NAGA

alpha-N-acetylgalactosaminidase, the group of Galactosidases alpha

Basic information

Region (hg38): 22:42058333-42070842

Links

ENSG00000198951 ∙ NCBI:4668 ∙ OMIM:104170 ∙ HGNC:7631 ∙ Uniprot:P17050 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• alpha-N-acetylgalactosaminidase deficiency type 2 (Definitive), mode of inheritance: AR
• alpha-N-acetylgalactosaminidase deficiency type 1 (Strong), mode of inheritance: AR
• alpha-N-acetylgalactosaminidase deficiency type 2 (Strong), mode of inheritance: AR
• alpha-N-acetylgalactosaminidase deficiency type 1 (Supportive), mode of inheritance: AR
• alpha-N-acetylgalactosaminidase deficiency type 2 (Supportive), mode of inheritance: AR
• alpha-N-acetylgalactosaminidase deficiency type 3 (Supportive), mode of inheritance: AR
• alpha-N-acetylgalactosaminidase deficiency type 1 (Strong), mode of inheritance: AR
• alpha-N-acetylgalactosaminidase deficiency (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Kanzaki disease; Alpha-n-acetylgalactosaminidase deficiency; Schindler disease type I; Schindler disease type III	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; Dermatologic; Neurologic	2564952; 2243144; 7707696; 8071745; 8040340; 8782044; 11313741; 11251574; 14685826; 15619430

ClinVar

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

• Alpha-N-acetylgalactosaminidase deficiency type 1 (190 variants)
• Alpha-N-acetylgalactosaminidase deficiency type 2 (64 variants)
• not provided (46 variants)
• Inborn genetic diseases (18 variants)
• not specified (9 variants)
• Alpha-N-acetylgalactosaminidase deficiency type 1;Alpha-N-acetylgalactosaminidase deficiency type 2 (4 variants)
• NAGA-Related Disorders (2 variants)
• Alpha-N-acetylgalactosaminidase deficiency (2 variants)
• Alpha-N-acetylgalactosaminidase deficiency type 3 (1 variants)
• Arthrogryposis multiplex congenita;Fetal akinesia deformation sequence 1 (1 variants)
• Alpha-N-acetylgalactosaminidase deficiency type 2;Alpha-N-acetylgalactosaminidase deficiency type 1;Alpha-N-acetylgalactosaminidase deficiency type 3 (1 variants)
• See cases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NAGA 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			5	40	1	46
missense			64	1	1	66
nonsense	6	3	1			10
start loss						0
frameshift	4		1			5
inframe indel						0
splice donor/acceptor (+/-2bp)		2				2
splice region			1	14	2	17
non coding			22	30	26	78
Total	10	5	93	71	28

Highest pathogenic variant AF is 0.0000526

Variants in NAGA

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

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

Position	Type	Phenotype	Significance	ClinVar
22-42058349-C-T		Alpha-N-acetylgalactosaminidase deficiency type 1 • Alpha-N-acetylgalactosaminidase deficiency type 2	Likely benign (Jan 12, 2018)
22-42058350-G-A		Alpha-N-acetylgalactosaminidase deficiency type 2 • Alpha-N-acetylgalactosaminidase deficiency type 1	Benign (Jan 12, 2018)
22-42058417-G-T		Alpha-N-acetylgalactosaminidase deficiency type 1 • Alpha-N-acetylgalactosaminidase deficiency type 2	Uncertain significance (Jan 13, 2018)
22-42058465-G-A		Alpha-N-acetylgalactosaminidase deficiency type 2 • Alpha-N-acetylgalactosaminidase deficiency type 1	Benign (Jan 12, 2018)
22-42058489-GA-G		Alpha-N-acetylgalactosaminidase deficiency type 2 • Alpha-N-acetylgalactosaminidase deficiency type 1	Uncertain significance (Jun 14, 2016)
22-42058489-GAA-G		Alpha-N-acetylgalactosaminidase deficiency type 2 • Alpha-N-acetylgalactosaminidase deficiency type 1	Benign (Jun 14, 2016)
22-42058555-G-C		Alpha-N-acetylgalactosaminidase deficiency type 2 • Alpha-N-acetylgalactosaminidase deficiency type 1	Uncertain significance (Jan 12, 2018)
22-42058583-G-A		Alpha-N-acetylgalactosaminidase deficiency type 1 • Alpha-N-acetylgalactosaminidase deficiency type 2	Benign (Jan 12, 2018)
22-42058724-G-A		Alpha-N-acetylgalactosaminidase deficiency type 2 • Alpha-N-acetylgalactosaminidase deficiency type 1	Uncertain significance (Jan 13, 2018)
22-42058778-G-C		Alpha-N-acetylgalactosaminidase deficiency type 1 • Alpha-N-acetylgalactosaminidase deficiency type 2	Uncertain significance (Jan 13, 2018)
22-42058795-T-C		Alpha-N-acetylgalactosaminidase deficiency type 1 • Alpha-N-acetylgalactosaminidase deficiency type 2	Uncertain significance (Jan 13, 2018)
22-42058946-A-G		Alpha-N-acetylgalactosaminidase deficiency type 1 • Alpha-N-acetylgalactosaminidase deficiency type 2	Benign (Jan 12, 2018)
22-42058968-A-G		Alpha-N-acetylgalactosaminidase deficiency type 2 • Alpha-N-acetylgalactosaminidase deficiency type 1	Likely benign (Jan 13, 2018)
22-42058980-G-A		Alpha-N-acetylgalactosaminidase deficiency type 2 • Alpha-N-acetylgalactosaminidase deficiency type 1	Uncertain significance (Jan 13, 2018)
22-42059027-A-G		Alpha-N-acetylgalactosaminidase deficiency type 2 • Alpha-N-acetylgalactosaminidase deficiency type 1	Uncertain significance (Jan 13, 2018)
22-42059176-A-G		Alpha-N-acetylgalactosaminidase deficiency type 2 • Alpha-N-acetylgalactosaminidase deficiency type 1	Benign (Jan 13, 2018)
22-42059189-C-T		Alpha-N-acetylgalactosaminidase deficiency type 1 • Alpha-N-acetylgalactosaminidase deficiency type 2	Uncertain significance (Jan 13, 2018)
22-42059244-C-T		Alpha-N-acetylgalactosaminidase deficiency type 2 • Alpha-N-acetylgalactosaminidase deficiency type 1	Benign (Jan 13, 2018)
22-42059353-G-C		Alpha-N-acetylgalactosaminidase deficiency type 1 • Alpha-N-acetylgalactosaminidase deficiency type 2	Uncertain significance (Jan 13, 2018)
22-42059549-A-G		Alpha-N-acetylgalactosaminidase deficiency type 2 • Alpha-N-acetylgalactosaminidase deficiency type 1	Uncertain significance (Jan 13, 2018)
22-42059707-C-T		Alpha-N-acetylgalactosaminidase deficiency type 1 • Alpha-N-acetylgalactosaminidase deficiency type 2	Uncertain significance (Jan 15, 2018)
22-42059724-G-A		Alpha-N-acetylgalactosaminidase deficiency type 2 • Alpha-N-acetylgalactosaminidase deficiency type 1	Likely benign (Jan 12, 2018)
22-42060011-C-T		Alpha-N-acetylgalactosaminidase deficiency type 1 • Alpha-N-acetylgalactosaminidase deficiency type 2	Uncertain significance (Jan 13, 2018)
22-42060103-G-C		Alpha-N-acetylgalactosaminidase deficiency type 2 • Alpha-N-acetylgalactosaminidase deficiency type 1	Uncertain significance (Jan 13, 2018)
22-42060109-C-T		Alpha-N-acetylgalactosaminidase deficiency type 2 • Alpha-N-acetylgalactosaminidase deficiency type 1	Benign/Likely benign (Feb 23, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
NAGA	protein_coding	protein_coding	ENST00000396398	9	12489

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.77e-11	0.116	125699	0	49	125748	0.000195

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.169	237	244	0.970	0.0000154	2723
Missense in Polyphen		70	76.964	0.90952		861
Synonymous	0.901	84	95.2	0.883	0.00000600	785
Loss of Function	0.510	18	20.5	0.878	0.00000100	210

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000297	0.000297
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.000196	0.000193
Middle Eastern	0.0000544	0.0000544
South Asian	0.000458	0.000457
Other	0.000653	0.000652

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Removes terminal alpha-N-acetylgalactosamine residues from glycolipids and glycopeptides. Required for the breakdown of glycolipids. {ECO:0000269|PubMed:9741689}.
• Disease: DISEASE: Schindler disease (SCHIND) [MIM:609241]: Form of NAGA deficiency characterized by early-onset neuroaxonal dystrophy and neurological signs (convulsion during fever, epilepsy, psychomotor retardation and hypotonia). NAGA deficiency is typically classified in three main phenotypes: NAGA deficiency type I (Schindler disease or Schindler disease type I) with severe manifestations; NAGA deficiency type II (Kanzazi disease or Schindler disease type II) which is mild; NAGA deficiency type III (Schindler disease type III) characterized by mild-to-moderate neurologic manifestations. NAGA deficiency results in the increased urinary excretion of glycopeptides and oligosaccharides containing alpha-N-acetylgalactosaminyl moieties. Inheritance is autosomal recessive. {ECO:0000269|PubMed:2243144, ECO:0000269|PubMed:8782044}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Kanzaki disease (KANZD) [MIM:609242]: Autosomal recessive disorder characterized by late-onset, angiokeratoma corporis diffusum and mild intellectual impairment. {ECO:0000269|PubMed:11251574, ECO:0000269|PubMed:8040340}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Lysosome - Homo sapiens (human);Glycosphingolipid biosynthesis - globo and isoglobo series - Homo sapiens (human);Glycosphingolipid biosynthesis - globoseries (Consensus)

Recessive Scores

• pRec: 0.394

Intolerance Scores

• loftool: 0.257
• rvis_EVS: -0.31
• rvis_percentile_EVS: 32.06

Haploinsufficiency Scores

• pHI: 0.338
• hipred: N
• hipred_score: 0.219
• ghis: 0.559

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.0945

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Naga
• Phenotype: homeostasis/metabolism phenotype; hematopoietic system phenotype; immune system phenotype

Gene ontology

• Biological process: oligosaccharide metabolic process;carbohydrate catabolic process;glycoside catabolic process;glycolipid catabolic process;glycosylceramide catabolic process
• Cellular component: cytoplasm;lysosome;extracellular exosome
• Molecular function: alpha-galactosidase activity;alpha-N-acetylgalactosaminidase activity;protein homodimerization activity