoplasmic dynein-dynactin motor complexes functions to pull the nucleus toward the centrosome; SYNE1 and SYNE2 may act redundantly. During INM at G1 phase mediates respective LINC complex association with kinesin to push the nucleus away from the centrosome. Involved in nuclear migration in retinal photoreceptor progenitors. Required for centrosome migration to the apical cell surface during early ciliogenesis. {ECO:0000250|UniProtKB:Q6ZWQ0, ECO:0000269|PubMed:12118075, ECO:0000269|PubMed:18396275, ECO:0000269|PubMed:19596800, ECO:0000269|PubMed:20724637, ECO:0000269|PubMed:22945352}.
• Disease: DISEASE: Emery-Dreifuss muscular dystrophy 5, autosomal dominant (EDMD5) [MIM:612999]: 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;miR-targeted genes in squamous cell - TarBase;Ovarian Infertility Genes (Consensus)

Intolerance Scores

• loftool: 0.852
• rvis_EVS: 3.84
• rvis_percentile_EVS: 99.63

Haploinsufficiency Scores

• pHI: 0.211
• hipred: N
• hipred_score: 0.469
• ghis: 0.441

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.644

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Syne2
• Phenotype: cellular phenotype; muscle phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); respiratory system 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)

Zebrafish Information Network

• Gene name: syne2a
• Affected structure: Muller cell
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: nuclear migration;centriole-centriole cohesion;nucleokinesis involved in cell motility in cerebral cortex radial glia guided migration;positive regulation of cell migration;nuclear migration along microfilament;centrosome localization;cytoskeletal anchoring at nuclear membrane;regulation of cilium assembly
• Cellular component: nucleus;nuclear envelope;nuclear outer membrane;nucleoplasm;cytoplasm;mitochondrion;centrosome;focal adhesion;integral component of membrane;aggresome;sarcoplasmic reticulum;Z disc;lamellipodium membrane;filopodium membrane;nuclear membrane;nuclear lumen;sarcoplasmic reticulum membrane;meiotic nuclear membrane microtubule tethering complex;intermediate filament cytoskeleton;extracellular exosome
• Molecular function: actin binding;protein binding;actin filament binding