GNS

Protein identityUniProt · HPA

UniProt accession

P15586

Gene

GNS

Ensembl

ENSG00000135677

Chromosome

12

Canonical length

552 aa

Protein class

Disease related genes, Enzymes, Human disease related genes, Metabolic proteins, Potential drug targets, Predicted intracellular proteins

Secretome location

Intracellular and membrane

OverviewNCBI Gene

The product of this gene is a lysosomal enzyme found in all cells. It is involved in the catabolism of heparin, heparan sulphate, and keratan sulphate. Deficiency of this enzyme results in the accumulation of undegraded substrate and the lysosomal storage disorder mucopolysaccharidosis type IIID (Sanfilippo D syndrome). Mucopolysaccharidosis type IIID is the least common of the four subtypes of Sanfilippo syndrome. [provided by RefSeq, Jul 2008]

Canonical amino-acid sequenceUniProt

552 residues, UniProt reviewed canonical sequence.

>P15586|GNS
     1  MRLLPLAPGR LRRGSPRHLP SCSPALLLLV LGGCLGVFGV AAGTRRPNVV LLLTDDQDEV
    61  LGGMTPLKKT KALIGEMGMT FSSAYVPSAL CCPSRASILT GKYPHNHHVV NNTLEGNCSS
   121  KSWQKIQEPN TFPAILRSMC GYQTFFAGKY LNEYGAPDAG GLEHVPLGWS YWYALEKNSK
   181  YYNYTLSING KARKHGENYS VDYLTDVLAN VSLDFLDYKS NFEPFFMMIA TPAPHSPWTA
   241  APQYQKAFQN VFAPRNKNFN IHGTNKHWLI RQAKTPMTNS SIQFLDNAFR KRWQTLLSVD
   301  DLVEKLVKRL EFTGELNNTY IFYTSDNGYH TGQFSLPIDK RQLYEFDIKV PLLVRGPGIK
   361  PNQTSKMLVA NIDLGPTILD IAGYDLNKTQ MDGMSLLPIL RGASNLTWRS DVLVEYQGEG
   421  RNVTDPTCPS LSPGVSQCFP DCVCEDAYNN TYACVRTMSA LWNLQYCEFD DQEVFVEVYN
   481  LTADPDQITN IAKTIDPELL GKMNYRLMML QSCSGPTCRT PGVFDPGYRF DPRLMFSNRG
   541  SVRTRRFSKH LL

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against GNS 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

0

Mean surface accessibility (rSASA)

0.26

Highest tissue expression

164 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about GNS.

Disease | AllUniProt

Conditions GNS is implicated in, by any mechanism.

• Mucopolysaccharidosis 3D (MPS3D) MIM:252940

Disease | GeneticClinVar

83 pathogenic / likely-pathogenic of 844 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Mucopolysaccharidosis, MPS-III-D
• Sanfilippo syndrome
• GNS-related disorder

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)

0.61

gnomAD pLI

0

gnomAD missense Z

1.37

DepMap mean gene effect

-0.04

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

• glycosaminoglycan catabolic process
• heparan sulfate proteoglycan catabolic process
• keratan sulfate proteoglycan catabolic process

Molecular functions

• glycosaminoglycan binding
• metal ion binding
• N-acetylglucosamine-6-sulfatase activity
• sulfate binding
• sulfuric ester hydrolase activity

Cellular components

• azurophil granule
• azurophil granule lumen
• extracellular exosome
• extracellular region
• ficolin-1-rich granule lumen
• lysosomal lumen

Protein domainsUniProt · Pfam · InterPro

• Sulfatase, N-terminal
• Alkaline-phosphatase-like, core domain superfamily
• Sulfatase, conserved site
• Sulfatase
• N-acetylglucosamine-6-sulfatase

KeywordsUniProt

• Calcium
• Glycoprotein
• Hydrolase
• Lysosome
• Metal-binding
• Mucopolysaccharidosis
• Phosphoprotein
• Signal

InteractionsUniProt · HPA

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

• IGF2R