SYNE2

Chr 14q23.2

spectrin repeat containing nuclear envelope protein 2

Aliases:: SYNE-2, DKFZP434H2235, Nesprin-2, NUANCE, NUA
MANE:: ENST00000555002.6

OMIM: 608442 ↗NCBI: 23224 ↗Ensembl ↗

Annotations refreshed 9 hours ago.

Predicted protein structure

AlphaFold predicted structure

SYNE2 · Q8WXH0-13isoform

No predicted structure exists for the canonical Q8WXH0 sequence; metrics below describe this isoform.

v62025-08-01

Predicted Aligned Error matrix for SYNE2 — diagonal shows residue index, colour shows pairwise prediction confidence (lower is better) — Predicted Aligned Error

Mean pLDDT

75.6/ 100

Confident

1,035 residues

Confidence breakdown

Very high(≥ 90)47%
Confident(70–90)24%
Low(50–70)4%
Very low(< 50)25%

Open interactive 3D viewer

AlphaFold (Jumper et al., 2021) · CC BY 4.0

Clinical relevance (Genomics England PanelApp)

Diagnostic Grade (Green)

Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Arthrogryposis
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Congenital muscular dystrophy
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Dilated Cardiomyopathy and conduction defects
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability
BIALLELIC, autosomal or pseudoautosomal

Disease associations (Open Targets)

Emery-Dreifuss muscular dystrophy
0.65
neurodegenerative disease
0.54
skin aging
0.35
hair color
0.35
cutaneous melanoma
0.35
cerebral palsy
0.34
gestational diabetes
0.32
atrial fibrillation
0.31
psoriasis
0.31
ventricular septal defect
0.31

Score is the Open Targets composite evidence score (0-1). Higher = stronger gene-disease association.

Protein function (UniProt)

Nesprin-2

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 (PubMed:34818527). 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. Facilitates the relaxation of mechanical stress imposed by compressive actin fibers at the rupture site through its nteraction with SYN2 (PubMed:34818527)