ADSL

Chr 22AR

adenylosuccinate lyase

Also known as: AMPS, ASASE, ASL

NCBI Gene: 158ENSG00000239900UniProt: P30566

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]

Primary Disease Associations & Inheritance

Adenylosuccinase deficiencyMIM #103050
AR
540
ClinVar variants
48
Pathogenic / LP
0.00
pLI score
1
Active trials
Clinical Summary— ADSL
🧬
Gene-Disease Validity (ClinGen)
adenylosuccinate lyase deficiency · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
48 Pathogenic / Likely Pathogenic· 302 VUS of 540 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
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?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.80Z-score
OE missense 0.87 (0.78–0.96)
244 obs / 281.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.74 (0.53–1.07)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.87 (0.78–0.96)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.87
0≤1.21.6
LoF obs/exp: 21 / 28.2Missense obs/exp: 244 / 281.9Syn Z: 1.05

ClinVar Variant Classifications

540 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic28
Likely Pathogenic20
VUS302
Likely Benign156
Benign20
Conflicting14
28
Pathogenic
20
Likely Pathogenic
302
VUS
156
Likely Benign
20
Benign
14
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
4
6
18
0
28
Likely Pathogenic
5
10
4
1
20
VUS
4
87
207
4
302
Likely Benign
0
3
87
66
156
Benign
0
2
16
2
20
Conflicting
—14
Total1310833273540

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

View in ClinVar →

Protein Context — Lollipop Plot

ADSL · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

ADSL-related adenylosuccinase deficiency

definitive
ARUndeterminedAltered Gene Product Structure
Dev. Disorders
G2P ↗
missense variantinframe deletioninframe insertion

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Adenylosuccinase deficiency

MIM #103050

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Adenylosuccinate lyase deficiency.
Jurecka A et al.·J Inherit Metab Dis
2015Review
ADSL deficiency is a secondary mitochondrial disease affecting organelle homeostasis and ERK2/AKT signaling in a linear genotype-phenotype relation.
Bordi M et al.·Cell Rep
2025
Disorders of purine biosynthesis metabolism.
Dewulf JP et al.·Mol Genet Metab
2022Review
Biochemical and structural analysis of 14 mutant adsl enzyme complexes and correlation to phenotypic heterogeneity of adenylosuccinate lyase deficiency.
Zikanova M et al.·Hum Mutat
2010
Silencing of Dicer enhances dacarbazine resistance in melanoma cells by inhibiting ADSL expression.
Yeh YW et al.·Aging (Albany NY)
2023
Mutations of ATIC and ADSL affect purinosome assembly in cultured skin fibroblasts from patients with AICA-ribosiduria and ADSL deficiency.
Baresova V et al.·Hum Mol Genet
2012Cohort
Human adenylosuccinate lyase (ADSL), cloning and characterization of full-length cDNA and its isoform, gene structure and molecular basis for ADSL deficiency in six patients.
Kmoch S et al.·Hum Mol Genet
2000Cohort
Clinical and molecular characterization of patients with adenylosuccinate lyase deficiency.
Mastrogiorgio G et al.·Orphanet J Rare Dis
2021Cohort
Investigating the relevance of nucleotide metabolism in the prognosis of glioblastoma through bioinformatics models.
Jiang LW et al.·Sci Rep
2025Functional
Nrf2-mediated adenylosuccinate lyase promotes resistance to gemcitabine in pancreatic ductal adenocarcinoma cells through ferroptosis escape.
Hsu TW et al.·J Cell Physiol
2024
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
16P11.2 Deletion Syndrome16p11.2 Duplications1Q21.1 Deletion

Online Study of People Who Have Genetic Changes and Features of Autism: Simons Searchlight

RECRUITING
NCT01238250Simons SearchlightStarted 2010-10

External Resources

Links to major genomics databases and tools