SYNE4

Protein identityUniProt · HPA

UniProt accession

Q8N205

Gene

SYNE4

Ensembl

ENSG00000181392

Chromosome

19

Canonical length

404 aa

Protein class

Disease related genes, Human disease related genes, Predicted intracellular proteins, Predicted membrane proteins

OverviewNCBI Gene

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 a kinesin-1 binding region. This protein localizes to the outer nuclear membrane, and is part of the linker of nucleoskeleton and cytoskeleton (LINC) complex in the nuclear envelope. LINC complexes are formed by SUN (Sad1, UNC-84)-KASH pairs, and are thought to mechanically couple nuclear components to the cytoskeleton. Mutations in this gene have been associated with progressive high-frequency hearing loss. The absence of this protein in mice also caused hearing loss, and changes in hair cell morphology in the ears. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Aug 2015]

Canonical amino-acid sequenceUniProt

404 residues, UniProt reviewed canonical sequence.

>Q8N205|SYNE4
     1  MALSLPLGPR LGSEPLNHPP GAPREADIVG CTVCPASGEE STSPEQAQTL GQDSLGPPEH
    61  FQGGPRGNEP AAHPPRWSTP SSYEDPAGGK HCEHPISGLE VLEAEQNSLH LCLLGLGRRL
   121  QDLEQGLGHW ALAQSGMVQL QALQVDLRGA AERVEALLAF GEGLAQRSEP RAWAALEQIL
   181  RALGAYRDSI FRRLWQLQAQ LVSYSLVFEE ANTLDQDLEV EGDSDWPGPG GVWGPWAPSS
   241  LPTSTELEWD PAGDIGGLGP LGQKTARTLG VPCELCGQRG PQGRGQGLEE ADTSHSRQDM
   301  LESGLGHQKR LARHQRHSLL RKPQDKKRQA SPHLQDVRLE GNPGAPDPAS RQPLTFLLIL
   361  FLLFLLLVGA MFLLPASGGP CCSHARIPRT PYLVLSYVNG LPPV

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against SYNE4 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Intracellular

Secreted

No

Transmembrane segments

1

Mean surface accessibility (rSASA)

0.58

Highest tissue expression

12 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about SYNE4.

Disease | AllUniProt

Conditions SYNE4 is implicated in, by any mechanism.

• Deafness, autosomal recessive, 76 (DFNB76) MIM:615540

Disease | GeneticClinVar

43 pathogenic / likely-pathogenic of 364 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Autosomal recessive nonsyndromic hearing loss 76
• Nonsyndromic genetic hearing loss
• Rare genetic deafness
• Ovarian serous cystadenocarcinoma

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

1.29

gnomAD pLI

0

gnomAD missense Z

0.49

DepMap mean gene effect

-0.1

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 6% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• establishment of epithelial cell apical/basal polarity

Cellular components

• meiotic nuclear membrane microtubule tethering complex
• nuclear outer membrane

Protein domainsUniProt · Pfam · InterPro

• KASH domain
• Nuclear envelope localisation domain
• Nesprin-4

KeywordsUniProt

• Deafness
• Disulfide bond
• Membrane
• Non-syndromic deafness
• Nucleus
• Transmembrane
• Transmembrane helix

InteractionsUniProt · HPA

Protein binding partners of SYNE4 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• KLC1
• CSGALNACT2
• KLC4
• OCLN