ASS1

Chr 9AR

argininosuccinate synthase 1

Also known as: ASS, CTLN1

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.

OMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
LOFmechanismARLOEUF 0.981 OMIM phenotype
VCEP Guidelines: Urea Cycle DisordersReleased
ClinGen Panel
Clinical SummaryASS1
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Gene-Disease Validity (ClinGen)
citrullinemia type I · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.98LOEUF
pLI 0.000
Z-score 1.62
OE 0.66 (0.460.98)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.76Z-score
OE missense 0.86 (0.770.97)
211 obs / 244.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.66 (0.460.98)
00.351.4
Missense OE0.86 (0.770.97)
00.61.4
Synonymous OE1.14
01.21.6
LoF obs/exp: 18 / 27.1Missense obs/exp: 211 / 244.3Syn Z: -1.11
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveASS1-related citrullinemiaLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.7035th %ile
GOF
0.5660th %ile
LOF
0.3454th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

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

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

ASS1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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