GNS

glucosamine (N-acetyl)-6-sulfatase, the group of Sulfatases

Basic information

Region (hg38): 12:64713445-64759431

Links

ENSG00000135677 ∙ NCBI:2799 ∙ OMIM:607664 ∙ HGNC:4422 ∙ Uniprot:P15586 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• mucopolysaccharidosis type 3D (Definitive), mode of inheritance: AR
• mucopolysaccharidosis type 3D (Strong), mode of inheritance: AR
• mucopolysaccharidosis type 3D (Strong), mode of inheritance: AR
• mucopolysaccharidosis type 3D (Supportive), mode of inheritance: AR
• mucopolysaccharidosis type 3D (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Mucopolysaccharidosis IIID (Sanfilippo syndrome D)	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Biochemical; Musculoskeletal; Neurologic	6450420; 12624138; 12573255; 17998446; 19650410; 20232353

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the GNS gene.

• Mucopolysaccharidosis, MPS-III-D (46 variants)
• not provided (3 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GNS gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			2	219	5	226
missense		1	161	5		167
nonsense	18	1	2			21
start loss						0
frameshift	24	2		1		27
inframe indel						0
splice donor/acceptor (+/-2bp)	5	11	2			18
splice region			7	48	1	56
non coding			50	120	34	204
Total	47	15	217	345	39

Highest pathogenic variant AF is 0.00000699

Variants in GNS

This is a list of pathogenic ClinVar variants found in the GNS region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
12-64713671-T-TAA		Sanfilippo syndrome	Likely benign (Jun 14, 2016)
12-64713897-C-T		Mucopolysaccharidosis, MPS-III-D	Uncertain significance (Jan 12, 2018)
12-64713898-G-A		Mucopolysaccharidosis, MPS-III-D	Uncertain significance (Jan 12, 2018)
12-64713953-AC-A		Sanfilippo syndrome	Uncertain significance (Jun 14, 2016)
12-64713958-G-A		Mucopolysaccharidosis, MPS-III-D	Uncertain significance (Jan 13, 2018)
12-64713990-G-A		Mucopolysaccharidosis, MPS-III-D	Likely benign (Jan 13, 2018)
12-64714001-C-T		Mucopolysaccharidosis, MPS-III-D	Uncertain significance (Jan 13, 2018)
12-64714006-G-A		Mucopolysaccharidosis, MPS-III-D	Uncertain significance (Jan 13, 2018)
12-64714042-C-G		Mucopolysaccharidosis, MPS-III-D	Uncertain significance (Jan 12, 2018)
12-64714085-C-T		Mucopolysaccharidosis, MPS-III-D	Uncertain significance (Jan 12, 2018)
12-64714116-C-T		Mucopolysaccharidosis, MPS-III-D	Uncertain significance (Jan 13, 2018)
12-64714129-C-A		Mucopolysaccharidosis, MPS-III-D	Uncertain significance (Apr 27, 2017)
12-64714129-C-CA		Sanfilippo syndrome	Likely benign (Jun 14, 2016)
12-64714170-A-G		Mucopolysaccharidosis, MPS-III-D	Uncertain significance (Jan 13, 2018)
12-64714181-A-C		Mucopolysaccharidosis, MPS-III-D	Uncertain significance (Jan 13, 2018)
12-64714252-A-G		Mucopolysaccharidosis, MPS-III-D	Uncertain significance (Jan 13, 2018)
12-64714294-C-T		Mucopolysaccharidosis, MPS-III-D	Uncertain significance (Jan 13, 2018)
12-64714335-T-C		Mucopolysaccharidosis, MPS-III-D	Uncertain significance (Jan 13, 2018)
12-64714380-G-C		Mucopolysaccharidosis, MPS-III-D	Benign (Jan 12, 2018)
12-64714440-C-T		Mucopolysaccharidosis, MPS-III-D	Uncertain significance (Jan 13, 2018)
12-64714463-T-G		Mucopolysaccharidosis, MPS-III-D	Uncertain significance (Jan 12, 2018)
12-64714595-C-T		Mucopolysaccharidosis, MPS-III-D	Uncertain significance (Jan 12, 2018)
12-64714642-C-T		Mucopolysaccharidosis, MPS-III-D	Uncertain significance (Jan 13, 2018)
12-64714709-A-T		Mucopolysaccharidosis, MPS-III-D	Uncertain significance (Jan 12, 2018)
12-64714751-T-C		Mucopolysaccharidosis, MPS-III-D	Benign (Jan 13, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
GNS	protein_coding	protein_coding	ENST00000258145	14	46003

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000564	0.999	125726	0	22	125748	0.0000875

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.37	234	301	0.777	0.0000155	3613
Missense in Polyphen		51	102.58	0.49718		1326
Synonymous	0.328	109	113	0.961	0.00000589	1065
Loss of Function	3.22	11	30.1	0.366	0.00000144	356

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000246	0.000239
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000123	0.000123
Middle Eastern	0.00	0.00
South Asian	0.0000327	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Disease: DISEASE: Mucopolysaccharidosis 3D (MPS3D) [MIM:252940]: A form of mucopolysaccharidosis type 3, an autosomal recessive lysosomal storage disease due to impaired degradation of heparan sulfate. MPS3 is characterized by severe central nervous system degeneration, but only mild somatic disease. Onset of clinical features usually occurs between 2 and 6 years; severe neurologic degeneration occurs in most patients between 6 and 10 years of age, and death occurs typically during the second or third decade of life. {ECO:0000269|PubMed:12573255, ECO:0000269|PubMed:20232353}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Lysosome - Homo sapiens (human);Glycosaminoglycan degradation - Homo sapiens (human);Lysosome Vesicle Biogenesis;Clathrin derived vesicle budding;Neutrophil degranulation;trans-Golgi Network Vesicle Budding;Vesicle-mediated transport;Membrane Trafficking;Metabolism of carbohydrates;Keratan sulfate degradation;Keratan sulfate/keratin metabolism;Glycosaminoglycan metabolism;Innate Immune System;Immune System;Metabolism (Consensus)

Recessive Scores

• pRec: 0.325

Intolerance Scores

• loftool: 0.262
• rvis_EVS: -0.31
• rvis_percentile_EVS: 31.93

Haploinsufficiency Scores

• pHI: 0.419
• hipred: Y
• hipred_score: 0.554
• ghis: 0.590

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.726

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Gns
• Phenotype: cellular phenotype; immune system phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); hematopoietic system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan)

Gene ontology

• Biological process: glycosaminoglycan catabolic process;keratan sulfate catabolic process;neutrophil degranulation
• Cellular component: extracellular region;lysosome;azurophil granule lumen;lysosomal lumen;extracellular exosome;ficolin-1-rich granule lumen
• Molecular function: protein binding;glycosaminoglycan binding;N-acetylglucosamine-6-sulfatase activity;sulfuric ester hydrolase activity;metal ion binding