SGSH

N-sulfoglucosamine sulfohydrolase, the group of Sulfatases

Basic information

Region (hg38): 17:80206715-80220923

Links

ENSG00000181523 ∙ NCBI:6448 ∙ OMIM:605270 ∙ HGNC:10818 ∙ Uniprot:P51688 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

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

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Mucopolysaccharidosis type IIIA (Sanfilippo syndrome A)	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; Neurologic	4252428; 6796310; 7856659; 7493035; 9158154; 9401012; 9554748; 9727849; 9950362; 10518291; 10727844; 11668611; 12000360; 12702166; 15637719; 21061399; 28595941
BMT has been described, but was not reported to have a beneficial effect on prognosis

ClinVar

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

• Mucopolysaccharidosis, MPS-III-A (862 variants)
• not provided (112 variants)
• Inborn genetic diseases (35 variants)
• not specified (26 variants)
• Sanfilippo syndrome (8 variants)
• Mucopolysaccharidosis (6 variants)
• SGSH-related condition (3 variants)
• 7 conditions (2 variants)
• Neurodegeneration (2 variants)
• Abnormality of metabolism/homeostasis (1 variants)
• See cases (1 variants)
• Abnormality of mucopolysaccharide metabolism (1 variants)
• Intellectual disability (1 variants)
• Abnormal circulating carbohydrate concentration (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SGSH 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	241	4	247
missense	8	41	239	9	5	302
nonsense	13	15	1			29
start loss	3					3
frameshift	25	28	2			55
inframe indel	1		10			11
splice donor/acceptor (+/-2bp)		12				12
splice region			11	20	1	32
non coding			29	96	20	145
Total	50	96	283	346	29

Highest pathogenic variant AF is 0.000387

Variants in SGSH

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

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

Position	Type	Phenotype	Significance	ClinVar
17-80206788-A-G			Benign (Oct 05, 2019)
17-80206819-A-C			Benign (Jul 09, 2018)
17-80206823-C-T			Likely benign (Oct 07, 2019)
17-80206951-T-C		Pityriasis rubra pilaris;Psoriasis 2	Likely benign (May 18, 2021)
17-80206953-C-T		Pityriasis rubra pilaris;Psoriasis 2	Likely benign (Jul 17, 2023)
17-80206962-C-A		Pityriasis rubra pilaris;Psoriasis 2	Likely benign (Aug 23, 2022)
17-80206965-C-A		Psoriasis 2;Pityriasis rubra pilaris	Likely benign (Aug 10, 2022)
17-80206972-C-T		Pityriasis rubra pilaris;Psoriasis 2	Likely benign (Jul 21, 2021)
17-80206991-G-A		Pityriasis rubra pilaris;Psoriasis 2	Uncertain significance (Jun 09, 2023)
17-80207003-A-G		Pityriasis rubra pilaris;Psoriasis 2	Uncertain significance (Nov 13, 2021)
17-80207004-G-A		Psoriasis 2;Pityriasis rubra pilaris	Uncertain significance (Dec 15, 2022)
17-80207013-C-G		Pityriasis rubra pilaris;Psoriasis 2 • Autoinflammatory syndrome	Uncertain significance (Nov 28, 2023)
17-80207018-C-A		Pityriasis rubra pilaris;Psoriasis 2 • Inborn genetic diseases	Uncertain significance (Dec 06, 2023)
17-80207020-C-G		Psoriasis 2;Pityriasis rubra pilaris	Uncertain significance (May 01, 2019)
17-80207041-C-T		Pityriasis rubra pilaris;Psoriasis 2 • Autoinflammatory syndrome	Benign (Jan 29, 2024)
17-80207042-G-A		Pityriasis rubra pilaris;Psoriasis 2	Uncertain significance (Nov 27, 2023)
17-80207047-C-T		Pityriasis rubra pilaris;Psoriasis 2	Likely benign (Jul 17, 2023)
17-80207048-C-A		Pityriasis rubra pilaris;Psoriasis 2	Uncertain significance (Jul 23, 2023)
17-80207050-C-T		Pityriasis rubra pilaris;Psoriasis 2 • Autoinflammatory syndrome	Benign (Jan 31, 2024)
17-80207051-G-A		Pityriasis rubra pilaris;Psoriasis 2 • Autoinflammatory syndrome • Inborn genetic diseases	Conflicting classifications of pathogenicity (Jan 09, 2024)
17-80207053-C-T		Pityriasis rubra pilaris;Psoriasis 2 • Autoinflammatory syndrome • Pityriasis rubra pilaris	Conflicting classifications of pathogenicity (Dec 02, 2023)
17-80207055-C-G		Psoriasis 2;Pityriasis rubra pilaris	Uncertain significance (Jul 17, 2023)
17-80207055-C-CT		Pityriasis rubra pilaris;Psoriasis 2	Uncertain significance (Nov 22, 2022)
17-80207062-C-T		Pityriasis rubra pilaris;Psoriasis 2	Likely benign (Dec 13, 2023)
17-80207063-G-A		Pityriasis rubra pilaris;Psoriasis 2	Uncertain significance (May 09, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SGSH	protein_coding	protein_coding	ENST00000326317	8	14208

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000102	0.988	125575	0	58	125633	0.000231

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.0538	336	333	1.01	0.0000252	3231
Missense in Polyphen		123	135.53	0.90752		1336
Synonymous	-0.907	166	152	1.09	0.0000129	1021
Loss of Function	2.24	10	21.1	0.474	0.00000101	214

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000470	0.000470
Ashkenazi Jewish	0.00	0.00
East Asian	0.000110	0.000109
Finnish	0.000363	0.000323
European (Non-Finnish)	0.000268	0.000264
Middle Eastern	0.000110	0.000109
South Asian	0.0000653	0.0000653
Other	0.000327	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Catalyzes a step in lysosomal heparan sulfate degradation. {ECO:0000269|PubMed:15146460, ECO:0000269|PubMed:24816101, ECO:0000269|PubMed:7493035}.
• Disease: DISEASE: Mucopolysaccharidosis 3A (MPS3A) [MIM:252900]: A severe 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. MPS3A is characterized by earlier onset, rapid progression of symptoms and shorter survival. {ECO:0000269|PubMed:11182930, ECO:0000269|PubMed:11793481, ECO:0000269|PubMed:12000360, ECO:0000269|PubMed:12702166, ECO:0000269|PubMed:15146460, ECO:0000269|PubMed:15637719, ECO:0000269|PubMed:15902564, ECO:0000269|PubMed:16311287, ECO:0000269|PubMed:17128482, ECO:0000269|PubMed:18407553, ECO:0000269|PubMed:21671382, ECO:0000269|PubMed:28101780, ECO:0000269|PubMed:9158154, ECO:0000269|PubMed:9285796, ECO:0000269|PubMed:9401012, ECO:0000269|PubMed:9554748, ECO:0000269|PubMed:9744479}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Lysosome - Homo sapiens (human);Glycosaminoglycan degradation - Homo sapiens (human);Metabolism of carbohydrates;HS-GAG degradation;Heparan sulfate/heparin (HS-GAG) metabolism;Glycosaminoglycan metabolism;Metabolism (Consensus)

Recessive Scores

• pRec: 0.175

Intolerance Scores

• loftool: 0.137
• rvis_EVS: 0.34
• rvis_percentile_EVS: 73.7

Haploinsufficiency Scores

• pHI: 0.120
• hipred: N
• hipred_score: 0.352
• ghis: 0.467

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.320

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Sgsh
• 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); hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); liver/biliary system phenotype; renal/urinary system phenotype; skeleton phenotype; immune system phenotype; vision/eye phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype; cellular phenotype; homeostasis/metabolism phenotype; craniofacial phenotype

Gene ontology

• Biological process: glycosaminoglycan catabolic process;heparan sulfate proteoglycan catabolic process
• Cellular component: lysosome;lysosomal lumen;extracellular exosome
• Molecular function: sulfuric ester hydrolase activity;N-sulfoglucosamine sulfohydrolase activity;metal ion binding