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 3C (Definitive), mode of inheritance: AR
• retinitis pigmentosa 73 (Moderate), mode of inheritance: AR
• inherited retinal dystrophy (Definitive), mode of inheritance: AR
• mucopolysaccharidosis type 3C (Strong), mode of inheritance: AR
• mucopolysaccharidosis type 3C (Definitive), mode of inheritance: AR
• mucopolysaccharidosis type 3C (Strong), mode of inheritance: AR
• retinitis pigmentosa 73 (Strong), mode of inheritance: AR
• mucopolysaccharidosis type 3 (Definitive), mode of inheritance: AR
• retinitis pigmentosa (Supportive), mode of inheritance: AD
• mucopolysaccharidosis type 3C (Supportive), mode of inheritance: AR
• mucopolysaccharidosis type 3C (Definitive), mode of inheritance: AR
• retinitis pigmentosa 73 (Limited), 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 (1113 variants)
• Retinitis_pigmentosa_73 (1028 variants)
• not_provided (100 variants)
• Inborn_genetic_diseases (90 variants)
• Retinal_dystrophy (54 variants)
• not_specified (38 variants)
• HGSNAT-related_disorder (21 variants)
• Sanfilippo_syndrome (20 variants)
• Mucopolysaccharidosis (4 variants)
• Retinitis_pigmentosa (4 variants)
• Intellectual_disability (3 variants)
• Synovial_plica_syndrome (1 variants)
• Retinal_disorder (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. These statistics are base on transcript: NM_000152419.3. 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			14	326	1	341
missense	7	30	312	18	4	371
nonsense	25	19	4	1		49
start loss			3			3
frameshift	38	23	2	1		64
splice donor/acceptor (+/-2bp)	14	29	5			48
Total	84	101	340	346	5

Highest pathogenic variant AF is 0.00005869052

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
		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

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

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