ADSS2

Chr 1

adenylosuccinate synthase 2

Also known as: ADEH, ADSS, ADSS 2

NCBI Gene: 159 ENSG00000035687 UniProt: P30520 OMIM: 103060

The protein is adenylosuccinate synthetase, which catalyzes the first committed step in converting inosine monophosphate to adenosine monophosphate in purine nucleotide biosynthesis. Mutations cause autosomal recessive adenylosuccinase deficiency, a disorder affecting the nervous system with developmental delay, intellectual disability, seizures, and autism spectrum features. The gene is moderately constrained against loss-of-function variants (LOEUF 0.454), reflecting the importance of purine metabolism for cellular function.

OMIM ResearchSummary from RefSeq, UniProt

This gene encodes the enzyme adenylosuccinate synthetase which catalyzes the first committed step in the conversion of inosine monophosphate to adenosine monophosphate. A pseudogene of this gene is found on chromosome 17.[provided by RefSeq, Nov 2010]

OMIM ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

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Pubs (1 yr)

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P/LP submissions

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P/LP missense

0.45

LOEUF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.45LOEUF

pLI 0.330

Z-score 3.65

OE 0.23 (0.13–0.45)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

2.22Z-score

OE missense 0.59 (0.52–0.68)

140 obs / 236.1 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.23 (0.13–0.45)

0≤0.351.4

Missense OE?0.59 (0.52–0.68)

0≤0.61.4

Synonymous OE?0.91

0≤1.21.6

LoF obs/exp: 6 / 26.1Missense obs/exp: 140 / 236.1Syn Z: 0.67

Background carrier burden — how many people carry a rare variant somewhere in ADSS2?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 300

401 rare PASS variants

Rare truncating (LoF)

1 in 5,900

60 rare PASS variants

Rare synonymous (reference)

1 in 520

197 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for ADSS2. 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 300	1 in 6,300
South Asian	~43k	1 in 400	1 in 4,200
Remaining (unassigned)	~30k	1 in 310	≈ 1 in 7,400
European (Finnish)	~27k	1 in 2,200	1 in 3,300
Admixed American	~22k	1 in 380	1 in 3,700
African / African American	~21k	1 in 340	≈ 1 in 8,100
East Asian	~20k	1 in 280	≈ 1 in 9,800
Ashkenazi Jewish	~13k	≈ 1 in 13,000	none seen
Middle Eastern	~2,884	1 in 210	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): 11 of 13 coding exons well covered in gnomAD exomes; exons 4, 7 marginal. Genomes: all 13.? see exons ↓