ADSL

adenylosuccinate lyase, the group of Purinosome

Basic information

Region (hg38): 22:40346460-40390463

Links

ENSG00000239900 ∙ NCBI:158 ∙ OMIM:608222 ∙ HGNC:291 ∙ Uniprot:P30566 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• adenylosuccinate lyase deficiency (Definitive), mode of inheritance: AR
• adenylosuccinate lyase deficiency (Strong), mode of inheritance: AR
• adenylosuccinate lyase deficiency (Supportive), mode of inheritance: AR
• adenylosuccinate lyase deficiency (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Adenylosuccinase 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	6150139; 3234432; 1405483; 1302001; 9266401; 9266351; 10090474; 10888601; 11042421; 12070256; 12833398; 17188615; 18524658; 18649008; 18830228; 20177786; 20933180; 22883297; 23055421; 23504561
As with many disorders involving seizures, appropriate interventions may be beneficial (eg, ketogenic diet has been reported as beneficial)

ClinVar

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

• Adenylosuccinate lyase deficiency (461 variants)
• not provided (141 variants)
• not specified (45 variants)
• Inborn genetic diseases (15 variants)
• ADSL-related condition (2 variants)
• Severe global developmental delay;Inability to walk;Difficulty standing;Progressive neurologic deterioration;Generalized myoclonic seizure (1 variants)
• Generalized myoclonic seizure;Progressive neurologic deterioration;Severe global developmental delay;Inability to walk;Difficulty standing (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ADSL 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			3	62	2	67
missense	6	19	198	3	2	228
nonsense	14	2				16
start loss						0
frameshift	7		2			9
inframe indel		2	3			5
splice donor/acceptor (+/-2bp)	2	6				8
splice region	1		18	20	2	41
non coding		1	21	66	22	110
Total	29	30	227	131	26

Highest pathogenic variant AF is 0.000223

Variants in ADSL

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

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

Position	Type	Phenotype	Significance	ClinVar
22-40346465-G-A		Adenylosuccinate lyase deficiency	Uncertain significance (Oct 03, 2023)
22-40346469-T-TCCCGC		Adenylosuccinate lyase deficiency	Benign (Jan 11, 2024)
22-40346472-C-T		Adenylosuccinate lyase deficiency	Uncertain significance (Aug 07, 2022)
22-40346473-G-C		Adenylosuccinate lyase deficiency	Uncertain significance (Aug 16, 2022)
22-40346472-C-CGCCCCGCCCCGTCCT		Adenylosuccinate lyase deficiency	Uncertain significance (Mar 25, 2022)
22-40346474-C-A		Adenylosuccinate lyase deficiency	Uncertain significance (Nov 25, 2020)
22-40346478-G-C		Adenylosuccinate lyase deficiency	Uncertain significance (Sep 01, 2022)
22-40346477-C-CGCCCCGTCCT		Adenylosuccinate lyase deficiency	Uncertain significance (Jun 05, 2022)
22-40346482-C-T		Adenylosuccinate lyase deficiency	Uncertain significance (May 12, 2022)
22-40346482-CGTCCTGCCCT-C		Adenylosuccinate lyase deficiency	Uncertain significance (Jul 26, 2022)
22-40346483-G-A		Adenylosuccinate lyase deficiency	Uncertain significance (Nov 15, 2022)
22-40346488-G-A		Adenylosuccinate lyase deficiency	Uncertain significance (Oct 16, 2023)
22-40346488-GC-G		Adenylosuccinate lyase deficiency	Uncertain significance (Mar 20, 2022)
22-40346489-C-G		Adenylosuccinate lyase deficiency	Uncertain significance (Dec 07, 2023)
22-40346489-C-T		Adenylosuccinate lyase deficiency	Uncertain significance (Feb 10, 2022)
22-40346492-T-G		Adenylosuccinate lyase deficiency	Uncertain significance (Jul 19, 2022)
22-40346493-G-A		Adenylosuccinate lyase deficiency	Uncertain significance (Aug 16, 2022)
22-40346495-C-A		Adenylosuccinate lyase deficiency	Uncertain significance (Sep 27, 2022)
22-40346503-T-A		Adenylosuccinate lyase deficiency	Uncertain significance (Dec 23, 2020)
22-40346508-G-A		Adenylosuccinate lyase deficiency	Uncertain significance (Feb 08, 2022)
22-40346510-T-C		Inborn genetic diseases • Adenylosuccinate lyase deficiency	Pathogenic/Likely pathogenic (Mar 20, 2023)
22-40346515-C-G		Adenylosuccinate lyase deficiency	Uncertain significance (May 26, 2021)
22-40346522-C-G		not specified • Adenylosuccinate lyase deficiency	Conflicting classifications of pathogenicity (Aug 09, 2022)
22-40346522-C-T		Adenylosuccinate lyase deficiency	Uncertain significance (May 12, 2022)
22-40346524-G-A			Uncertain significance (Oct 23, 2014)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ADSL	protein_coding	protein_coding	ENST00000216194	13	43961

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
8.92e-12	0.454	125713	0	35	125748	0.000139

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.803	244	282	0.865	0.0000175	3171
Missense in Polyphen		96	116.9	0.82123		1330
Synonymous	1.05	87	100	0.867	0.00000536	936
Loss of Function	1.26	21	28.2	0.744	0.00000171	301

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000233	0.000233
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.0000550	0.0000544
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000162	0.000158
Middle Eastern	0.0000550	0.0000544
South Asian	0.000196	0.000196
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Catalyzes two non-sequential steps in de novo AMP synthesis: converts (S)-2-(5-amino-1-(5-phospho-D- ribosyl)imidazole-4-carboxamido)succinate (SAICAR) to fumarate plus 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide, and thereby also contributes to de novo IMP synthesis, and converts succinyladenosine monophosphate (SAMP) to AMP and fumarate. {ECO:0000269|PubMed:10888601}.
• Pathway: Alanine, aspartate and glutamate metabolism - Homo sapiens (human);Purine metabolism - Homo sapiens (human);Purine Nucleoside Phosphorylase Deficiency;Mercaptopurine Action Pathway;Azathioprine Action Pathway;Xanthine Dehydrogenase Deficiency (Xanthinuria);Adenylosuccinate Lyase Deficiency;AICA-Ribosiduria;Thioguanine Action Pathway;Adenine phosphoribosyltransferase deficiency (APRT);Mitochondrial DNA depletion syndrome;Myoadenylate deaminase deficiency;Purine Metabolism;Hypoacetylaspartia;Aspartate Metabolism;Molybdenum Cofactor Deficiency;Adenosine Deaminase Deficiency;Gout or Kelley-Seegmiller Syndrome;Lesch-Nyhan Syndrome (LNS);Xanthinuria type I;Xanthinuria type II;Canavan Disease;Nucleotide Metabolism;adenosine ribonucleotides <i>de novo</i> biosynthesis;Metabolism of nucleotides;Alanine Aspartate Asparagine metabolism;Metabolism;Nucleobase biosynthesis;Purine nucleotides nucleosides metabolism;superpathway of purine nucleotide salvage;inosine-5,-phosphate biosynthesis;Purine ribonucleoside monophosphate biosynthesis;purine nucleotides <i>de novo</i> biosynthesis (Consensus)

Recessive Scores

• pRec: 0.312

Intolerance Scores

• loftool: 0.183
• rvis_EVS: -0.6
• rvis_percentile_EVS: 18.06

Haploinsufficiency Scores

• pHI: 0.771
• hipred: N
• hipred_score: 0.494
• ghis: 0.627

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.958

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Adsl
• 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); pigmentation phenotype; vision/eye phenotype

Gene ontology

• Biological process: response to hypoxia;purine nucleotide biosynthetic process;AMP biosynthetic process;'de novo' IMP biosynthetic process;response to nutrient;aerobic respiration;purine ribonucleoside monophosphate biosynthetic process;response to muscle activity;response to starvation;'de novo' AMP biosynthetic process;protein tetramerization
• Cellular component: cytosol
• Molecular function: N6-(1,2-dicarboxyethyl)AMP AMP-lyase (fumarate-forming) activity;(S)-2-(5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamido)succinate AMP-lyase (fumarate-forming) activity