AGA

aspartylglucosaminidase

Basic information

Region (hg38): 4:177430774-177442437

Links

ENSG00000038002 ∙ NCBI:175 ∙ OMIM:613228 ∙ HGNC:318 ∙ Uniprot:P20933 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• aspartylglucosaminuria (Definitive), mode of inheritance: AR
• aspartylglucosaminuria (Definitive), mode of inheritance: AR
• aspartylglucosaminuria (Strong), mode of inheritance: AR
• aspartylglucosaminuria (Supportive), mode of inheritance: AR
• aspartylglucosaminuria (Strong), mode of inheritance: AR
• aspartylglucosaminuria (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Aspartylglucosaminuria	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	Allergy/Immunology/Infectious; Biochemical; Cardiovascular; Craniofacial; Dermatologic; Musculoskeletal; Neurologic	4173687; 5512217; 6796777; 6883788; 3228136; 1904874; 1722323; 1703489; 1765378; 1756604; 1301945; 8405810; 8064811; 9427148; 9627765; 10353787; 11174635; 11796409; 12022293; 12366426; 15127757; 16218917; 23271757

ClinVar

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

• Aspartylglucosaminuria (482 variants)
• not_provided (49 variants)
• Inborn_genetic_diseases (29 variants)
• not_specified (8 variants)
• Intellectual_disability (6 variants)
• AGA-related_disorder (5 variants)
• Autism (1 variants)
• Neurodevelopmental_disorder (1 variants)
• Aspartylglucosaminuria,_finnish_type (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the AGA gene is commonly pathogenic or not. These statistics are base on transcript: NM_000000027.4. 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			4	130	1	135
missense	4	14	112	11	1	142
nonsense	7	14	2			23
start loss	1	2				3
frameshift	20	25	4			49
splice donor/acceptor (+/-2bp)	4	21				25
Total	36	76	122	141	2

Highest pathogenic variant AF is 0.000346406

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
AGA	protein_coding	protein_coding	ENST00000264595	9	11734

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00000428	0.848	125698	0	50	125748	0.000199

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.445	214	196	1.09	0.0000102	2253
Missense in Polyphen		78	73.882	1.0557		813
Synonymous	0.500	61	66.2	0.922	0.00000346	684
Loss of Function	1.43	11	17.4	0.631	8.48e-7	208

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000445	0.000445
Ashkenazi Jewish	0.00	0.00
East Asian	0.000217	0.000217
Finnish	0.00	0.00
European (Non-Finnish)	0.000229	0.000229
Middle Eastern	0.000217	0.000217
South Asian	0.000131	0.000131
Other	0.000652	0.000652

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Cleaves the GlcNAc-Asn bond which joins oligosaccharides to the peptide of asparagine-linked glycoproteins. {ECO:0000269|PubMed:1703489, ECO:0000269|PubMed:1904874, ECO:0000269|PubMed:2401370}.
• Disease: DISEASE: Aspartylglucosaminuria (AGU) [MIM:208400]: An inborn lysosomal storage disease causing excess accumulation of glycoasparagine in the body tissues and its increased excretion in urine. Clinical features include mild to severe mental retardation manifesting from the age of two, coarse facial features and mild connective tissue abnormalities. {ECO:0000269|PubMed:11309371, ECO:0000269|PubMed:1703489, ECO:0000269|PubMed:1904874, ECO:0000269|PubMed:2011603, ECO:0000269|PubMed:8776587, ECO:0000269|PubMed:9137882}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Lysosome - Homo sapiens (human);Other glycan degradation - Homo sapiens (human);Neutrophil degranulation;Innate Immune System;Immune System;asparagine degradation;Urea cycle and metabolism of arginine, proline, glutamate, aspartate and asparagine (Consensus)

Recessive Scores

• pRec: 0.220

Intolerance Scores

• loftool: 0.308
• rvis_EVS: 0.75
• rvis_percentile_EVS: 86.71

Haploinsufficiency Scores

• pHI: 0.0366
• hipred: N
• hipred_score: 0.174
• ghis: 0.403

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.532

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Aga
• 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); renal/urinary system phenotype; liver/biliary system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms 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); 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); homeostasis/metabolism phenotype; cellular phenotype; growth/size/body region phenotype

Gene ontology

• Biological process: proteolysis;protein deglycosylation;neutrophil degranulation;protein maturation
• Cellular component: extracellular region;extracellular space;cytoplasm;lysosome;endoplasmic reticulum;azurophil granule lumen
• Molecular function: N4-(beta-N-acetylglucosaminyl)-L-asparaginase activity;peptidase activity;hydrolase activity;protein self-association