ADSL

Chr 22AR

adenylosuccinate lyase

Also known as: AMPS, ASASE, ASL

NCBI Gene: 158 ENSG00000239900 UniProt: P30566 OMIM: 608222

The encoded protein catalyzes two non-sequential reactions in the de novo purine biosynthetic pathway, converting SAICAR to AICAR and adenylosuccinate to adenosine monophosphate. Autosomal recessive mutations cause adenylosuccinase deficiency, characterized by psychomotor retardation, epilepsy, and autistic features. The pathogenic mechanism involves loss of enzyme function disrupting purine metabolism.

OMIM ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

The protein encoded by this gene belongs to the lyase 1 family. It is an essential enzyme involved in purine metabolism, and catalyzes two non-sequential reactions in the de novo purine biosynthetic pathway: the conversion of succinylaminoimidazole carboxamide ribotide (SAICAR) to aminoimidazole carboxamide ribotide (AICAR) and the conversion of adenylosuccinate (S-AMP) to adenosine monophosphate (AMP). Mutations in this gene are associated with adenylosuccinase deficiency (ADSLD), a disorder marked with psychomotor retardation, epilepsy or autistic features. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Dec 2015]

OMIM ResearchGenerating clinical summary…

DNmechanismARLOEUF 1.071 OMIM phenotype

Clinical Summary— ADSL

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Gene-Disease Validity (ClinGen)

adenylosuccinate lyase deficiency · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

80 unique Pathogenic / Likely Pathogenic· 517 VUS of 923 total submissions

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Clinical Trials

1 active or recruiting trial — potential therapeutic options may be available

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.07LOEUF

pLI 0.000

Z-score 1.26

OE 0.74 (0.53–1.07)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.80Z-score

OE missense 0.87 (0.78–0.96)

244 obs / 281.9 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.74 (0.53–1.07)

0≤0.351.4

Missense OE?0.87 (0.78–0.96)

0≤0.61.4

Synonymous OE?0.87

0≤1.21.6

LoF obs/exp: 21 / 28.2Missense obs/exp: 244 / 281.9Syn Z: 1.05

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

definitiveADSL-related adenylosuccinase deficiencyOTHERAR

This gene — mechanism propensity

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

0.6937th %ile

GOF

0.5562th %ile

LOF

0.4038th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

923 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic38

Likely Pathogenic42

VUS517

Likely Benign226

Benign45

Conflicting44

Pathogenic

Likely Pathogenic

517

VUS

226

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	23	9	6	0	38
Likely Pathogenic	11	27	3	1	42
VUS	5	215	292	5	517
Likely Benign	0	4	122	100	226
Benign	0	2	41	2	45
Conflicting	—				44
Total	39	257	464	108	912

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

24 pathogenic / likely-pathogenic (of 30) ClinVar copy-number / structural variants overlap ADSL — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →