GALNS

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

Basic information

Region (hg38): 16:88813734-88856970

Links

ENSG00000141012 ∙ NCBI:2588 ∙ OMIM:612222 ∙ HGNC:4122 ∙ Uniprot:P34059 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• mucopolysaccharidosis type 4A (Definitive), mode of inheritance: AR
• mucopolysaccharidosis type 4A (Strong), mode of inheritance: AR
• mucopolysaccharidosis type 4A (Supportive), mode of inheritance: AR
• mucopolysaccharidosis type 4A (Strong), mode of inheritance: AR
• mucopolysaccharidosis type 4A (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Mucopolysaccharidosis IVA (Morquio syndrome A)	AR	Biochemical; Cardiovascular; Musculoskeletal; Ophthalmologic; Pulmonary	Enzyme replacement therapy has been shown to be beneficial related to certain clinical (as well as biochemical) parameters; The condition may involve cardiac manifestations including cardiac valve abnormalities, and awareness may allow surveillance and prompt recognition and treatment (eg, through surgical interventions); As individuals are at risk of injury due to spinal stenosis, awareness may allow appropriate precautions (eg, during surgeries or medical procedures); Awareness of the risk of certain ophthalmological complications (including glaucoma) can allow prompt awareness and treatment; Measures to optimize pulmonary function can be beneficial	Biochemical; Dental; Musculoskeletal; Ophthalmologic; Pulmonary	770035; 5704829; 17569489; 3129221; 7607677; 8651279; 9298823; 10814710; 16287098; 20574428; 22078177; 22178352; 22231379; 22358740; 22521955; 22976768; 23313879; 23371450; 23385297; 23452954; 23665161; 23844448; 23860310; 23876334; 24810369; 25496828; 25545067; 25582974; 28595941

ClinVar

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

• Mucopolysaccharidosis,_MPS-IV-A (1117 variants)
• not_provided (150 variants)
• not_specified (75 variants)
• Morquio_syndrome (65 variants)
• Inborn_genetic_diseases (38 variants)
• GALNS-related_disorder (27 variants)
• Skeletal_dysplasia (2 variants)
• Abnormality_of_metabolism/homeostasis (1 variants)
• Abnormality_of_the_skeletal_system (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GALNS gene is commonly pathogenic or not. These statistics are base on transcript: NM_000000512.5. Only rare variants are included in the table.

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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	238	3	242
missense	16	174	289	18	4	501
nonsense	32	19	1			52
start loss	3	3	1			7
frameshift	28	33	1			62
splice donor/acceptor (+/-2bp)	30	33	3			66
Total	109	262	296	256	7

Highest pathogenic variant AF is 0.00156374

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
GALNS	protein_coding	protein_coding	ENST00000268695	14	43237

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.96e-10	0.726	125694	0	51	125745	0.000203

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.435	324	303	1.07	0.0000199	3369
Missense in Polyphen		119	119.81	0.99325		1271
Synonymous	-2.90	174	132	1.32	0.0000102	1017
Loss of Function	1.51	19	27.5	0.690	0.00000122	304

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000443	0.000442
Ashkenazi Jewish	0.0000993	0.0000992
East Asian	0.0000544	0.0000544
Finnish	0.000325	0.000323
European (Non-Finnish)	0.000194	0.000193
Middle Eastern	0.0000544	0.0000544
South Asian	0.000229	0.000229
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Disease: DISEASE: Mucopolysaccharidosis 4A (MPS4A) [MIM:253000]: A form of mucopolysaccharidosis type 4, an autosomal recessive lysosomal storage disease characterized by intracellular accumulation of keratan sulfate and chondroitin-6-sulfate. Key clinical features include short stature, skeletal dysplasia, dental anomalies, and corneal clouding. Intelligence is normal and there is no direct central nervous system involvement, although the skeletal changes may result in neurologic complications. There is variable severity, but patients with the severe phenotype usually do not survive past the second or third decade of life. {ECO:0000269|PubMed:1522213, ECO:0000269|PubMed:16287098, ECO:0000269|PubMed:24726177, ECO:0000269|PubMed:7581409, ECO:0000269|PubMed:7633425, ECO:0000269|PubMed:7668283, ECO:0000269|PubMed:7795586, ECO:0000269|PubMed:8651279, ECO:0000269|PubMed:8826435, ECO:0000269|PubMed:9298823, ECO:0000269|PubMed:9375852, ECO:0000269|PubMed:9521421}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Lysosome - Homo sapiens (human);Glycosaminoglycan degradation - Homo sapiens (human);Neutrophil degranulation;chondroitin sulfate degradation (metazoa);Innate Immune System;Immune System (Consensus)

Intolerance Scores

• loftool: 0.0838
• rvis_EVS: 0.47
• rvis_percentile_EVS: 78.85

Haploinsufficiency Scores

• pHI: 0.123
• hipred: N
• hipred_score: 0.393
• ghis: 0.434

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.967

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Galns
• Phenotype: renal/urinary system phenotype; skeleton phenotype; vision/eye phenotype; homeostasis/metabolism phenotype; cellular phenotype

Gene ontology

• Biological process: keratan sulfate catabolic process;neutrophil degranulation
• Cellular component: extracellular region;azurophil granule lumen;lysosomal lumen;extracellular exosome
• Molecular function: N-acetylgalactosamine-4-sulfatase activity;sulfuric ester hydrolase activity;N-acetylgalactosamine-6-sulfatase activity;metal ion binding