ASS1

Chr 9AR

argininosuccinate synthase 1

Also known as: ASS, CTLN1

NCBI Gene: 445 ENSG00000130707 UniProt: P00966 OMIM: 603470

The protein catalyzes the penultimate step of arginine biosynthesis by synthesizing argininosuccinate from citrulline and aspartate. Mutations cause citrullinemia, an autosomal recessive disorder of the urea cycle that results in hyperammonemia and elevated plasma citrulline levels. The pathogenic mechanism involves loss of enzyme function leading to impaired conversion of citrulline to argininosuccinate in the cytosol.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

The protein encoded by this gene catalyzes the penultimate step of the arginine biosynthetic pathway. There are approximately 10 to 14 copies of this gene including the pseudogenes scattered across the human genome, among which the one located on chromosome 9 appears to be the only functional gene for argininosuccinate synthetase. Mutations in the chromosome 9 copy of this gene cause citrullinemia. Two transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Aug 2012]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

CitrullinemiaMIM #215700

UniProtCitrullinemia 1

Clinical highlights

Gene-disease validity (ClinGen)

citrullinemia type I · ARDefinitivesufficient evidence for diagnostic panels

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

111

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.98

LOEUF

LOF

Mechanism· G2P

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