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…

DNmechanismLOEUF 0.45

Clinical Summary— ADSS2

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.23) despite low pLI — interpret in context.

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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

This gene — mechanism propensity

0.6455th %ile

GOF

0.6052th %ile

LOF

0.4234th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

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