NAGLU

N-acetyl-alpha-glucosaminidase, the group of Glycoside hydrolases

Basic information

Region (hg38): 17:42536241-42544449

Links

ENSG00000108784 ∙ NCBI:4669 ∙ OMIM:609701 ∙ HGNC:7632 ∙ Uniprot:P54802 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• mucopolysaccharidosis type 3B (Definitive), mode of inheritance: AR
• mucopolysaccharidosis type 3B (Definitive), mode of inheritance: AR
• mucopolysaccharidosis type 3B (Strong), mode of inheritance: AR
• mucopolysaccharidosis type 3B (Supportive), mode of inheritance: AR
• Charcot-Marie-Tooth disease axonal type 2V (Supportive), mode of inheritance: AD
• Charcot-Marie-Tooth disease axonal type 2V (Limited), mode of inheritance: AD
• mucopolysaccharidosis type 3B (Strong), mode of inheritance: AR
• mucopolysaccharidosis type 3B (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Mucopolysaccharidosis type IIIB (Sanfilippo syndrome B)	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; Musculoskeletal; Neurologic	4261742; 3118713; 1606713; 1293388; 8650226; 3118713; 11068184; 12202988; 15933803; 18218046; 20852935; 21937992; 21712855; 22976768; 25818867
BMT has been reported as beneficial

ClinVar

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

• Mucopolysaccharidosis,_MPS-III-B (1275 variants)
• Charcot-Marie-Tooth_disease_axonal_type_2V (1155 variants)
• not_provided (158 variants)
• Inborn_genetic_diseases (67 variants)
• not_specified (58 variants)
• NAGLU-related_disorder (23 variants)
• Mucopolysaccharidosis (8 variants)
• Intellectual_disability (8 variants)
• Tip-toe_gait (5 variants)
• Abnormality_of_metabolism/homeostasis (3 variants)
• Mucopolysaccharidosistype_IIIB (3 variants)
• Hepatosplenomegaly (2 variants)
• Coarse_facial_features (2 variants)
• Intellectual_disability,_severe (2 variants)
• Thick_eyebrow (2 variants)
• Sanfilippo_syndrome (2 variants)
• Abnormal_facial_shape (2 variants)
• Hypertrichosis (2 variants)
• Mucopolysacchariduria (2 variants)
• See_cases (1 variants)
• Spastic_ataxia (1 variants)
• Charcot-Marie-Tooth_disease (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NAGLU gene is commonly pathogenic or not. These statistics are base on transcript: NM_000000263.4. 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			13	453	3	469
missense	24	101	404	22	2	553
nonsense	39	20	5			64
start loss	4	2				6
frameshift	68	33	3			104
splice donor/acceptor (+/-2bp)	4	11	1			16
Total	139	167	426	475	5

Highest pathogenic variant AF is 0.00014993253

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
NAGLU	protein_coding	protein_coding	ENST00000225927	6	8278

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.37e-8	0.948	125687	0	61	125748	0.000243

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.988	313	366	0.855	0.0000239	4692
Missense in Polyphen		119	152.07	0.78253		1907
Synonymous	-0.513	168	160	1.05	0.0000108	1591
Loss of Function	1.96	17	28.2	0.602	0.00000180	262

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000603	0.000573
Ashkenazi Jewish	0.00	0.00
East Asian	0.000218	0.000217
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000306	0.000299
Middle Eastern	0.000218	0.000217
South Asian	0.000229	0.000229
Other	0.000337	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Involved in the degradation of heparan sulfate.
• Disease: DISEASE: Charcot-Marie-Tooth disease 2V (CMT2V) [MIM:616491]: An axonal form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. Charcot-Marie-Tooth disease is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathies (designated CMT1 when they are dominantly inherited) and primary peripheral axonal neuropathies (CMT2). Neuropathies of the CMT2 group are characterized by signs of axonal degeneration in the absence of obvious myelin alterations, normal or slightly reduced nerve conduction velocities, and progressive distal muscle weakness and atrophy. CMT2V is an autosomal dominant sensory neuropathy with late onset. The main clinical feature is recurrent leg pain that progresses to constant painful paraesthesias in the feet and later the hands. As it evolves, some patients develop a mild sensory ataxia. {ECO:0000269|PubMed:25818867}. 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: 0.528

Intolerance Scores

• loftool: 0.159
• rvis_EVS: -0.75
• rvis_percentile_EVS: 13.67

Haploinsufficiency Scores

• pHI: 0.114
• hipred: Y
• hipred_score: 0.554
• ghis: 0.590

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.731

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Naglu
• Phenotype: cellular phenotype; craniofacial phenotype; growth/size/body region phenotype; 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); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); renal/urinary system phenotype; skeleton phenotype; immune system phenotype; vision/eye phenotype; hearing/vestibular/ear 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); pigmentation 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); hematopoietic system 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); liver/biliary system phenotype

Gene ontology

• Biological process: glycosaminoglycan catabolic process;lysosome organization;nervous system development;cerebellar Purkinje cell layer development;middle ear morphogenesis;locomotor rhythm;retinal rod cell development;inner ear receptor cell development
• Cellular component: lysosome;lysosomal lumen;extracellular exosome
• Molecular function: alpha-N-acetylglucosaminidase activity