GSN

Protein identityUniProt · HPA

UniProt accession

P06396

Gene

GSN

Ensembl

ENSG00000148180

Chromosome

9

Canonical length

782 aa

Protein class

Cancer-related genes, Disease related genes, Human disease related genes, Plasma proteins, Predicted intracellular proteins, Predicted secreted proteins

Subcellular location

Actin filaments

Secretome location

Secreted to blood

OverviewNCBI Gene

The protein encoded by this gene binds to the """"""""""""""""""""""""""""""""plus"""""""""""""""""""""""""""""""" ends of actin monomers and filaments to prevent monomer exchange. The encoded calcium-regulated protein functions in both assembly and disassembly of actin filaments. Defects in this gene are a cause of familial amyloidosis Finnish type (FAF). Multiple transcript variants encoding several different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

Canonical amino-acid sequenceUniProt

782 residues, UniProt reviewed canonical sequence.

>P06396|GSN
     1  MAPHRPAPAL LCALSLALCA LSLPVRAATA SRGASQAGAP QGRVPEARPN SMVVEHPEFL
    61  KAGKEPGLQI WRVEKFDLVP VPTNLYGDFF TGDAYVILKT VQLRNGNLQY DLHYWLGNEC
   121  SQDESGAAAI FTVQLDDYLN GRAVQHREVQ GFESATFLGY FKSGLKYKKG GVASGFKHVV
   181  PNEVVVQRLF QVKGRRVVRA TEVPVSWESF NNGDCFILDL GNNIHQWCGS NSNRYERLKA
   241  TQVSKGIRDN ERSGRARVHV SEEGTEPEAM LQVLGPKPAL PAGTEDTAKE DAANRKLAKL
   301  YKVSNGAGTM SVSLVADENP FAQGALKSED CFILDHGKDG KIFVWKGKQA NTEERKAALK
   361  TASDFITKMD YPKQTQVSVL PEGGETPLFK QFFKNWRDPD QTDGLGLSYL SSHIANVERV
   421  PFDAATLHTS TAMAAQHGMD DDGTGQKQIW RIEGSNKVPV DPATYGQFYG GDSYIILYNY
   481  RHGGRQGQII YNWQGAQSTQ DEVAASAILT AQLDEELGGT PVQSRVVQGK EPAHLMSLFG
   541  GKPMIIYKGG TSREGGQTAP ASTRLFQVRA NSAGATRAVE VLPKAGALNS NDAFVLKTPS
   601  AAYLWVGTGA SEAEKTGAQE LLRVLRAQPV QVAEGSEPDG FWEALGGKAA YRTSPRLKDK
   661  KMDAHPPRLF ACSNKIGRFV IEEVPGELMQ EDLATDDVML LDTWDQVFVW VGKDSQEEEK
   721  TEALTSAKRY IETDPANRDR RTPITVVKQG FEPPSFVGWF LGWDDDYWSV DPLDRAMAEL
   781  AA

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against GSN 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

Secreted

Secreted

Yes

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.27

Highest tissue expression

2,454 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about GSN.

Disease | AllUniProt

Conditions GSN is implicated in, by any mechanism.

• Amyloidosis, hereditary systemic 4, Finnish type (AMYLD4) MIM:105120

Disease | GeneticClinVar

6 pathogenic / likely-pathogenic of 988 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Finnish type amyloidosis
• Inborn genetic diseases

Disease | ImmuneIEDB

Conditions an epitope on GSN was assayed in.

• rheumatoid arthritis B and T cell

ReferencesPubMed · IEDB

Publications for GSN from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. IEDB — curated epitope assays from the Immune Epitope Database (Vita et al., Nucleic Acids Research 2019). Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

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)

0.84

gnomAD pLI

0

gnomAD missense Z

0.96

DepMap mean gene effect

0.01

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• actin filament capping
• actin filament depolymerization
• actin filament organization
• actin filament polymerization
• actin filament severing
• actin polymerization or depolymerization
• amyloid fibril formation
• barbed-end actin filament capping
• cardiac muscle cell contraction
• cell projection assembly
• cellular response to type II interferon
• central nervous system development
• cilium assembly
• hepatocyte apoptotic process
• host-mediated suppression of symbiont invasion
• phagocytosis, engulfment
• positive regulation of actin nucleation
• positive regulation of gene expression
• positive regulation of keratinocyte apoptotic process
• positive regulation of protein processing in phagocytic vesicle
• protein destabilization
• relaxation of cardiac muscle
• renal protein absorption
• response to muscle stretch
• striated muscle atrophy
• regulation of establishment of T cell polarity
• regulation of plasma membrane raft polarization
• regulation of receptor clustering

Molecular functions

• actin binding
• actin filament binding
• calcium ion binding
• myosin II binding
• phosphatidylinositol 3-kinase catalytic subunit binding
• phosphatidylinositol-4,5-bisphosphate binding

Cellular components

• actin cap
• actin cytoskeleton
• blood microparticle
• cytoplasm
• cytosol
• extracellular exosome
• extracellular region
• extracellular space
• ficolin-1-rich granule lumen
• focal adhesion
• lamellipodium
• phagocytic vesicle
• plasma membrane
• sarcoplasm
• secretory granule lumen

Protein domainsUniProt · Pfam · InterPro

• Villin/Gelsolin
• Gelsolin-like domain
• ADF-H/Gelsolin-like domain superfamily
• Gelsolin repeat

KeywordsUniProt

• Acetylation
• Actin capping
• Actin-binding
• Alternative initiation
• Amyloid
• Amyloidosis
• Calcium
• Cilium biogenesis/degradation
• Corneal dystrophy
• Cytoplasm
• Cytoskeleton
• Disulfide bond
• Metal-binding
• Phosphoprotein
• Repeat
• Secreted
• Signal

InteractionsUniProt · HPA

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

• FLII
• EIF2AK2
• ACTB
• AR
• ARRB1
• ARRB2
• DISC1