ASL

argininosuccinate lyase

Basic information

Region (hg38): 7:66075800-66094697

Links

ENSG00000126522

∙ NCBI:435 ∙ OMIM:608310 ∙ HGNC:746 ∙ Uniprot:P04424 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

argininosuccinic aciduria (Definitive), mode of inheritance: AR
argininosuccinic aciduria (Definitive), mode of inheritance: AR
argininosuccinic aciduria (Strong), mode of inheritance: AR
argininosuccinic aciduria (Definitive), mode of inheritance: AR
argininosuccinic aciduria (Supportive), mode of inheritance: AR
argininosuccinic aciduria (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Argininosuccinic aciduria	AR	Biochemical; Pharmacogenomic	Dietary and medical therapy (eg, with low-protein diet supplemented with arginine), may be beneficial, and special care to prevent/treat acute metabolic decompensation (eg, with IV glucose and ammonia-reducing agents) may be effective; Certain agents (such as enflurane, an anesthetic agent) should be avoided due to reports of adverse reactions	Biochemical; Dermatologic; Neurologic	13503250; 5836520; 84150; 2263616; 1897577; 1594374; 9504797; 12408190; 12384776; 17326097; 22541557; 20236848; 19635676; 22541557; 22841516; 23040521; 25135652

ClinVar

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

Argininosuccinate_lyase_deficiency (821 variants)
not_provided (94 variants)
not_specified (60 variants)
Inborn_genetic_diseases (36 variants)
ASL-related_disorder (12 variants)
Neurodevelopmental_disorder (3 variants)
Autism (1 variants)
Congenital_myasthenic_syndrome_4C (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ASL gene is commonly pathogenic or not. These statistics are base on transcript: NM_000000048.4. 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	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous			12 clinvar	234 clinvar	2 clinvar	248
missense	16 clinvar	113 clinvar	114 clinvar	9 clinvar	1 clinvar	253
nonsense	16 clinvar	16 clinvar	1 clinvar			33
start loss		1				1
frameshift	22 clinvar	28 clinvar				50
splice donor/acceptor (+/-2bp)	15 clinvar	28 clinvar	1 clinvar	1 clinvar		45
Total	69	186	128	244	3

Highest pathogenic variant AF is 0.0018317379

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ASL	protein_coding	protein_coding	ENST00000304874	16	17761

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
8.57e-10	0.899	125678	0	66	125744	0.000262

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.749	247	282	0.875	0.0000195	3011
Missense in Polyphen		78	107.79	0.72365		1152
Synonymous	-1.37	134	115	1.16	0.00000822	908
Loss of Function	1.83	19	29.8	0.638	0.00000168	303

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000150	0.000150
Ashkenazi Jewish	0.000199	0.000198
East Asian	0.000383	0.000381
Finnish	0.000200	0.000185
European (Non-Finnish)	0.000360	0.000352
Middle Eastern	0.000383	0.000381
South Asian	0.000263	0.000261
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

Disease: DISEASE: Argininosuccinic aciduria (ARGINSA) [MIM:207900]: An autosomal recessive disorder of the urea cycle. The disease is characterized by mental and physical retardation, liver enlargement, skin lesions, dry and brittle hair showing trichorrhexis nodosa microscopically and fluorescing red, convulsions, and episodic unconsciousness. {ECO:0000269|PubMed:12408190, ECO:0000269|PubMed:1705937, ECO:0000269|PubMed:17326097, ECO:0000269|PubMed:19703900, ECO:0000269|PubMed:2263616, ECO:0000269|PubMed:24166829}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway: Alanine, aspartate and glutamate metabolism - Homo sapiens (human);Arginine biosynthesis - Homo sapiens (human);Argininemia;Hyperornithinemia with gyrate atrophy (HOGA);Creatine deficiency, guanidinoacetate methyltransferase deficiency;L-arginine:glycine amidinotransferase deficiency;Hyperornithinemia-hyperammonemia-homocitrullinuria [HHH-syndrome];Guanidinoacetate Methyltransferase Deficiency (GAMT Deficiency);Citrullinemia Type I;Carbamoyl Phosphate Synthetase Deficiency;Argininosuccinic Aciduria;Hypoacetylaspartia;Urea Cycle;Aspartate Metabolism;Prolinemia Type II;Prolidase Deficiency (PD);Ornithine Transcarbamylase Deficiency (OTC Deficiency);Arginine and Proline Metabolism;Hyperprolinemia Type I;Hyperprolinemia Type II;Ornithine Aminotransferase Deficiency (OAT Deficiency);Arginine: Glycine Amidinotransferase Deficiency (AGAT Deficiency);Canavan Disease;Alanine and aspartate metabolism;Urea cycle and metabolism of amino groups;Citrate cycle;Alanine Aspartate Asparagine metabolism;Metabolism of polyamines;Metabolism of amino acids and derivatives;Metabolism;citrulline-nitric oxide cycle;urea cycle;Arginine Proline metabolism;Urea cycle (Consensus)

Recessive Scores

pRec: 0.454

Intolerance Scores

loftool: 0.0497
rvis_EVS: -0.98
rvis_percentile_EVS: 8.85

Haploinsufficiency Scores

pHI: 0.0865
hipred: N
hipred_score: 0.112
ghis: 0.460

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: E
gene_indispensability_score: 0.964

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Asl
Phenotype: endocrine/exocrine gland 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); muscle phenotype; renal/urinary system phenotype; immune system phenotype; homeostasis/metabolism phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); hematopoietic system 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); 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); normal phenotype;

Gene ontology

Biological process: urea cycle;locomotory behavior;post-embryonic development;ammonia assimilation cycle;arginine biosynthetic process via ornithine
Cellular component: cytoplasm;cytosol;extracellular exosome
Molecular function: argininosuccinate lyase activity;protein binding;identical protein binding