SYNE4 (spectrin repeat containing nuclear envelope family member 4)

Gene

• Entrez ID: 163183
• Gene name: Spectrin repeat containing nuclear envelope family member 4
• Gene symbol: SYNE4
• Synonyms (NCBI Gene): C19orf46, DFNB76, KASH4, Nesp4
• Chromosome: 19
• Chromosome location: 19q13.12
• Summary: This gene is a member of the nesprin family of genes, that encode KASH (Klarsicht, Anc-1, Syne Homology) domain-containing proteins. In addition to the KASH domain, this protein also contains a coiled-coil and leucine zipper region, a spectrin repeat, and

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs141202530	C>G,T	Conflicting-interpretations-of-pathogenicity	Missense variant, coding sequence variant
rs200484521	C>T	Likely-pathogenic	Coding sequence variant, stop gained
rs587777072	AT>-	Pathogenic	Frameshift variant, coding sequence variant
rs750797779	G>A	Likely-pathogenic	Stop gained, coding sequence variant, intron variant
rs758800042	->TC	Pathogenic	Frameshift variant, coding sequence variant
rs774276326	C>T	Conflicting-interpretations-of-pathogenicity	Missense variant, coding sequence variant
rs1555785625	GCCCAGGCCCTGGGCT>-	Pathogenic	Intron variant, coding sequence variant, frameshift variant

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0005515	Function	Protein binding	IPI	21516116, 25416956, 25910212, 26871637, 31515488, 32296183, 32814053, 33058875, 33393904, 33961781
GO:0005634	Component	Nucleus	IEA
GO:0005635	Component	Nuclear envelope	IEA
GO:0005640	Component	Nuclear outer membrane	IBA
GO:0005640	Component	Nuclear outer membrane	IEA
GO:0005640	Component	Nuclear outer membrane	ISS
GO:0016020	Component	Membrane	IEA
GO:0034993	Component	Meiotic nuclear membrane microtubule tethering complex	IEA
GO:0045198	Process	Establishment of epithelial cell apical/basal polarity	IBA
GO:0045198	Process	Establishment of epithelial cell apical/basal polarity	IEA
GO:0045198	Process	Establishment of epithelial cell apical/basal polarity	ISS

Other IDs

• MIM: 615535
• HGNC: 26703
• e!Ensembl: ENSG00000181392

Protein

• UniProt ID: Q8N205
• Protein name: Nesprin-4 (KASH domain-containing protein 4) (KASH4) (Nuclear envelope spectrin repeat protein 4)
• Protein function: 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
• PDB: 6R16, 6WMD
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF10541	KASH	349 → 404	Nuclear envelope localisation domain	Domain

• Sequence:

  MALSLPLGPRLGSEPLNHPPGAPREADIVGCTVCPASGEESTSPEQAQTLGQDSLGPPEH
  FQGGPRGNEPAAHPPRWSTPSSYEDPAGGKHCEHPISGLEVLEAEQNSLHLCLLGLGRRL
  QDLEQGLGHWALAQSGMVQLQALQVDLRGAAERVEALLAFGEGLAQRSEPRAWAALEQIL
  RALGAYRDSIFRRLWQLQAQLVSYSLVFEEANTLDQDLEVEGDSDWPGPGGVWGPWAPSS
  LPTSTELEWDPAGDIGGLGPLGQKTARTLGVPCELCGQRGPQGRGQGLEEADTSHSRQDM
  LESGLGHQKRLARHQRHSLLRKPQDKKRQASPHLQDVRLEGNPGAPDPASRQPLTFLLIL
  FLLFLLLVGAMFLLPASGGPCCSHARIPRTPYLVLSYVNGLPPV

• Sequence length: 404

Associated diseases

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession
Autosomal recessive nonsyndromic hearing loss 76	Likely pathogenic; Pathogenic	rs754343113, rs2514041516, rs750797779, rs2514038071, rs368669131, rs2145346614, rs776772746, rs2514051953, rs772404105, rs748326281, rs758800042, rs587777072	RCV005016782 RCV005017203 RCV005025348 RCV005029926 RCV003155585 RCV005022027 RCV005014917 RCV005015042 RCV005030316 RCV005015075 RCV005019028 RCV000074459
Nonsyndromic genetic hearing loss	Likely pathogenic; Pathogenic	rs2514041516, rs2514038071, rs2514026839, rs766580479	RCV002308678 RCV003155796 RCV005406652 RCV004783122
Ovarian serous cystadenocarcinoma	Likely pathogenic	rs748326281	RCV005936608
Rare genetic deafness	Likely pathogenic; Pathogenic	rs750797779	RCV000213729

Unknown
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession
Familial cancer of breast	Conflicting classifications of pathogenicity	rs141202530	RCV005895160
SYNE4-related disorder	Likely benign; Benign; Conflicting classifications of pathogenicity	rs201169558, rs73928380, rs147433902, rs200484521, rs138787817, rs141202530, rs186898202, rs199853331, rs373148223, rs200630302, rs137899688, rs149158221, rs145204031, rs199916743, rs112382150, rs373270664, rs200744016	RCV003896248 RCV003955251 RCV003929880 RCV003417771 RCV003907801 RCV003977638 RCV004755986 RCV003945458 RCV003900364 RCV003953008 RCV003905635 RCV003908030 RCV004756024 RCV003948013 RCV003928317 RCV003908138 RCV003910723
SYNE4-related hearing loss	Uncertain significance	rs549535425	RCV002465363

Associations from Text Mining
Disease Name	Relationship Type	References
Deafness	Associate	35682719
Glucosephosphate Dehydrogenase Deficiency	Associate	35682719
Hearing Loss	Associate	28958982, 35682719
Hearing Loss Sensorineural	Associate	28958982