Details for: GALNS

Gene ID: 2588

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: GALNS

Ensembl ID: ENSG00000141012

Description: galactosamine (N-acetyl)-6-sulfatase

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • melanocyte CL0000148
    CSI 3.72
    rCSI 2.75%
    PRS 93.39
  • bronchus fibroblast of lung CL2000093
    CSI 3.14
    rCSI 2.55%
    PRS 95.35
  • inhibitory interneuron CL0000498
    CSI 2.82
    rCSI 6.51%
    PRS 89.68
  • myeloid leukocyte CL0000766
    CSI 2.79
    rCSI 2.58%
    PRS 96.53
  • glioblast CL0000030
    CSI 2.79
    rCSI 4.45%
    PRS 90.32
  • ciliated epithelial cell CL0000067
    CSI 2.63
    rCSI 2.31%
    PRS 89.48
  • choroid plexus epithelial cell CL0000706
    CSI 2.62
    rCSI 4.29%
    PRS 91.27
  • respiratory suprabasal cell CL4033048
    CSI 2.58
    rCSI 3.31%
    PRS 96.13
  • pvalb GABAergic cortical interneuron CL4023018
    CSI 2.51
    rCSI 3.12%
    PRS 85.91
  • retina horizontal cell CL0000745
    CSI 2.48
    rCSI 3.78%
    PRS 93.44
  • VIP GABAergic cortical interneuron CL4023016
    CSI 2.39
    rCSI 2.86%
    PRS 87.78
  • multi-ciliated epithelial cell CL0005012
    CSI 2.31
    rCSI 2.31%
    PRS 91.49
  • ciliated cell CL0000064
    CSI 2.29
    rCSI 3.71%
    PRS 90.47
  • ependymal cell CL0000065
    CSI 2.24
    rCSI 4.55%
    PRS 82.64
  • peripheral nervous system neuron CL2000032
    CSI 2.05
    rCSI 2.79%
    PRS 91.39
  • sst GABAergic cortical interneuron CL4023017
    CSI 2.01
    rCSI 2.59%
    PRS 88.63
  • lung ciliated cell CL1000271
    CSI 1.92
    rCSI 2.22%
    PRS 91.79
  • astrocyte of the cerebral cortex CL0002605
    CSI 1.78
    rCSI 3.99%
    PRS 88.06
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 1.67
    rCSI 2.95%
    PRS 87.35
  • lymphoid lineage restricted progenitor cell CL0000838
    CSI 1.55
    rCSI 6.05%
    PRS 99.26
  • mesenchymal cell CL0008019
    CSI 1.54
    rCSI 3.91%
    PRS 92.86
  • kidney connecting tubule epithelial cell CL1000768
    CSI 1.49
    rCSI 3.77%
    PRS 92.17
  • stromal cell CL0000499
    CSI 1.14
    rCSI 3.22%
    PRS 93.14
  • deuterosomal cell CL4033044
    CSI 1.14
    rCSI 3.86%
    PRS 90.62
  • ciliated columnar cell of tracheobronchial tree CL0002145
    CSI 1.13
    rCSI 2.58%
    PRS 89.82
  • L5 extratelencephalic projecting glutamatergic cortical neuron CL4023041
    CSI 0.69
    rCSI 2.49%
    PRS 86.21

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

Explore relationships of the current gene. Select an Interaction Source: 'ONTOLOGY' for shared pathways (GO/Reactome) or 'STRING' for protein-protein interactions. Further refine by selecting context genes and comparing Cell Significance Index (CSI) scores between baseline and target cell types and their specific contexts.

Comma-separated if multiple.
Comma-separated if multiple.
Legend:
  • Query Gene
  • Node Color (Target Cell CSI, relative to current network):
    • Very High
    • High
    • Medium
    • Low
    • Very Low
    • CSI N/A
  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary [GALNS](/details-gene/2588) (galactosamine (N-acetyl)-6-sulfatase) is a protein-coding gene located on chromosome 16q24.3 that encodes the lysosomal enzyme N-acetylgalactosamine-6-sulfatase. This enzyme plays a critical role in the catabolism of glycosaminoglycans (GAGs) by hydrolyzing the 6-sulfate groups from N-acetylgalactosamine-6-sulfate units of chondroitin-6-sulfate and from galactose-6-sulfate units of keratan sulfate. Deficiencies in [GALNS](/details-gene/2588) function, caused by genetic mutations, disrupt GAG degradation and lead to the lysosomal storage disorder Mucopolysaccharidosis IVA (MPS IVA), also known as Morquio A syndrome ([Link](https://omim.org/entry/253000)), a condition characterized primarily by skeletal dysplasia ([Link](https://doi.org/10.1006/geno.1994.1443), [Link](https://doi.org/10.1172/jci115919)). Expression data indicates that while its function is essential in many tissues, [GALNS](/details-gene/2588) has particularly high significance in a diverse range of cell types, including [melanocytes](/details-cell/CL0000148), [fibroblasts](/details-cell/CL2000093), various neuronal subtypes, and [myeloid leukocytes](/details-cell/CL0000766), suggesting a broad role in extracellular matrix maintenance and cellular homeostasis across multiple organ systems. ## Cellular Roles and Expression Landscape **Overall**, the expression profile of [GALNS](/details-gene/2588) suggests it is a crucial enzyme for cellular function across a wide variety of lineages, consistent with its fundamental role in GAG turnover. The gene shows the highest significance in [melanocytes](/details-cell/CL0000148) (CSI: 3.72), indicating a potentially important role in the biology of pigmented cells beyond its canonical functions. The gene also demonstrates high significance in cell types integral to tissue structure and the nervous system. This includes [bronchus fibroblasts of lung](/details-cell/CL2000093) (CSI: 3.14), which are responsible for secreting and maintaining the extracellular matrix, as well as several neuronal and glial cell types. Notably, its high significance in [inhibitory interneurons](/details-cell/CL0000498) (CSI: 2.82), [glioblasts](/details-cell/CL0000030) (CSI: 2.79), and [ependymal cells](/details-cell/CL0000065) (CSI: 2.24) points towards a key role in the maintenance of the central nervous system microenvironment. Furthermore, [GALNS](/details-gene/2588) is significantly expressed in various epithelial cells, particularly those with cilia, such as [ciliated epithelial cells](/details-cell/CL0000067) (CSI: 2.63) and [multi-ciliated epithelial cells](/details-cell/CL0005012) (CSI: 2.31). This pattern, combined with its significance in [myeloid leukocytes](/details-cell/CL0000766) (CSI: 2.79), suggests an active role in tissues with high metabolic turnover and mucosal immunity. The broad but distinct cellular landscape of [GALNS](/details-gene/2588) underscores its importance as a housekeeping enzyme whose activity is particularly vital in cells that actively remodel their extracellular matrix or are embedded within GAG-rich environments. ## Pathways and Molecular Function The molecular function of [GALNS](/details-gene/2588) is centered on its enzymatic activity as a sulfuric ester hydrolase. Gene Ontology annotations confirm its role in [Arylsulfatase activity](/details-go/GO:0004065) and, more specifically, [N-acetylgalactosamine-6-sulfatase activity](/details-go/GO:0043890). Its cellular localization is primarily within the [lysosomal lumen](/details-go/GO:0043202), which is the principal site of GAG degradation. Interestingly, its presence is also noted in the [azurophil granule lumen](/details-go/GO:0035578) of neutrophils, aligning with its expression in [myeloid leukocytes](/details-cell/CL0000766) and its functional annotation in the [Neutrophil degranulation](/details-pathway/R-HSA-6798695) pathway. Reactome pathway analysis reinforces the gene's central role in metabolism. It is a key component of [Glycosaminoglycan metabolism](/details-pathway/R-HSA-1630316), with a specific function in [Keratan sulfate degradation](/details-pathway/R-HSA-2022857). The clinical significance of [GALNS](/details-gene/2588) is directly highlighted by its involvement in disease pathways, most notably [Mps iv - morquio syndrome a](/details-pathway/R-HSA-2206290) and the broader category of [Mucopolysaccharidoses](/details-pathway/R-HSA-2206281). The identification of numerous pathogenic mutations underpins its critical, non-redundant function ([Link](https://doi.org/10.1093/hmg/4.3.341), [Link](https://doi.org/10.1002/(sici)1098-1004(1997)10:3<223::aid-humu8>3.0.co;2-j)). ## Research Directions The widespread expression of [GALNS](/details-gene/2588) and the systemic nature of Morquio A syndrome highlight the importance of GAG turnover in nearly all tissues. However, the varying levels of significance across different cell types suggest that certain cells may be more vulnerable to its deficiency or rely more heavily on its function. This leads to several testable hypotheses. 1. **Hypothesis 1:** The high significance of [GALNS](/details-gene/2588) in multiple interneuron subtypes, such as [inhibitory interneurons](/details-cell/CL0000498), suggests that its enzymatic activity is critical for the maintenance of perineuronal nets (PNNs), which are keratan sulfate-rich structures that regulate neuronal plasticity and stability. Disruption of [GALNS](/details-gene/2588) function may lead to abnormal PNN structures, contributing to the less-defined neurological symptoms associated with MPS IVA. 2. **Hypothesis 2:** The top-ranking significance of [GALNS](/details-gene/2588) in [melanocytes](/details-cell/CL0000148) implies a specialized role in skin biology. It is plausible that [GALNS](/details-gene/2588) is required for processing specific sulfated proteoglycans essential for melanosome maturation, pigment transfer to keratinocytes, or the integrity of the basement membrane to which melanocytes attach. **Experimental Approach for Hypothesis 1:** To test the role of [GALNS](/details-gene/2588) in PNN maintenance, a conditional knockout mouse model could be generated to specifically delete *Galns* in parvalbumin-positive interneurons. The structural integrity of PNNs in the cortex and hippocampus could then be assessed via fluorescent microscopy using Wisteria floribunda agglutinin staining. Subsequent electrophysiological analysis of these neurons would reveal any functional deficits in synaptic transmission or firing patterns, directly linking the molecular function of GALNS to neuronal circuit stability. **Therapeutic Potential:** As MPS IVA is a monogenic, loss-of-function disorder, [GALNS](/details-gene/2588) itself is the primary therapeutic target. The therapeutic strategy is **replacement**, not inhibition. Enzyme replacement therapy (ERT) with a recombinant form of human GALNS (elosulfase alfa) is the current standard of care, aiming to restore the deficient enzymatic activity. Future therapeutic avenues focus on gene therapy to provide a permanent source of functional [GALNS](/details-gene/2588) enzyme, potentially offering a more complete and long-lasting correction of the metabolic defect.

Genular Protein ID: 3608982954

Symbol: GALNS_HUMAN

Name: N-acetylgalactosamine-6-sulfatase

UniProtKB Accession Codes:

P34059 Q86VK3

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 BRENDA 2 Bgee 1 BioCyc 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 1 CORUM 1 CTD 1 ChEBI 6 ChEMBL 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 DrugBank 1 EC 2 EMBL 14 Ensembl 1 EvolutionaryTrace 1 ExpressionAtlas 1 GO 9 Gene3D 1 GeneCards 1 GeneReviews 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyConnect 1 GlyCosmos 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 5 KEGG 1 MANE-Select 1 MIM 3 MalaCards 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 Orphanet 1 OrthoDB 1 PANTHER 2 PDB 2 PDBsum 2 PIR 1 PRO 1 PROSITE 2 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 2 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 Pumba 1 RNAct 1 Reactome 3 RefSeq 1 SIGNOR 1 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 SwissPalm 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 1755850

Title: Morquio disease: isolation, characterization and expression of full-length cDNA for human N-acetylgalactosamine-6-sulfate sulfatase.

PubMed ID: 1755850

DOI: 10.1016/0006-291x(91)91244-7

PubMed ID: 8001980

Title: Morquio A syndrome: cloning, sequence, and structure of the human N-acetylgalactosamine 6-sulfatase (GALNS) gene.

PubMed ID: 8001980

DOI: 10.1006/geno.1994.1443

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 19159218

Title: Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry.

PubMed ID: 19159218

DOI: 10.1021/pr8008012

PubMed ID: 25944712

Title: N-terminome analysis of the human mitochondrial proteome.

PubMed ID: 25944712

DOI: 10.1002/pmic.201400617

PubMed ID: 22940367

Title: The structure of human GALNS reveals the molecular basis for mucopolysaccharidosis IV A.

PubMed ID: 22940367

DOI: 10.1016/j.jmb.2012.08.020

PubMed ID: 1522213

Title: Mucopolysaccharidosis type IVA. N-acetylgalactosamine-6-sulfate sulfatase exonic point mutations in classical Morquio and mild cases.

PubMed ID: 1522213

DOI: 10.1172/jci115919

PubMed ID: 7668283

Title: Mucopolysaccharidosis IVA: identification of a common missense mutation I113F in the N-Acetylgalactosamine-6-sulfate sulfatase gene.

PubMed ID: 7668283

PubMed ID: 7795586

Title: Mucopolysaccharidosis IVA: screening and identification of mutations of the N-acetylgalactosamine-6-sulfate sulfatase gene.

PubMed ID: 7795586

DOI: 10.1093/hmg/4.3.341

PubMed ID: 7633425

Title: Mucopolysaccharidosis type IVA: identification of six novel mutations among non-Japanese patients.

PubMed ID: 7633425

DOI: 10.1093/hmg/4.4.741

PubMed ID: 7581409

Title: Two new mutations, Q473X and N487S, in a Caucasian patient with mucopolysaccharidosis IVA (Morquio disease).

PubMed ID: 7581409

DOI: 10.1002/humu.1380060218

PubMed ID: 8651279

Title: Mucopolysaccharidosis IVA: four new exonic mutations in patients with N-acetylgalactosamine-6-sulfate sulfatase deficiency.

PubMed ID: 8651279

PubMed ID: 8826435

Title: Heteroallelic missense mutations of the galactosamine-6-sulfate sulfatase (GALNS) gene in a mild form of Morquio disease (MPS IVA).

PubMed ID: 8826435

DOI: 10.1002/(sici)1096-8628(19960628)63:4&lt;558::aid-ajmg9&gt;3.0.co;2-k

PubMed ID: 9298823

Title: Identification of 31 novel mutations in the N-acetylgalactosamine-6-sulfatase gene reveals excessive allelic heterogeneity among patients with Morquio A syndrome.

PubMed ID: 9298823

DOI: 10.1002/(sici)1098-1004(1997)10:3&lt;223::aid-humu8&gt;3.0.co;2-j

PubMed ID: 9375852

Title: Fourteen novel mucopolysaccharidosis IVA producing mutations in GALNS gene.

PubMed ID: 9375852

DOI: 10.1002/(sici)1098-1004(1997)10:5&lt;368::aid-humu6&gt;3.0.co;2-b

PubMed ID: 9521421

Title: Molecular heterogeneity in mucopolysaccharidosis IVA in Australia and Northern Ireland: nine novel mutations including T312S, a common allele that confers a mild phenotype.

PubMed ID: 9521421

DOI: 10.1002/(sici)1098-1004(1998)11:3&lt;202::aid-humu4&gt;3.0.co;2-j

PubMed ID: 9452036

Title: Fifteen polymorphisms in the N-acetylgalactosamine-6-sulfate sulfatase (GALNS) gene: diagnostic implications in Morquio disease.

PubMed ID: 9452036

DOI: 10.1002/humu.1380110115

PubMed ID: 16287098

Title: Mutation and polymorphism spectrum of the GALNS gene in mucopolysaccharidosis IVA (Morquio A).

PubMed ID: 16287098

DOI: 10.1002/humu.20257

PubMed ID: 16959974

Title: The consensus coding sequences of human breast and colorectal cancers.

PubMed ID: 16959974

DOI: 10.1126/science.1133427

PubMed ID: 24726177

Title: Molecular testing of 163 patients with Morquio A (Mucopolysaccharidosis IVA) identifies 39 novel GALNS mutations.

PubMed ID: 24726177

DOI: 10.1016/j.ymgme.2014.03.004

Sequence Information:

  • Length: 522
  • Mass: 58026
  • Checksum: 1D086E528AAAE949
  • Sequence:
    • MAAVVAATRW WQLLLVLSAA GMGASGAPQP PNILLLLMDD MGWGDLGVYG EPSRETPNLD 
RMAAEGLLFP NFYSANPLCS PSRAALLTGR LPIRNGFYTT NAHARNAYTP QEIVGGIPDS 
EQLLPELLKK AGYVSKIVGK WHLGHRPQFH PLKHGFDEWF GSPNCHFGPY DNKARPNIPV 
YRDWEMVGRY YEEFPINLKT GEANLTQIYL QEALDFIKRQ ARHHPFFLYW AVDATHAPVY 
ASKPFLGTSQ RGRYGDAVRE IDDSIGKILE LLQDLHVADN TFVFFTSDNG AALISAPEQG 
GSNGPFLCGK QTTFEGGMRE PALAWWPGHV TAGQVSHQLG SIMDLFTTSL ALAGLTPPSD 
RAIDGLNLLP TLLQGRLMDR PIFYYRGDTL MAATLGQHKA HFWTWTNSWE NFRQGIDFCP 
GQNVSGVTTH NLEDHTKLPL IFHLGRDPGE RFPLSFASAE YQEALSRITS VVQQHQEALV 
PAQPQLNVCN WAVMNWAPPG CEKLGKCLTP PESIPKKCLW SH

Genular Protein ID: 3250203457

Symbol: Q96I49_HUMAN

Name: N/A

UniProtKB Accession Codes:

Q96I49

Database IDs:

ARBA 2 AlphaFoldDB 1 BioGRID-ORCS 1 CTD 1 ChEBI 1 ChiTaRS 1 DNASU 1 DisGeNET 1 EMBL 2 GO 1 Gene3D 2 InterPro 3 KEGG 1 NCBI Taxonomy 1 OrthoDB 1 PANTHER 2 PeptideAtlas 1 Pfam 3 PharmGKB 1 RefSeq 3 SMR 1 SUPFAM 1

Citations:

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

Sequence Information:

  • Length: 238
  • Mass: 26148
  • Checksum: BC4810E73D89D5ED
  • Sequence:
    • FTSDNGAALI SAPEQGGSNG PFLCGKQTTF EGGMREPALA WWPGHVTAGQ VSHQLGSIMD 
LFTTSLALAG LTPPSDRAID GLNLLPTLLQ GRLMDRPIFY YRGDTLMAAT LGQHKAHFWT 
WTNSWENFRQ GIDFCPGQNV SGVTTHNLED HTKLPLIFHL GRDPGERFPL SFASAEYQEA 
LSRITSVVQQ HQEALVPAQP QLNVCNWAVM NWAPPGCEKL GKCLTPPESI PKKCLWSH

Genular Protein ID: 1926451998

Symbol: Q6YL38_HUMAN

Name: N/A

UniProtKB Accession Codes:

Q6YL38

Database IDs:

ARBA 2 AlphaFoldDB 1 BioGRID-ORCS 1 CTD 1 ChEBI 1 DNASU 1 DisGeNET 1 EMBL 2 GO 1 Gene3D 2 InterPro 3 NCBI Taxonomy 1 OrthoDB 1 PANTHER 2 PeptideAtlas 1 Pfam 3 RefSeq 1 SMR 1 SUPFAM 1

Sequence Information:

  • Length: 337
  • Mass: 37579
  • Checksum: 7D6A6DBF166CE355
  • Sequence:
    • MVGRYYEEFP INLKTGEANL TQIYLQEALD FIKRQARHHP FFLYWAVDAT HAPVYASKPF 
LGTSQRGRYG DAVREIDDSI GKILELLQDL HVADNTFVFF TSDNGAALIS APEQGGSNGP 
FLCGKQTTFE GGMREPALAW WPGHVTAGQV SHQLGSIMDL FTTSLALAGL TPPSDRAIDG 
LNLLPTLLQG RLMDRPIFYY RGDTLMAATL GQHKAHFWTW TNSWENFRQG IDFCPGQNVS 
GVTTHNLEDH TKLPLIFHLG RDPGERFPLS FASAEYQEAL SRITSVVQQH QEALVPAQPQ 
LNVCNWAVMN WAPPGCEKLG KCLTPPESIP KKCLWSH