ADSL Gene - Adenylosuccinate Lyase
Adenylosuccinate Lyase: Function, Mutations, and Associated Disorders
Gene Information Card
| Symbol | ADSL |
|---|---|
| Full Name | Adenylosuccinate Lyase |
| Gene Type | Protein coding |
| Chromosomal Location | 22q13.1 |
| NCBI Gene ID | 158 ncbi.nlm.nih.gov/gene/158 |
| Ensembl ID | ENSG00000100299 |
| UniProt ID | P30566 |
| OMIM ID | 608222 |
| HGNC ID | 291 |
| Aliases | AMPS, ASASE, ASL, MGC117402, MGC117403 |
Description
The ADSL gene encodes adenylosuccinate lyase, an enzyme involved in the de novo synthesis of purine nucleotides. It catalyzes the conversion of adenylosuccinate to AMP and fumarate, and of SAICAR to AICAR and fumarate. Mutations in ADSL cause adenylosuccinate lyase deficiency, a rare autosomal recessive disorder characterized by psychomotor retardation, seizures, and autistic features.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Adenylosuccinate Lyase Deficiency | Loss-of-function mutations impair purine nucleotide synthesis, leading to accumulation of succinylpurines and neurological symptoms. | ClinVar, OMIM |
| Autism Spectrum Disorder | Some ADSL variants have been associated with autistic features, though direct causality is not fully established. | ClinVar, OMIM |
| Epileptic Encephalopathy | Severe ADSL deficiency can present with early-onset seizures and developmental delay. | ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Liver | 8.3 | Medium |
| Kidney | 7.1 | Medium |
| Heart | 6.4 | Medium |
| Skeletal Muscle | 5.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 10.2 | High expression |
| HeLa | 8.5 | Medium expression |
| K562 | 6.3 | Medium expression |
| HepG2 | 7.8 | Medium expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1277G>A (p.Arg426His) | Missense | Common | Reduced enzyme activity, associated with ADSL deficiency |
| c.1435C>T (p.Arg479Ter) | Nonsense | Rare | Premature truncation, loss of function |
| c.1186G>A (p.Val396Met) | Missense | Rare | Impaired catalytic activity |
| c.1A>G (p.Met1Val) | Missense | Rare | Start codon loss, likely null |
Mutation functional classification
Loss of Function (LOF)
Most ADSL mutations result in loss of enzyme activity, leading to accumulation of succinylaminoimidazole carboxamide riboside (SAICAr) and succinyladenosine (S-Ado).
Gain of Function (GOF)
No gain-of-function mutations reported.
Dominant Negative (DN)
No dominant-negative effects documented; disease is autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
| • Adenylosuccinate lyase activity | • Purine nucleotide biosynthetic process |
| • Fumarate metabolic process | • AMP biosynthetic process |
| • Cytoplasm |
Pathways
• Purine metabolism (KEGG: hsa00230)
• De novo purine biosynthesis
Protein Summary
Adenylosuccinate lyase (ADSL) is a homotetrameric enzyme that catalyzes two steps in purine nucleotide biosynthesis: the conversion of adenylosuccinate to AMP and fumarate, and the conversion of SAICAR to AICAR and fumarate. The protein is localized in the cytoplasm and is expressed in various tissues, with highest levels in brain and liver. Mutations in ADSL lead to a rare autosomal recessive disorder characterized by neurological impairment.
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