ASL

argininosuccinate lyase

Basic information

Region (hg38): 7:66075799-66094697

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 (641 variants)
• not provided (104 variants)
• not specified (33 variants)
• Inborn genetic diseases (16 variants)
• ASL-related condition (3 variants)
• Neurodevelopmental disorder (3 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.

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			2	189	2	193
missense	19	56	83	7	1	166
nonsense	12	16				28
start loss						0
frameshift	15	26				41
inframe indel	1		1			2
splice donor/acceptor (+/-2bp)	10	20		1		31
splice region		1	12	49	1	63
non coding			8	86	31	125
Total	57	118	94	283	34

Highest pathogenic variant AF is 0.000341

Variants in ASL

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

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

Position	Type	Phenotype	Significance	ClinVar
7-66075865-G-A		Argininosuccinate lyase deficiency • not specified	Conflicting classifications of pathogenicity (Jan 12, 2018)
7-66075866-C-T		not specified	Likely benign (Mar 14, 2016)
7-66076048-A-G		Argininosuccinate lyase deficiency	Uncertain significance (Apr 27, 2017)
7-66076051-G-A		Argininosuccinate lyase deficiency • not specified	Conflicting classifications of pathogenicity (Jan 13, 2018)
7-66076066-C-T		Argininosuccinate lyase deficiency	Uncertain significance (Jan 12, 2018)
7-66076086-C-A		Argininosuccinate lyase deficiency • Inborn genetic diseases	Uncertain significance (Dec 11, 2023)
7-66076101-G-A		Argininosuccinate lyase deficiency	Likely benign (Jul 13, 2022)
7-66076103-A-T		Argininosuccinate lyase deficiency	Likely benign (Dec 19, 2023)
7-66076104-C-A		Argininosuccinate lyase deficiency	Likely benign (Jan 30, 2024)
7-66076107-C-T		Argininosuccinate lyase deficiency	Likely benign (Dec 26, 2023)
7-66076108-G-T		Argininosuccinate lyase deficiency	Likely benign (Apr 28, 2023)
7-66076110-G-A		Argininosuccinate lyase deficiency	Likely benign (Jul 08, 2023)
7-66076113-C-A		Argininosuccinate lyase deficiency	Likely benign (Apr 07, 2023)
7-66076198-C-T		Argininosuccinate lyase deficiency	Benign (Jul 01, 2021)
7-66076320-C-G			Benign (Jun 14, 2018)
7-66081579-CA-C			Likely benign (Oct 20, 2019)
7-66081784-T-C		Argininosuccinate lyase deficiency	Likely benign (Jan 22, 2022)
7-66081789-G-T		Argininosuccinate lyase deficiency	Likely benign (Feb 18, 2023)
7-66081791-T-A		Argininosuccinate lyase deficiency	Likely benign (Apr 28, 2023)
7-66081793-T-C		Argininosuccinate lyase deficiency	Likely benign (Dec 15, 2020)
7-66081795-C-T		Argininosuccinate lyase deficiency	Likely benign (Dec 18, 2023)
7-66081796-T-C		Argininosuccinate lyase deficiency	Likely benign (May 17, 2023)
7-66081799-C-T		Argininosuccinate lyase deficiency	Likely benign (Jan 28, 2024)
7-66081801-A-G		Argininosuccinate lyase deficiency	Likely pathogenic (Dec 31, 2022)
7-66081802-G-C		Argininosuccinate lyase deficiency	Likely pathogenic (Aug 22, 2017)

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