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ADSS2 – Schizophrenia

Evidence regarding ADSS2 in schizophrenia is conflicted. One study using a multifactor dimensionality reduction analysis in a Chinese cohort of 488 schizophrenia probands and 516 controls detected a significant interaction between a polymorphism in ADSS2 and variants in ATM (PMID:19115993), suggesting a potential role in disease susceptibility. However, a second independent association study in a similarly sized Chinese sample (480 schizophrenia probands and 502 controls) reported no significant differences in allele, genotype, or haplotype distributions of ADSS2 variants between cases and controls (PMID:18721483).

In parallel, functional assessments of ADSS2, conducted via site‐directed mutagenesis in Escherichia coli, have elucidated key residues (e.g. the G15V mutant, here represented as c.43G>T (p.Gly15Val)) that are critical for enzyme catalysis and structure (PMID:8179335, PMID:9115248, PMID:9632649). Although these robust in vitro studies underscore the biological relevance of ADSS2, the lack of consistent genetic association weakens its current clinical validity. In summary, despite compelling functional evidence, inconsistent genetic findings have rendered the association between ADSS2 and schizophrenia disputed, limiting its diagnostic utility at this time.

References

  • BMC Medical Genetics • 2008 • Association analyses of the interaction between the ADSS and ATM genes with schizophrenia PMID:19115993
  • Behavioral and Brain Functions : BBF • 2008 • An association study of ADSS gene polymorphisms with schizophrenia PMID:18721483
  • Archives of Biochemistry and Biophysics • 1994 • Characterization of the putative GTP-binding site residues of Escherichia coli adenylosuccinate synthetase by site‑directed mutagenesis PMID:8179335
  • The Journal of Biological Chemistry • 1997 • Residues essential for catalysis and stability of the active site of Escherichia coli adenylosuccinate synthetase as revealed by directed mutation and kinetics PMID:9115248
  • The Journal of Biological Chemistry • 1998 • Ambiguities in mapping the active site of a conformationally dynamic enzyme by directed mutation. Role of dynamics in structure‑function correlations in Escherichia coli adenylosuccinate synthetase PMID:9632649

Evidence Based Scoring (AI generated)

Gene–Disease Association

Disputed

Two association studies in Chinese cohorts (488 schizophrenia probands PMID:19115993 and 480 schizophrenia probands PMID:18721483) yielded conflicting findings, with one study reporting a significant gene–gene interaction, while the other found no association.

Genetic Evidence

Disputed

Case–control analyses involving approximately 968 schizophrenia cases and 1018 controls provided inconsistent support for an association, with significant gene–gene interaction observed in one study (PMID:19115993) failing replication in another (PMID:18721483).

Functional Evidence

Moderate

In vitro functional studies employing site‑directed mutagenesis have identified critical residues (e.g. the G15V change, represented here as c.43G>T (p.Gly15Val)) that affect enzyme kinetics and structure, supporting ADSS2’s biochemical relevance (PMID:8179335, PMID:9115248, PMID:9632649).