ASPA

aspartoacylase

Basic information

Region (hg38): 17:3472374-3503405

Links

ENSG00000108381 ∙ NCBI:443 ∙ OMIM:608034 ∙ HGNC:756 ∙ Uniprot:P45381 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Canavan disease (Definitive), mode of inheritance: AR
• Canavan disease (Definitive), mode of inheritance: AR
• Canavan disease (Strong), mode of inheritance: AR
• severe Canavan disease (Supportive), mode of inheritance: AR
• mild Canavan disease (Supportive), mode of inheritance: AR
• Canavan disease (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Aspartoacylase deficiency (Canavan disease)	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	Neurologic; Ophthalmologic	2512436; 8252036; 8023850; 10909858; 12638939; 16437572; 18070137

ClinVar

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

• Spongy_degeneration_of_central_nervous_system (432 variants)
• Inborn_genetic_diseases (55 variants)
• Canavan_Disease,_Familial_Form (39 variants)
• not_provided (35 variants)
• not_specified (20 variants)
• ASPA-related_disorder (7 variants)
• Mild_Canavan_disease (2 variants)
• Autism (1 variants)
• Abnormality_of_metabolism/homeostasis (1 variants)
• Intellectual_disability (1 variants)
• Fraser_syndrome_3 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ASPA gene is commonly pathogenic or not. These statistics are base on transcript: NM_000000049.4. 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		1	8	119		128
missense	9	53	104	8	1	175
nonsense	11	9	2			22
start loss		3				3
frameshift	27	29				56
splice donor/acceptor (+/-2bp)	4	19				23
Total	51	114	114	127	1

Highest pathogenic variant AF is 0.0007090168

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ASPA	protein_coding	protein_coding	ENST00000263080	6	31046

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
		125722	0	26	125748	0.000103

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.479	154	172	0.897	0.00000913	2080
Missense in Polyphen		57	67.504	0.8444		848
Synonymous	0.404	57	61.0	0.934	0.00000356	575
Loss of Function	1.33	7	12.0	0.585	5.04e-7	165

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000152	0.000152
Ashkenazi Jewish	0.00129	0.00129
East Asian	0.00	0.00
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.0000617	0.0000615
Middle Eastern	0.00	0.00
South Asian	0.0000654	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Catalyzes the deacetylation of N-acetylaspartic acid (NAA) to produce acetate and L-aspartate. NAA occurs in high concentration in brain and its hydrolysis NAA plays a significant part in the maintenance of intact white matter. In other tissues it act as a scavenger of NAA from body fluids.
• Pathway: Alanine, aspartate and glutamate metabolism - Homo sapiens (human);Histidine metabolism - Homo sapiens (human);Hypoacetylaspartia;Aspartate Metabolism;Canavan Disease;Alanine and aspartate metabolism;Alanine Aspartate Asparagine metabolism;Metabolism of amino acids and derivatives;Metabolism;Amino acid synthesis and interconversion (transamination) (Consensus)

Intolerance Scores

• loftool: 0.144
• rvis_EVS: -0.12
• rvis_percentile_EVS: 45.13

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.938

Gene Damage Prediction

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

Gene ontology

• Biological process: aspartate catabolic process;cellular amino acid biosynthetic process;central nervous system myelination;positive regulation of oligodendrocyte differentiation
• Cellular component: nucleus;cytosol
• Molecular function: aminoacylase activity;protein binding;hydrolase activity, acting on ester bonds;aspartoacylase activity;identical protein binding;metal ion binding