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 (1087 variants)
Retinitis_pigmentosa_73 (1002 variants)
not_provided (91 variants)
Inborn_genetic_diseases (73 variants)
Retinal_dystrophy (54 variants)
not_specified (32 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)

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	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous			14 clinvar	317 clinvar	2 clinvar	333
missense	7 clinvar	25 clinvar	310 clinvar	18 clinvar	4 clinvar	364
nonsense	24 clinvar	19 clinvar	4 clinvar	1 clinvar		48
start loss			3			3
frameshift	36 clinvar	23 clinvar	2 clinvar	1 clinvar		62
splice donor/acceptor (+/-2bp)	14 clinvar	28 clinvar	1 clinvar			43
Total	81	95	334	337	6

Highest pathogenic variant AF is 0.0000433792

Loading clinvar variants...

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