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…

Primary Disease Associations & Inheritance

Adenylosuccinase deficiencyMIM #103050

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · adenylosuccinate lyase deficiency · AR · ClinGen 2020

Active trials

Pubs (1 yr)

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P/LP submissions

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P/LP missense

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LOEUF

Mechanism· predicted

Some data sources returned errors (1)

gnomad: Error: gnomAD API error: 400

Population Genetics & Constraint

gnomAD

Constraint data not available from gnomAD.

Background carrier burden — how many people carry a rare variant somewhere in ADSL?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 85

630 rare PASS variants

Rare truncating (LoF)

1 in 1,100

115 rare PASS variants

Rare synonymous (reference)

1 in 240

245 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for ADSL. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 100	1 in 1,800
South Asian	~43k	1 in 94	1 in 2,300
Remaining (unassigned)	~30k	1 in 83	1 in 740
European (Finnish)	~27k	1 in 250	1 in 820
Admixed American	~22k	1 in 97	1 in 870
African / African American	~21k	1 in 110	1 in 3,600
East Asian	~20k	1 in 89	1 in 2,100
Ashkenazi Jewish	~13k	1 in 1,600	≈ 1 in 3,300
Middle Eastern	~2,884	1 in 130	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 13 coding exons well covered in gnomAD exomes and genomes.? see exons ↓