ASNS

asparagine synthetase (glutamine-hydrolyzing)

Basic information

Region (hg38): 7:97851677-97872542

Links

ENSG00000070669 ∙ NCBI:440 ∙ OMIM:108370 ∙ HGNC:753 ∙ Uniprot:P08243 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• congenital microcephaly - severe encephalopathy - progressive cerebral atrophy syndrome (Definitive), mode of inheritance: AR
• congenital microcephaly - severe encephalopathy - progressive cerebral atrophy syndrome (Strong), mode of inheritance: AR
• congenital microcephaly - severe encephalopathy - progressive cerebral atrophy syndrome (Supportive), mode of inheritance: AR
• congenital microcephaly - severe encephalopathy - progressive cerebral atrophy syndrome (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Asparagine synthetase deficiency	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; Neurologic	24139043; 27469131; 28776279; 29279279

ClinVar

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

• not_provided (678 variants)
• Congenital_microcephaly_-_severe_encephalopathy_-_progressive_cerebral_atrophy_syndrome (146 variants)
• Inborn_genetic_diseases (52 variants)
• not_specified (19 variants)
• ASNS-related_disorder (12 variants)
• Abnormal_cerebral_morphology (3 variants)
• Neurodevelopmental_delay (2 variants)
• Neurodevelopmental_abnormality (2 variants)
• Spinocerebellar_ataxia,_autosomal_recessive_29 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ASNS gene is commonly pathogenic or not. These statistics are base on transcript: NM_000001673.5. 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			6	220	2	228
missense	3	35	198	8		244
nonsense	16	14	2			32
start loss	3	1				4
frameshift	50	19				69
splice donor/acceptor (+/-2bp)	2	25				27
Total	74	94	206	228	2

Highest pathogenic variant AF is 0.0000433727

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ASNS	protein_coding	protein_coding	ENST00000175506	11	20425

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00000936	0.997	125711	0	37	125748	0.000147

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.86	220	312	0.704	0.0000168	3694
Missense in Polyphen		60	97.587	0.61484		1291
Synonymous	1.02	99	113	0.878	0.00000616	1050
Loss of Function	2.62	13	27.9	0.466	0.00000145	352

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000466	0.000460
Ashkenazi Jewish	0.0000993	0.0000992
East Asian	0.000218	0.000217
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000159	0.000158
Middle Eastern	0.000218	0.000217
South Asian	0.000131	0.000131
Other	0.000164	0.000163

dbNSFP

Source: dbNSFP

• Disease: DISEASE: Asparagine synthetase deficiency (ASNSD) [MIM:615574]: An inborn error of asparagine biosynthesis that results in a severe neurologic disorder characterized by microcephaly, severely delayed psychomotor development, progressive encephalopathy, cortical atrophy, and seizure or hyperekplexic activity. {ECO:0000269|PubMed:24139043}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Alanine, aspartate and glutamate metabolism - Homo sapiens (human);Ammonia Recycling;Hypoacetylaspartia;Aspartate Metabolism;Canavan Disease;ATF4 activates genes;Photodynamic therapy-induced unfolded protein response;Amino Acid metabolism;Alanine Aspartate Asparagine metabolism;Metabolism of amino acids and derivatives;asparagine biosynthesis;Metabolism;glutamine degradation/glutamate biosynthesis;Amino acid synthesis and interconversion (transamination) (Consensus)

Recessive Scores

• pRec: 0.260

Intolerance Scores

• loftool: 0.926
• rvis_EVS: -0.03
• rvis_percentile_EVS: 51.92

Haploinsufficiency Scores

• pHI: 0.479
• hipred: Y
• hipred_score: 0.641
• ghis: 0.507

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.949

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Asns
• Phenotype: hematopoietic system phenotype; growth/size/body region 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); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan)

Gene ontology

• Biological process: liver development;asparagine biosynthetic process;glutamine metabolic process;cellular amino acid biosynthetic process;response to light stimulus;response to mechanical stimulus;response to toxic substance;response to methotrexate;response to follicle-stimulating hormone;cellular response to hormone stimulus;PERK-mediated unfolded protein response;cellular response to glucose starvation;negative regulation of apoptotic process;response to amino acid;positive regulation of mitotic cell cycle;L-asparagine biosynthetic process
• Cellular component: cytosol
• Molecular function: asparagine synthase (glutamine-hydrolyzing) activity;protein binding;ATP binding;protein homodimerization activity;cofactor binding