HGSNAT

heparan-alpha-glucosaminide N-acetyltransferase

Basic information

Region (hg38): 8:43140464-43202855

Previous symbols: [ "TMEM76" ]

Links

ENSG00000165102 ∙ NCBI:138050 ∙ OMIM:610453 ∙ HGNC:26527 ∙ Uniprot:Q68CP4 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• mucopolysaccharidosis type 3 (Definitive), mode of inheritance: AR
• mucopolysaccharidosis type 3C (Definitive), mode of inheritance: AR
• mucopolysaccharidosis type 3C (Strong), mode of inheritance: AR
• mucopolysaccharidosis type 3C (Definitive), mode of inheritance: AR
• retinitis pigmentosa 73 (Moderate), mode of inheritance: AR
• retinitis pigmentosa (Supportive), mode of inheritance: AD
• mucopolysaccharidosis type 3C (Supportive), mode of inheritance: AR
• retinitis pigmentosa 73 (Limited), mode of inheritance: AR
• mucopolysaccharidosis type 3C (Strong), mode of inheritance: AR
• retinitis pigmentosa 73 (Strong), mode of inheritance: AR
• mucopolysaccharidosis type 3C (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Mucopolysaccharidosis type IIIC (Sanfilippo syndrome C); Retinitis pigmentosa 73	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	Audiologic/Otolaryngologic; Biochemical; Gastrointestinal; Neurologic; Ophthalmologic	33384; 3142713; 16960811; 17033958; 18024218; 18518886; 19479962; 20583299; 20825431; 25859010

ClinVar

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

• Mucopolysaccharidosis, MPS-III-C;Retinitis pigmentosa 73 (39 variants)
• Retinitis pigmentosa 73;Mucopolysaccharidosis, MPS-III-C (23 variants)
• Mucopolysaccharidosis, MPS-III-C (16 variants)
• not provided (11 variants)
• Sanfilippo syndrome (9 variants)
• Inborn genetic diseases (2 variants)
• Retinal dystrophy (2 variants)
• Mucopolysaccharidosis (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the HGSNAT 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			3	277	3	283
missense	4	10	256	8	3	281
nonsense	22	18	4	1		45
start loss						0
frameshift	27	14	2			43
inframe indel			15			15
splice donor/acceptor (+/-2bp)	12	22	1			35
splice region			20	66	2	88
non coding	1	2	65	208	40	316
Total	66	66	346	494	46

Highest pathogenic variant AF is 0.000131

Variants in HGSNAT

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

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

Position	Type	Phenotype	Significance	ClinVar
8-43140481-C-CGAGCGGGCGGCGGGCAT		not specified • Inborn genetic diseases	Likely benign (Jun 07, 2024)
8-43140481-C-CGAGCGGGCGGCGGGCATGAGCGGGCGGCGGGCAT		Inborn genetic diseases	Uncertain significance (Sep 18, 2021)
8-43140494-G-C		Mucopolysaccharidosis, MPS-III-C	Uncertain significance (Jan 12, 2018)
8-43140502-C-A		Inborn genetic diseases • Mucopolysaccharidosis, MPS-III-C;Retinitis pigmentosa 73	Conflicting classifications of pathogenicity (Oct 03, 2023)
8-43140502-C-T		Mucopolysaccharidosis, MPS-III-C;Retinitis pigmentosa 73	Likely benign (Nov 02, 2023)
8-43140502-CG-C		Mucopolysaccharidosis, MPS-III-C;Retinitis pigmentosa 73	Pathogenic (Jun 17, 2022)
8-43140503-G-C		Mucopolysaccharidosis, MPS-III-C;Retinitis pigmentosa 73	Uncertain significance (Aug 24, 2021)
8-43140504-G-C		Mucopolysaccharidosis, MPS-III-C;Retinitis pigmentosa 73	Uncertain significance (Apr 09, 2022)
8-43140505-G-A		Retinitis pigmentosa 73;Mucopolysaccharidosis, MPS-III-C	Likely benign (Apr 06, 2023)
8-43140504-G-GGC		Mucopolysaccharidosis, MPS-III-C	Likely pathogenic (Jun 06, 2018)
8-43140506-G-C		Retinitis pigmentosa 73;Mucopolysaccharidosis, MPS-III-C	Benign (Nov 20, 2023)
8-43140508-G-A		Mucopolysaccharidosis, MPS-III-C;Retinitis pigmentosa 73 • Mucopolysaccharidosis, MPS-III-C	Likely benign (Jan 31, 2024)
8-43140508-G-C		Retinitis pigmentosa 73;Mucopolysaccharidosis, MPS-III-C	Likely benign (Mar 14, 2021)
8-43140508-G-T		Retinitis pigmentosa 73;Mucopolysaccharidosis, MPS-III-C	Likely benign (Apr 10, 2023)
8-43140510-G-T		Mucopolysaccharidosis, MPS-III-C;Retinitis pigmentosa 73 • Inborn genetic diseases	Uncertain significance (Nov 18, 2023)
8-43140513-G-A		Mucopolysaccharidosis, MPS-III-C • Retinitis pigmentosa 73;Mucopolysaccharidosis, MPS-III-C • Retinal dystrophy • Inborn genetic diseases	Conflicting classifications of pathogenicity (Jan 29, 2024)
8-43140514-G-A		Mucopolysaccharidosis, MPS-III-C;Retinitis pigmentosa 73	Likely benign (Dec 13, 2023)
8-43140516-C-T			Uncertain significance (Dec 02, 2022)
8-43140516-CGCTGGCCGCGCTGCT-C		Mucopolysaccharidosis, MPS-III-C • Mucopolysaccharidosis, MPS-III-C;Retinitis pigmentosa 73	Uncertain significance (Sep 06, 2022)
8-43140517-G-A		Retinitis pigmentosa 73;Mucopolysaccharidosis, MPS-III-C	Likely benign (Jun 05, 2023)
8-43140523-C-A		Mucopolysaccharidosis, MPS-III-C;Retinitis pigmentosa 73	Likely benign (Jan 26, 2024)
8-43140524-G-C		Mucopolysaccharidosis, MPS-III-C;Retinitis pigmentosa 73 • Inborn genetic diseases	Uncertain significance (Jan 08, 2024)
8-43140526-G-A		Retinitis pigmentosa 73;Mucopolysaccharidosis, MPS-III-C • Retinal dystrophy	Conflicting classifications of pathogenicity (Oct 01, 2023)
8-43140525-C-CGCTGCTGCTGGCCGCGTCCGT		Mucopolysaccharidosis, MPS-III-C • Mucopolysaccharidosis, MPS-III-C;Retinitis pigmentosa 73 • not specified	Uncertain significance (Aug 09, 2022)
8-43140528-T-C		Mucopolysaccharidosis, MPS-III-C;Retinitis pigmentosa 73 • Mucopolysaccharidosis, MPS-III-C • Inborn genetic diseases • HGSNAT-related disorder	Uncertain significance (Dec 29, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
HGSNAT	protein_coding	protein_coding	ENST00000379644	18	62443

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
6.34e-8	0.999	124915	0	69	124984	0.000276

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.706	283	318	0.889	0.0000171	4076
Missense in Polyphen		54	86.326	0.62553		983
Synonymous	0.0496	126	127	0.994	0.00000743	1281
Loss of Function	2.85	18	36.6	0.492	0.00000211	405

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00113	0.00111
Ashkenazi Jewish	0.00	0.00
East Asian	0.000282	0.000278
Finnish	0.000325	0.000325
European (Non-Finnish)	0.000223	0.000221
Middle Eastern	0.000282	0.000278
South Asian	0.000208	0.000196
Other	0.000331	0.000328

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Lysosomal acetyltransferase that acetylates the non- reducing terminal alpha-glucosamine residue of intralysosomal heparin or heparan sulfate, converting it into a substrate for luminal alpha-N-acetyl glucosaminidase. {ECO:0000269|PubMed:16960811, ECO:0000269|PubMed:17033958, ECO:0000269|PubMed:19823584, ECO:0000269|PubMed:20650889}.
• Disease: DISEASE: Mucopolysaccharidosis 3C (MPS3C) [MIM:252930]: 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:16960811, ECO:0000269|PubMed:17033958, ECO:0000269|PubMed:17397050, ECO:0000269|PubMed:18024218, ECO:0000269|PubMed:19479962, ECO:0000269|PubMed:19823584, ECO:0000269|PubMed:20583299, ECO:0000269|PubMed:20825431, ECO:0000269|PubMed:28101780}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Retinitis pigmentosa 73 (RP73) [MIM:616544]: A retinal dystrophy belonging to the group of pigmentary retinopathies. Retinitis pigmentosa is characterized by retinal pigment deposits visible on fundus examination and primary loss of rod photoreceptor cells followed by secondary loss of cone photoreceptors. Patients typically have night vision blindness and loss of midperipheral visual field. As their condition progresses, they lose their far peripheral visual field and eventually central vision as well. {ECO:0000269|PubMed:25859010}. 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;Innate Immune System;Immune System (Consensus)

Intolerance Scores

• loftool: 0.388
• rvis_EVS: 0.16
• rvis_percentile_EVS: 64.82

Haploinsufficiency Scores

• pHI: 0.129
• hipred: N
• hipred_score: 0.492
• ghis: 0.504

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.666

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Hgsnat
• Phenotype: renal/urinary system 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); 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); respiratory system phenotype; liver/biliary system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); cellular phenotype; homeostasis/metabolism phenotype

Gene ontology

• Biological process: glycosaminoglycan catabolic process;lysosomal transport;neutrophil degranulation;protein complex oligomerization
• Cellular component: lysosomal membrane;plasma membrane;integral component of membrane;specific granule membrane;tertiary granule membrane
• Molecular function: heparan-alpha-glucosaminide N-acetyltransferase activity;transferase activity, transferring acyl groups